Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy followed by adjuvant chemotherapy in locally advanced nasopharyngeal carcinoma

Abstract

Background

Concurrent chemoradiotherapy followed by adjuvant chemotherapy (CCRT-AC) is currently recommended as the standard treatment for locally advanced nasopharyngeal carcinoma (LA-NPC). Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy (NAC-CCRT) is an alternative strategy for decreasing tumor size and controlling micrometastases before main treatment. The aim of this study was to investigate and compare survival outcomes between LA-NPC patients treated with CCRT-AC and those treated with NAC-CCRT.

Methods

This retrospective cohort study included consecutive histologically confirmed LA-NPC patients that were treated with NAC-CCRT or CCRT-AC at Siriraj Hospital during the March 2010 to October 2014 study period. CCRT in both protocols consisted of 3-week cycles of cisplatin 100 mg/m² with concurrent radiotherapy. Either NAC or AC consisted of 3-week cycles of cisplatin on day 1 and fluorouracil/leucovorin on days 1–4 for a maximum three cycles. The primary endpoint was 5-year overall survival (OS). Flexible parametric survival analysis was used, because the proportional hazards assumption of Cox regression was violated.

Results

Of the 266 LA-NPC patients that received treatment during the study period, 79 received NAC-CCRT and 187 received CCRT-AC. Median follow-up was 37 months. Significantly more patients with advanced clinical stage (stage IVA-IVB) received NAC-CCRT (86% in NAC-CCRT vs. 29% in CCRT-AC; p < 0.001). Compared to CCRT-AC in crude analysis, 3-year and 5-year OS of NAC-CCRT were 72% vs. 86% and 62% vs. 75% respectively (p = 0.059). Interestingly, the 3-year and 5-year post-estimation adjusted OS was 84% and 74% for NAC-CCRT and 81% and 70% for CCRT-AC, respectively (HR: 0.83, 95% confidence interval (CI): 0.45–1.56; p = 0.571). Also, adjusted analysis of distant-metastasis survival, NAC-CCRT showed HR was 0.79 (95% CI:0.37–1.72, p = 0.557). Conversely, adjusted analysis of locoregional relapse (LLR)-free survival revealed NAC-CCRT to have a significantly higher risk of LRR (HR: 2.18, 95% CI: 0.98–4.87; p = 0.057).

Conclusions

The results suggested that prognosis in the NAC-CCRT treated patients was not superior to that of the CCRT-AC treated individuals. In patients that receive neoadjuvant chemotherapy, locoregional relapse should be of concern. High-risk distant metastasis patients (N3 stage) that could achieve survival advantage from NAC-CCRT is an interesting and important topic for further study.

https://ift.tt/2ITeFbW

Erlotinib treatment after platinum-based therapy in elderly patients with non-small-cell lung cancer in routine clinical practice – results from the ElderTac study

Abstract

Background

In this prospective non-interventional study, the effectiveness and tolerability of erlotinib in elderly patients with non-small-cell lung cancer (NSCLC) after ≥1 platinum-based chemotherapy were assessed.

Methods

A total of 385 patients ≥65 years of age with advanced NSCLC receiving erlotinib were observed over 12 months. The primary endpoint was the 1-year overall survival (OS) rate.

Results

Patients were predominantly Caucasian (99.2%), a mean of 73 years old; 24.7% had an Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2. Most common tumor histologies were adenocarcinoma (64.9%) and squamous cell carcinoma (22.3%). Of 119 patients tested, 15.1% had an activating epidermal growth factor receptor gene (EGFR) mutation. The 1-year OS rate was 31% (95% CI 25–36) with a median OS of 7.1 months (95% CI 6.0–7.9). OS was significantly better in females than males (p = 0.0258) and in patients with an EGFR mutation compared to EGFR wild-type patients (p = 0.0004). OS was not affected by age (p = 0.3436) and ECOG PS (p = 0.5364). Patients with squamous NSCLC tended to live longer than patients with non-squamous EGFR wild-type tumors (median OS: 8.6 vs 5.5 months). Cough and dyspnea improved during the observation period. The erlotinib safety profile was comparable to that in previous studies with rash (45.2%) and diarrhea (22.6%) being the most frequently reported adverse events.

Conclusions

Erlotinib represents a suitable palliative treatment option in further therapy lines for elderly patients with advanced NSCLC. The results obtained under real-life conditions add to our understanding of the benefits and risks of erlotinib in routine clinical practice.

Trial registration

BfArM (https://www.bfarm.de; ML23023); ClinicalTrials.gov (NCT01535729; 20 Feb 2012).

https://ift.tt/2GctO6l

Detection of circulating tumor cells in patients with pituitary tumors

Abstract

Background

Circulating tumor cells (CTCs) are tumor cells that have shed from a primary tumor and circulate in the peripheral blood. Recent experimental and clinical studies show that CTCs can be detected in early-stage disease.

Case presentation

We report three cases of pituitary adenoma (PA) in which tumor cells with particles were detected in the interstitial vascular compartment by transmission electron microscopy. Tumors were completely resected. Immunohistochemical analysis showed a β-catenin score of 10.5 ± 1.5 in the three cases with CTCs compared with 2.4 ± 0.5 in 24 control adenomas. The Ki-67 labeling index was 2.1 ± 0.7 in CTCs vs. 0.2 ± 0.3 in control cases (p = 0.043), and the p53 score was 4.33 ± 1.3 vs. 0.31 ± 0.17 (p = 0.000). The E-cadherin score did not differ significantly between the two groups.

Conclusions

CTCs can be detected in benign tumors such as PAs and not only in late-stage malignant tumors with apparent distant metastases. The present findings suggest that pituitary carcinomas develop from adenomas.

https://ift.tt/2ITeAoE

Development of primary human pancreatic cancer organoids, matched stromal and immune cells and 3D tumor microenvironment models

Abstract

Background

Patient-derived tumor models are the new standard for pre-clinical drug testing and biomarker discovery. However, the emerging technology of primary pancreatic cancer organoids has not yet been broadly implemented in research, and complex organotypic models using organoids in co-culture with stromal and immune cellular components of the tumor have yet to be established. In this study, our objective was to develop and characterize pancreatic cancer organoids and multi-cell type organotypic co-culture models to demonstrate their applicability to the study of pancreatic cancer.

Methods

We employed organoid culture methods and flow cytometric, cytologic, immunofluorescent and immunohistochemical methods to develop and characterize patient-derived pancreatic cancer organoids and multi-cell type organotypic co-culture models of the tumor microenvironment.

Results

We describe the culture and characterization of human pancreatic cancer organoids from resection, ascites and rapid autopsy sources and the derivation of adherent tumor cell monocultures and tumor-associated fibroblasts from these sources. Primary human organoids displayed tumor-like cellular morphology, tissue architecture and polarity in contrast to cell line spheroids, which formed homogenous, non-lumen forming spheres. Importantly, we demonstrate the construction of complex organotypic models of tumor, stromal and immune components of the tumor microenvironment. Activation of myofibroblast-like cancer associated fibroblasts and tumor-dependent lymphocyte infiltration were observed in these models.

Conclusions

These studies provide the first report of novel and disease-relevant 3D in-vitro models representing pancreatic tumor, stromal and immune components using primary organoid co-cultures representative of the tumor-microenvironment. These models promise to facilitate the study of tumor-stroma and tumor-immune interaction and may be valuable for the assessment of immunotherapeutics such as checkpoint inhibitors in the context of T-cell infiltration.

https://ift.tt/2pKtlBx

To fast, or not to fast before chemotherapy, that is the question

Abstract

Fasting in disease prevention and treatment has recently become a popular topic, particularly in the context of oncology. Unfortunately, the growing attention paid by the media has created a background of speculations and ambiguous messages.

The attitude towards the role of fasting in cancer patients should be very cautious, as the risk of malnutrition/sarcopenia and disinformation may be associated with this approach.

Whether the results obtained by fasting in the cellular and animal models can be transferred to cancer patients is still to be ascertained. At the moment, more preclinical studies are required to determine in which cancers, at which stage, and in what combinations fasting, fasting-mimicking diets or caloric restriction mimetics may prove effective.

So, despite the "rumors" of marketing and media, nowadays fasting and calorie restriction around CT represent only a promising intuition, which requires proper efforts and time to be validated by evidence-based clinical data.

https://ift.tt/2IVo7eZ

The prognostic significance of topoisomerase II alpha protein in early stage luminal breast cancer

Abstract

Background

Topoisomerase II alpha (TOP2A) protein has been shown to be a proliferation marker associated with tumor grade and Ki67 index. The prognostic effect of TOP2A seems different among different subtypes of breast cancer. The current study evaluated the prognostic impact of TOP2A protein on luminal breast cancer.

Method

Altogether 434 stage I-II luminal breast cancer patients who underwent curative surgery in Sun Yat-Sen University Cancer Center between 2007 and 2009 were enrolled. TOP2A protein expression was assessed by immunohistochemistry. Clinical and pathological data were retrospectively collected.

Result

With a cut-off value of 30%, 127 (29.3%) patients were classified as TOP2A overexpression. TOP2A overexpression was associated with a higher tumor grade and Ki67 index. Patients with TOP2A high expression showed a significantly higher rate of distant metastasis and shorter distant metastasis free survival (DMFS) compared with patients with low TOP2A expression. The prognostic influence of TOP2A expression was more significant in years 5–8 after diagnosis, and more pronounced in stage II patients, luminal B disease, and patients treated with adjuvant endocrine therapy alone. Multivariate survival analysis revealed TOP2A overexpression was an independent fact for worse DMFS.

Conclusion

TOP2A protein showed a time dependent influence on prognosis in stage I-II luminal breast cancer, suggesting it might be a potential predictor of late recurrence for this group of patients.

https://ift.tt/2GdCgSU

Shorter survival in adolescent and young adult patients, compared to adult patients, with stage IV colorectal cancer in Japan

Abstract

Background

The incidence of colorectal cancer in adolescent and young adult patients is increasing. However, survival and clinical features of young patients, especially those with stage IV disease, relative to adult patients remain unclear.

Methods

This retrospective single-institution cohort study was conducted at a tertiary care cancer center. Subjects were 861 consecutive patients who were diagnosed with stage IV colorectal cancer at the age of 15 to 74 years and who were referred to the division of surgery or gastrointestinal oncology at the National Cancer Center Hospital from 1999 to 2013. Overall survival (OS) was investigated and clinicopathological variables were analyzed for prognostic significance.

Results

Of these, 66 (8%) were adolescent and young adult patients and 795 (92%) were adult patients. Median survival time was 13.6 months in adolescent and young adult patients and 22.4 months in adult patients, and 5-year OS rates were 17.3% and 20.3%, respectively, indicating significant worse prognosis of adolescent and young adult patients (p = 0.042). However, age itself was not an independent factor associated with prognosis by multivariate analysis. When compared with adult patients, adolescent and young adult patients consisted of higher proportion of the patients who did not undergo resection of primary tumor, which was an independent factor associated with poor prognosis in multivariate analysis. In patients who did not undergo resection (n = 349), OS of adolescent and young adult patients were significantly worse (p = 0.033).

Conclusions

Prognoses were worse in adolescent and young adult patients with stage IV colorectal cancer compared to adult patients in Japan, due to a higher proportion of patients who did not undergo resection with more advanced and severe disease, but not due to age itself.

https://ift.tt/2ITeu0g

Outcomes of Pemetrexed-based chemotherapies in HER2 -mutant lung cancers

Abstract

Background

HER2 mutation has been found to be an oncogenic driver gene in non-small cell lung cancers(NSCLC) and HER2-directed therapies have shown promising results in this unique population, while little is known about its association with outcomes of chemotherapy. The aim of this study was to investigate the efficacy of first line chemotherapy in patients with advanced HER2-mutant lung adenocarcinomas.

Methods

Patients with advanced NSCLC(N = 1714) initially underwent testing for EGFR, KRAS, BRAF mutations and ALK, ROS1 rearrangements, and negative cases were then assessed for HER2 mutations using the method of amplification refractory mutation system(ARMS). The efficacy of first line pemetrexed-based chemotherapy was investigated in patients with HER2-mutant and those with EGFR-mutant, ALK/ROS1-rearranged and KRAS-mutant advanced adenocarcinomas.

