Objectives:Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is an established treatment for selected patients with colorectal peritoneal metastases (CPM). The recently proposed concept of textbook oncologic outcomes (TOO) offers a composite benchmark for surgical quality, but its applicability and prognostic relevance in CPM remain largely unexplored. Methods:We conducted a retrospective single-centre analysis of all patients undergoing CRS and HIPEC for CPM between 2007 and 2025. Primary endpoint was overall survival (OS); secondary analyses assessed individual TOO components and associated factors. Results:Eighty-four patients met inclusion criteria (age 54.1 ± 12.1 years, PCI 5.8 ± 4.5). CC0 resection was achieved in 88.1 %, severe postoperative complications occurred in 34.5 %, and reoperation was required in 20.2 % of patients. Ninety-day mortality was 1.2 %. Complete TOO was achieved in 14.3 % of patients as only 31/84 were recommended adjuvant chemotherapy. Median OS was 39.2 months. Absence of reoperation (p=0.02), and negative lymph node status (p=0.04) were significantly associated with improved OS. Conclusions:TOO was achieved in <50 % of patients, mainly due to the absence of adjuvant chemotherapy. Absence of reoperation was associated with survival, suggesting its validity as quality indicator. Refinement of TOO definitions, incorporating patient-centred recovery measures, may improve their applicability.

Achieving negative resection margins (R0) is central to curative surgery for pancreatic ductal adenocarcinoma (PDAC), but its prognostic relevance in multivisceral resections has been unclear. Using the largest international registry of multivisceral pancreatic resections, we performed a propensity score-matched analysis comparing R0 and R1 resections in patients undergoing multivisceral resection for PDAC. After 1:1 matching on pre- and intra-operative covariates, 222 patients were analyzed (111 R0, 111 R1). Perioperative morbidity, 90-day mortality, and intraoperative complications were comparable between groups. Median overall survival was 22.3 months after R0 resection versus 14.5 months after R1 resection; R1 status remained independently associated with poorer survival after adjustment for residual imbalances (hazard ratio [HR] 1.45, 95% confidence interval [CI] 1.02–2.07). Margin-negative resection is associated with improved long-term survival in multivisceral pancreatic surgery without an accompanying increase in perioperative risk, supporting R0 resection as a goal of surgical strategy at specialized centers.

Background: Achieving negative resection margins (R0) is considered essential for curative surgery in pancreatic ductal adenocarcinoma (PDAC). However, in the setting of complex multivisceral pancreatic resections, the prognostic relevance of margin status and its association with perioperative morbidity and long-term survival remain uncertain. We aimed to evaluate the association between resection margin status (R0 vs R1) and short-term and long-term outcomes in patients undergoing multivisceral pancreatic resections for PDAC. Methods: In this retrospective, international, multicentre cohort study, we analysed data from the largest global database of multivisceral pancreatic resections. Patients were recruited from multiple high-volume centres across several countries. Eligible participants were adults undergoing multivisceral pancreatic resection for histologically confirmed PDAC. Patients with incomplete key covariate data were excluded from propensity score matching (PSM). Clinical and pathological data were retrieved from institutional medical records and prospectively maintained databases.Propensity score matching (1:1) was performed using age, sex, body mass index, Charlson Comorbidity Index, ASA score, ECOG performance status, tumour stage, type of resection, and number of resected organs. The primary outcome was overall survival (OS). Secondary outcomes included 90-day mortality, perioperative morbidity (Clavien–Dindo classification), postoperative pancreatic fistula, delayed gastric emptying, reoperation, intraoperative complications, and ICU length of stay. Findings: After matching, 186 patients were analysed (93 R0; 93 R1). Ninety-day mortality was identical in both groups (6·5%). Rates of major morbidity, postoperative pancreatic fistula, delayed gastric emptying, reoperation, blood loss, operative time, and ICU stay were comparable between groups. Median OS was 23·6 months (95% CI 18·7–39·3) in the R0 group and 14·5 months (9·0–22·8) in the R1 group. After adjustment for residual imbalances, R1 resection was independently associated with poorer survival (HR 1·57, 95% CI 1·05–2·35; p=0·027). Interpretation: R0 resection in multivisceral pancreatic surgery is independently associated with improved long-term survival without increased perioperative morbidity or mortality. Margin-negative resection should remain the surgical goal in specialised high-expertise centres.

