Short-term Outcomes of Robotic Versus Open Pancreatoduodenectomy: Propensity Score-matched Analysis.

OBJECTIVE: The goal of the current study was to investigate the perioperative outcomes of robotic pancreaticoduodenectomy (RPD) and open pancreaticoduodenectomy (OPD) in a high-volume center. BACKGROUND: Despite RPDs prospective advantages over OPD, current evidence comparing the 2 has been limited and has prompted further investigation. The aim of this study was to compare both approaches while including the learning curve phase for RPD. METHODS: A 1:1 propensity score-matched analysis of a prospective database of RPD with OPD (2017-2022) at a high-volume center was performed. The main outcomes were overall- and pancreas-specific complications. RESULTS: Of 375 patients who underwent PD (OPD n=276; RPD n=99), 180 were included in propensity score-matched analysis (90 per group). RPD was associated with less blood loss [500 (300-800) vs 750 (400-1000) mL; P =0.006] and more patients without a complication (50% vs 19%; P <0.001). Operative time was longer [453 (408-529) vs 306 (247-362) min; P <0.001]; in patients with ductal adenocarcinoma, fewer lymph nodes were harvested [24 (18-27) vs 33 (27-39); P <0.001] with RPD versus OPD. There were no significant differences for major complications (38% vs 47%; P =0.291), reoperation rate (14% vs 10%; P =0.495), postoperative pancreatic fistula (21% vs 23%; P =0.858), and patients with the textbook outcome (62% vs 55%; P =0.452). CONCLUSIONS: Including the learning phase, RPD can be safely implemented in high-volume settings and shows potential for improved perioperative outcomes versus OPD. Pancreas-specific morbidity was unaffected by the robotic approach. Randomized trials with specifically trained pancreatic surgeons and expanded indications for the robotic approach are needed.

Distal Pancreatectomy: Extent of Resection Determines Surgical Risk Categories.

BACKGROUND: Recently, subclassification of pancreatoduodenectomy in 4 differing types has been reported, because additional major vascular and multivisceral resections have been shown to be associated with an increased risk of postoperative morbidity and mortality. OBJECTIVE: To classify distal pancreatectomy (DP) based on the extent of resection and technical difficulty and to evaluate postoperative outcomes with regards to this classification system. METHODS: All consecutive patients who had undergone DP between 2001 and 2020 in a high-volume pancreatic surgery center were included in this study. DPs were subclassified into 4 distinct categories reflecting the extent of resection and technical difficulty, including standard DP (type 1), DP with venous (type 2), multivisceral (type 3), or arterial resection (type 4). Patient characteristics, perioperative data, and postoperative outcomes were analyzed and compared among the 4 groups. RESULTS: A total of 2135 patients underwent DP. Standard DP was the most frequently performed procedure (64.8%). The overall 90-day mortality rate was 1.6%. Morbidity rates were higher in patients with additional vascular or multivisceral resections, and 90-day mortality gradually increased with the extent of resection from standard DP to DP with arterial resection (type 1: 0.7%; type 2: 1.3%; type 3: 3%; type 4: 8.7%; P <0.0001). Multivariable analysis confirmed the type of DP as an independent risk factor for 90-day mortality. CONCLUSIONS: Postoperative outcomes after DP depend on the extent of resection and correlate with the type of DP. The implementation of the 4-type classification system allows standardized reporting of surgical outcomes after DP improving comparability of future studies.

The PAncreatic Surgery Composite Endpoint PACE - Development and Validation of a Clinically Relevant Endpoint Requiring Lower Sample Sizes.

