Stapfer I and II duodenal perforations after endoscopic procedures: how surgical delay impacts outcomes.

BACKGROUND: Post-endoscopic duodenal perforation is a severe adverse event with high morbidity and mortality rates. Managing this rare event is challenging owing to limited clear guidelines. This retrospective study aimed to examine the relationship between time-to-treatment and morbidity among patients with post-endoscopic duodenal perforations. METHODS: Over 20 years, 78 consecutive patients with post-endoscopic duodenal perforations were analyzed. Among these, most patients underwent endoscopic procedures at the Paoli-Calmettes Institute, whereas some were referred from other centers after a diagnosis of perforation. We described the characteristics of patients who underwent medical treatment alone or interventional procedures. Among patients who underwent interventional management, we compared the outcomes following early or delayed procedures (later than 24 h post-duodenal perforation diagnosis). RESULTS: Overall, 78 patients with post-endoscopic duodenal perforation were identified between September 2003 and September 2022. Of these, 17 (22%) patients underwent non-operative management, and 61 (78%) with peritonitis or adverse clinical features were treated with endoscopic or surgical procedures. Additionally, among these patients, 40 (65%) underwent immediate invasive procedures, surgically (n = 20) or endoscopically (n = 20). Patients with delayed procedures experienced more major Clavien-Dindo ≥ 3 complications and had an increase by 21 of the median comprehensive complication index. Overall, mortality occurred in 7 (8.9%) patients in the entire cohort and in 3 (14.3%) with delayed invasive procedures. CONCLUSIONS: Delayed decision-making is a key factor complicating post-endoscopic duodenal perforation. Therefore, invasive procedures should be performed promptly in cases of adverse conditions requiring additional procedures, ideally within the first 24 h of perforation diagnosis.

Impact on survival of sarcopenia, systemic inflammatory response and anthropometric factors after pancreatectomy for resectable pancreatic adenocarcinoma.

INTRODUCTION: Pancreatic adenocarcinoma (PDAC) is becoming a public health issue with a 5-years survival rate around 10%. Patients with PDAC are often sarcopenic, which impacts postoperative outcome. At the same time, overweight population is increasing and adipose tissue promotes tumor related-inflammation. With several studies supporting independently these data, we aimed to assess if they held an impact on survival when combined. METHODS: We included 232 patients from two university hospitals (CHU de Lille, Institut Paoli Calmette), from January 2011 to December 2018, who underwent Pancreaticoduodenectomy (PD) for resectable PDAC. Preoperative CT scan was used to measure sarcopenia and visceral fat according to international cut-offs. Neutrophil to lymphocyte (NLR) and platelet to lymphocyte ratios (PLR) were used to measure inflammation. For univariate and multivariate analyses, the Cox proportional-hazard model was used. P-values below 0.05 were considered significant. RESULTS: Sarcopenic patients with visceral obesity were less likely to survive than the others in multivariate analysis (OS, HR 1.65, p= 0.043). Cutaneous obesity did not influence survival. We also observed an influence on survival when we studied sarcopenia with visceral obesity (OS, p= 0.056; PFS, p = 0.014), sarcopenia with cutaneous obesity (PFS, p= 0.005) and sarcopenia with PLR (PFS, p= 0.043). This poor prognosis was also found in sarcopenic obese patients with high PLR (OS, p= 0.05; PFS, p= 0.01). CONCLUSION: Sarcopenic obesity was associated with poor prognosis after PD for PDAC, especially in patients with systemic inflammation. Pre operative management of these factors should be addressed in pancreatic cancer patients.

Enucleation for Sporadic Nonfunctioning Pancreatic Neuroendocrine Tumors Larger than 2 Centimeters Is Associated with Equivalent Morbidity and Survival Compared to Smaller Tumors: A Multi-Institutional Study.