BACKGROUND:As a result of adjuvant therapies for pancreatic cancer including new techniques, such as arterial divestment, and, for instance, as a result of more main-duct intraductal papillary mucinous neoplasms being diagnosed, the number of total pancreatectomies is increasing. Results of these complex operations are only available as centre analyses. The aim of this study was to analyse mortality after total pancreatectomy using real-world data. METHODS:An observational retrospective study based on routine data of the nationwide German diagnosis-related group (DRG) statistics was performed. All total pancreatectomies from 2010 to 2020 were analysed and classified into four types. Univariable and multivariable analyses were performed for in-hospital mortality as the endpoint. RESULTS:During the study interval, 13 946 patients underwent total pancreatectomy; 7060 patients (50.6%) underwent type 1 standard total pancreatectomy, 1682 patients (12.1%) underwent type 2 total pancreatectomy (included venous procedures), 3921 patients (28.1%) underwent type 3 total pancreatectomy (included multivisceral resections), and 1283 patients (9.2%) underwent type 4 total pancreatectomy (included arterial procedures). Relaparotomy was necessary for 3232 patients (23.2%). Overall, the in-hospital mortality rate was 22.0% (3072 patients), which varied depending on the type of total pancreatectomy (type 1, 15.6% (1102 patients); type 2, 17.2% (290 patients); type 3, 31.5% (1235 patients); and type 4, 34.7% (445 patients); P < 0.001). The worst outcome of 60.7% in-hospital mortality was related to a small subgroup of 56 patients who were operated on in hospitals that performed one to ten type 4 total pancreatectomies in 2010-2020. With increasing caseload, in-hospital mortality significantly decreased (P < 0.001) for all resection types. CONCLUSION:The mortality after total pancreatectomy differs significantly between hospitals based on nationwide administrative data across all hospitals. Further in-depth analysis of more granular data to understand the case volume-mortality relationship for total pancreatectomy is warranted.

BACKGROUND:Post-hepatectomy bile leakage is a challenging issue that can lead to morbidities and mortality after liver resection. This leakage can occur either from a bilioenteric anastomosis (BEA) or from the transected surface of the liver. This study investigated the incidence, risk factors, and effective management of BEA leakage after major liver resection. METHODS:Bile leakage was diagnosed through drain fluid analysis based on the International Study Group of Liver Surgery definition. Leakage from a BEA was confirmed via fluoroscopy during percutaneous interventions or reoperation. Perioperative data and data on the management of patients with BEA leakage were collected and analysed. Bivariate analysis used Mann-Whitney U and χ2 tests, and binary logistic regression identified risk factors for BEA leakage, with variables having P < 0.200 included in multivariable analysis. RESULTS:Of 2936 patients undergoing hepatectomy between 2008 and 2023, 229 underwent liver resection with BEA. Leakage from the BEA was identified in 44 patients (19.2%). These patients had a higher rate of post-hepatectomy haemorrhage (P = 0.005), major complications (P = 0.001), BEA stenosis (P = 0.006), and mortality (P = 0.043). The success rate of the management of BEA leakage was 70% for reoperation and 58% for percutaneous transhepatic cholangiography and drainage (PTCD). CONCLUSION:BEA leakage after major liver resection is a severe complication associated with higher morbidity and mortality rates. Surgical treatment appeared to be more successful than PTCD in the early postoperative phase. PTCD proved to be a valuable additional therapy option following reoperation. These conclusions should be taken with caution and need to be confirmed through further prospective studies.

