Proteostasis and metabolic dysfunction in a distinct subset of storage-induced senescent erythrocytes targeted for clearance.

Although refrigerated storage slows the metabolism of volunteer donor RBCs, cellular aging still occurs throughout this in vitro process, which is essential in transfusion medicine. Storage-induced microerythrocytes (SMEs) are morphologically-altered senescent RBCs that accumulate during storage and which are cleared from circulation following transfusion. However, the molecular and cellular alterations that trigger clearance of this RBC subset remain to be identified. Using a staining protocol that sorts long-stored SMEs (i.e., CFSE high ) and morphologically-normal RBCs (CFSE low ), these in vitro aged cells were characterized. Metabolomics analysis identified depletion of energy, lipid-repair, and antioxidant metabolites in CFSE high RBCs. By redox proteomics, irreversible protein oxidation primarily affected CFSE high RBCs. By proteomics, 96 proteins, mostly in the proteostasis family, had relocated to CFSE high RBC membranes. CFSE high RBCs exhibited decreased proteasome activity and deformability; increased phosphatidylserine exposure, osmotic fragility, and endothelial cell adherence; and were cleared from the circulation during human spleen ex vivo perfusion. Conversely, molecular, cellular, and circulatory properties of long-stored CFSE low RBCs resembled those of short-stored RBCs. CFSE high RBCs are morphologically and metabolically altered, have irreversibly oxidized and membrane-relocated proteins, and exhibit decreased proteasome activity. In vitro aging during storage selectively alters metabolism and proteostasis in SMEs, targeting these senescent cells for clearance.

Clearance of pathogenic erythrocytes is maintained despite spleen dysfunction in children with sickle cell disease.

In children with sickle cell disease (SCD), splenectomy is immediately beneficial for acute sequestration crises and hypersplenism (ASSC/HyS) but portends a long-term risk of asplenia-related complications. We retrieved peripheral and splenic red blood cells (RBCs) from 17 SCD children/teenagers undergoing partial splenectomy for ASSC/HyS, 12 adult subjects without RBC-related disease undergoing splenectomy (controls), five human spleens perfused ex vivo with HbSS- and HbAA-RBC, and quantified abnormal RBC by microscopy, spleen-mimetic RBC filtration, and adhesion assays. Spleens were analyzed by immunohistochemistry and transmission electron microscopy (TEM). In circulating blood of SCD and control subjects, dysmorphic (elongated/spherocytic) RBCs were <2%, while proportions of pocked-RBC were 4.3-fold higher in SCD children than in controls. Compared to controls, splenic RBCs were more frequently dysmorphic (29.3% vs. 0.4%), stiffer (42.2% vs. 12.4%), and adherent (206 vs. 22 adherent RBC/area) in SCD subjects. By TEM, both polymer-containing and homogenous RBC contributed to spleen congestion, resulting in 3.8-fold higher RBC population density in SCD spleens than in control spleens, predominantly in the cords. Perfused spleens with normal function displayed similar congestion and retention of dysmorphic RBC as SCD spleens. The population density of active macrophages was similar in SCD and control spleens, with a relative deficit in phagocytosis of polymer-containing RBC. Despite the existence of hyposplenism, splenectomy in SCD children removes an organ that still efficiently filters out potentially pathogenic altered RBC. Innovative treatments allowing fine-tuned reduction of RBC retention would alleviate spleen congestion, the major pathogenic process in ASSC/HyS, while preserving spleen protective functions for the future.

Laparoscopic floppy Nissen fundoplication with valve calibration: a safe and efficient procedure.

PURPOSES: A floppy Nissen fundoplication with valve calibration (FNF-VC) performed by laparotomy has been described, to reduce postoperative dysphagia and gas bloating after 360°-fundoplication. As laparoscopy is the gold standard for fundoplication, this study reports the first results of a modified FNF-VC adapted for laparoscopy (LFNF). METHODS: Seventy-two consecutive patients, who underwent LFNF for refractory GERD between 2012 and 2021, were included. Postoperative outcomes and quality of life (QoL) by GERSS, GERD-HRQL, and GIQLI scores before and after surgery were assessed. RESULTS: The main symptoms were pyrosis (81%), regurgitation (39%), Ear-Nose-Throat symptoms (22%), and thoracic pain (24%). Hiatal hernia was present in 85% (n = 61) of the patients. There was no postoperative mortality, and the severe postoperative morbidity rate (Dindo-Clavien ≥ III) was 6%. After a median follow-up of 3.6 years, only 8% of patients were still taking proton-pump inhibitors. Long-term residual dysphagia was noted in 15% of the patients, but none required reoperation or interventional endoscopic procedures. QoL improved, with a significant reduction in GERSS and GERD-HRQL scores and a postoperative GIQLI of 101.75 (75-117.5). CONCLUSION: This series reports the safety and efficacy of an FNF-VC adapted for laparoscopy to treat GERD with a limited rate of residual dysphagia.