Results

HER2 mutations were detected in 29 of 572(5.1%) specimens from a selected population of EGFR/KRAS/BRAF/ALK/ROS1 negative patients. All of them are adenocarcinomas. Among patients with HER2-mutant lung cancers, 25 received pemetrexed-based first line chemotherapy. The objective response rate(ORR) was 36.0%. Their median progression free survival(PFS) was 5.1 months, which was similar with that of KRAS-mutant group (n = 40,5.0 months, p = 0.971), numerically shorter than that of EGFR-mutant group(n = 74, 6.5 months, p = 0.247) and statistically significantly shorter than that of ALK/ROS1-rearranged group (n = 39,9.2 months, p = 0.004). Furthermore, HER2 variants subgroup analysis showed that PFS was inferior in A775_G776insYVMA group compared with other variants (4.2 vs 7.2 months, p = 0.085).

Conclusions

Patients with advanced HER2-mutant lung adenocarcinomas showed an inferior outcome of first line pemetrexed-based chemotherapy compared to those with ALK/ROS1 rearrangements, which strengthen the need for effective HER2-targeted drugs in clinical practice.

https://ift.tt/2GfzOLR

Knockdown delta-5-desaturase in breast cancer cells that overexpress COX-2 results in inhibition of growth, migration and invasion via a dihomo-γ-linolenic acid peroxidation dependent mechanism

Abstract

Background

Cyclooxygenase-2 (COX-2), the inducible COX form, is a bi-functional membrane-bound enzyme that typically metabolizes arachidonic acid (downstream ω-6 fatty acid) to form 2-series of prostaglandins known to be involved in cancer development. Overexpression of COX-2 has been found in a majority of breast carcinomas, and has also been associated with increased severity and the development of the metastasis. Our lab recently demonstrated that COX-2 can also metabolize dihomo-γ-linolenic acid (DGLA, a precursor of ω-6 arachidonic acid) to produce an anti-cancer byproduct, 8-hydroxyoctanoic acid (8-HOA) that can inhibit growth and migration of colon and pancreatic cancer cells. We thus tested whether our strategy of knocking down delta-5-desaturase (D5D, the key enzyme that converts DGLA to arachidonic acid) in breast cancer cells overexpressing COX-2 can also be used to promote 8-HOA formation, thereby suppressing cancer growth, migration, and invasion.

Methods

SiRNA and shRNA transfection were used to knock down D5D expression in MDA-MB 231 and 4 T1 cells (human and mouse breast cancer cell lines expressing high COX-2, respectively). Colony formation assay, FITC Annexin V/PI double staining, wound healing and transwell assay were used to assess the effect of our strategy on inhibition of cancer growth, migration, and invasion. GC/MS was used to measure endogenous 8-HOA, and western blotting was performed to evaluate the altered key protein expressions upon the treatments.

Results

We demonstrated that D5D knockdown licenses DGLA to inhibit growth of breast cancer cells via promoting formation of 8-HOA that can inhibit histone deacetylase and activate cell apoptotic proteins, such as procaspase 9 and PARP. Our strategy can also significantly inhibit cancer migration and invasion, associated with altered expression of MMP-2/− 9, E-cadherin, vimentin and snail. In addition, D5D knockdown and DGLA supplementation greatly enhanced the efficacy of 5-fluorouracil on breast cancer growth and migration.

Conclusions

Consistent to our previous studies on colon and pancreatic cancer, here we demonstrate again that the high level of COX-2 in breast cancer cells can be capitalized on inhibiting cancer growth and migration. The outcome of this translational research could guide us to develop new anti-cancer strategy and/or to improve current chemotherapy for breast cancer treatment.

https://ift.tt/2IXXeHo

A phase I/Ib study of OTSGC-A24 combined peptide vaccine in advanced gastric cancer

Abstract

Background

We conducted a phase I/Ib, open-label, single-arm trial to assess the safety, tolerability and optimal scheduling regimen of OTSGC-A24 cancer vaccine in patients with advanced gastric cancer.

Methods

Patients with advanced gastric cancer with HLA-A*24:02 haplotype were included in this study. OTSGC-A24 was administered at 1 mg in 3-weekly (3w), 2-weekly (2w), and weekly (1w) cohorts to evaluate the safety, immunological response and schedule. Based on the highest specific cytotoxic T lymphocyte (CTL) induction rate at 4 weeks, using the ELISPOT test, cohorts were expanded to define the optimal dosing schedule for OTSGC-A24.

Results

In this study, 24 advanced gastric cancer patients with HLA-A*24:02 haplotype were enrolled and treated in 3 cohorts (3w cohort: 3; 2w cohort: 11 and 1w cohort: 10 patients). The most common adverse events were decreased appetite (29%), diarrhea (21%), myalgia (25%). The most common treatment-related adverse event was injection site erythema (25%). No dose-limiting toxicities were observed in any cohort and OTSGC-A24 was well tolerated. Positive CTL responses after vaccination were observed in 15 patients (75%) at 4 weeks: 3w cohort (33%), 2w cohort (88%), 1w cohort (78%). At 12 weeks, 18 patients had responded (90%); 3w cohort (100%), 2w cohort (100%), 1w cohort (78%). The best radiological was stable disease (40%). Median progression free survival was 1.7 months (95% CI: 1.4 to 3.5) and median overall survival was 5.7 months (95% CI 3.8 to 8.6).

Conclusions

OTSGC-A24 combined peptide cancer vaccine was well tolerated. Significant responses in CTL were observed and the recommended phase 2 dose is 1 mg OTSGC-A24 sub-cutaneous, every 2 weeks. Although no radiological response was observed, a respectable overall survival was achieved, consistent with other immunotherapy agents being investigated in gastric cancer.

Trial registration

ClinicalTrials.gov Identifier: NCT01227772, Date registered: 21 Oct 2010.

https://ift.tt/2pLCj1d

FOLFIRI plus panitumumab in the treatment of wild-type KRAS and wild-type NRAS metastatic colorectal cancer

Abstract

Background

The aim of this study was to investigate the efficacy and safety of first-line panitumumab plus folinic acid, 5-fluorouracil and irinotecan (FOLFIRI) in patients with wild-type KRAS and wild-type NRAS metastatic colorectal cancer (mCRC).

Methods

Patients with wild-type KRAS and wild-type NRAS mCRC presenting to the medical oncology department of the Okmeydani Training and Research Hospital in Istanbul, Turkey, between April 2014 and January 2018 were enrolled in this study.

Results

A total of 64 patients (35 males and 29 females) with a median age of 59 (35–81) years old were enrolled. The median follow-up was 18.9 months, and the median progression-free survival was 13 months. The median overall survival (OS) was 26 months in the patients with wild-type KRAS and wild-type NRAS mCRC. It was 90.4% for the 6-month OS, 79.5% for the 1-year OS, 53.7% for the 2-year OS and 31.1% for the 3-year OS. The median OS of the patients who underwent metastasectomies was 40 [95% confidence interval (CI) = 19.9–60.1] months, and the median OS of the patients without metastasectomies was 22 (95% CI = 17.7–26.4) months. There was a statistically significant difference between these (P = 0.007).

Conclusion

The first-line FOLFIRI plus panitumumab was associated with favourable efficacy in the patients with wild-type KRAS and wild-type NRAS mCRC, and it was well tolerated. The removal of the metastases that became resectable after chemotherapy further prolonged the patients' survival.

Trial registration

Retrospectively registered: 33886

https://ift.tt/2DXty9i

CalliSpheres drug-eluting beads versus lipiodol transarterial chemoembolization in the treatment of hepatocellular carcinoma: a short-term efficacy and safety study

Abstract

Background

The present study aimed to evaluate the short-term efficacy and safety of drug-eluting beads transarterial chemoembolization (DEB-TACE) with CalliSpheres Beads loaded with doxorubicin (DOX) in the treatment of Chinese patients with hepatocellular carcinoma (HCC) compared to conventional TACE (cTACE).

Methods

A total of 54 patients with HCC treated by TACE from June 2016 to February 2017 were retrospectively analyzed. These included 24 cases in the DEB-TACE group and 30 cases in the cTACE group. The clinical efficacy, tumor recurrence rate, and complications were compared between the two groups. Furthermore, liver function tests and alpha-feto protein levels were compared between the two groups before and at 1 week and 1 month after interventional treatment.

Results

There were no significant differences in baseline characteristics (p > 0.05). Tumor response rates and disease control rates in the DEB-TACE group were significantly higher than those in the cTACE group at 3 and 6 months after treatment (p < 0.05). Recurrence rates at 6 months were significantly higher for cTACE compared to DEB-TACE (43.3 vs. 16.7%; p = 0.036). At 1 month, the AFP level in the DEB-TACE group was significantly lower than that in the cTACE group (p = 0.008). At the end of follow-up, four cases in the DEB-TACE group and two cases in the cTACE group were treated with salvage surgery after downstaging the disease. Liver function of both groups improved at 1 month. However, alanine aminotransferase, aspartate aminotransferase, and total bilirubin levels in the DEB-TACE group were better than those in the cTACE group (p < 0.05). The incidence of DOX-related complications in the DEB-TACE group was significantly lower than in the cTACE group (p < 0.05).

Conclusion

The short-term efficacy of DEB-TACE is better, and the complication rates are lower compared to cTACE in the treatment of Chinese patients with HCC. However, long-term clinical efficacy and survival benefit should be analyzed in future studies.

https://ift.tt/2GsSo6u

Mesh-reinforced pancreaticojejunostomy versus conventional pancreaticojejunostomy after pancreaticoduodenectomy: a retrospective study of 126 patients

Abstract

Background

Pancreatic fistula is a major cause of morbidity and mortality after pancreaticoduodenectomy. The aim of this study is to compare the safety and efficacy of a newly developed technique, namely mesh-reinforced pancreaticojejunostomy, in comparison with the conventional use of pancreaticojejunostomy after undergoing a pancreaticoduodenectomy.

Methods

Data was collected from regarding 126 consecutive patients, who underwent the mesh-reinforced pancreaticojejunostomy or conventional pancreaticojejunostomy, after standard pancreaticoduodenectomy by one group of surgeons, between the time period of 2005 and 2016. This data was collected retrospectively. Surgical parameters and perioperative outcomes were compared between these two groups.

Results

A total of 65 patients received mesh-reinforced pancreaticojejunostomy and 61 underwent conventional pancreaticojejunostomy. There were no substantial differences in surgical parameters, mortality, biliary leakage, delayed gastric emptying, gastrojejunostomy leakage, intra-abdominal fluid collection, postpancreatectomy hemorrhage, reoperation, and the total hospital costs between the two groups. Pancreatic fistula rate (15 versus 34%; p = 0.013), overall surgical morbidity (25 versus 43%; p = 0.032), and length of hospital stay (18 ± 9 versus 23 ± 12 days; p = 0.016) were significantly reduced after mesh-reinforced pancreaticojejunostomy. Multivariate analysis of the postoperative pancreatic fistula revealed that the independent factors that were highly associated with pancreatic fistula were a soft pancreatic texture and the type of conventional pancreaticojejunostomy.

Conclusions

This retrospective single-center study showed that mesh-reinforced pancreaticojejunostomy appears to be a safe technique for pancreaticojejunostomy. It may reduce pancreatic fistula rate and surgical complications after pancreaticoduodenectomy.

Trial registration

This research is waivered from trial registration because it is a retrospective analysis of medical records.

https://ift.tt/2E1gksw

Treatment of intraoperatively detected peritoneal carcinomatosis of colorectal origin with cytoreductive surgery and intraperitoneal chemotherapy

Abstract

Background

Diagnosis of peritoneal carcinomatosis (PC) may be missed by preoperative imaging. We are presenting our experience with incidentally detected PC of colorectal origin treated with cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC) at the same operation.

Methods

Between January 2010 and September 2016, 19 patients underwent CRS and IPC due to incidentally detected PC of colorectal origin. Data were analyzed from a prospectively collected database.

Results

The median age was 59 (29–78). In three patients, PC was diagnosed during emergency surgery. The primary tumor was located in the rectum (three patients; one with recurrent disease), left colon (9 patients), and right colon (7 patients). All patients underwent CRS and IPC, and one patient operated laparoscopically. Median peritoneal cancer index (PCI) was 5 (range, 3–14), and complete cytoreduction (CC-0) was achieved in 14 patients. After CRS, 8 patients received early postoperative intraperitoneal chemotherapy (EPIC), 7 patients received hyperthermic intraperitoneal chemotherapy (HIPEC), and 4 patients received both HIPEC and EPIC. The median hospital stay was 9 (6–29) days. Postoperative complications occurred in 6 patients. There was no postoperative mortality. Median follow-up was 40.2 (12–94) months. Five-year overall survival was 63.2%. Estimated mean survival time is longer in patients who underwent complete cytoreduction compared to patients having CC-1 or CC-2 cytoreduction (87.7 vs. 20.3 months; p < 0.001).