INTRODUCTION: Nonfunctioning pancreatic neuroendocrine tumor (NF-PanNET) ≤2 cm can be observed or resected. Surgery remains recommended for NF-PanNET >2 cm but its extent, enucleation (EN) versus formal resection, remains controversial. METHODS: Multicentric retrospective cohort of sporadic NF-PanNET patients treated with EN. Short- and long-term outcomes were compared according to tumor size on imaging ≤2 cm versus >2 cm. RESULTS: 131 patients underwent EN for NF-PanNET, including 103 (79.0%) ≤2 cm and 28 (21.0%) >2 cm (extremes, 4-55 mm). Patients' characteristics were comparable, and tumor characteristics only differed in their diameter. Clavien III-IV complications were similar (18.4% vs. 17.9%, p = 1.00) with one death in NF-PanNET ≤2 cm. Grade B/C pancreatic fistula were comparable (16.5% vs. 10.7%, p = 0.850). In NF-PanNET >2 cm there were more pT2/3 stage tumors (85.7% vs. 21.4%, p < 0.001), similar rates of grade G2/3 tumors (25% vs. 16.5%, p = 0.408) with a median Ki67 of 2 (interquartile range: 1-3), and of lymphovascular and perineural invasions. Lymph node picking was done in 46 (35.1%) patients, with a higher median number of harvested lymph nodes in NF-PanNET >2 cm (4 vs. 3, p = 0.01). All were pN0. R0 resection rate (78.6% vs. 82.5%, respectively; p = 0.670) was equivalent. Five-year overall (100% vs. 99%, p = 0.602) and 10-year disease-free (96% vs. 92%, respectively; p = 0.532) survivals were comparable. CONCLUSIONS: EN for selected NF-PanNET >2 cm carries equivalent morbidity, overall and disease-free survivals compared to those observed with NF-PanNET ≤2 cm.

Minimally invasive versus open distal pancreatectomy for resectable pancreatic neuroendocrine tumors: A propensity score matched multicentric comparative French study.

BACKGROUND: Minimally invasive surgery has gained momentum for left pancreatic resections. However, debate remains about whether it has any advantage over open surgery for distal pancreatectomy for pancreatic neuroendocrine tumors. METHODS: This retrospective review examined pancreatectomies performed for resectable pancreatic neuroendocrine tumors at 21 centers in France between January 2014 and December 2018. Short and long-term outcomes were compared before and after propensity score matching based on tumor size, sex, age, body mass index, center, and method of pancreatic transection. RESULTS: During the period study, 274 patients underwent left pancreatic resection for pancreatic neuroendocrine tumors [109 underwent distal splenopancreatectomy, and 165 underwent spleen-preserving distal pancreatectomy [(splenic vessel preservation (n = 97; 58.7%)/splenic vessel resection (n = 68; 41.3%)]. Before propensity score matching, minimally invasive surgery was associated with a lower rate of major morbidity (P = .004), lower rate of postoperative delayed gastric emptying (P = .04), and higher rate of "textbook" outcomes (P = .04). After propensity score matching, there were 2 groups of 54 patients (n = 30 distal splenopancreatectomy; n = 78 spleen-preserving distal pancreatectomy). Minimally invasive surgery was associated with less blood loss (P = .05), decreased rate of major morbidity (6% vs. 24%; P = .02), less delayed gastric emptying (P = .05) despite similar rates of postoperative fistula, hemorrhage, and reoperation (P > .05). The 5-year overall survival (79% vs. 75%; P = .74) and recurrence-free survival (10% vs 17%; P = .39) were similar. CONCLUSION: Minimally invasive surgery for left pancreatic resection can be safely proposed for patients with resectable left pancreatic neuroendocrine tumors. Minimally invasive surgery decreases the rate of major complications while providing comparable long-term oncologic outcomes.

The impact of cirrhosis on short and long postoperative outcomes after distal pancreatectomy.

BACKGROUND: The impact of cirrhosis on the postoperative outcomes of distal pancreatectomy is yet to be reported. We aimed to evaluate the outcomes of distal pancreatectomy in patients with cirrhosis. METHODS: We conducted a retrospective, multicentric study patients with cirrhosis who underwent planned distal pancreatectomy between 2008 and 2020 in French high volume centers. Patients with cirrhosis were matched 1:4 for demographic, surgical, and histologic criteria with patients without cirrhosis. The primary endpoint was severe morbidity (Clavien-Dindo grade ≥III). The secondary endpoints were postoperative complications, specifically related to cirrhosis and pancreatic surgery, and survival for patients with pancreatic adenocarcinoma. RESULTS: Overall, 32 patients with cirrhosis were matched with 128 patients without cirrhosis. Most patients (93.5%) had Child-Pugh A cirrhosis. The severe morbidity rate after distal pancreatectomy was higher in patients with cirrhosis than in those without cirrhosis (28.13% vs 25.75%, P = .11. The operative time was significantly longer in the cirrhotic group compared with controls (P = .01). However, patients with and without cirrhosis had comparable blood loss and conversion rates. Postoperatively, the two groups had similar rates of pancreatic fistula, hemorrhage, reoperation, postoperative mortality, and survival rates at 1, 3, and 5 years. CONCLUSION: The current study suggests that distal pancreatectomy in high-volume centers is feasible for patients with compensated cirrhosis.