Lung Ultrasound Score on Postoperative Day 1 Is Predictive of the Occurrence of Pulmonary Complications after Major Abdominal Surgery: A Multicenter Prospective Observational Study.

BACKGROUND: Postoperative pulmonary complications after major abdominal surgery are frequent and carry high morbidity and mortality. Early identification of patients at risk of pulmonary complications by lung ultrasound may allow the implementation of preemptive strategies. The authors hypothesized that lung ultrasound score would be associated with pulmonary postoperative complications. The main objective of the study was to evaluate the performance of lung ultrasound score on postoperative day 1 in predicting pulmonary complications after major abdominal surgery. Secondary objectives included the evaluation of other related measures for their potential prediction accuracy. METHODS: A total of 149 patients scheduled for major abdominal surgery were enrolled in a bicenter observational study. Lung ultrasound score was performed before the surgery and on days 1, 4, and 7 after surgery. Pulmonary complications occurring before postoperative day 10 were recorded. RESULTS: Lung ultrasound score on postoperative day 1 was higher in patients developing pulmonary complications before day 10 (median, 13; interquartile range, 8.25 to 18; vs. median, 10; interquartile range, 6.5 to 12; Mann-Whitney P = 0.002). The area under the curve for predicting postoperative pulmonary complications before day 10 was 0.65 (95% CI, 0.55 to 0.75; P = 0.003). Lung ultrasound score greater than 12 had a sensitivity of 0.54 (95% CI, 0.40 to 0.67), specificity of 0.77 (95% CI, 0.67 to 0.85), and negative predictive value of 0.74 (95% CI, 0.65 to 0.83). Lung ultrasound score greater than 17 had sensitivity of 0.33 (95% CI, 0.21 to 0.47), specificity of 0.95 (95% CI, 0.88 to 0.98), and positive predictive value of 0.78 (95% CI, 0.56 to 0.93). Anterolateral lung ultrasound score and composite scores using lung ultrasound score and other patient characteristics showed similar predictive accuracies. CONCLUSIONS: An elevated lung ultrasound score on postoperative day 1 is associated with the occurrence of pulmonary complications within the first 10 days after major abdominal surgery.

Impact of COVID-19 on the management of hepatocellular carcinoma in a high-prevalence area: What's new 12 months later?

INTRODUCTION AND OBJECTIVES: The lockdown policy introduced in 2020 to minimize the spread of the COVID-19 pandemic, significantly affected the management and care of patients affected by hepatocellular carcinoma (HCC). The aim of this follow-up study was to determine the 12 months impact of the COVID-19 pandemic on the cohort of patients affected by HCC during the lockdown, within six French academic referral centers in the metropolitan area of Paris. MATERIALS AND METHODS: We performed a 12 months follow-up of the cross-sectional study cohort included in 2020 on the management of patients affected by HCC during the first six weeks of the COVID-19 pandemic (exposed), compared to the same period in 2019 (unexposed). Overall survival were compared between the groups. Predictors of mortality were analysed with Cox regression. RESULTS: From the initial cohort, 575 patients were included (n = 263 Exposed_COVID, n = 312 Unexposed_COVID). Overall and disease free survival at 12 months were 59.9 ± 3.2% vs 74.3 ± 2.5% (p<0.001) and 40.2 ± 3.5% vs 63.5 ± 3.1% (p<0.001) according to the period of exposure (Exposed_COVID vs Unexposed_COVID, respectively). Adjusted Cox regression revealed that the period of exposure (Exposed_COVID HR: 1.79, 95%CI (1.36, 2.35) p<0.001) and BCLC stage B, C and D (BCLC B HR: 1.82, 95%CI (1.07, 3.08) p = 0.027 - BCLC C HR: 1.96, 95%CI (1.14, 3.38) p = 0.015 - BCLC D HR: 3.21, 95%CI (1.76, 5.85) p<0.001) were predictors of death. CONCLUSIONS: Disruption of routine healthcare services because of the pandemic translated to reduced 1 year overall and disease-free survival among patients affected by HCC, in the metropolitan area of Paris, France.