Conclusion

Cytoreductive surgery and IPC can be performed safely in patients with intraoperatively detected incidental PC of colorectal origin.

https://ift.tt/2GsS9IC

The IARC Perspective on Colorectal Cancer Screening

Colorectal cancer, which is the third most common cancer in men and the second most common in women, represents almost 10% of the annual global cancer incidence. Incidence rates of colorectal cancer show a strong positive gradient with an increasing level of economic development. Even so, the net…

https://ift.tt/2DXQ9CF

Nomograms predict long-term survival for patients with periampullary adenocarcinoma after pancreatoduodenectomy

Abstract

Background

The prognosis of patients with periampullary adenocarcinoma after pancreatoduodenectomy is diverse and not yet clearly illustrated. The aim of this study was to develop a nomogram to predict individual risk of overall survival (OS) and progression-free survival (PFS) in patients with periampullary adenocarcinoma after pancreatoduodenectomy.

Methods

A total of 205 patients with periampullary adenocarcinoma after pancreatoduodenectomy were retrospectively included. OS and PFS were evaluated by the Kaplan-Meier method. Two nomograms for predicting OS and PFS were established, and the predictive accuracy was measured by the concordance index (Cindex) and calibration plots.

Results

Lymph node ratio (LNR), carbohydrate antigen 19–9 (CA19–9) and anatomical location were incorporated into the nomogram for OS prediction and LNR, CA19–9; anatomical location and tumor differentiation were incorporated into the nomogram for PFS prediction. All calibration plots for the probability of OS and PFS fit well. The Cindexes of the nomograms for OS and PFS prediction were 0.678 and 0.68, respectively. The OS and PFS survival times were stratified significantly using the nomogram-predicted survival probabilities.

Conclusions

The present nomograms for OS and PFS prediction can provide valuable information for tailored decision-making for patients with periampullary adenocarcinoma after pancreatoduodenectomy.

https://ift.tt/2uocDgM

Anti-EGFR targeted therapy delivered before versus during radiotherapy in locoregionally advanced nasopharyngeal carcinoma: a big-data, intelligence platform-based analysis

Abstract

Background

Little is known about the prognostic difference of anti-EGFR therapy, cetuximab (CTX) or nimotuzumab (NTZ), concurrently with induction chemotherapy (IC, investigational arm) or RT (control arm) for patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC). We conducted this retrospective study to address this.

Methods

We identified 296 patients with newly diagnosed LA-NPC at Sun Yat-Sen University Cancer Center between January 2012 and May 2015. Patients were treated by IC with CCRT or RT and CTX/NTZ was delivered during IC or radiotherapy. Survival outcomes and toxicities between different arms were compared.

Results

In total, there were 149 patients in the investigational arm and 147 in control arm. The 3-year disease-free survival, overall survival, distant metastasis-free survival and locoregional relapse-free survival rates for investigational arm vs. control arm were 84.3% vs. 74.3% (P = 0.027), 94.0% vs. 92.1% (P = 0.673), 88.0% vs. 81.8% (P = 0.147) and 93.3% vs. 88.0% (P = 0.093). Multivariate analysis revealed patients in the control arm achieved significantly worse disease-free survival (HR, 1.497; 95% CI, 1.016–2.206; P = 0.026) compared with those in the investigational arm; however, no significant difference was identified for other endpoints. Patients in the investigational arm experienced more grade 3–4 skin reaction (15.4% vs. 2.0%, P <  0.001) and mucositis (10.1% vs. 3.4%, P = 0.022) during induction phase, but less skin reaction (5.4% vs. 25.9%, P <  0.001) and mucositis (24.8% vs. 36.7%, P = 0.026) during RT.

Conclusions

Our findings suggested that CTX/NTZ concurrently with IC may be a more effective and promising strategy for patients with LA-NPC receiving intensity-modulated radiotherapy.

https://ift.tt/2GrqYOr

Mental disorders around cancer diagnosis and increased hospital admission rate - a nationwide cohort study of Swedish cancer patients

Abstract

Background

Whether the emotional distress around cancer diagnosis is associated with the long-term outcomes and care utilization is unknown. We aimed to examine the association of mental disorders around cancer diagnosis with the hospital admission rates of cancer patients thereafter.

Methods

We conducted a nationwide cohort study including 218,508 cancer patients diagnosed in Sweden during 2004–2009 and followed them from 90 days after cancer through 2010. We used a clinical diagnosis of stress-related mental disorders from 90 days before to 90 days after cancer diagnosis as the exposure. We studied first all hospital admissions and then separately three common admissions, including external injuries, infections, and cardiovascular diseases. The Cox model was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs).

Results

Four thousand one hundred five patients received a diagnosis of stress-related mental disorders around the cancer diagnosis, and experienced a 35% increased rate of any hospital admission during follow-up (HR: 1.35, 95%CI: 1.28–1.41) as well as hospital admissions for external injuries (HR: 1.89, 95%CI: 1.67–2.14), infections (HR: 1.28, 95%CI: 1.08–1.52), and cardiovascular diseases (HR: 1.16, 95%CI: 1.03–1.30). Similar association was noted for most common cancer types.

Conclusions

These data suggest that cancer patients diagnosed with a stress-related mental disorder immediately before or after cancer diagnosis are subsequently at increased risk of hospital admissions for major comorbidities of cancer.

https://ift.tt/2uocuKg

Frequency of HPV in oral cavity squamous cell carcinoma

Abstract

Background

The prevalence of high-risk human papillomavirus (HPV) DNA in cases of oral cavity squamous cell carcinoma (SCC) varies widely. The aim of this study is to investigate the frequency of high-risk HPV DNA in a large Brazilian cohort of patients with oral cavity SCC.

Methods

Biopsy and resected frozen and formalin-fixed paraffin-embedded specimens of oral cavity SCC were available from 101 patients who were recruited at two Brazilian centres. Stringent measures with respect to case selection and prevention of sample contamination were adopted to ensure reliability of the data. Nested PCR using MY09/MY11 and GP5⁺/GP6⁺ as well as PGMY09/11 L1 consensus primers were performed to investigate the presence of HPV DNA in the tumours. HPV-positive cases were subjected to direct sequencing. Shapiro–Wilk and Student t test were used to evaluate data normality and to compare the means, respectively. Qualitative variables were analysed by logistic regression.

Results

Our results demonstrate that the frequency of high-risk HPV types in oral cavity SCC is very low and is less than 4%. All HPV-positive cases were HPV16. In addition, our results do not show a significant association between the tumour clinical features and the risk factors (tobacco, alcohol and HPV) for oral cavity SCC.

Conclusion

In the current study, we observed an overlapping pattern of risk factors that are related to tumour development. This, along with a low frequency of high-risk HPV DNA, supports the findings that HPV is not involved in the genesis of oral cavity SCC in Brazilian population.

https://ift.tt/2GwazYY

GDF15 predict platinum response during first-line chemotherapy and can act as a complementary diagnostic serum biomarker with CA125 in epithelial ovarian cancer

Abstract

Background

Growth differentiation factor 15 (GDF15) has attracted much interest as a novel biomarker for epithelial ovarian carcinoma (EOC). Research focus has been directed at GDF15 as a diagnostic detection, while the prognostic determination of GDF15 in EOC patients remains to be clearly elucidated. The present study aimed to investigate GDF15 level relative to clinicopathological characters, chemoresponse, and clinical outcome of EOC patients.

Methods

Serum from 122 patients with primary diagnosed EOC were analyzed for GDF15 and serum cancer antigen 125 (CA125). All cases were treated with debulking surgery and first-line chemotherapy, and samples were obtained just before debulking surgical treatment and first-line chemotherapy. Subsequently, clinical characteristics, responses to chemotherapy and progression-free survival (PFS) were recorded.

Results

Increasing levels of serum GDF15 was significantly associated with FIGO stage and lymphonodus metastasis. GDF15 and CA125 detection are complementary in the diagnosis of EOC and can be simultaneously profiled. The chemo-resistant EOC patients (median, 1225.0 pg/mL) showed significantly higher GDF15 than chemo-sensitive patients (median, 824.2 pg/mL; P = 0.013). Highly expressed GDF15 was an independent negative prognostic indicator in the PFS (P = 0.026) of the 122 EOC cases in the multivariate analysis. Additionally, patients with high level of serum CA125 significantly associated with suboptimal (P = 0.043) debulking surgery.

Conclusions

Our results provide valuable evidence that GDF15 is related with first-line chemo-resistance, with highly expressed GDF15 being a strong and an independent indicator of shorter PFS in EOC patients.

https://ift.tt/2uoBBN6

Depletion of nuclear import protein karyopherin alpha 7 (KPNA7) induces mitotic defects and deformation of nuclei in cancer cells

Abstract

Background

Nucleocytoplasmic transport is a tightly regulated process carried out by specific transport machinery, the defects of which may lead to a number of diseases including cancer. Karyopherin alpha 7 (KPNA7), the newest member of the karyopherin alpha nuclear importer family, is expressed at a high level during embryogenesis, reduced to very low or absent levels in most adult tissues but re-expressed in cancer cells.

Methods

We used siRNA-based knock-down of KPNA7 in cancer cell lines, followed by functional assays (proliferation and cell cycle) and immunofluorescent stainings to determine the role of KPNA7 in regulation of cancer cell growth, proper mitosis and nuclear morphology.

Results

In the present study, we show that the silencing of KPNA7 results in a dramatic reduction in pancreatic and breast cancer cell growth, irrespective of the endogenous KPNA7 expression level. This growth inhibition is accompanied by a decrease in the fraction of S-phase cells as well as aberrant number of centrosomes and severe distortion of the mitotic spindles. In addition, KPNA7 depletion leads to reorganization of lamin A/C and B1, the main nuclear lamina proteins, and drastic alterations in nuclear morphology with lobulated and elongated nuclei.

Conclusions

Taken together, our data provide new important evidence on the contribution of KPNA7 to the regulation of cancer cell growth and the maintenance of nuclear envelope environment, and thus deepens our understanding on the impact of nuclear transfer proteins in cancer pathogenesis.

https://ift.tt/2GtWM5k

Is double-approach surgery and tenodesis without a gastrocnemius flap better for dealing with proximal fibular osteosarcoma?

Abstract

Background

Resection of proximal fibular osteosarcoma involving the posteromedial aspect of the fibula is challenging. Reconstruction using a gastrocnemius flap may result in significant lateral instability and abnormal knee movement. Furthermore, postoperative gait may be disturbed by foot drop resulting from scarification of the common peroneal nerve.

Methods

Between January 2011 and December 2013, five patients with proximal fibular osteosarcoma were treated via the double-approach procedure using en bloc resection without a gastrocnemius flap. Simultaneously, all patients received one-stage tenodesis of the anterior tibial and toe extensor tendons. Clinical outcomes, including local tumor recurrence, complications, and functional outcomes, were evaluated.

Results

The mean follow-up duration was 47.2 months (range 42–52 months). No patients experienced local recurrence. The patients' Enneking functional scores were excellent (80%) or good (20%) at the final follow-up.

Conclusions

In patients with proximal fibular osteosarcoma, the double-approach procedure allows easier and safer en bloc tumor resection with vessel and nerve protection. One-stage tenodesis without a gastrocnemius flap is associated with good functional outcomes.

https://ift.tt/2um2wsK

Investigating the enigmatic link between periodontal inflammation and retinal degeneration

Many clinical studies link Chronic Periodontitis (CP) to various systemic disorders and lately age-related macular degeneration (AMD), a leading cause of irreversible vision loss in elderly, is found to be associated with periodontal disease. The keystone oral-pathobiont and one of the major causative organism for CP, Porphyromonas gingivalis (Pg), has been identified with the ability to invade epithelial, fibroblasts and dendritic cells.

https://ift.tt/2DXCZWo

Effects of periodontitis on the colon microbiome

Severe gum disease is among the most prevalent chronic infection in particular in African-American populations and is associated with complex microbial infection in the sub-gingival cavity. The polybacterial nature of periodontal disease is a risk factor for several various systemic diseases.

https://ift.tt/2pLpiET

The IARC Perspective on Colorectal Cancer Screening

New England Journal of Medicine, Ahead of Print.


https://ift.tt/2GdnEH6

Treatment of B-cell precursor acute lymphoblastic leukemia with the Galectin-1 inhibitor PTX008

Abstract

Background

Drug resistance of B-cell precursor acute lymphoblastic leukemia (BP-ALL) cells is conferred by both intrinsic and extrinsic factors, which could be targeted to promote chemo-sensitization. Our previous studies showed that Galectin-3, a lectin that clusters galactose-modified glycoproteins and that has both an intracellular and extracellular location, protects different subtypes of BP-ALL cells against chemotherapy. Galectin-1 is related to Galectin-3 and its expression was previously reported to be restricted to the MLL subtype of BP-ALL.

