Gene alterations as predictors of radiation-induced toxicity in head and neck squamous cell carcinoma.

BackgroundOptimizing the therapeutic ratio for radiation therapy (RT) in head and neck squamous cell carcinoma (HNSCC) is uniquely challenging owing to high rates of early and late toxicity involving nearby organs at risk. These toxicities have a profound impact on treatment compliance and quality of life. Emerging evidence suggests that RT dose alone cannot fully account for the variable severity of RT-related adverse events (rtAEs) observed in HNSCC patients. Next-generation sequencing has become an increasingly valuable tool with widespread use in the oncology field and is being robustly explored for predicting rtAEs beyond dosimetric data.MethodsPatients who had Foundation Medicine sequencing data and received RT for primary or locally recurrent HNSCC were selected for this study. Early and late toxicity data were collected and reported based on Common Terminology Criteria for Adverse Events version 5.0. Dosimetric parameters were collected for pertinent structures.ResultsA total of HNSCC 37 patients were analyzed in this study. Genetic alterations in BRCA2, ERBB3, NOTCH1 and CCND1 were all associated with higher mean grade of toxicity with BRCA2 alteration implicated in all toxicity parameters evaluated including mucositis, early dysphagia, xerostomia and to a lesser extent, late dysphagia. Interestingly, patients who exhibited alterations in both BRCA2 and ERBB3 experienced a twofold or greater increase in early dysphagia, early xerostomia and late dysphagia compared to ERBB3 alteration alone. Furthermore, several gene alterations were associated with improved toxicity outcomes. Within an RT supersensitive patient subset, alterations were found in TNFAIP3, HNF1A, SPTA1 and CASP8. All of these alterations were not found in the RT insensitive patient subset. We found 17 gene alterations in the RT insensitive patient subset that were not found in the RT supersensitive patient subset.ConclusionDespite consistent RT dosimetric parameters, patients with HNSCC experience heterogeneous patterns of rtAEs. Identifying factors associated with toxicity outcomes offers a new avenue for personalized precision RT therapy and prophylactic management. Here, next-generation sequencing in a population of HNSCC patients correlates several genetic alterations with severity of rtAEs. Further analysis is urgently needed to identify genetic patterns associated with rtAEs in order to reduce harmful outcomes in this challenging population

Short-Term Assessment of Obstructive Sleep Apnea Syndrome Remission Rate after Sleeve Gastrectomy: a Cohort Study

International audienceBackgroundSevere obesity is associated with a high prevalence of moderate-to-severe obstructive sleep apnea syndrome (OSA). Bariatric surgery has been shown to effectively reduce excess weight and comorbidities.MethodsWe evaluated the remission rate of moderate-to-severe OSA (apnea-hypopnea index (AHI)>= 15) following sleeve gastrectomy. We performed a single-center retrospective chart review of all patients who underwent preoperative polysomnography (PSG) or polygraphy before primary sleeve gastrectomy. Patients with moderate-to-severe OSA treated by continuous positive airway pressure (CPAP) also underwent postoperative PSG. Bivariate analysis was performed to evaluate the criteria associated with remission of moderate-to-severe OSA.ResultsFrom 2013 to 2018, 39 of 162 patients (24.1%) scheduled for sleeve gastrectomy (SG) presented moderate-to-severe OSA requiring CPAP. Postoperative PSG was performed in 36 patients a mean of 9.96.1 months after SG. Mean BMI decreased from 47.4 +/- 8.4 to 36.3 +/- 7.1 kg/m(2) (p<0.001), and all patients reported clinical improvement of OSA symptoms. A remission of moderate-to-severe OSA was observed in 72.2% of patients with a mean decrease of AHI from 45.8 events/h to 11.3 events/h (p<0.001). Postoperative neck circumference was the only factor associated with OSA remission.Conclusion SG is associated with a rapid improvement of moderate-to-severe OSA partially as a result of a reduction of neck circumference. However, the absence of correlation with excess weight loss suggests that other weight-independent factors may also be involved

Compliance with a multidisciplinary team meeting's decision prior to bariatric surgery protects against major postoperative complications