OBJECTIVE:Optimal treatment strategies for small (≤2 cm) nonfunctioning pancreatic neuroendocrine neoplasms are still subject to discussion. The aim of this study was to analyze real-world data of patients with pancreatic neuroendocrine neoplasms ≤2 cm regarding the indications for surgery and long-term postresection survival. METHODS:All patients undergoing surgery for nonfunctioning pancreatic neuroendocrine neoplasms ≤2 cm between 2003 and 2023 were analyzed. Indications for surgery, clinicopathologic parameters, and long-term survival were assessed. Differences between pancreatic neuroendocrine neoplasms <1 cm and 1-2 cm were evaluated. RESULTS:Of a total of 806 resected pancreatic neuroendocrine neoplasms, 237 patients had a lesion ≤2 cm (29.4%), 85 of which were smaller than 1 cm. The 3 most common indications for surgery for pancreatic neuroendocrine neoplasms ≤2 cm were either suspicion of a non-neuroendocrine neoplasm malignancy (55.2%), suspicion of neuroendocrine tumor (25.9%), or obstruction of the pancreatic duct (9.4%). Tumor differentiation was 84% G1, 15% G2, and 1.3% G3. Noticeably, 5.1% of pancreatic neuroendocrine neoplasms ≤2 cm had lymph node metastasis (pN1). Five patients with a small pancreatic neuroendocrine neoplasm developed distant metastasis (pM1). The 10-year overall survival was 86.9% for <1 cm and 84.5% for 1-2 cm (P = .964). 10-year disease-free survival was 83.1% in patients with a pancreatic neuroendocrine neoplasms <1 cm and 81.1% for pancreatic neuroendocrine neoplasms 1-2 cm (P = .784). CONCLUSION:Surgical treatment of small (≤2 cm) pancreatic neuroendocrine neoplasms provides excellent long-term survival. Since even small pancreatic neuroendocrine neoplasms can develop lymph node and distant metastases, treatment decisions should not be determined on the basis of tumor size alone.

BACKGROUND:Tumor regression after neoadjuvant chemoradiotherapy can improve the long-term outcomes of rectal cancer. However, it is unclear how the tumor regression grade (TRG) relates to long-term outcomes. We evaluated how the TRG affects overall survival in patients with rectal cancer who underwent neoadjuvant chemoradiotherapy prior to radical surgery. METHODS:All patients who underwent low anterior resection for rectal cancer after chemoradiotherapy over a 13-year period were included in this study. Perioperative and histopathological data of patients, including the TRG (categorized as no regression, minimal regression, moderate regression, near complete regression and complete regression) were evaluated. The correlation of TRG with overall survival was assessed using the log-rank test and Cox proportional hazards regression analysis. RESULTS:During the study period,193 patients underwent low anterior rectal resection after neoadjuvant chemoradiotherapy. The 90-day mortality rate was 1.5 % and the median follow up was 69.5 months. The 5-year and 10-year overall survival rates were 85.0 % and 69.8 %, respectively. Patients with complete regression had a significantly higher 10-year overall survival rate than other patients (87.3 % vs. 66.5 %, p = 0.031). Multivariate analysis revealed that older age (hazard ratio [HR] = 2.4,95 % confidence interval [95 % CI] = 1.3-4.6, p = 0.007) and complete pathological response (HR = 0.23, 95 % CI = 0.06-0.96, p = 0.044) were independent predictors of overall survival. CONCLUSION:Complete pathological response after neoadjuvant therapy for rectal cancer improves overall survival after surgery. Further studies are needed to determine the factors that predict complete TRG to identify patients who would benefit most from neoadjuvant chemoradiotherapy.