Methods and results

Here, we report that Galectin-1 is expressed at different levels in and on different subclasses of BP-ALLs. Bone marrow plasma also contains high levels of Galectin-1. PTX008 is an allosteric inhibitor which inhibits Galectin-1 but not Galectin-3-mediated agglutination. The compound reduces migration of BP-ALL cells to CXCL12 and OP9 stromal cells and inhibits fibronectin-mediated adhesion. It also affects cell cycle progression of BCP-ALL cells. PTX008 is cytostatic for BP-ALL cells even when these are co-cultured with protective stroma, and can sensitize ALL cells to vincristine chemotherapy in vitro and in mice.

Conclusions

PTX008 inhibits multiple functions that contribute to BP-ALL survival. The effects of Galectin-1 inhibition on both BP-ALL cell proliferation and migration suggest both the leukemia cells as well as the microenvironment that protects these cells may be targeted.

https://ift.tt/2IV4Gmx

Approach to oligometastatic disease in head and neck cancer, on behalf of the GORTEC

Future Oncology, Ahead of Print.


https://ift.tt/2DXTRw7

Treatment of hepatocellular carcinoma: a cost analysis of yttrium-90 transarterial radioembolization versus sorafenib

Future Oncology, Ahead of Print.


https://ift.tt/2GcUfgA

Changing vision: a review of pharmacogenetic studies for treatment response in age-related macular degeneration patients

Pharmacogenomics, Ahead of Print.


https://ift.tt/2umFOAX

Are haplotypes in a single methotrexate pathway more predictive for response in rheumatoid arthritis than in different pathways?

Pharmacogenomics, Ahead of Print.


https://ift.tt/2IRSUJA

Ramucirumab as Second-Line Therapy in Metastatic Gastric Cancer: Real-World Data from the RAMoss Study

Abstract

Background

Ramucirumab—alone or combined with paclitaxel—represents one of the main options for patients failing first-line treatment for advanced gastric cancer.

Objective

The RAMoss study aimed to evaluate the safety and efficacy profile of ramucirumab in the "real-life setting".

Patients and Methods

Patients from 25 Italian hospitals started therapy consisting of ramucirumab 8 mg/kg i.v. d1,15q28 with or without paclitaxel 80 mg/m² i.v. d1,8,15q28. The primary endpoint was safety, and secondary endpoints were overall response rate (ORR), progression-free survival (PFS), and overall survival (OS).

Results

One hundred sixty-seven patients with disease progression on first-line therapy received ramucirumab as monotherapy (10%) or combined with paclitaxel (90%). Median treatment duration was 4 months (1–17 months). Global incidence of grade (G) 3–4 toxicity was 9.6%, and for neutropenia 5.4%; treatment was discontinued due to toxicity in 3% of patients. The most frequent adverse events (AE) were G1–2 fatigue (27.5%), G1–2 neuropathy (26.3%), and G1–2 neutropenia (14.9%). ORR was 20.2%. Stable disease was observed in 39.2% of patients, with a disease control rate of 59.4%. With a median follow-up of 11 months, median PFS was 4.3 months (95% confidence interval [CI] 4.1–4.7), whereas median OS was 8.0 months (95% CI: 7.09–8.9). In a multivariate analysis, ECOG performance status <1 or ≥1 (HR 1.13, 95% CI 1.0–1.27, p = 0.04) and the presence versus absence of peritoneal metastases (HR 1.57, 95% CI 1.63–2.39, p = 0.03) were independent poor prognostic factors.

Conclusions

These "real-life" efficacy data on ramucirumab treatment are in line with previous randomized trials. Ramucirumab is well tolerated in daily clinical practice.

https://ift.tt/2pGMyDW

The IARC Perspective on Colorectal Cancer Screening

New England Journal of Medicine, Ahead of Print.


https://ift.tt/2GdnEH6

Carcinoembryonic antigen as a marker of radioresistance in colorectal cancer: a potential role of macrophages

Abstract

Background

We sought to identify the carcinoembryonic antigen (CEA) as a marker of radioresistance in rectal cancer.

Methods

From July 1997 to January 2008, 104 patients with stage II or III rectal cancer who were treated with post-operative radiotherapy (PORT) were included in this study. The doses of radiotherapy ranged from 45 to 54.6 Gy. The CEA levels were measured before surgery. We analyzed the actuarial rates of overall survival (OS), distant metastasis (DM), and local recurrence (LR) using Kaplan-Meier curves. Multivariate analyses were performed with Cox regression models. We used THP-1 monocyte cell lines for macrophage differentiation (M0, M1 or M2). The RNA extracted from the macrophages was analyzed via a genomic method in the core laboratory. The radiosensitivities of CEA-rich LS1034 cells were compared between cells with and without the conditioned media from CEA-stimulated macrophages.

Results

Preoperative CEA levels ≥10 ng/mL were independent predictive factors for OS (p = 0.005), DM (p = 0.026), and LR (p = 0.004). The OS rates among the patients with pretreatment CEA levels < 10 ng/mL and ≥10 ng/mL were 64.5% and 35.9% (p = 0.004), respectively. The corresponding rates of DM were 40.6% and 73.1% (p = 0.024). The corresponding rates of LR were 6.6% and 33.9% (p = 0.002). In the M0 macrophages, exogenous CEA elicited a dose-response relationship with M2 differentiation. In the CEA-stimulated M0 cells, some mRNAs were upregulated by as much as 5-fold, including MMP12, GDF15, and JAG1. In the CEA-stimulated M2 cells, a 4-fold up-regulation of GADD45G mRNA was noted. The conditioned media from the CEA-stimulated M2 cells elicited an increase in the numbers of LS180, SW620, and LS1034 cells after irradiation. CEA caused the M2 differentiation of the macrophages.

Conclusion

Pretreatment CEA levels ≥10 ng/mL are a significant risk factor for OS, DM, and LR following PORT for rectal cancer. CEA causes radioresistance in the presence of M2 macrophages. More comprehensive examinations prior to surgery and intensive adjuvant therapy are suggested for patients with CEA levels ≥10 ng/mL. Further studies of these mechanisms are needed.

https://ift.tt/2unOiHR

Knockdown of IFI27 inhibits cell proliferation and invasion in oral squamous cell carcinoma

Abstract

Background

The development of oral squamous cell carcinoma (OSCC) involves genetic mutations, epigenetic gene expression modification, and other processes. It has been reported that IFI27 is upregulated in OSCC, but its function is unknown. The aim of this study was to investigate the role of IFI27 on OSCC cell proliferation and invasion.

Methods

The protein level of IFI27 in OSCC tissues and adjacent tissues was detected by immunohistochemistry. In the OSCC cell model, we designed the IFI27 siRNA to downregulate the expression of IFI27; gene and protein of IFI27 in those models were then detected by Q-PCR and Western blot. MTT assay was used to detect the effect of -IFI27 knockdown on cell proliferation; Annexin V-PI staining flow cytometry was used to detect the effect of IFI27 downregulation on apoptosis of cancer cells. The effect of IFI27 downregulation on oral cancer cell invasion was detected using Transwell assay.

Results

IFI27 was highly expressed in OSCC tissues by immunohistochemical assay. In the OSCC cell model, IFI27 siRNA could downregulate the mRNA and protein expression level of IFI27. As showed in MTT assay, Annexin V-PI assay, and Transwell assay, through the downregulation of IFI27, TSCCA and TCA8113 cell proliferation were inhibited, OSCC cell apoptosis was promoted, and its migration and invasion were inhibited.

Conclusion

IFI27 is involved in the development and progression of OSCC. Its high expression promotes cell proliferation and invasion and reduces apoptosis. These findings may provide new biomarkers and therapeutic targets for OSCC diagnosis and clinical treatment.

https://ift.tt/2I8cBM1

In Vitro Model for Studying of the Role of IGFBP6 Gene in Breast Cancer Metastasizing

IGFBP6 gene plays an important role in the pathogenesis of breast cancer. In this work, we performed knockdown of IGFBP6 gene in MDA-MB-231 cells and obtained a stable cell line. Knockdown of IGFBP6 gene was confirmed by the real-time PCR. The influence of IGFBP6 gene on migration and proliferation of breast cancer cells was studied. Knockdown of IGFBP6 gene reduced migration activity of MDA-MB-231 cells and increased their proliferation rate. This in vitro cell model can be used for the further analysis of the role of IGFBP6 gene in the pathogenesis of breast cancer.

https://ift.tt/2un3ncF

Novel Ciprofloxacin-Modifying Enzyme (CrpP) Encoded by the Pseudomonas aeruginosa pUM505 Plasmid [PublishAheadOfPrint]

The pUM505 plasmid, isolated from a clinical Pseudomonas aeruginosa isolate, confers resistance to ciprofloxacin (CIP) when transferred into the standard P. aeruginosa PAO1 strain. CIP is an antibiotic of the quinolone family that is used to treat P. aeruginosa infections. In silico analysis, performed to identify CIP-resistance genes, revealed that the 65-amino acid product encoded by the orf131 gene in pUM505 displays 40% amino acid identity to the Mycobacterium smegmatis aminoglycoside phosphotransferase (an enzyme that phosphorylates and inactivates aminoglycoside antibiotics). We cloned orf131 (renamed as crpP for ciprofloxacin-resistance protein plasmid-encoded) into the pUCP20 shuttle vector. The resulting recombinant plasmid, pUC-crpP, conferred resistance to CIP in the Escherichia coli J53-3 strain, suggesting that the product of this gene encodes a protein involved in CIP resistance. Using a coupled enzymatic analysis, we determined that the activity of CrpP on CIP is ATP-dependent, while little activity was detected towards norfloxacin, suggesting that CIP may undergo phosphorylation. Using a recombinant His-tagged CrpP protein and liquid chromatography--tandem mass spectrometry, we also showed that CIP was phosphorylated prior to its degradation. Thus, our findings demonstrate that CrpP, encoded on the pUM505 plasmid, represents a new mechanism of CIP-resistance in P. aeruginosa, which involves phosphorylation of the antibiotic.

https://ift.tt/2IXBjA8

PHARMACOKINETICS OF INTRAVENOUS POSACONAZOLE IN CRITICALLY ILL PATIENTS [PublishAheadOfPrint]

To date, there is no information on the IV posaconazole pharmacokinetics in ICU patients. This prospective observational study aimed to describe the pharmacokinetics of a single dose of IV posaconazole in critically ill patients. Patients with no history of allergy to triazole antifungals and requiring systemic antifungal therapy were enrolled if aged ≥ 18 years, central venous access was available, were not pregnant, and didn't receive prior posaconazole or drugs interacting with posaconazole. A single dose of 300 mg posaconazole was administered over 90 minutes. Total plasma concentrations were measured from serial plasma samples collected over 48 h, using a validated chromatographic method. The pharmacokinetic data set was analyzed by non-compartmental methods. Eight patients (7 male) were enrolled; median (interquartile range, IQR) age 46 years (40-51), weight 68 kg (65-82) and albumin concentration 20 g/L (18-24). Median (IQR) pharmacokinetic parameter estimates were Cmax, 1,702 ng/mL (1,352-2,141); AUC_0-, 17,932 ng*h/mL (13,823 — 27, 905); CL, 16.8 L/h (11.1-21.7); and Vd, 529.1 L (352.2 — 720.6). The Vd and CL were greater than two fold and AUC_0- was 39% of values reported for heathy volunteers. The AUC_0- was only 52% of the steady-state AUC_0-24 reported for hematology patients. The median of estimated average steady-steady state concentrations was 747 ng/mL (IQR, 576 -1,163), which is within but close to the lower end of previously recommended therapeutic range of 500 to 2,500 ng/mL. In conclusion, we observed different pharmacokinetics of intravenous posaconazole in this cohort of critically ill patients compared to healthy volunteers and hematology patients.

https://ift.tt/2pHIALo

Determination of the dynamically-linked indices of fosfomycin for Pseudomonas aeruginosa in the Hollow Fiber Infection Model (HFIM) [PublishAheadOfPrint]