International audienceBackground: Good surgical practice guidelines in France state that patients eligible for bariatric surgery must always be discussed at a multidisciplinary team (MDT) meeting. Objective: Describe MDT meetings and assess their possible impact on the postoperative course. Setting: University Hospital, France, public practice. Methods: From April 2009 to March 2013, we included all patients reviewed in a MDT meeting before bariatric surgery. The primary endpoint was the case validation rate. The secondary endpoints were the number of MDT meetings, the number of submissions discussed or refused, outcomes in patients who underwent surgery in another center after refusal, or deferral in our MDT meeting. Results: Forty-nine MDT meetings were held representing 1099 case files (816 patients) that were discussed. Of the case files, 84.5% concerned first-line surgery, 14% concerned second-line surgery, and 1.4% concerned third-line surgery. Overall, 776 (70.6%) of these submissions were approved, accounting for 95% of the patients. Further investigation before a decision was required in 13.3%. Surgery was definitively refused in 1% (n = 11). For the 776 patients having undergone surgery, the complication rate was 10.1%, the major complication rate was 6%, and the reoperation rate was 3.2%. For the 11 patients for whom bariatric surgery was refused, 7 patients underwent surgery in another center (without MDT meetings). There were 4 postoperative complications (57.1%; 3 major and 1 minor). Conclusion: The MDT meeting's decision is important for standardizing the management of obese patients before bariatric surgery. MDT meetings might help to reduce complication by optimizing patient selection and preoperative care. (C) 2017 American Society for Metabolic and Bariatric Surgery. All rights reserved

Differential regulation of TNFα and IL-6 expression contributes to immune evasion in prostate cancer

BackgroundThe role of the inflammatory milieu in prostate cancer progression is not well understood. Differences in inflammatory signaling between localized and metastatic disease may point to opportunities for early intervention.MethodsWe modeled PCa disease progression by analyzing RNA-seq of localized vs. metastatic patient samples, followed by CIBERSORTx to assess their immune cell populations. The VHA CDW registry of PCa patients was analyzed for anti-TNF clinical outcomes.ResultsWe observed statistically significant opposing patterns of IL-6 and TNFα expression between localized and metastatic disease. IL-6 was robustly expressed in localized disease and downregulated in metastatic disease. The reverse was observed with TNFα expression. Metastatic disease was also characterized by downregulation of adhesion molecule E-selectin, matrix metalloproteinase ADAMTS-4 and a shift to M2 macrophages whereas localized disease demonstrated a preponderance of M1 macrophages. Treatment with anti-TNF agents was associated with earlier stage disease at diagnosis.ConclusionsOur data points to clearly different inflammatory contexts between localized and metastatic prostate cancer. Primary localized disease demonstrates local inflammation and adaptive immunity, whereas metastases are characterized by immune cold microenvironments and a shift towards resolution of inflammation and tissue repair. Therapies that interfere with these inflammatory networks may offer opportunities for early intervention in monotherapy or in combination with immunotherapies and anti-angiogenic approaches

Comparing indications, complexity and outcomes of laparoscopic liver resection between centers with and without a liver transplant program: a French nationwide study

International audienceBackground: There are no data to evaluate the difference in populations and impact of centers with liver transplant programs in performing laparoscopic liver resection (LLR).Methods: This was a multicenter study including patients undergoing LLR for benign and malignant tumors at 27 French centers from 1996 to 2018. The main outcomes were postoperative severe morbidity and mortality.Results: A total of 3154 patients were included, and 14 centers were classified as transplant centers (N = 2167 patients, 68.7 %). The transplant centers performed more difficult LLRs and more resections for hepatocellular carcinoma (HCC) in patients who more frequently had cirrhosis. A higher rate of performing the Pringle maneuver, a lower rate of blood loss and a higher rate of open conversion (all p < 0.05) were observed in the transplant centers. There was no association between the presence of a liver transplant program and either postoperative severe morbidity (<10 % in each group; p = 0.228) or mortality (1 % in each group; p = 0.915).Conclusions: Most HCCs, difficult LLRs, and cirrhotic patients are treated in transplant centers. We show that all centers can achieve comparable safety and quality of care in LLR independent of the presence of a liver transplant program

Benchmark performance of laparoscopic left lateral sectionectomy and right hepatectomy in expert centers

International audienceHerein, we aimed to establish benchmark values - based on a composite indicator of healthcare quality - for the performance of laparoscopic left lateral sectionectomy (LLLS) and laparoscopic right hepatectomy (LRH) using data from expert centers

Assessment of Factors Associated with Morbidity and Textbook Outcomes of Laparoscopic Liver Resection in Obese Patients. A French Nationwide Study