Incidence and risk factors for Chyle leak after pancreatic surgery for cancer: A comprehensive systematic review.

BACKGROUND: Chyle leak (CL) is a clinically relevant complication after pancreatectomy. Its incidence and the associated risk factors are ill defined, and various treatments options have been described. There is no consensus, however, regarding optimal management. The present study aims to systematically review the literature on CL after pancreatectomy. METHODS: A systematic review from PubMed, Scopus and Embase database was performed. Studies using a clear definition for CL and published from January 2000 to January 2021 were included. The PRISMA guidelines were followed during all stages of this systematic review. The MINORS score was used to assess methodological quality. RESULTS: Literature search found 361 reports, 99 of which were duplicates. The titles and abstracts of 262 articles were finally screened. The references from the remaining 181 articles were manually assessed. After the exclusions, 43 articles were thoroughly assessed. A total of 23 articles were ultimately included for this review. The number of patients varied from 54 to 3532. Incidence of post pancreatectomy CL varied from 1.3% to 22.1%. Main risk factors were the extent of the surgery and early oral or enteral feeding. CL dried up spontaneously or after conservative management within 14 days in 53% to 100% of the cases. CONCLUSIONS: The extent of surgery is the most common predictor of risk of CL. Conservative treatment has been shown to be effective in most cases and can be considered the treatment of choice. We propose a management algorithm based on the current available evidence.

Ovarian metastases of pancreatic adenocarcinoma: clinical presentation, role of surgery, and potential value of the mutational profile for the differential diagnosis with primary mucinous ovarian carcinoma.

BACKGROUND: Ovarian metastases (OM) of pancreatic adenocarcinoma (PA) (OM-PA) can mimic primary ovarian mucinous carcinoma (POMC) on imaging and histology. These metastases are often symptomatic and not highly chemosensitive, so that oophorectomy may be considered. AIMS: The aims of this study were to compare the characteristics of OM-PA and POMC, and discuss the role of surgery. PATIENTS AND METHODS: Clinical, imaging, and histological data of patients with OM-PA and POMC (2000-2017) in three tertiary centers were reviewed. Twenty-six genes were analyzed by next generation sequencing (NGS) on both primary PA and OM-PA. RESULTS: Twenty-two women with OM-PA (n = 13, 11 with surgical resection) or POMC (n = 9) were selected. OM-PA were smaller than POMC (p = 0.02); imaging, histological, and immunohistochemistry data did not clearly differentiate OM-PA from POMC in 12 of 22 cases (54%). Seven PA/OM-PA pairs were analyzed, and a concordant KRAS mutation was identified in all cases. In four OM-PA, concordant mutations were also found in TP53 (n = 3), SMAD4 (n = 1), MET (n = 1), and PDGFRA (n = 1) genes. The aim of oophorectomy in 11 OM-PA was for antalgic (n = 6) or curative (n = 5) intent. Pain improved in 4/6 of the former patients, but 2/6 had significant morbidity, and 2/6 died of rapid tumor progression. After oophorectomy, median progression-free and overall survivals were 6 (0-11) and 8 months (1-131), respectively. CONCLUSION: Analysis of mutation profiles in both primary PA and ovarian tumors, especially KRAS, can help to determine the pancreatic origin of OM-PA. Surgical resection of OM-AP in highly selected patients may improve pelvic symptoms but may also cause significant morbidity. The benefit to survival requires further studies.

Tumor downstaging after neoadjuvant chemotherapy determines survival after surgery for gastric adenocarcinoma.