Peak Risk of Recurrence Occurs during the First Two Years after a Pancreatectomy in Patients Receiving Neoadjuvant FOLFIRINOX.

No codified/systematic surveillance program exists for borderline/locally advanced pancreatic ductal carcinoma treated with neoadjuvant FOLFIRINOX and a secondary resection. This study aimed to determine the trend of recurrence in patients who were managed using such a treatment strategy. From 2010, 101 patients received FOLFIRINOX and underwent a pancreatectomy, in a minimum follow-up of 5 years. Seventy-one patients (70%, R group) were diagnosed with recurrence after a median follow-up of 11 months postsurgery. In the multivariable analysis, patients in the R-group had a higher rate of weight loss (p = 0.018), higher carbohydrate antigen (CA 19-9) serum levels at diagnosis (p = 0.012), T3/T4 stage (p = 0.017), and positive lymph nodes (p < 0.01) compared to patients who did not experience recurrence. The risk of recurrence in patients with T1/T2 N0 R0 was the lowest (19%), and all recurrences occurred during the first two postoperative years. The peak risk of recurrence for the entire population was observed during the first two postoperative years. The probability of survival decreased until the second year and rebounded to 100% permanently, after the ninth postoperative year. Close monitoring is needed at reduced intervals during the first 2 years following a pancreatectomy and should be extended to later than 5 years for those with unfavorable pathological results.

Factors Associated with 1-Year Mortality in Elderly Patients (Age ≥ 80 Years) with Cancer Undergoing Major Abdominal Surgery: A Retrospective Cohort Study.

BACKGROUND: The number of elderly patients undergoing major abdominal surgery is increasing, but the factors affecting their postoperative outcomes remain unclear. This study aimed to identify the factors associated with 1-year mortality among elderly patients (age ≥ 80 years) with cancer undergoing major abdominal surgery. METHODS: This retrospective cohort study was conducted from March 2009 to December 2020. The study enrolled 378 patients 80 years old or older who underwent major abdominal surgery. The main outcome was 1-year mortality, and the factors associated with mortality were analyzed. RESULTS: Of the 378 patients, 92 died at 1 year (24.3%), whereas the 30-day mortality rate was 4% (n = 15). In the multivariate analysis, the factors independently associated with 1-year mortality were preoperative Eastern Cooperative Oncology Group (ECOG) performance status (PS) score higher than 1 (odds ratio [OR], 3.189; 95% confidence interval [CI], 1.595-6.377; p = 0.001), preoperative weight loss greater than 3 kg (OR, 2.145; 95% CI, 1.044-4.404; p = 0.038), use of an intraoperative vasopressor (OR, 3.090; 95% CI, 1.188-8.042; p = 0.021), and postoperative red blood cell units (OR, 1.212; 95% CI, 1.045-1.405; p = 0.011). Survival was associated with perioperative management according to an enhanced recovery after surgery (ERAS) protocol (OR, 0.370; 95% CI, 0.160-0.854; p = 0.006) and supramesocolic surgery (OR, 0.371; 95% CI, 0.158-0.871; p = 0.023). CONCLUSION: The study identified several factors associated with an encouraging 1-year mortality rate in this setting. These results highlight the need for identification of suitable targets to optimize pre-, intra-, and postoperative management in order to improve outcomes for this vulnerable population.

An optimised liver-first strategy for synchronous metastatic rectal cancer leads to higher protocol completion and lower surgical morbidity.