OBJECTIVE:To evaluate short-term outcomes and identify predictors of morbidity and mortality following multivisceral oncologic resections involving the pancreas. SUMMARY BACKGROUND DATA:Multivisceral resections including the pancreas are required for locally advanced abdominal malignancies but are associated with considerable perioperative risk. While smaller series suggest acceptable outcomes in selected patients, large-scale international data are lacking to guide surgical decision-making and risk stratification. METHODS:This was a retrospective cohort study of 1,283 patients from 31 international centers who underwent multivisceral oncologic resections involving the pancreas. Patient demographics, tumor characteristics, operative details, and 90-day postoperative outcomes were analyzed. RESULTS:The cohort had a mean age of 64.7 years, and 54.7% were male. Distal pancreatectomy was the most frequent procedure (60.5%), and R0 resection was achieved in 60.9% of cases. Ninety-day mortality was 6.9%, highest in patients with gastric adenocarcinoma (16.7%). Major complications (Clavien-Dindo grade III-V) occurred in 34.4% of patients. Higher ASA classification and open surgical approach were independently associated with increased morbidity and mortality. Prolonged operative time was associated with morbidity only. Female gender and treatment at high-volume centers were protective. In patients with pancreatic tumors, resection involving the colon (OR 1.78, p<0.001), stomach (OR 1.33, p = 0.042), or three or more organs (OR 1.75, p = 0.006) significantly increased complication rates. CONCLUSIONS:Multivisceral resections involving the pancreas are associated with relevant perioperative risk. Optimizing patient selection, favoring minimally invasive techniques when feasible in selected patients, and centralizing care to high-volume centers may help improve outcomes for these complex surgical procedures.

BACKGROUND:Pancreatic adenosquamous carcinoma has historically poor overall survival, and the impact of perioperative chemotherapy remains unclear. We aimed to evaluate the impact of various chemotherapy regimens in patients with resected adenosquamous carcinoma. METHODS:Patients with resected adenosquamous carcinoma were identified from 3 high-volume programs between 2001 and 2022. We analyzed their clinicopathologic data and used Kaplan-Meier survival curves to assess the median overall survival and recurrence-free survival with 95% confidence intervals. Prognostic factors were assessed with a multivariable Cox-regression model adjusting for resectability status and Clavien-Dindo complications. RESULTS:Among 168 patients, cohorts of neoadjuvant chemotherapy (41, 24%) and upfront surgery (127, 76%) showed similar demographics and TNM staging. The median overall survival was shorter in the neoadjuvant chemotherapy cohort compared with the upfront surgery cohort (13 vs 21 months, P = .133). Median overall survival by treatment approach was no chemotherapy (4 months), only neoadjuvant chemotherapy (8 months), only adjuvant therapy (24 months), and both neoadjuvant chemotherapy and adjuvant therapy (17 months). Recurrence-free survival data (69 patients) showed upfront surgery had significantly longer recurrence-free survival compared with neoadjuvant chemotherapy (18 months vs 5 months, P = .046). Multivariable analysis showed adjuvant therapy was associated with improved overall survival (hazard ratio, 0.27; P < .001), whereas age ≥65 (hazard ratio, 1.79, P = .030) was associated with worse overall survival. CONCLUSION:The outcomes of resected adenosquamous carcinoma remain poor. Patients receiving neoadjuvant chemotherapy exhibited shorter recurrence-free survival and median overall survival, suggesting minimal benefit of neoadjuvant chemotherapy in treating this aggressive cancer. Meanwhile, adjuvant therapy appears to be protective but requires further investigation.