BACKGROUND: Since 2006, surgery combined with perioperative chemotherapy is the standard of care for resectable gastric adenocarcinoma in Europe. Specific effects of neoadjuvant chemotherapy remain unknown. The aim was to evaluate the rate of tumor downstaging and its impact on survival in patients undergoing curative resection after neoadjuvant chemotherapy (NeoCT) for gastric adenocarcinoma. MATERIAL AND METHODS: All patients treated in a curative intent for gastric or esophagogastric junction adenocarcinomas between 1996 and 2016 in our high-volume center were retrospectively included. Tumor downstaging after NeoCT was defined as ypTN inferior to cTN. The accuracy of clinical staging was evaluated in patients treated by upfront surgery before 2006. RESULTS: During the study period, 491 patients were operated for gastric adenocarcinoma, and 449 patients were finally analyzed. Among the 163 (36.3%) patients who received NeoCT, 61 (37.4%) had tumor downstaging. Overall survival and disease-free survival were longer in patients with tumor downstaging compared to patients without it (5-year survival: 84.8% vs 49.7%; P = .002 and 61.7% vs 43.4%; P = .054). In multivariate analysis tumor downstaging was an independent prognosis factor for better overall survival (HR = 5.258; P = .002) and disease-free survival (HR = 2.286; P = .028). Moreover, 45.5% of patients staged cT1-T2N0, in whom upfront surgery was performed, were understaged and ultimately had a more advanced tumor on pathological analysis. CONCLUSION: Response to neoadjuvant chemotherapy constitutes a major prognostic factor for overall and disease-free survival. In the absence of predictive factors for tumor downstaging, the indication for perioperative chemotherapy should remain broad, in particular because of the low accuracy of pretherapeutic staging and therefore the high risk of understaging tumors.

Acute Pancreatitis as the Initial Presentation of Pancreatic Adenocarcinoma does not Impact Short- and Long-term Outcomes of Curative Intent Surgery: A Study of the French Surgical Association.

BACKGROUND: Acute pancreatitis (AP) can be one of the earliest clinical presentation of pancreatic ductal adenocarcinoma (PDAC). Information about the impact of AP on postoperative outcomes as well as its influences on PDAC survival is scarce. This study aimed to determine whether AP as initial clinical presentation of PDAC impact the short- and long-term outcomes of curative intent pancreatic resection. PATIENTS AND METHODS: From 2004 to 2009, 1449 patients with PDAC underwent pancreatic resection in 37 institutions (France, Belgium and Switzerland). We used univariate and multivariate analysis to identify factors associated with severe complications and pancreatic fistula as well as overall and disease-free survivals. RESULTS: There were 764 males (52,7%), and the median age was 64 years. A total of 781 patients (53.9%) developed at least one complication, among whom 317 (21.8%) were classified as Clavien-Dindo ≥ 3. A total of 114 (8.5%) patients had AP as the initial clinical manifestation of PDAC. This situation was not associated with any increase in the rates of postoperative fistula (21.2% vs 16.4%, P = 0.19), postoperative complications (57% vs 54.2%, P = 0.56), and 30 day mortality (2.6% vs 3.4%, P = 1). In multivariate analysis, AP did not correlate with postoperative complications or pancreatic fistula. The median length of follow-up was 22.4 months. The median overall survival after surgery was 29.9 months in the AP group and 30.5 months in the control group. Overall recurrence rate and local recurrence rate did not differ between groups. CONCLUSION: AP before PDAC resection did not impact postoperative morbidity and mortality, as well as recurrence rate and survival.

Rapid clearance of storage-induced microerythrocytes alters transfusion recovery.

Permanent availability of red blood cells (RBCs) for transfusion depends on refrigerated storage, during which morphologically altered RBCs accumulate. Among these, a subpopulation of small RBCs, comprising type III echinocytes, spheroechinocytes, and spherocytes and defined as storage-induced microerythrocytes (SMEs), could be rapidly cleared from circulation posttransfusion. We quantified the proportion of SMEs in RBC concentrates from healthy human volunteers and assessed correlation with transfusion recovery, investigated the fate of SMEs upon perfusion through human spleen ex vivo, and explored where and how SMEs are cleared in a mouse model of blood storage and transfusion. In healthy human volunteers, high proportion of SMEs in long-stored RBC concentrates correlated with poor transfusion recovery. When perfused through human spleen, 15% and 61% of long-stored RBCs and SMEs were cleared in 70 minutes, respectively. High initial proportion of SMEs also correlated with high retention of RBCs by perfused human spleen. In the mouse model, SMEs accumulated during storage. Transfusion of long-stored RBCs resulted in reduced posttransfusion recovery, mostly due to SME clearance. After transfusion in mice, long-stored RBCs accumulated predominantly in spleen and were ingested mainly by splenic and hepatic macrophages. In macrophage-depleted mice, splenic accumulation and SME clearance were delayed, and transfusion recovery was improved. In healthy hosts, SMEs were cleared predominantly by macrophages in spleen and liver. When this well-demarcated subpopulation of altered RBCs was abundant in RBC concentrates, transfusion recovery was diminished. SME quantification has the potential to improve blood product quality assessment. This trial was registered at www.clinicaltrials.gov as #NCT02889133.