INTRODUCTION: The optimal management of rectal cancer with synchronous liver metastases remains debatable. Thus, we propose an optimised liver-first (OLF) strategy that combines concomitant pelvic irradiation with hepatic management. This study aimed to evaluate the feasibility and oncological quality of the OLF strategy. MATERIALS AND METHODS: Patients underwent systemic neoadjuvant chemotherapy followed by preoperative radiotherapy. Liver resection was performed in one step (between radiotherapy and rectal surgery) or in two steps (before and after radiotherapy). The data were collected prospectively and analysed retrospectively as intent to treat. RESULTS: Between 2008 and 2018, 24 patients underwent the OLF strategy. The rate of treatment completion was 87.5%. Three patients (12.5%) did not proceed to the planned second-stage liver and rectal surgery because of progressive disease. The postoperative mortality rate was 0%, and the overall morbidity rates after liver and rectal surgeries were 21% and 28.6%, respectively. Only two patients developed severe complications. Liver and rectal complete resection was performed in 100% and 84.6%, respectively. A rectal-sparing strategy was performed in 6 patients who underwent local excision (n = 4) or a watch and wait strategy (n = 2). Among patients who completed treatment, the median overall and disease-free survivals were 60 months (range 12-139 months) and 40 months (range 10-139 months), respectively. Eleven patients (47.6%) developed recurrence, among whom five underwent further treatment with curative intent. CONCLUSION: The OLF approach is feasible, relevant, and safe. Organ preservation was feasible for a quarter of patients and may be associated with reduced morbidity.

Preoperative liver arterial conditioning in patients scheduled for a Mayo Clinic class Ia distal pancreatectomy: embolization or ligation?

BACKGROUND: Liver ischemia may occur during intraoperative common hepatic artery ligation in Mayo Clinic class I distal pancreatectomy with en bloc celiac axis resection (DP-CAR). Preoperative liver arterial conditioning could be used to avoid this outcome. This retrospective study compared arterial embolization (AE) or laparoscopic ligation (LL) of the common hepatic artery before class Ia DP-CAR. METHODS: From 2014 to 2022, 18 patients were scheduled for class Ia DP-CAR after neoadjuvant FOLFIRINOX treatment. Two were excluded due to hepatic artery variation, six underwent AE, ten underwent LL. RESULTS: Two procedural complications occurred in the AE group: an incomplete dissection of the proper hepatic artery and a distal migration of coils in the right branch of the hepatic artery. Neither complication prevented surgery. The median delay between conditioning and DP-CAR was 19 days; decreased to five days in the last six patients. None required arterial reconstruction. Morbidity and 90-day mortality rates were 26.7% and 12.5%, respectively. No patient developed postoperative liver insufficiency after LL. CONCLUSION: Preoperative AE and LL seem comparable in averting arterial reconstruction and postoperative liver insufficiency in patients scheduled for class Ia DP-CAR. However, serious complications that may arise during AE led us to prefer the LL technique.

Establishment and external validation of neutrophil-to-lymphocyte ratio in excluding postoperative pancreatic fistula after pancreatoduodenectomy.

BACKGROUND: Factors excluding postoperative pancreatic fistula (POPF), facilitating early drain removal and hospital discharge represent a novel approach in patients undergoing enhanced recovery after pancreatic surgery. This study aimed to establish the relevance of neutrophil-to-lymphocyte ratio (NLR) in excluding POPF after pancreatoduodenectomy (PD). METHODS: A prospectively maintained database of patients who underwent PD at two high-volume centres was used. Patients were divided into three cohorts (training, internal, and external validation). The primary endpoints of this study were accuracy, optimal timing, and cutoff values of NLR for excluding POPF after PD. RESULTS: From 2012 to 2020, in a 2:1 ratio, 451 consecutive patients were randomly sampled as training (n = 301) and validation (n = 150) cohorts. Additionally, the external validation cohort included 197 patients between 2018 and 2020. POPF was diagnosed in 135 (20.8 per cent) patients. The 90-day mortality rate was 4.1 per cent. NLR less than 8.5 on postoperative day 3 (OR, 95 per cent c.i.) was significantly associated with the absence of POPF in the training (2.41, 1.19 to 4.88; P = 0.015), internal validation (5.59, 2.02 to 15.43; P = 0.001), and external validation (5.13, 1.67 to 15.76; P = 0.004) cohorts when adjusted for relevant clinical factors. Postoperative outcomes significantly differed using this threshold. CONCLUSION: NLR less than 8.5 on postoperative day 3 may be a simple, independent, cost-effective, and easy-to-use criterion for excluding POPF.