Fosfomycin is the only expoxide antimicrobial and is currently under development in the United States as an intravenously administered product. We were interested in identifying the exposure indices most closely linked to the ability to kill bacterial cells and to suppress amplification of less-susceptible subpopulations. We employed the Hollow Fiber Infection model for this investigation and studied wild-type Pseudomonas aeruginosa PAO1. Because of anticipated rapid resistance emergence, we shortened study duration to 24 hours but sampled the system more intensively. Doses and schedules of 12 and 18 g/day and daily, 8 hourly administration and continuous infusion were studied at each daily dose. We measured fosfomycin concentrations (by LC/MS/MS), total bacterial burden and less-susceptible burden. We applied a mathematical model to all the data simultaneously. There was rapid emergence of resistance in all doses and schedules. Prior to the resistance emergence, an initial kill of 2-3 Log₁₀(CFU/ml) was observed. The model demonstrated that AUC/MIC Ratio was linked to total bacterial kill, while Time > MIC (equivalently C_min/MIC ratio) was linked to resistance suppression. These findings were also seen in other investigations with Enterobacteriaceae (in vitro systems) and P. aeruginosa (murine system). We conclude that for serious high bacterial burden infections, fosfomycin may be of value as a new therapeutic and may be optimized by administering the agent as a continuous or prolonged infusion or by a short dosing interval. For indications such as Ventilator-Associated Bacterial Pneumonia, it may be prudent to administer fosfomycin as part of a combination regimen.

https://ift.tt/2IVIJDU

Dextromethorphan Attenuates NADPH Oxidase-regulated GSK-3{beta} and NF-{kappa}B Activation and Reduces Nitric Oxide Production in Group A Streptococcal Infection [PublishAheadOfPrint]

Group A streptococcus (GAS) is an important human pathogen that causes a wide spectrum of diseases, including necrotizing fasciitis and streptococcal toxic shock syndrome. Dextromethorphan (DM), an antitussive drug, has been demonstrated to efficiently reduce inflammatory responses thereby contributing to an increased survival rate of GAS-infected mice. However, the anti-inflammatory mechanisms underlying DM treatment in GAS infection remain unclear. DM is known to exert neuroprotective effects through a NADPH oxidase-dependent regulated process. In the present study, membrane translocation of NADPH oxidase subunit p47^phox and subsequent reactive oxygen species (ROS) generation induced by GAS infection were significantly inhibited via DM treatment in RAW264.7 murine macrophage cells. Further determination of proinflammatory mediators revealed that DM effectively suppressed inducible nitric oxide synthase (iNOS) expression, NO, TNF-α and IL-6 generation in GAS-infected RAW264.7 cells as well as in air-pouch-infiltrating cells from GAS/DM-treated mice. GAS infection caused AKT dephosphorylation, glycogen synthase kinase-3β (GSK-3β) activation, and subsequent NF-B nuclear translocation, which were also markedly inhibited by treatment with DM and NADPH oxidase inhibitor, diphenylene iodonium. These results suggest that DM attenuates GAS infection-induced overactive inflammation by inhibiting NADPH oxidase-mediated ROS production that leads to down-regulation of the GSK-3β/NF-B/NO signaling pathway.

https://ift.tt/2pIQC6I

Survival in Patients with Candida glabrata Bloodstream Infections is Associated with Fluconazole Dose [PublishAheadOfPrint]

Robust pharmacodynamic indices that align fluconazole dose or exposure with outcome in invasive candidiasis due to C. glabrata remain elusive. The purpose of this retrospective, multicenter study was to evaluate a cohort of 127 patients with C. glabrata fungemia treated with fluconazole using adjusted analyses to identify risk factors for 28-day mortality. No significant correlations were found between fluconazole AUC, AUC:MIC, or MIC and survival. However, on multivariable logistic regression, higher average fluconazole dose (odds ratio (OR) 1.006, 95% confidence interval (CI), 1.001-1.010, p=0.008), average fluconazole dose ≥ 400 mg (OR 3.965, 95% CI 1.509-10.418, p=0.005), and higher fluconazole dose on day 1 of therapy (OR 1.007, 95% CI 1.002-1.011, p=0.002) were found to be independent predictors of 28-day survival. Additionally, the presence of a central venous catheter at the time of infection was found to be a significant risk factor for mortality. In conclusion, we found fluconazole dose to be an independent predictor for 28-day survival in patients with C. glabrata fungemia, with doses ≥ 400mg/day associated with 28-day survival approaching 90%. These data inform the use and efficacy of fluconazole in the treatment of this serious infection. Aggressive dosing appears necessary when using fluconazole for the treatment of C. glabrata fungemia, irrespective of MIC.

https://ift.tt/2IXBj36

Molecular characterization of OXA-198 carbapenemase producing Pseudomonas aeruginosa clinical isolates [PublishAheadOfPrint]

Carbapenemase-producing Pseudomonadaceae have increasingly been reported worldwide, with an ever-increasing heterogeneity of carbapenem resistance mechanisms depending on the bacterial species and its geographical location. OXA-198 is a plasmid-encoded class D β-lactamase involved in carbapenem-resistance in one Pseudomonas aeruginosa isolate from Belgium. In the setting of a multicentre survey of carbapenem-resistance in P. aeruginosa in Belgian hospitals in 2013, three additional OXA-198 producing P. aeruginosa originating from patients hospitalized at one hospital were detected. To reveal the molecular mechanism underlying the reduced susceptibility to carbapenems, MICs, whole genome sequencing (WGS) and PCR reactions to confirm the genetic organization were performed. The plasmid harboring bla_OXA-198 gene was characterized alongside with the genetic relatedness of the four P. aeruginosa isolates. The bla_OXA-198 gene was harbored on a class 1 integron carried itself by a ca. 49-kb IncP-type plasmid proposed as IncP11. The same plasmid was present in all four P. aeruginosa isolates. MLST typing revealed that they all belonged to ST-446 and SNP analysis revealed only a few differences between these isolates. This report describes the structure of a 49-kb plasmid harbouring the bla_OXA-198 gene and the first description of OXA-198 producing P. aeruginosa isolates associated with a hospital-associated cluster episode.

https://ift.tt/2Gf9n99

Pharmacokinetics and Pharmacodynamics of Fosfomycin and its Activity against ESBL-, Plasmid-mediated AmpC- and Carbapenemase-Producing Escherichia coli in a Murine Urinary Tract Infection Model [PublishAheadOfPrint]

Fosfomycin has become an attractive treatment alternative for urinary tract infections (UTIs) due to increasing multidrug-resistance (MDR) in Escherichia coli. In this study, we evaluated the pharmacokinetic and pharmacodynamic (PK/PD) indices of fosfomycin and its in vivo activity in an experimental murine model of ascending UTI. Subcutaneous administration of fosfomycin showed that the mean peak plasma concentrations of fosfomycin were 36, 280, and 750 mg/L following administration of a single dose of 0.75, 7.5, and 30 mg/mouse, respectively, with an elimination half-life of 28 min; and urine peak concentrations of 1100, 33400, and 70000 mg/L expected to sustain above the MIC of the test strain (NU14, 1 mg/L) for 5, 8 and 9.5 h, respectively. The optimal PK/PD indices for reducing urine colony counts (CFU/ml) were determined to be AUC/MIC_0-72h and C_max/MIC based on the dose-dependent bloodstream PK and evaluation of six dosing regimens. With a dosing regimen of 15 mg/mouse twice (q36h), fosfomycin significantly reduced the CFU/ml in urine of susceptible strains, including clinical MDR strains, except for one clinical strain (p = 0.062). A variable degree of reduction was observed in the bladder and kidneys. No significant reduction in CFU/ml were observed with the resistant strains. In conclusion, fosfomycin shows concentration-dependent in vivo activity and the results suggest that fosfomycin is an effective alternative to carbapenems in treating MDR E. coli in uncomplicated UTIs. The data for effectiveness on the MDR isolates along with PK/PD modeling should facilitate further development of improved recommendations for clinical use.

https://ift.tt/2IT6OuW

Chemotherapy with Phage Lysins Reduces Pneumococcal Colonization of the Respiratory Tract [PublishAheadOfPrint]

Bacteriophage-encoded lytic enzymes, also named lysins, or enzybiotics, are efficient agents to kill bacterial pathogens. Colonization of the respiratory tract by Streptococcus pneumoniae is a prerequisite for the establishment of the infection process. Hence, we have evaluated the antibacterial activity of three different lysins against pneumococcal colonization using human nasopharyngeal and lung epithelial cells as well as a mouse model of nasopharyngeal colonization. The lysins tested were the wild type Cpl-1, the engineered Cpl-7S, and the chimera Cpl-711. Moreover, we have included amoxicillin as a comparator antibiotic. Human epithelial cells were infected with three different multidrug-resistant clinical isolates of S. pneumoniae followed by a single dose of the corresponding lysin. The antimicrobial activity of these lysins was also evaluated using a mouse nasopharyngeal carriage model. Exposure of infected epithelial cells to Cpl-7S did not result in the killing of any of the pneumococcal strains investigated. However, treatment with Cpl-1 or Cpl-711 increased the killing of S. pneumoniae adhered to both types of human epithelial cells with Cpl-711 being more effective than Cpl-1, at sub-inhibitory concentrations. In addition, treatment with amoxicillin had no effect reducing the carrier state whereas mice treated by the intranasal route with Cpl-711 showed significantly reduced nasopharyngeal colonization with no detection of bacterial load in 20-40% of the mice. This study indicates that Cpl-1 and Cpl-711 lysins might be promising antimicrobial candidates for therapy against pneumococcal colonization.

https://ift.tt/2pKdfHX

Clinical and Microbiological Characteristics of Candida guilliermondii and Candida fermentati [PublishAheadOfPrint]

The 46 clinical isolates of Candida guilliermondii and Candida famata were re-identified genetically, resulting in 27 C. guilliermondii and 12 Candida fermentati strains. The majority of C. guilliermondii, but no C. fermentati, were isolated from blood cultures. C. fermentati was more sensitive to antifungals, hydrogen peroxide and killing by murine macrophages than C. guilliermondii. The C. guilliermondii isolates were echinocandin susceptible in vitro but resistant to micafungin in a murine model of invasive candidiasis.

https://ift.tt/2IVIt7U

Combination of amphotericin B and terbinafine against melanized fungi associated with chromoblastomycosis [PublishAheadOfPrint]

Our in vitro studies showed that combination of amphotericin B and terbinafine had synergistic effects against the majority of melanized fungi associated with chromoblastomycosis (CBM) and similar infections, including Cladophialophora carrionii, C. arxii, Exophiala dermatitidis, E. spinifera, Fonsecaea monophora, F. nubica, F. pedrosoi, and Phialophora verrucosa. This combination could provide an option for treatment of severe or unresponsive cases of CBM, particularly in cases due to species of Fonsecaea and Cladophialophora.

https://ift.tt/2GcpUdM

Genetic Relationships among Multidrug-Resistant Salmonella enterica Serovar Typhimurium Strains from Humans and Animals [PublishAheadOfPrint]

We identified 20—22 resistance genes, carried in four incompatibility groups of plasmid, in each of five genetically closely-related Salmonella enterica serovar Typhimurium strains recovered from humans, pigs, and chicken. The genes conferred resistance to aminoglycosides, chloramphenicol, sulfonamides, trimethoprim, tetracycline, fluoroquinolones, extended-spectrum cephalosporins and cefoxitin, and azithromycin. This study demonstrates the transmission of multidrug-resistant Salmonella strains among humans and food animals and may be the first identification of mphA in azithromycin-resistant Salmonella strains in Taiwan.

https://ift.tt/2IVInNA

Profiling of PDR1 and MSH2 in Candida glabrata Bloodstream Isolates from a Multi-Center Study in China [PublishAheadOfPrint]

Among 158 Candida glabrata bloodstream isolates collected from multicenter in China, resistance to fluconazole were seen in 8.9% of isolates. Three isolates (1.9%) were resistant to all echinocandins. MLST ST7 (65.8%) was the most common type and followed by ST3 (7.6%). PDR1 polymorphisms were associated with acquisition of fluconazole resistance in C. glabrata isolates, while MSH2 polymorphisms were associated with the STs and microsatellite genotypes, irrespective of fluconazole resistance.

https://ift.tt/2GfcLkc

Antifungal prophylaxis with Posaconazole delayed-release tablet and oral suspension in a Real-life setting: plasma levels, efficacy and tolerability [PublishAheadOfPrint]

We continuously determined Posaconazole plasma concentrations (PPCs) in 61 patients with hematological malignancies receiving Posaconazole (PCZ) delayed-release tablet (DRT) (48 patients, median duration of intake 92 days) and PCZ oral solution (OS) (13 patients, median duration of intake 124 days). PCZ DRT and OS antifungal prophylaxis was efficient and well tolerated. Thirty-four of 48 patients (71%) receiving DRT always had PPCs >0.7 mg/L, while 14 of 48 patients (29%) had at least one PPC ≤0.7 mg/L. In patients receiving OS 4 of 13 patients (31%) always had PPCs >0.7 mg/L, 6 of 13 patients (46%) had at least one PPC ≤0.7 mg/L, and 3 (23%) patients never reached a PPC of 0.7 mg/L. In patients with at least one determined PPCs the mean proportion of all PPCs >0.7 mg/L was 91% for PCZ DRT versus 52% for PCZ OS (p=0.001). In per sample analysis PPCs in patients receiving DRT were significantly more likely to be >0.7 mg/L when compared to PPCs in patients receiving OS [lsqb]91.4% (297/325) of PPCs >0.7 mg/L in DRT versus 70.3% (85/121) in OS; p<0.001[rsqb]. PCZ DRT has higher proportions of PPCs >0.7 mg/L compared to OS, both in per patient and in per sample analysis. Two patients (3%) had side effects during PCZ prophylaxis and one (2%) had fungal breakthrough infection. TDM enables to detect extended periods of PPCs ≤0.7 mg/L (e.g., due to non-adherence or GHVD), which may be associated also with loss of protective intracellular PCZ concentrations regardless of PCZ formulation.

https://ift.tt/2ITbuBf

Biomarker discovery from we to me: Is learning from each patient a new approach?