BACKGROUND:Resections of the pancreatic body and tail reaching to the left of the superior mesenteric vein are defined as distal pancreatectomy. Most distal pancreatectomies are elective treatments for chronic pancreatitis, benign or malignant diseases, and they have high morbidity rates of up to 40%. Pancreatic fistula formation is the main source of postoperative morbidity, associated with numerous further complications. Researchers have proposed several surgical resection and closure techniques of the pancreatic remnant in an attempt to reduce these complications. The two most common techniques are scalpel resection followed by hand-sewn closure of the pancreatic remnant and stapler resection and closure.OBJECTIVES:To compare the rates of pancreatic fistula in people undergoing distal pancreatectomy using scalpel resection followed by hand-sewn closure of the pancreatic remnant versus stapler resection and closure.SEARCH METHODS:We searched Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Biosis and Science Citation Index from database inception to October 2015.SELECTION CRITERIA:We included randomised controlled trials (RCTs) comparing stapler versus scalpel resection followed by hand-sewn closure of the pancreatic remnant for distal pancreatectomy (irrespective of language or publication status).DATA COLLECTION AND ANALYSIS:Two authors independently assessed trials for inclusion and extracted the data. Taking into consideration the clinical heterogeneity between the trials (e.g. different endpoint definitions), we analysed data using a random-effects model with Review Manager (RevMan), calculating risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI).MAIN RESULTS:In two eligible trials, a total of 381 participants underwent distal pancreatic resection and were randomised to closure of the pancreatic remnant either with stapler (n = 191) or scalpel resection followed by hand-sewn closure (n = 190). One was a single centre pilot RCT and the other was a multicentre blinded RCT. The single centre pilot RCT evaluated 69 participants in five intervention arms (stapler, hand-sewn, fibrin glue, mesh and pancreaticojejunostomy), although we only assessed the stapler and hand-sewn closure groups (14 and 15 participants, respectively). The multicentre RCT had two interventional arms: stapler (n = 177) and hand-sewn closure (n = 175). The rate of postoperative pancreatic fistula was the main outcome, and it occurred in 79 of 190 participants in the hand-sewn group compared to 65 of 191 participants in the stapler group. Neither the individual trials nor the meta-analysis showed a significant difference between resection techniques (RR 0.90; 95% CI 0.55 to 1.45; P = 0.66). In the same way, postoperative mortality and operation time did not differ significantly. The single centre RCT had an unclear risk of bias in the randomisation, allocation and both blinding domains. However, the much larger multicentre RCT had a low risk of bias in all domains. Due to the small number of events and the wide confidence intervals that cannot exclude clinically important benefit or harm with stapler versus hand-sewn closure, there is a serious possibility of imprecision, making the overall quality of evidence moderate.AUTHORS' CONCLUSIONS:The quality of evidence is moderate and mainly based on the high weight of the results of one multicentre RCT. Unfortunately, there are no other completed RCTs on this topic except for one relevant ongoing trial. Neither stapler nor scalpel resection followed by hand-sewn closure of the pancreatic remnant for distal pancreatectomy showed any benefit compared to the other method in terms of postoperative pancreatic fistula, overall postoperative mortality or operation time. Currently, the choice of closure is left up to the preference of the individual surgeon and the anatomical characteristics of the patient. Another (non-European) multicentre trial (e.g. with an equality or non-inferiority design) would help to corroborate the findings of this meta-analysis. Future trials assessing novel methods of stump closure should compare them either with stapler or hand-sewn closure as a control group to ensure comparability of results.

Intraductal papillary mucinous neoplasm (IPMN)-derived pancreatic cancer is typically managed like pancreatic intraepithelial neoplasia (PanIN)-derived pancreatic cancer. However, in IPMN-derived pancreatic cancer, the role of chemotherapy remains controversial, particularly in the neoadjuvant setting (NAT). To evaluate the role of neoadjuvant chemotherapy in IPMN-derived pancreatic cancer. Patients with IPMN-derived pancreatic cancer treated with either upfront surgery (US) or NAT were identified from eight international centers (2000-2023). Clinicopathologic data were compared. Date of first treatment was used for Kaplan-Meier and log-rank tests to compare overall (OS) and recurrence free survival (RFS). Multivariable Cox-regression was performed in patients that underwent NAT. In 1,019 patients, 76 (7%) underwent NAT. Patients who received NAT had higher baseline CA19-9 levels (P<0.001). Of these 76 patients, 27 (36%), 20 (26%), and 29 (38%) had resectable, borderline resectable, or locally advanced pancreatic cancer at diagnosis, respectively. Advanced resectability stage was significantly more common in the NAT patients as compared to those who underwent US (P<0.001). OS for US patients was 38.0 months (95%CI: 33.7.1-44.3), which was not statistically different than those that received NAT [27.5 mo (95%CI: 23.1-46.7), P=0.121]. This was also valid for patients with resectable disease [US: 38.1 mo vs. NAT: 35.6 mo, P=0.920)]. Complete or marked pathological treatment response (P=0.046) and serological CA19-9 normalization after NAT (P=0.017) were associated with improved survival. On Cox-regression for OS, N2 disease [HR: 4.15 (95%CI: 1.71-10.10)], elevated CA19-9 [HR: 2.02 (95%CI:1.06-3.85)] and R1 margin [HR: 2.36 (95%CI:1.20-4.61)] was independently associated with OS after NAT, while resectability status was not. After NAT and resection, advanced resectability stage was not associated with worse OS indicating the value of this approach for borderline resectable and locally advanced IPMN-derived pancreatic cancer. The benefit of NAT in resectable disease is unclear and may require an individualized approach. Biological treatment effect can be assessed with CA19-9 and confirmed by pathologic response.