Defining Benchmark Outcomes for Distal Pancreatectomy: Results of a French Multicentric Study.

OBJECTIVE: Defining robust and standardized outcome references for distal pancreatectomy (DP) by using Benchmark analysis. BACKGROUND: Outcomes after DP are recorded in medium or small-sized studies without standardized analysis. Therefore, the best results remain uncertain. METHODS: This multicenter study included all patients undergoing DP for resectable benign or malignant tumors in 21 French expert centers in pancreas surgery from 2014 to 2018. A low-risk cohort defined by no significant comorbidities was analyzed to establish 18 outcome benchmarks for DP. These values were tested in high risk, minimally invasive and benign tumor cohorts. RESULTS: A total of 1188 patients were identified and 749 low-risk patients were screened to establish Benchmark cut-offs. Therefore, Benchmark rate for mini-invasive approach was ≥36.8%. Benchmark cut-offs for postoperative mortality, major morbidity grade ≥3a and clinically significant pancreatic fistula rates were 0%, ≤27%, and ≤28%, respectively. The benchmark rate for readmission was ≤16%. For patients with pancreatic adenocarcinoma, cut-offs were ≥75%, ≥69.5%, and ≥66% for free resection margins (R0), 1-year disease-free survival and 3-year overall survival, respectively. The rate of mini-invasive approach in high-risk cohort was lower than the Benchmark cut-off (34.1% vs ≥36.8%). All Benchmark cut-offs were respected for benign tumor group. The proportion of benchmark cases was correlated to outcomes of DP. Centers with a majority of low-risk patients had worse results than those operating complex cases. CONCLUSION: This large-scale study is the first benchmark analysis of DP outcomes and provides robust and standardized data. This may allow for comparisons between surgeons, centers, studies, and surgical techniques.

Management and outcomes of brain metastases from pancreatic adenocarcinoma: a pooled analysis and literature review.

Background: Brain metastases (BM) are rare in pancreatic ductal adenocarcinoma (PDAC) and little data exists concerning these patients and their outcomes. Aim: We aimed to analyze the management, practices, and outcomes of patients presenting BM from PDAC both in our institution and in all cases reported in the literature. Methods: We conducted a retrospective, monocentric analysis using a data mining tool (ConSoRe) to identify all patients diagnosed with PDAC and BM in our comprehensive cancer center (Paoli-Calmettes Institute), from July 1997 to June 2022 (cohort 1). Simultaneously, we reviewed and pooled the case reports and case series of patients with PDAC and BM in the literature (cohort 2). The clinical characteristics of patients in each cohort were described and survival analyses were performed using the Kaplan-Meier method. Results: In cohort 1, 19 patients (0.3%) with PDAC and BM were identified with a median age of 69 years (range: 39-81). Most patients had metastatic disease (74%), including 21% with BM, at diagnosis. Lung metastases were present in 58% of patients. 68% of patients had neurological symptoms and 68% were treated by focal treatment (surgery: 21%, radiotherapy: 42%, Gamma Knife radiosurgery: 5%). In cohort 2, among the 61 PDAC patients with BM described in the literature, 59% had metastatic disease, including 13% with BM at diagnosis. Lung metastases were present in 36% of patient and BM treatments included: surgery (36%), radiotherapy (36%), radiosurgery (3%), or no local treatment (25%). After the pancreatic cancer diagnosis, the median time to develop BM was 7.8 months (range: 0.0-73.9) in cohort 1 and 17.0 months (range: 0.0-64.0) in cohort 2. Median overall survival (OS) in patients of cohort 1 and cohort 2 was 2.9 months (95% CI [1.7,4.0]) and 12.5 months (95% CI [7.5,17.5]), respectively. Conclusion: BM are very uncommon in PDAC and seem to occur more often in younger patients with lung metastases and more indolent disease. BM are associated with poor prognosis and neurosurgery offers the best outcomes and should be considered when feasible.

Effect of the Use of Reinforced Stapling on the Occurrence of Pancreatic Fistula After Distal Pancreatectomy: Results of the REPLAY (REinforcement of the Pancreas in distaL pAncreatectomY) Multicenter Randomized Clinical Trial.