BACKGROUND: Liver surgeons need to know the expected outcomes of laparoscopic liver resection (LLR) in obese patients.OBJECTIVE: The purpose of the present study is to assess morbidity, mortality and textbook outcomes (TO) after LLR in obese patients.METHODS: This is a French multicenter study of patients undergoing LLR between 1996 and 2018. Obesity was defined by a BMI at or above 30 kg/m(2). Short-term outcomes and TO were compared between obese (ob) and nonobese (non-ob) patients. Factors associated with severe morbidity and TO were investigated.RESULTS: Of 3,154 patients included, 616 (19.5%) were obese. Ob-group patients had significantly higher American Society of Anesthesiologists (ASA) score and higher incidence of metabolic syndrome and chronic liver disease and were less likely to undergo major hepatectomy. Mortality rates were similar between ob and non-ob groups (0.8 vs 1.1%; p = 0.66). Overall morbidity and hospital stay were significantly increased in the ob group compared with the non-ob group (39.4 vs 34.7%, p = 0.03; and 9.5 vs 8.6 days, p = 0.02), whereas severe 90-day morbidity (at or above Clavien-Dindo grade III) was similar between groups (8% in both groups; p = 0.90). TO rate was significantly lower for the ob group than the non-ob group (58.3 vs 63.7%; p = 0.01). In multivariate analysis, obesity did not emerge as a risk factor for severe 90-day morbidity but was associated with a lower TO rate after LLR (odds ratio = 0.8, 95% CI 0.7-1.0; p = 0.03).CONCLUSIONS: LLR in obese patients is safe and effective with acceptable mortality and morbidity. Obesity had no impact on severe morbidity but was a factor for failing to achieve TO after LLR. (C) 2022 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved

Laparoscopic versus open liver resection for intrahepatic cholangiocarcinoma. Report of an international multicenter cohort study with propensity score matching

Background: Intrahepatic cholangiocarcinoma is a rare disease with a poor prognosis. In patients where surgical resection is possible, outcome is influenced by perioperative morbidity and lymph node status. Laparoscopic liver resection is associated with improved clinical and oncological outcomes in primary and metastatic liver cancer compared with open liver resection, but evidence on intrahepatic cholangiocarcinoma is still insufficient.The primary aim of this study was to compare overall survival for a large series of patients treated for intrahepatic cholangiocarcinoma by open or laparoscopic approach. Secondary objectives were to compare disease-free survival, predictors of death, and recurrence.Methods: Patients treated with laparoscopic or open liver resection for intrahepatic cholangiocarcinoma from 2000 to 2018 from 3 large international databases were analyzed retrospectively. Each patient in the laparoscopic resection group (case) was matched with 1 open resection control (1:1 ratio), through a propensity score calculated on clinically relevant preoperative covariates. Overall and disease-free survival were compared between the matched groups. Predictors of mortality and recurrence were analyzed with Cox regression, and the Textbook Outcomes were described.Results: During the study period, 855 patients met the inclusion criteria (open liver resection = 709, 82.9%; laparoscopic liver resection = 146, 17.1%). Two groups of 89 patients each were analyzed after propensity score matching, with no significant difference regarding pre-and postoperative variables. Overall survival at 1, 3, and 5 years was 92%, 75%, and 63% in the laparoscopic liver resection group versus 92%, 58%, and 49% in the open liver resection group (P = .0043). Adjusted Cox regression revealed severe postoperative complications (hazard ratio: 10.5, 95% confidence interval [1.01-109] P = .049) and steatosis (hazard ratio: 13.8, 95% confidence interval [1.23-154] P = .033) as predictors of death, and transfusion (hazard ratio: 19.2, 95% confidence interval [4.04-91.4] P &lt; .001) and severe postoperative complications (hazard ratio: 4.07, 95% confidence interval [1.15-14.4] P = .030) as predictors of recurrence.Conclusion: The survival advantage of laparoscopic liver resection over open liver resection for intrahepatic cholangiocarcinoma is equivocal, given historical bias and missing data. (C) 2021 Elsevier Inc. All rights reserved

Risk factors for emergency surgery for diverticulitis: A retrospective multicentric French study at 41 hospitals

International audienceBackgroundThe observed increase in the incidence of complicated diverticulitis may lead to the performance of more emergency surgeries. This study aimed to assess the rate and risk factors of emergency surgery for sigmoid diverticulitis.MethodThe primary outcomes were the rate of emergency surgery for sigmoid diverticulitis and its associated risk factors. The urgent or elective nature of the surgical intervention was provided by the surgeon and in accordance with the indication for surgical treatment. A mixed logistic regression with a random intercept after multiple imputations by the chained equation was performed to consider the influence of missing data on the results.ResultsBetween 2010 and 2021, 6,867 patients underwent surgery for sigmoid diverticulitis in the participating centers, of which one-third (n = 2317) were emergency cases. In multivariate regression analysis with multiple imputation by chained equation, increasing age, body mass index &lt;18.5 kg/m2, neurologic and pulmonary comorbidities, use of anticoagulant drugs, immunocompromised status, and first attack of sigmoid diverticulitis were independent risk factors for emergency surgery. The likelihood of emergency surgery was significantly more frequent after national guidelines, which were implemented in 2017, only in patients with a history of sigmoid diverticulitis attacks.ConclusionThe present study highlights a high rate (33%) of emergency surgery for sigmoid diverticulitis in France, which was significantly associated with patient features and the first attack of diverticulitis