Intraductal papillary mucinous neoplasm (IPMN)-derived pancreatic cancer was previously categorized into tubular, colloid, and oncocytic subtypes. Intraductal oncocytic papillary neoplasms (IOPN) has long been associated with superior prognosis/indolent behavior, however, there is discordant emerging evidence. This study aimed to investigate this conflicting literature. Patients with resected IOPN-derived and IPMN-derived pancreatic cancer were identified from six international centers. Log-rank tests compared time to (TtR) and survival after (SAR) recurrence and five-year overall survival (OS). A multivariable mixed model was used to determine hazard ratios (HR) with confidence intervals (95

Pancreatic ductal adenocarcinoma (PDAC) often arises from preexisting cystic lesions such as intraductal papillary mucinous neoplasms (IPMN) and mucinous cystic neoplasms (MCN). This study investigated the molecular heterogeneity and mutational landscape of MCN in relation to PDAC, highlighting the significance of KRAS mutations in tumor progression. Utilizing targeted next-generation sequencing on low-grade MCN and invasive PDAC samples, we identified a substantial overlap in mutational profiles, particularly mutations in KRAS, TP53, and FBXW7. Specifically, 69.2% of MCN exhibited somatic mutations, with KRAS mutations being a predominant oncogenic driver. The characterization of mutant versus wildtype KRAS variant allele frequencies (VAF) indicated higher mutation levels in PDAC compared to MCN, suggesting an evolutionary trajectory toward malignancy. Further histological analysis of 12 additional MCN cases revealed significant intratumor heterogeneity, with variant KRAS mutation distributions correlating with distinct cellular morphologies and dysplastic features. Additionally, we explored the potential of liquid biopsies, demonstrating a concordance rate of 71.4% for KRAS mutation detection in circulating tumor DNA (ctDNA) relative to tissue biopsies across cohorts. Our findings underscore the relevance of evaluating KRAS mutations-herein referred to as VAF per microdissected region-as they relate to histopathological markers of dysplasia, contributing to improved stratification of pancreatic lesions and facilitating personalized treatment strategies. In conclusion, this comprehensive analysis of MCN highlights the importance of KRAS as a crucial biomarker for both malignant progression and therapeutic decision-making in pancreatic pathology. Ultimately, our study suggests that characterizing the mutational landscape and histological features of MCN can enhance early detection and intervention strategies for at-risk patients. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