Adrenal gland as a sanctuary site for immunotherapy in patients with microsatellite instability-high metastatic colorectal cancer.

Metastatic colorectal cancers (mCRC) harboring microsatellite instability (MSI) are sensitive to immune checkpoint inhibitors (ICIs), but the mechanisms of resistance to ICIs remain unclear. Dissociated responses in patients with ICI-treated cancer suggest that certain organs may serve as sanctuary sites due to the tumor microenvironment. This case series describes five patients with ICI-treated MSI mCRC with disease progression limited to the adrenal glands. At ICI initiation, three patients were free of metastasis in the adrenal glands. Four patients experienced objective response per RECIST (Response Evaluation Criteria in Solid Tumors) while treated with ICI. ICI treatment was discontinued due to progressive disease limited to the adrenal glands (n=3) or toxicity (n=2). The time between ICI initiation and progression in the adrenal glands ranged from 11 to 39 months. Adrenalectomy (n=3) and stereotactic body radiation therapy (n=2) were performed. At the last follow-up, all patients were alive and progression free. Molecular analyses were performed in one patient. A significant impairment of the antigen presentation pathway was observed in the ICI-resistant lesion of the adrenal gland, which could be explained by the presence of glucocorticoids in the adrenal gland microenvironment. We also detected an overexpression of TSC22D3, a glucocorticoid-target gene that functions as a mediator of anti-inflammation and immunosuppression. This case series suggests that the adrenal glands may be the sanctuary sites for ICI-treated MSI mCRC through the glucocorticoid-induced impairment of the antigen presentation machinery.

Simultaneous Versus Delayed Resection for Initially Resectable Synchronous Colorectal Cancer Liver Metastases: A Prospective, Open-label, Randomized, Controlled Trial.

OBJECTIVE: To answer whether synchronous colorectal cancer liver metastases (SLM) should be resected simultaneously with primary cancer or should be delayed. SUMMARY BACKGROUND DATA: Numerous studies have compared both strategies. All were retrospective and conclusions were contradictory. METHODS: Adults with colorectal cancer and resectable SLM were randomly assigned to either simultaneous or delayed resection of the metastases. The primary outcome was the rate of major complications within 60 days following surgery. Secondary outcomes included overall and disease-free survival. RESULTS: A total of 105 patients were recruited. Eighty-five patients (39 and 46 in the simultaneous- and delayed-resection groups, respectively) were analyzed. The percentage of major perioperative complications did not differ between groups (49% and 46% in the simultaneous- and delayed-resection groups, respectively, adjusted OR 0.84, 95% CI 0.35-2.01; P = 0.70, logistic regression). Complications rates were 28% and 13% (P = 0.08, χ2 test) at colorectal site and 15% and 17% (P = 0.80, χ2 test) at liver site, in simultaneous- and delayed-resection groups, respectively. In the delayed-resection group, 8 patients did not reach the liver resection stage, and this was due to disease progression in 6 cases. After 2 years, overall and disease-free survival tended to be improved in simultaneous as compared with delayed-resection groups (P = 0.05), a tendency which persisted for OS after a median follow-up of 47 months. CONCLUSIONS: Complication rates did not appear to differ when colorectal cancer and synchronous liver metastases are resected simultaneously. Delayed resection tended to impair overall survival.

Impact of COVID-19 on the management of hepatocellular carcinoma in a high-prevalence area.