The immune response is a dynamic multistep process, with a complex system regulation. Identification of predictive biomarkers is therefore challenging. Deep investigation of an exceptional responder to pembrolizumab in ovarian cancer identifies new mechanism of response and highlights the power of individualized medicine strategy.

https://ift.tt/2uoekec

Higher Absolute Lymphocyte Counts Predict Lower Mortality from Early-Stage Triple-Negative Breast Cancer

Background: Tumor-infiltrating lymphocytes (TILs) in pre-treatment biopsies are associated with improved survival in triple-negative breast cancer (TNBC). We investigated whether higher peripheral lymphocyte counts are associated with lower breast cancer-specific mortality (BCM) and overall mortality (OM) in TNBC. Methods: Data on treatments and diagnostic tests from electronic medical records of two healthcare systems were linked with demographic, clinical, pathologic, and mortality data from the California Cancer Registry. Multivariable regression models adjusted for age, race/ethnicity, socioeconomic status, cancer stage, grade, neoadjuvant/adjuvant chemotherapy use, radiotherapy use, and germline BRCA1/2 mutations were used to evaluate associations between absolute lymphocyte count (ALC), BCM and OM. For a subgroup with TILs data available, we explored the relationship between TILs and peripheral lymphocyte counts. Results: 1,463 Stage I-III TNBC patients were diagnosed from 2000-2014; 1113 (76%) received neoadjuvant/adjuvant chemotherapy within one year of diagnosis. Of 759 patients with available ALC data, 481 (63.4%) were ever lymphopenic (minimum ALC <1.0 K/μL). On multivariable analysis, higher minimum ALC, but not absolute neutrophil count, predicted lower OM (hazard ratio [HR]: 0.23, 95% confidence interval [CI]: 0.16-0.35) and BCM (HR: 0.19, CI: 0.11-0.34). Five-year probability of BCM was 15% for patients who were ever lymphopenic versus 4% for those who were not. An exploratory analysis (N=70) showed a significant association between TILs and higher peripheral lymphocyte counts during neoadjuvant chemotherapy. Conclusion: Higher peripheral lymphocyte counts predicted lower mortality from early-stage, potentially curable TNBC, suggesting that immune function may enhance the effectiveness of early TNBC treatment.

https://ift.tt/2IVoDtx

Data Analysis Strategies in Medical Imaging

Radiographic imaging continues to be one of the most effective and clinically useful tools within oncology. Sophistication of artificial intelligence (AI) has allowed for detailed quantification of radiographic characteristics of tissues using predefined engineered algorithms or deep learning methods. Precedents in radiology as well as a wealth of research studies hint at the clinical relevance of these characteristics. However, there are critical challenges associated with the analysis of medical imaging data. While some of these challenges are specific to the imaging field, many others like reproducibility and batch effects are generic and have already been addressed in other quantitative fields such as genomics. Here, we identify these pitfalls and provide recommendations for analysis strategies of medical imaging data including data normalization, development of robust models, and rigorous statistical analyses. Adhering to these recommendations will not only improve analysis quality, but will also enhance precision medicine by allowing better integration of imaging data with other biomedical data sources.

https://ift.tt/2uisQUU

The long neglected player: modeling tumor uptake to guide optimal dosing

Pharmacokinetic modeling is widely used to support decision making in translational medicine and patient care, traditionally using circulating drug exposure. The development of mechanistic computational models that integrate drug concentrations at the site of action making use of existing knowledge opens a new paradigm in optimal dosing.

https://ift.tt/2IVo82D

ER+ breast cancers resistant to prolonged neoadjuvant letrozole exhibit an E2F4 transcriptional program sensitive to CDK4/6 inhibitors

Purpose:This study aimed to identify biomarkers of resistance to endocrine therapy in ER+ breast cancers (BC) treated with prolonged neoadjuvant letrozole. Experimental Design: We performed targeted DNA and RNA-sequencing in 68 ER+ BC from patients treated with preoperative letrozole (median 7 months). Results:Twenty-four tumors (35%) exhibited a PEPI score ≥4 and/or recurred after a median of 58 months and were considered endocrine resistant. Integration of the 47 most upregulated genes (log FC>1, FDR<0.03) in letrozole-resistant tumors with transcription binding data showed significant overlap with 20 E2F4-regulated genes (p=2.56E-15). In patients treated with the CDK4/6 inhibitor palbociclib before surgery, treatment significantly decreased expression of 24 of the 47 most upregulated genes in letrozole-resistant tumors, including 18 of the 20 E2F4 target genes. In long term estrogen-deprived ER+ BC cells, palbociclib also downregulated all 20 E2F4-target genes and P-RB levels, whereas the ER downregulator fulvestrant or paclitaxel only partially suppressed expression of this set of genes and had no effect on P-RB. Finally, an E2F4 activation signature was strongly associated with resistance to aromatase inhibitors in the ACOSOG Z1031B neoadjuvant trial and with an increased risk of relapse in adjuvant treated ER+ tumors in METABRIC. Conclusions: In tumors resistant to prolonged neoadjuvant letrozole, we identified a gene expression signature of E2F4 target activation. CDK4/6 inhibition suppressed E2F4 target gene expression in estrogen-deprived ER+ BC cells and in patients' ER+ tumors, suggesting a potential benefit of adjuvant CDK4/6 inhibitors in patients with ER+ breast cancer who fail to respond to preoperative estrogen deprivation.

https://ift.tt/2umvd99

Identification of Pik3ca mutation as a genetic driver of prostate cancer that cooperates with Pten loss to accelerate progression and castration-resistant growth [Research Articles]

Genetic alterations that potentiate PI3K signalling are frequent in prostate cancer, yet how different genetic drivers of the PI3K cascade contribute to prostate cancer is unclear. Here, we report PIK3CA mutation/amplification correlates with poor prostate cancer patient survival. To interrogate the requirement of different PI3K genetic drivers in prostate cancer, we employed a genetic approach to mutate Pik3ca in mouse prostate epithelium. We show Pik3caH1047R mutation causes p110α-dependent invasive prostate carcinoma in-vivo. Furthermore, we report PIK3CA mutation and PTEN loss co-exist in prostate cancer patients, and can cooperate in-vivo to accelerate disease progression via AKT-mTORC1/2 hyperactivation. Contrasting single mutants that slowly acquire castration-resistant prostate cancer (CRPC), concomitant Pik3ca mutation and Pten loss caused de-novo CRPC. Thus, Pik3ca mutation and Pten deletion are not functionally redundant. Our findings indicate that PIK3CA mutation is an attractive prognostic indicator for prostate cancer that may cooperate with PTEN loss to facilitate CRPC in patients.

https://ift.tt/2IUxN9B

Making Better CARs for Kids [News in Brief]

Prior chemotherapy may impair ability to manufacture effective therapies, prompting shift in clinical practice.

https://ift.tt/2umvatZ

Height and overall cancer risk and mortality: evidence from a Mendelian randomisation study on 310,000 UK Biobank participants

Height and overall cancer risk and mortality: evidence from a Mendelian randomisation study on 310,000 UK Biobank participants

Height and overall cancer risk and mortality: evidence from a Mendelian randomisation study on 310,000 UK Biobank participants, Published online: 27 March 2018; doi:10.1038/s41416-018-0063-4

Height and overall cancer risk and mortality: evidence from a Mendelian randomisation study on 310,000 UK Biobank participants

https://ift.tt/2ukiiVh

MiR-144 suppresses proliferation, invasion, and migration of breast cancer cells through inhibiting CEP55

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https://ift.tt/2Gdd4vO

Effects of miR-144 on the sensitivity of human anaplastic thyroid carcinoma cells to cisplatin by autophagy regulation

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https://ift.tt/2GrsAaZ

Rapid exhaustion of auditory neural conduction in a prototypical mitochondrial disease, Friedreich ataxia

The importance of neural processing of temporal cues by the auditory system has been stressed by the discovery of auditory neuropathy spectrum disorders (ANSD) (Starr et al., 1996; Rance and Starr, 2015), in which disrupted auditory-nerve conduction leads to a characteristic pattern of hearing disorder. One striking complaint of ANSD patients is the presence of impaired speech understanding out of proportion with what the auditory sensitivity would predict, particularly in the presence of noise (Kraus et al., 2000; Zeng and Liu, 2006).

https://ift.tt/2Gw820Y

Phantom somatosensory evoked potentials following selective intraneural electrical stimulation in two amputees

Following a limb amputation and consequent truncation of nerves, some of the nerve fibers originally directed to the lost part of the body suffer from retrograde Wallerian degeneration. However, a significant part of them survive in the residual portion of the nerve (Navarro et al., 2007). Due to the development of neural interfaces for the peripheral nervous system, i.e. intraneural multichannel electrodes (Navarro et al., 2005), it was recently demonstrated that it is possible to induct meaningful sensations (Dhillon et al., 2005) in the phantom hand of amputees by stimulating the surviving fibers through these interfaces.

https://ift.tt/2unM23q

COMPLETE HETEROTOPIC PANCREAS

https://ift.tt/2Gz2jau

Gene expression-phenotype associations in adults with eosinophilic esophagitis

Gene expression patterns have not been extensively examined in the context of clinical features of eosinophilic esophagitis (EoE).

https://ift.tt/2pIvygQ

P.05.16 ENDOCUFF VISION-ASSISTED RESECTION FOR “DIFFICULT” COLONIC LESIONS. EFFICACY AND SAFETY IN A PILOT RANDOMIZED STUDY

https://ift.tt/2GtuOXo

Epidemiology, Characteristics, and Outcomes of ICU-Managed Homeless Patients: A Population-Based Study

Background. The population-level demand for critical care services among the homeless (H) remains unknown, with only sparse data on the characteristics and outcomes of those managed in the ICU. Methods. The Texas Inpatient Public Use Data File and annual federal reports were used to identify H hospitalizations and annual estimates of the H population between 2007 and 2014. The incidence of ICU admissions in the H population, the characteristics of ICU-managed H, and factors associated with their short-term mortality were examined. Results. Among 52,206 H hospitalizations 15,553 (29.8%) were admitted to ICU. The incidence of ICU admission among state H population rose between 2007 and 2014 from 28.0 to 96.6/1,000 , respectively. Adults aged ≥ 45 years and minorities accounted for 70.2% and 57.6%, respectively, of the growth in volume of ICU admissions. Short-term mortality was 3.2%, with odds of death increased with age, comorbidity burden, and number of failing organs. Conclusions. The demand for critical care services was increasingly high among the H and was contrasted by low short-term mortality among ICU admissions. These findings, coupled with the persistent health disparities among minority H, underscore the need to effectively address homelessness and reduce barriers to longitudinal appropriate prehospital care among the H.

https://ift.tt/2pJB5o0

Tumor Microenvironment in Functional Adrenocortical Adenomas: Immune Cell Infiltration in Cortisol-producing Adrenocortical Adenoma

The tumor microenvironment plays pivotal roles in various human neoplasms. However, that of benign tumor, particularly hormone-secreting endocrine tumors, has remained virtually unknown. Therefore, we firstly attempted to analyze the tumor microenvironment of autonomous hormone-secreting adrenocortical adenomas. We first histologically evaluated 21 cortisol-producing adrenocortical adenoma (CPA) and 13 aldosterone-producing adrenocortical adenoma (APA) cases. Quantitative histological analysis revealed that intratumoral immune cell infiltration (ICI) was more pronounced in CPAs than APAs.

https://ift.tt/2up6uB7

Pancreatic neuroendocrine carcinomas reveal a closer relationship to ductal adenocarcinomas than to neuroendocrine tumors G3