BACKGROUND:Perioperative thoracic epidural analgesia (EDA) and patient-controlled intravenous analgesia (PCIA) are common forms of analgesia after pancreatic surgery. Current guidelines recommend EDA over PCIA, and evidence suggests that EDA may improve long-term survival after surgery, especially in cancer patients. The aim of this study was to determine whether perioperative EDA is associated with an improved patient prognosis compared to PCIA in pancreatic surgery. METHODS:The PAKMAN trial was an adaptive, pragmatic, international, multicenter, randomized controlled superiority trial conducted from June 2015 to October 2017. Three to five years after index surgery a long-term follow-up was performed from October 2020 to April 2021. RESULTS:For long-term follow-up of survival, 109 patients with EDA were compared to 111 patients with PCIA after partial pancreatoduodenectomy (PD). Long-term follow-up of quality of life (QoL) and pain assessment was available for 40 patients with EDA and 45 patients with PCIA (questionnaire response rate: 94%). Survival analysis revealed that EDA, when compared to PCIA, was not associated with improved overall survival (OS, HR, 1.176, 95% HR-CI, 0.809-1.710, P = .397, n = 220). Likewise, recurrence-free survival did not differ between groups (HR, 1.116, 95% HR-CI, 0.817-1.664, P = .397, n = 220). OS subgroup analysis including only patients with malignancies showed no significant difference between EDA and PCIA (HR, 1.369, 95% HR-CI, 0.932-2.011, P = .109, n = 179). Similar long-term effects on QoL and pain severity were observed in both groups (EDA: n = 40, PCIA: n = 45). CONCLUSIONS:Results from this long-term follow-up of the PAKMAN randomized controlled trial do not support favoring EDA over PCIA in pancreatic surgery. Until further evidence is available, EDA and PCIA should be considered similar regarding long-term survival.

Abstract Background Statins, metformin, and aspirin have been reported to reduce the incidence of hepatocellular carcinoma (HCC). However, the effect of their perioperative use on survival outcomes of HCC patients following curative liver resection still remains unclear. Method Three hundred and fifty three patients with a first diagnosis of HCC who underwent curative liver resection were included. Propensity score matching analysis with a users: nonusers ratio of 1:2 were performed for each of the medications (statins, metformin, and aspirin). Overall survival (OS) and recurrence‐free survival (RFS) were evaluated and multivariable Cox proportional hazard analysis was performed. Results Sixty two patients received statins, 48 patients used metformin, and 53 patients received aspirin for ≥90 days before surgery. None of the medications improved OS. RFS of statin users was significantly longer than that of nonusers (p = 0.021) in the matched cohort. Users of hydrophilic statins, but not lipophilic ones had a significantly longer RFS than nonusers. Multivariable analysis showed that statin use significantly improved RFS (hazard ratio [HR]: 0.41, 95% confidence interval [CI]: 0.17–0.97, p = 0.044). No difference was seen in RFS between metformin users and nonusers. Among patients with diabetes, RFS was nonsignificantly longer in metformin users than in non‐metformin users (84.1% vs. 60.85%, p = 0.069) in the matched cohort. No difference in postoperative RFS was seen between aspirin users and nonusers. Conclusion Preoperative use of statins in patients with HCC can increase RFS after curative liver resection, but metformin and aspirin were not associated with improved survival. Randomized controlled trials are needed to confirm the findings of the present study.

Study objective: Higher levels of carbon dioxide (CO2) increase the invasive abilities of colon cancer cells in vitro. Studies assessing target values for end-tidal CO2 concentrations (EtCO2) to improve surgical outcome after colorectal cancer surgery are lacking. Therefore, we evaluated whether intraoperative EtCO2 was associated with differences in recurrence-free survival after elective colorectal cancer (CRC) surgery. Design: Single center, retrospective analysis. Setting: Anesthesia records, surgical databases and hospital information system of a tertiary university hospital. Patients: We analyzed 528 patients undergoing elective resection of colorectal cancer at Heidelberg University Hospital between 2009 and 2018. Interventions: None. Measurements: Intraoperative mean EtCO2 values were calculated. The study cohort was equally stratified into low-and high-EtCO2 groups. The primary endpoint measure was recurrence-free survival until last known followup. Groups were compared using Kaplan-Meier analysis. Cox-regression analysis was used to control for covariates. Sepsis, reoperations, surgical site infections and cardiovascular events during hospital stay, and overall survival were secondary outcomes. Main results: Mean EtCO2 was 33.8 mmHg +/- 1.2 in the low- EtCO2 group vs. 37.3 mmHg +/- 1.6 in the high-EtCO2 group. Median follow-up was 3.8 (Q1-Q3, 2.5-5.1) years. Recurrence-free survival was higher in the low-EtCO2 group (log-rank-test: p = .024). After correction for confounding factors, lower EtCO2 was associated with increased recurrence-free survival (HR = 1.138, 95%-CI:1.015-1.276, p = .027); the hazard for the primary outcome decreased by 12.1% per 1 mmHg decrease in mean EtCO2. 1-year and 5-year survival was also higher in the low-EtCO2 group. We did not find differences in the other secondary endpoints. Conclusions: Lower intraoperative EtCO2 target values in CRC surgery might benefit oncological outcome and should be evaluated in confirmative studies.