OBJECTIVE: The aim of the study was to evaluate the impact of the use of a reinforced stapler (RS) during distal pancreatectomy (DP) on postoperative outcomes. BACKGROUND: DP remains associated with significant postoperative morbidity owing to pancreatic fistula (PF). To date, there is no consensus on the management of the pancreatic stump. The use of an RS potentially represents a simple way to decrease the rate of PF. METHODS: The REPLAY study (NCT03030170) is a prospective, multicenter, randomized study. Patients who underwent DP were randomized (1:1 ratio) in 2 groups for the use of a standard stapler (SS) or an RS to close remnant pancreatic parenchyma. The primary endpoint was the rate of overall PF. Secondary endpoints included severity of PF, length of hospital stay, overall morbidity, and rate of readmission for a PF within 90 days. Participants were blinded to the procedure actually carried out. RESULTS: A total of 199 were analyzed (SS, n=99; RS, n=100). One patient who did not undergo surgery was excluded. Baseline characteristics were comparable in both groups. The rate of overall PF was higher in RS group (SS: 67.7%, RS: 83%, P =0.0121), but the rate of clinically relevant PF was similar (SS: 11.1%, RS: 14%, P =0.5387). Mean length of total hospital stay, readmission for PF, postoperative morbidity, and mortality at 90 days were similar. CONCLUSION: The results of this randomized clinical trial did not favor the use of RS during DP to reduce the rate of PF.

Local Ablative Therapy Associated with Immunotherapy in Locally Advanced Pancreatic Cancer: A Solution to Overcome the Double Trouble?-A Comprehensive Review.

Pancreatic ductal adenocarcinoma (PDAC) remains a major killer and is a challenging clinical research issue with abysmal survival due to unsatisfactory therapeutic efficacy. Two major issues thwart the treatment of locally advanced nonresectable pancreatic cancer (LAPC): high micrometastasis rate and surgical inaccessibility. Local ablative therapies induce a systemic antitumor response (i.e., abscopal effect) in addition to local effects. Thus, the incorporation of additional therapies could be key to improving immunotherapy's clinical efficacy. In this systematic review, we explore recent applications of local ablative therapies combined with immunotherapy to overcome immune resistance in PDAC and discuss future perspectives and challenges. Particularly, we describe four chemoradiation studies and nine reports on irreversible electroporation (IRE). Clinically, IRE is the ablative therapy of choice, utilized in all but two clinical trials, and may create a favorable microenvironment for immunotherapy. Various immunotherapies have been used in combination with IRE, such as NK cell- or γδ T cell-based therapy, as well as immune checkpoint inhibitors. The results of the clinical trials presented in this review and the advancement potential of these therapies to phase II/III trials remain unknown. A multiple treatment approach involving chemotherapy, local ablation, and immunotherapy holds promise in overcoming the double trouble of LAPC.

Will Patients With Liver Metastasis From Aggressives Cancers Benefit From Surgical Resection?

Background: We aimed to evaluate the outcomes of resections for liver metastases (LMs) originating from pancreatic ductal adenocarcinoma (PDAC), non-small cell lung cancer (NSCLC), and esophagus/gastric cancers (EGCs), which we label as major killers (MKs; overall survival (OS) under 10%). We hypothesized that LM resection must provide the patient with almost a year of OS postoperatively that is considered beneficial. Methods: From January 2005 to December 2020, 23 patients underwent resection for isolated LM from MKs. These patients underwent surgery after a multidisciplinary discussion about their performance status, disease evolution during prolonged medical treatment, and the existence or absence of extrahepatic metastases. Results: LM originated from an PDAC, EGC, or NSCLC in 10 patients (43%), nine patients (39%), and four patients (18%), respectively. The median delay between primary cancer and LM diagnoses was 12 months, and the median delay between LM diagnosis and liver resection was 10 months. Most patients, who had objectively responded to medical treatment (57%), had a solitary (61%) and unilobar (70%) LM. Severe morbidity and 90-day mortality rates were 13% and 4.3%, respectively. Margin-free resection was achieved in 16 patients (70%). After liver resection, the median OS was 24 months without a statistical difference when considering the primary tumor site; 1, 3-, and 5-year OS were 70%, 23%, and 23%, respectively. Conclusion: Selection based on criteria such as good clinical condition, response to treatment, and long observation period helped identify patients with LM of MKs who seemed to benefit from resection.