BACKGROUND & AIMS: Patients affected by hepatocellular carcinoma (HCC) represent a vulnerable population during the COVID-19 pandemic and may suffer from altered allocation of healthcare resources. The aim of this study was to determine the impact of the COVID-19 pandemic on the management of patients with HCC within 6 referral centres in the metropolitan area of Paris, France. METHODS: We performed a multicentre, retrospective, cross-sectional study on the management of patients with HCC during the first 6 weeks of the COVID-19 pandemic (exposed group), compared with the same period in 2019 (unexposed group). We included all patients discussed in multidisciplinary tumour board (MTB) meetings and/or patients undergoing a radiological or surgical programmed procedure during the study period, with curative or palliative intent. Endpoints were the number of patients with a modification in the treatment strategy, or a delay in decision-to-treat. RESULTS: After screening, n = 670 patients were included (n = 293 exposed to COVID, n = 377 unexposed to COVID). Fewer patients with HCC presented to the MTB in 2020 (p = 0.034) and fewer had a first diagnosis of HCC (n = 104 exposed to COVID, n = 143 unexposed to COVID, p = 0.083). Treatment strategy was modified in 13.1% of patients, with no differences between the 2 periods. Nevertheless, 21.5% vs. 9.5% of patients experienced a treatment delay longer than 1 month in 2020 compared with 2019 (p <0.001). In 2020, 7.1% (21/293) of patients had a diagnosis of an active COVID-19 infection: 11 (52.4%) patients were hospitalised and 4 (19.1%) patients died. CONCLUSIONS: In a metropolitan area highly impacted by the COVID-19 pandemic, we observed fewer patients with HCC, and similar rates of treatment modification, but with a significantly longer treatment delay in 2020 vs. 2019. LAY SUMMARY: During the coronavirus disease 2019 (COVID-19) pandemic era, fewer patients with hepatocellular carcinoma (HCC) presented to the multidisciplinary tumour board, especially with a first diagnosis of HCC. Patients with HCC had a treatment delay that was longer in the COVID-19 period than in 2019.

Testing for ROS1, ALK, MET, and HER2 rearrangements and amplifications in a large series of biliary tract adenocarcinomas.

Biliary tract carcinomas are divided into intrahepatic, perihilar, distal extrahepatic cholangiocarcinomas, and gallbladder adenocarcinomas. Therapies targeting ROS1, ALK, MET, and HER2 alterations are currently evaluated in clinical trials. We assessed ROS1 and ALK translocations/amplifications as well as MET and HER2 amplifications for each tumor subtype by fluorescent in situ hybridization (FISH) and immunohistochemistry (IHC) in 73 intrahepatic, 40 perihilar bile duct, 36 distal extrahepatic cholangiocarcinomas, and 45 gallbladder adenocarcinomas (n = 194). By FISH, we detected targetable alterations in 5.2% of cases (n = 10): HER2 and MET amplifications were found in 4.1% (n = 8) and 1.0% (n = 2), respectively. The HER2-amplified cases were mostly gallbladder adenocarcinomas (n = 5). The MET- and HER2-amplified cases were all positive by IHC. Fourteen cases without MET amplification were positive by IHC, whereas HER2 over-expression was detected by IHC only in HER2-amplified cases. We detected no ALK or ROS1 translocation or amplification. Several alterations were consistent with aneuploidy: 24 cases showed only one copy of ROS1 gene, 4 cases displayed a profile of chromosomal instability, and an over-representation of centromeric alpha-satellite sequences was found in five cases. We confirm a relatively high rate of HER2 amplifications in gallbladder adenocarcinomas and the efficacy of IHC to screen these cases. Our results also suggest the value of IHC to screen MET amplification. Contrary to initial publications, ROS1 rearrangements seem to be very rare in biliary tract adenocarcinomas. We confirm a relatively high frequency of aneuploidy and chromosomal instability and reveal the over-representation of centromeric alpha-satellite sequences in intrahepatic cholangiocarcinomas.

Para-aortic lymph node metastasis detected intraoperatively by systematic frozen section examination in pancreatic head adenocarcinoma: is resection improving the prognosis?