Pancreatic neuroendocrine carcinoma is a rare aggressive tumor commonly harboring TP53 and RB1 alterations and lacking neuroendocrine related genetic changes such as mutations in MEN1 and ATRX/DAXX. Little is known about its genetic profile with regard to that of pancreatic ductal adenocarcinoma. We therefore conducted a detailed genetic study in 12 pancreatic neuroendocrine carcinomas of large cell (n=9) and small cell type (n=3) using massive parallel sequencing applying a 409 gene panel on an Ion Torrent system.

https://ift.tt/2pGGEU7

Minute Mesenchymal Chondrosarcoma within Osteochondroma: An Unexpected Diagnosis Confirmed by HEY1-NCOA2 Fusion

Mesenchymal chondrosarcoma is rare and can be challenging to diagnose. Herein, we report a minute mesenchymal chondrosarcoma within an osteochondroma. A 12-year-old girl presented with an asymptomatic exophytic lesion of the rib. The tumor was clinically diagnosed as osteochondroma, and was excised after observation for 3years. The resected specimen revealed an unexpected minute (0.9cm) "monophasic" mesenchymal chondrosarcoma in the apex of the lesion. The sarcoma consisted of monomorphic spindle cells without hyaline cartilage.

https://ift.tt/2ulSesL

Microscopic ileitis in diverted and non-diverted enteric segments: an under-recognized condition with a multifactorial etiology

Microscopic ileitis has been infrequently reported in the literature with the few reported cases usually associated with concurrent microscopic colitis. Having encountered a case of collagenous ileitis involving the diverted distal limb of a loop ileostomy and sparing the proximal limb, we examined additional cases of loop ileostomy, end ileostomy, colostomy, and the accompanying diverted colorectal segment for features of microscopic ileitis and colitis. A total of 101 cases of diverted and non-diverted enteric segments were examined from 37 loop ileostomies, 16 end ileostomies and 12 colostomies status post Hartmann's procedure.

https://ift.tt/2pHietJ

Preference for Palliative Care in Cancer Patients: Are Men and Women Alike?

Men and those with low educational attainment are less likely to receive palliative care. Understanding these disparities is a high priority issue.

https://ift.tt/2Gpr0GD

Let’s Work Together: Collaborative Research is Needed to Overcome Difficulty Enrolling Families for Bereaved Sibling Research

Understanding the impact of palliative care services for bereaved siblings has been identified as a priority for pediatric palliative care (PPC) research (1). Bereavement care interventions in pediatrics have been studied sparingly (2), and even less attention has been directed towards school-based interventions. Given that school-age children spend a large proportion of their time in school, understanding and improving school-based interventions for bereaved siblings is an important unexplored area.

https://ift.tt/2pFxZAG

Validation of the Edmonton Symptom Assessment System: Ascites Modification.

Few patient-reported outcomes are available to measure the symptoms associated with malignant-related ascites in patient care and clinical research. Although the Edmonton Symptom Assessment System: Ascites Modification (ESAS:AM) is a brief tool to measure symptoms associated with malignant-related ascites, it remains to be fully validated.

https://ift.tt/2GpqUyL

NEWSworthy but Not Ready for Prime Time

https://ift.tt/2IVexJ9

Heterogeneity in Definitions of Efficacy and Safety Endpoints for Clinical Trials of Crohn’s Disease: A Systematic Review for Development of a Core Outcome Set

Endpoints in randomized controlled trials (RCTs) of Crohn's disease (CD) are evolving. We performed a systematic review of efficacy and safety outcomes reported in placebo-controlled RCTs of patients with CD.

https://ift.tt/2GeLChk

208 Combination Phosphate-Binder (PB) Therapy Including Sucroferric Oxyhydroxide (SO) Results in Sustained Improved Phosphorus Control in Difficult to Control Patients; Results of a 1-Year Retrospective Real-World Hemodialysis Cohort

https://ift.tt/2G92D0f

291 Weil’S Disease Masquerading as Acute Alcoholic Hepatitis

https://ift.tt/2unyQLW

259 An Economic Analysis of Potential Cost Savings Associated with Switching from Sevelamer to Sucroferric Oxyhydroxide for the Treatment of Hyperphosphatemia in Hemodialysis Patients in A U.S. Setting

https://ift.tt/2GcSyPS

307 Analyzing Hospital Readmissions in End-Stage Renal Disease Patients with and Without Heart Failure

https://ift.tt/2unysgs

275 A Case of Triple Nephrotoxicity

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243 Membranoproliferative Glomerulonephritis from Monoclonal Gammopathy of Renal Significance

https://ift.tt/2unyll2

211 Glycemic Control and Survival Among a Multiracial South East Asian Haemodialysis Population

https://ift.tt/2G92gCT

299 Longitudinal Weight Change in Kidney Transplant Recipients from Waiting Period to Late Post-Transplantation

https://ift.tt/2urGipu

283 Training Patients to be Mentors: The Peer Up! Experience

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267 Descriptive Analysis of an Ambulatory Kidney Palliaitve Care Program

https://ift.tt/2utVTVF

251 Evaluation of Lung Ultrasound in Emergency Department Disposition of Patients with Endstage Renal Disease on Hemodialysis

https://ift.tt/2G917vc

311 Acute Antibody Mediated Rejection Presenting as Necrotizing and Crescentic Glomerulonephritis

https://ift.tt/2uiQbWi

303 Acute Kidney Injury in Patients Treated with Anti-Mitochondrial Targeted Therapy: A Retrospective Cohort Analysis

https://ift.tt/2G90YYG

295 Icosapent Ethyl Reduces Potentially Atherogenic Lipid and Inflammatory Markers in High-Risk Statin-Treated Patients with Persistent High Triglycerides, EGFR <90 Ml/Min/1.73 M^2, and Diabetes Mellitus

https://ift.tt/2utVTF9

287 Clinical Urine Findings in A Community with a High Burden of Mesoamerican Nephropathy

https://ift.tt/2G991Vn

279 Acute Kidney Injury (AKI) in Subjects with Chronic Kidney Disease (CKD) Undergoing Total Joint Arthroplasty (TJA)

https://ift.tt/2un5ehU

271 Determinants of Serum Urate in Hemodialysis Patients

https://ift.tt/2G98Qtb

263 Traumatic Acidosis: A Case of SGLT-2 Inhibitors Related Euglycemic DKA in a Trauma Patient

https://ift.tt/2uigI6k

255 A Peripelvic Renal Cyst Resulting in Clinically Symptomatic Ureteropelvic Junction Obstruction

https://ift.tt/2G98D9n

247 Chronic Kidney Disease and Herbicidal Exposure with Incidental Finding of Renal Oncocytosis

https://ift.tt/2up07Od

Oral Squamous Cell Carcinoma in Young Patients–A Case-Control Analysis

A subgroup of younger patients develop squamous cell carcinoma (SCC) of the oral cavity without identifiable risk factors. Controversy exists in the literature regarding the tumor biology and pathogenesis in this group of patients and its effects on prognosis and survival.

https://ift.tt/2I2JrxG

Survival in Asian-Americans With Nasopharyngeal Cancer Undergoing Definitive Radiation Therapy

Biologic and clinical differences have been observed in nasopharyngeal carcinomas (NPC) arising in Asian and North American populations. However, it is unclear if these differences are also present within Asian and non-Asian NPC patients living in the United States.

https://ift.tt/2Gpjsnh

Changing Demographics of HPV-Associated Oropharyngeal Squamous Cell Carcinoma

To evaluate demographic changes over the past 15 years for patients with HPV-associated oropharyngeal squamous cell carcinoma (OPSCC).

https://ift.tt/2I6kdyw

Trends and Patterns of Proton Therapy Utilization Among Patients With Head and Neck Cancer: Analysis from the National Cancer Database (2005-2014)

To analyze national trends and patterns of proton therapy use among patients with head and neck cancer.

https://ift.tt/2GtEpxf

The Role of Human Papillomavirus and Epstein-Barr Virus Co-infection in Oropharyngeal Squamous Cell Tumor Differentiation

The recent epidemic of human papillomavirus (HPV)–related oropharyngeal squamous cell carcinoma (OPSCC) has resulted in the identification of a patient subpopulation with distinct clinical features and outcomes. Viral-related cancers of the head and neck typically have a better prognosis and response to current standard treatment. As both Epstein-Barr virus (EBV) and HPV are most associated with the lymphoid-rich sites of the head and neck, albeit different sites, we aimed to determine if co-infection of these two viruses plays a role in OPSCC.

https://ift.tt/2GpjrzJ

Prognostic Value of Hematologic Markers in Head and Neck Squamous Cell Carcinoma

The purpose of our study was to investigate the potential prognostic role of pretreatment hematologic markers, neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR), in patients with head and neck squamous cell carcinoma (HNSCC) treated with chemoradiation therapy in our institution.

https://ift.tt/2I8fIn1

Head and Neck Cancers Associated With Exposure to the September 11, 2001, World Trade Center Terrorist Attacks

Following the World Trade Center (WTC) terrorist attacks on September 11, 2001, over 100,000 people were exposed to respirable toxins, resulting in numerous adverse health consequences. The dust cloud that formed following the building collapse contained many known carcinogens and exposure at the collapse site has been linked to an increase in overall cancer risk. Herein, we describe the oncologic characteristics and disease outcomes of WTC-exposed patients with HNC who have presented to our institution.

https://ift.tt/2GwT8aH

Nodal Radiographic Prognostic Factors in the New Stage I p16-Positive Oropharyngeal Cancer of the AJCC 8th Edition: Are All N1 Disease the Same?

The AJCC 8th edition cancer staging manual consolidates all patients with p16+ oropharyngeal cancer with unilateral nodal disease no larger than 6 cm in size within the new clinical N1 group. The new classification system comprises a heterogeneous group of disease with varying radiographic findings. Our objective was to identify the radiographic characteristics which may portend a poor prognosis.

https://ift.tt/2I5AVxX

Significance of Negative Posttreatment 18-FDG PET/CT Imaging in Patients With p16/HPV-positive Oropharyngeal Cancer

Patients with p16/HPV-associated oropharyngeal squamous cell carcinoma have a favorable outcome after treatment. In this group of patients who potentially have a long life expectancy, the optimal surveillance strategy and modality is not well established. We aim to determine the ability of a negative postradiation PET/CT scan in predicting the risk of subsequent relapse in these patients.

https://ift.tt/2Gs7pp8

High Abnormal Rate in the Repetitive Nerve Stimulation Test in Acute Onset Myasthenia Gravis

Liik and Punga (2016) reported > 10% decremental response in the repetitive nerve stimulation (RNS) in 1 of 9 patients in the acute onset (AO) group (duration < 4 weeks) of generalized myasthenia gravis (MG). This finding is rather unexpected and contradictory to our common experience of a high rate of abnormal RNS findings in AO MG patients. Because this issue has not been adequately addressed in the literature, we are reporting our findings on this issue.

https://ift.tt/2GgVcjW

Relationship between age and nerve dimensions in Charcot-Marie-Tooth disease. Do we know the reality?