Background and AimsTimely and accurate detection of tumor recurrence in pancreatic ductal adenocarcinoma (PDAC) patients is an urgent and unmet medical need. This study aimed to develop a noninvasive molecular diagnostic procedure for the detection of recurrence after PDAC resection based on quantification of circulating mRNA and miRNA biomarkers in serum samples.MethodsIn a multicentric study, serum samples from a total of 146 patients were prospectively collected after resection. Samples were classified into a "No Evidence of Disease" and a "Recurrence" group based on clinical follow-up data. A multianalyte biomarker panel was composed of mRNAs and miRNA markers and simultaneously analyzed in serum samples using custom microfluidic qPCR arrays (TaqMan array cards). A diagnostic algorithm was developed combining a 7-gene marker signature with CA19-9 data.ResultsThe best-performing marker combination achieved 90% diagnostic accuracy in predicting the presence of tumor recurrence (98% sensitivity; 84% specificity), clearly outperforming the singular CA 19-9 analysis. Moreover, time series data obtained by analyzing successively collected samples from 5 patients during extended follow-up suggested that molecular diagnosis has the potential to detect recurrence earlier than routine clinical procedures.ConclusionsTaqMan array card measurements were found to be biologically valid and technically reproducible. The BioPac multianalyte marker panel is capable of sensitive and accurate detection of recurrence in patients resected for PDAC using a simple blood test. This could allow a closer follow-up using shorter time intervals than currently used for imaging, thus potentially prompting an earlier work-up with additional modalities to allow for earlier therapeutic intervention. This study provides a promising approach for improved postoperative monitoring of resected PDAC patients, which is an urgent and unmet clinical need.

ABSTRACT Background Disease recurrence after surgical resection for pancreatic ductal adenocarcinoma can affect more than 50% of patients in the first 12 months after resection. The goal of this current systematic review and meta‐analysis is to assess the ability of preoperative inflammatory scores to predict early recurrence after resection and to identify the best candidates for surgical resection. Methods Medline and Web of Science databases were searched for studies reporting inflammatory scores and oncological outcomes in patients with PDAC after curative‐intent resection. The systematic review revealed that the most common scores were modified Glasgow Prognostic Score (mGPS), Prognostic Nutritional Index (PNI), platelet‐to‐lymphocyte ratio (PLR), neutrophil‐to‐lymphocyte ratio (NLR), and Systemic Immune‐Inflammation Index (SII). After, a meta‐analysis was performed to determine the prognostic value of these scores in early recurrence (12 months) after resection. A subgroup analysis was also carried out in patients who had upfront surgery and in those who underwent neoadjuvant chemotherapy. The ROBINS‐I tool was used to assess the risk of bias. Results The literature search retrieved 1864 articles, 16 of which were eligible for analysis. The included studies comprised 4460 patients. Nine studies reported outcomes for mGPS, four studies for PNI, seven studies for PLR, eight studies for NLR, and two studies for SII. In the meta‐analysis, mGPS, NLR, and PLR showed significantly higher rates of early recurrence in the high‐score groups compared to the low‐score groups. Analyzing the sensitivity and specificity of these scores showed no significant difference in their diagnostic accuracy (mGPS area under the curve [AUC] = 0.534; NLR AUC = 0.628, and PLR AUC = 0.607). High and low PNI and SII scores demonstrated similar rates of early recurrence. Conclusion mGPS, PNI, PLR, NLR, and SII scores did not show a suitable diagnostic accuracy to predict PDAC recurrence in the first 12 months after resection. Therefore, these inflammatory scores should not be used to select the best candidates or to preclude a possible surgical indication.