BACKGROUND: This study aimed to evaluate the controversial benefit of a pancreaticoduodenectomy (PD) in patients with PALN metastasis intraoperatively detected by systematic frozen section examination in pancreatic adenocarcinoma. METHODS: PALN intraoperative examination by frozen section was systematically performed from January 2006 to February 2018 prior to performing PD for pancreatic adenocarcinoma. Until June 2012, PALN + patients still underwent PD (PALN+/PD group) in the framework of a prospective study. Since July 2012, PALN+ was considered as contraindicating the planned PD (PALN+/No-PD group). Post-operative morbidity and survival were compared between these two groups. RESULTS: Of the 32 PALN + patients intraoperatively detected, the first 13 underwent a PD, while the last 19 did not undergo resection. Seven patients (54%) among 13 PALN+/PD patients developed a post-operative complication against 3 (16%) among 19 PALN+/No-PD patients (p = 0.049). The median length of stay was 5 days longer for PALN+/PD patients (p = 0.001). The median survival did not differ between PALN+/No-PD and PALN+/PD groups (respectively 13.4 months (95%CI:7.6-19.3) and 11.5 months (95%CI:5.9-17.1), p = 0.471). No patient was alive 4 years after surgery in both the PALN+/No-PD or PALN+/PD groups. CONCLUSION: In case of PALN detected intraoperatively in pancreatic adenocarcinoma, PD does not improve survival compared to current palliative treatment.

Ten-year impact of pancreaticoduodenectomy on bowel function and quality of life of patients with ileal pouch-anal anastomosis for familial adenomatous polyposis.

BACKGROUND: Patients with familial adenomatous polyposis (FAP) carry a risk of duodenal adenocarcinoma. These patients, who already have an ileal pouch-anal anastomosis (IPAA), sometimes require pancreaticoduodenectomy (PD). This work aims to evaluate the long-term consequences of the combination of PD + IPAA. METHODS: All patients with IPAA due to FAP who underwent PD from 1991 to 2017 were included (PD + IPAA group). Patients were matched 1:1 according to age, sex, ASA score and presence of colorectal cancer. Fecal continence and quality of life (QoL) were assessed using the Wexner score and the EORTC-QLQ-C30 questionnaire. RESULTS: Thirty-two PD + IPAA patients were matched with thirty-two IPAA-only patients. In each group, the response rate to the questionnaire was 78% (25/32). No differences were noted between PD + IPAA and IPAA-only groups in terms of daytime fecal frequency (6.0 vs 6.0; p = 0.362), Wexner score (3/20 vs 4/20; p = 0.984) and global QoL score (83.3/100 vs 83.3/100; p = 0.401). In the PD + IPAA group, 26% of patients developed diabetes a median period of 10.0 years after PD. The global QoL for these patients was significantly altered (p = 0.011), while daytime fecal frequency was unaffected (p = 0.092) as fecal continence (p = 0.475). CONCLUSION: In FAP patients with IPAA, PD does not affect bowel function or QoL.

Evaluation of the prognostic impact of pathologic response to preoperative chemotherapy using Mandard's Tumor Regression Grade (TRG) in gastric adenocarcinoma.

BACKGROUND: Perioperative chemotherapy is the gold standard in gastric cancer management. The prognostic significance of pathological response has been investigated in many malignancies, using Tumor Regression Grade (TRG). Its prognostic value in gastric cancer remains poorly known. AIMS: This study aimed to assess the prognostic value of pathological response to chemotherapy, using Mandard's TRG in gastric cancer, and to identify factors predictive of response to chemotherapy. METHODS: We retrospectively identified patients with gastric adenocarcinoma from two institutional surgical databases, with preoperative chemotherapy and subsequent gastrectomy. Pathological response was centrally reviewed using Mandard's TRG. RESULTS: From 325 patients resected from a gastric cancer between 1997 and 2016, 109 underwent a preoperative chemotherapy. 42% were pathologic responders (TRG1-3) and 58% non-responders (TRG4-5). Five-years overall survival (OS) was 35% for non-responders, and 73% for responders (p = 0,006). Five-years disease-free survival (DFS) was 34% for non-responders and 65% for responders (p = 0,013). In multivariate analysis, pathological response was an independent prognostic factor of poor OS: HR = 2.736 (CI95% = 1.335-5.608; p = 0.006) and DFS: HR = 2.241 (CI95% = 1.130-4.446; p = 0.021). CONCLUSION: TRG after preoperative chemotherapy is an important prognostic factor in patients resected for a gastric adenocarcinoma. Further studies should be performed to evaluate if adjuvant therapy should be adapted to pathological response.