We have read with attention and interest the manuscript by Fabrizi and colleagues, entitled "The spectrum of Charcot-Marie-Tooth disease due to myelin protein zero: An electrodiagnostic, nerve ultrasound and histological study" (Fabrizi et al., 2018). The authors explored, in a wide way, the characteristics of patients affected by myelin protein zero (MPZ)-related Charcot-Marie-Tooth (CMT) disease. They assessed the patients considering clinical examination, nerve conduction study, ultrasound and, in a patient subgroup, biopsy.

https://ift.tt/2G9BwCz

Reply to “High Abnormal Rate in the Repetitive Nerve Stimulation Test in Acute Onset Myasthenia Gravis”

The Letter to the Editor by Lee and Oh in the current issue of Clinical Neurophysiology shows that the decrement was abnormal in the majority of cases with acute onset (AO) myasthenia gravis (MG), derived from the MG database in Alabama between 1987-2014 (Lee and Oh, 2018). This is in contrast to our previous study (Liik and Punga, 2016), which demonstrated a low prevalence of decrement in AO MG patients (< 4 weeks from symptom onset).

https://ift.tt/2DXLosS

Long-term outcomes of combined endoscopic resection and chemoradiotherapy for esophageal squamous cell carcinoma with submucosal invasion

https://ift.tt/2pHrZbk

P.05.15 BALANCED DIET IS AS EFFECTIVE AS LOW FODMAPS AND GLUTEN FREE ONE IN IMPROVING HEALTH RELATED QUALITY OF LIFE IN IBS PATIENTS

https://ift.tt/2pJm2tQ

P.09.18 DIETARY INTAKE IN PATIENTS WITH NON-ALCOHOLIC STEATOHEPATITIS: QUALITATIVE AND QUANTITATIVE EVALUATION

https://ift.tt/2pH9BiP

Height and overall cancer risk and mortality: evidence from a Mendelian randomisation study on 310,000 UK Biobank participants

https://ift.tt/2G8qVaI

Evidence for DNA Sequence Encoding of an Accessible Nucleosomal Array across Vertebrates

Nucleosome-depleted regions around which nucleosomes order following the "statistical" positioning scenario were recently shown to be encoded in the DNA sequence in human. This intrinsic nucleosomal ordering strongly correlates with oscillations in the local GC content as well as with the interspecies and intraspecies mutation profiles, revealing the existence of both positive and negative selection. In this letter, we show that these predicted nucleosome inhibitory energy barriers (NIEBs) with compacted neighboring nucleosomes are indeed ubiquitous to all vertebrates tested.

https://ift.tt/2G8XQvY

Determination of Dynamical Heterogeneity from Dynamic Neutron-Scattering of Proteins

Motional displacements of hydrogen (H) in proteins can be measured using incoherent neutron-scattering methods. These displacements can also be calculated numerically using data from molecular dynamics simulations. An enormous amount of data on the average mean-square motional displacement (MSD) of H as a function of protein temperature, hydration, and other conditions has been collected. H resides in a wide spectrum of sites in a protein. Some H are tightly bound to molecular chains, and the H motion is dictated by that of the chain.

https://ift.tt/2pMDhKW

Applicability of Publicly Reported Hospital Readmission Measures to Unreported Conditions and Other Patient Populations A Cross-Sectional All-Payer Study

Background:

Readmission rates after hospitalizations for heart failure (HF), acute myocardial infarction (AMI), and pneumonia among Medicare beneficiaries are used to assess quality and determine reimbursement. Whether these measures reflect readmission rates for other conditions or insurance groups is unknown.

Objective:

To investigate whether hospital-level 30-day readmission measures for publicly reported conditions (HF, AMI, and pneumonia) among Medicare patients reflect those for Medicare patients hospitalized for unreported conditions or non-Medicare patients hospitalized with HF, AMI, or pneumonia.

Design:

Cross-sectional.

Setting:

Population-based.

Participants:

Hospitals in the all-payer Nationwide Readmissions Database in 2013 and 2014.

Measurements:

Hospital-level 30-day all-cause risk-standardized excess readmission ratios (ERRs) were compared for 3 groups of patients: Medicare beneficiaries admitted for HF, AMI, or pneumonia (Medicare reported group); Medicare beneficiaries admitted for other conditions (Medicare unreported group); and non-Medicare beneficiaries admitted for HF, AMI, or pneumonia (non-Medicare group).

Results:

Within-hospital differences in ERRs varied widely among groups. Medicare reported ratios differed from Medicare unreported ratios by more than 0.1 for 29% of hospitals and from non-Medicare ratios by more than 0.1 for 46% of hospitals. Among hospitals with higher readmission ratios, ERRs for the Medicare reported group tended to overestimate ERRs for the non-Medicare group but underestimate those for the Medicare unreported group.

Limitations:

Medicare groups and risk adjustment differed slightly from those used by the Centers for Medicare & Medicaid Services.

Conclusion:

Hospital ERRs, as estimated by Medicare to determine financial penalties, have poor agreement with corresponding measures for populations and conditions not tied to financial penalties. Current publicly reported measures may not be good surrogates for overall hospital quality related to 30-day readmissions.

Primary Funding Source:

Richard A. and Susan F. Smith Center for Outcomes Research in Cardiology.

https://ift.tt/2GcMd2R

Association of E-Cigarette Use With Smoking Cessation Among Smokers Who Plan to Quit After a Hospitalization A Prospective Study

Background:

Many smokers report using e-cigarettes to help them quit smoking, but whether e-cigarettes aid cessation efforts is uncertain.

Objective:

To determine whether e-cigarette use after hospital discharge is associated with subsequent tobacco abstinence among smokers who plan to quit and are advised to use evidence-based treatment.

Design:

Secondary data analysis of a randomized controlled trial. (ClinicalTrials.gov: NCT01714323 [parent trial])

Setting:

3 hospitals.

Participants:

1357 hospitalized adult cigarette smokers who planned to stop smoking, received tobacco cessation counseling in the hospital, and were randomly assigned at discharge to a tobacco treatment recommendation (control) or free tobacco treatment (intervention).

Measurements:

Self-reported e-cigarette use (exposure) was assessed 1 and 3 months after discharge; biochemically validated tobacco abstinence (outcome) was assessed 6 months after discharge.

Results:

Twenty-eight percent of participants used an e-cigarette within 3 months after discharge. In an analysis of 237 propensity score–matched pairs, e-cigarette users were less likely than nonusers to abstain from tobacco use at 6 months (10.1% vs. 26.6%; risk difference, −16.5% [95% CI, −23.3% to −9.6%]). The association between e-cigarette use and quitting varied between intervention patients, who were given easy access to conventional treatment (7.7% vs. 29.8%; risk difference, −22.1% [CI, −32.3% to −11.9%]), and control patients, who received only treatment recommendations (12.0% vs. 24.1%; risk difference, −12.0% [CI, −21.2% to 2.9%]) (P for interaction = 0.143).

Limitations:

Patients self-selected e-cigarette use. Unmeasured confounding is possible in an observational study.

Conclusion:

During 3 months after hospital discharge, more than a quarter of smokers attempting to quit used e-cigarettes, mostly to aid cessation, but few used them regularly. This pattern of use was associated with less tobacco abstinence at 6 months than among smokers who did not use e-cigarettes. Additional study is needed to determine whether regular use of e-cigarettes aids or hinders smoking cessation.

Primary Funding Source:

National Heart, Lung, and Blood Institute.

https://ift.tt/2ITp87m

Genomic Analysis to Avoid Misdiagnosis of Adults With Bilateral Renal Cysts

https://ift.tt/2GfGpGd

Ethical Obligations Regarding Short-Term Global Health Clinical Experiences: An American College of Physicians Position Paper

This American College of Physicians position paper aims to inform ethical decision making surrounding participation in short-term global health clinical care experiences. Although the positions are primarily intended for practicing physicians, they may apply to other health care professionals and should inform how institutions, organizations, and others structure short-term global health experiences. The primary goal of short-term global health clinical care experiences is to improve the health and well-being of the individuals and communities where they occur. In addition, potential benefits for participants in global health include increased awareness of global health issues, new medical knowledge, enhanced physical diagnosis skills when practicing in low-technology settings, improved language skills, enhanced cultural sensitivity, a greater capacity for clinical problem solving, and an improved sense of self-satisfaction or professional satisfaction. However, these activities involve several ethical challenges. Addressing these challenges is critical to protecting patient welfare in all geographic locales, promoting fair and equitable care globally, and maintaining trust in the profession. This paper describes 5 core positions that focus on ethics and the clinical care context and provides case scenarios to illustrate them.

https://ift.tt/2IUcbdt

Balancing Innovation and Safety When Integrating Digital Tools Into Health Care

Some observers see danger in the way that software applications, personal sensors, and new types of data and data analysis are changing how we diagnose and treat disease. However, others think that these dangers can be avoided if proper safeguards are included, and this article helps us understand when to use such safeguards.

https://ift.tt/2pHoP6G

Ethical Obligations in Short-Term Global Health Clinical Experiences: The Devil Is in the Details

This issue includes the American College of Physicians ethics recommendations for physicians considering participation in short-term global health experiences. The editorialists commend the effort and identify additional issues that are pertinent to the ethics of such experiences and valuable to the host locations.

https://ift.tt/2IVjr8W

Publicly Reported Readmission Measures and the Hospital Readmissions Reduction Program: A False Equivalence?

In their current report, Butala and colleagues assess whether a hospital's performance on the 3 Hospital Readmissions Reduction Program conditions (acute myocardial infarction, heart failure, and pneumonia) reflects readmission rates for other conditions or for insurance groups other than Medicare. The editorialists discuss the findings and the need to evaluate and improve current readmission measures and policies.

https://ift.tt/2GeiSFn

Use of E-Cigarettes Among Smokers Who Plan to Quit After a Hospitalization

https://ift.tt/2IUbS2j

Cancer Cytopathology, Ahead of Print.

Cancer Cytopathology, Ahead of Print.


https://ift.tt/2Gx3AyQ

Cancer Cytopathology, Ahead of Print.

Cancer Cytopathology, Ahead of Print.


https://ift.tt/2GbbWsM

Blood Lead Levels of Children in Flint, Michigan: 2006-2016

We evaluated the increases in blood lead levels (BLLs) observed in young children in Flint, Michigan, during their exposure to corrosive Flint River water during the years 2014 and 2015 and compared their BLLs to those of Flint children measured during the years 2006-2013 and 2016.

https://ift.tt/2um08lR

Acute Responses to Diuretic Therapy in Extremely Low Gestational Age Newborns: Results from the Prematurity and Respiratory Outcomes Program Cohort Study

To determine if daily respiratory status improved more in extremely low gestational age (GA) premature infants after diuretic exposure compared with those not exposed in modern neonatal intensive care units.

https://ift.tt/2IVeqxh

Technique and Patient Selection Criteria of Right Anterior Mini-Thoracotomy for Minimal Access Aortic Valve Replacement

The goal of this protocol is to describe in detail the technique of minimally invasive aortic valve replacement through a right anterior mini-thoracotomy and central aortic cannulation. This technique can potentially enhance patients' comfort and, by reducing post-operative morbidity, promote lowering the length of stay and global costs.

https://ift.tt/2GchqHu

What are the soft food and mechanical soft food diets?

There are many reasons why someone may need to go on a soft food diet. Reasons might include surgery, cancer, difficulty swallowing, or dental problems. The diet should consist of a variety of foods that can be mashed or pureed. Read on find out which types of food to include, and tips for following this diet.

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Higher Risk of Heart Failure Seen in Some Cancers

Some people who have been treated for breast cancer or lymphoma have a higher risk of developing congestive heart failure than people who haven't had cancer, results from a new study show.

https://ift.tt/2GezrRF

Characterization of Cell Membrane Extensions and Studying Their Roles in Cancer Cell Adhesion Dynamics

This study demonstrates the utility and ease of quantitative cell membrane extension measurement and its correlation to adhesive capacity of cells. As a representative example, we show here that Dickkopf-related protein 3 (DKK3) promotes increased lobopodia formation and cell adhesiveness in adrenocortical carcinoma cells in vitro.

https://ift.tt/2I68n7M

Eclipse Kratom by Tamarack: Recall - Possible Salmonella Contamination

Audience: Consumer, Patient [Posted 03/26/2018] ISSUE: Tamarack is voluntarily recalling Eclipse Kratom-containing powder products because it has the potential to be contaminated with Salmonella, an organism which can cause serious and sometimes...

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Impact of change in serum albumin level during and after chemoradiotherapy in patients with locally advanced esophageal cancer

Abstract

Background

In patients with locally advanced esophageal cancer treated by concurrent chemoradiotherapy (CCRT), baseline malnutrition and its progression have been shown to be associated with a poor outcome. We conducted this study to determine the variation in four blood test parameters including serum albumin level (ALB), creatinine (Cre), hemoglobin (Hb) and platelet (Plt) during CCRT for stage III esophageal cancer patients and its effect on patients' outcome.

Methods

One hundred eighty-three patients diagnosed with stage III esophageal cancer were retrospectively investigated. In addition to known prognostic factors, baseline level of the four blood test parameters and their variation at day 105 (ΔALB, ΔCre, ΔHb and ΔPlt, respectively) were analyzed.

Results

The median observation period for patients who survived was 57.2 months, and the 5-year overall survival rate was 35.6% (95% CI 34.2–36.9%). In multivariate analyses, baseline ALB (≥ 3.6 g/dL), higher ΔALB (≥ + 0.3 g/dL) were independent predictors for overall survival (p = 0.001 and < 0.001, respectively), in addition to other clinical factors including T stage and overall treatment time (OTT). For disease-free survival, ΔALB was only a predictor in hematological parameters (p = 0.001) in addition to T stage and OTT. No hematological and clinical parameters had significant correlation with local control in multivariate analysis. Furthermore, ΔALB showed significant correlation with OS and DFS in log-rank test (p = 0.002 and 0.002, respectively).

Conclusions

Our results suggest improvement in ALB after treatment might be a favorable prognostic factor in esophageal cancer patients treated by CCRT.

https://ift.tt/2IUMQjA