OBJECTIVE: To provide a composite endpoint in pancreatic surgery. SUMMARY BACKGROUND DATA: Single endpoints in prospective and randomized studies have become impractical due to their low frequency and the marginal benefit of new interventions. METHODS: Data from prospective studies were used to develop (n=1273) and validate (n=544) a composite endpoint based on postoperative pancreatic fistula, post-pancreatectomy hemorrhage as well as reoperation and reinterventions. All patients had pancreatectomies of different extents. The association of the developed PAncreatic surgery Composite Endpoint (PACE) with prolonged length of hospital stay (LOS) >75th percentile and mortality was assessed. A single-institution database was used for external validation (n = 2666). Sample size calculations were made for single outcomes and the composite endpoint. RESULTS: In the internal validation cohort, the PACE demonstrated an AUC of 78.0%, a sensitivity of 90.4% and a specificity of 67.6% in predicting a prolonged LOS. In the external cohort, the AUC was 76.9%, the sensitivity 73.8% and the specificity 80.1%. The 90-day mortality rate was significantly different for patients with a positive versus a negative PACE both in the development and internal validation cohort (5.1% vs 0.9%; P< 0.001), as well as in the external validation cohort (8.5% vs 1.2%, P< 0.001). The PACE enabled sample size reductions of up to 80.5% compared to single outcomes. CONCLUSION: The PACE performed well in predicting prolonged hospital stays and can be used as a standardized and clinically relevant endpoint for future prospective trials enabling lower sample sizes and therefore improved feasibility compared to single outcome parameters.

Who Do We Fail to Rescue after Pancreatoduodenectomy? Outcomes Among >4000 Procedures Expose Windows of Opportunity.

OBJECTIVE: Our investigation on in-hospital mortality after 4474 pancreatoduodenectomies aimed to identify time-dependent risks as well as windows of opportunity to rescue patients from complications. BACKGROUND: Pancreatoduodenectomy is generally considered a safe procedure with a 1-10% perioperative mortality based on complexity and surgical volume. Yet, patients are susceptible for life-threatening complications particularly with extended resections. Recognition of distinct vulnerabilities over time while patients recover is required to permit focused monitoring, sophisticated resource allocation, and greatest surgical safety. METHODS: Patients who deceased in-hospital after pancreatoduodenectomy between 2003-2021 were retrieved from the institutional pancreatectomy registry and analyzed in detail with respect to their postoperative course. RESULTS: Among 4474 pancreatoduodenectomies, 156 patients deceased in-hospital (3.5%). When assessing root causes of mortality, we observed 3 different clusters of complications which were postpancreatectomy-specific (47.4%), visceral vasculature-associated (25.6%), or cardiopulmonary in origin (23.7%). The median times of root cause onset in the 3 categories were postoperative day (POD) 9, POD 4.5 (P=0.008) and POD 3 (P<0.001), and medians of in-hospital mortality were POD 31, POD 18 (P=0.009) and POD 8 (P<0.001), respectively. Intervals between root cause onset and mortality varied with medians of 23 days, 11 days (P=0.017), and 1 days (P<0.001). The 3 categories were similarly distributed between different types of surgical complexity. CONCLUSION: Postpancreatectomy-specific complications prompt almost half of in-hospital mortalities after pancreatoduodenectomy, with rather long intervals for interventions to prevent failure to rescue. In contrast, visceral vasculature-related events and cardiopulmonary complications dominate early in-hospital mortalities with short intervals until mortality, demanding rigorous management of such events or preoperative conditioning. These data externally validate a previous high-volume initiative and highlight distinct windows of opportunity to optimize perioperative safety.

Preoperative Surgical or Endoscopic Bile Duct Drainage in Pancreatic Cancer.

BACKGROUND: Patients with pancreatic cancer and obstructive jaundice routinely undergo endoscopic stent placement (ES). It is well known that ES causes bacterial contamination and infectious complications after pancreatic resection. OBJECTIVE: To compare short-term outcomes and survival in patients undergoing pancreatic head resection after preoperative ES vs preoperative surgical drainage (SD) via T-tube insertion. METHODS: Patients with obstructive jaundice who underwent SD or ES from 2016 to 2022 were identified from a prospective database. Outcome analyses included microbiological bile contamination, overall morbidity and assessment of the overall complication burden using the Comprehensive Complication Index (CCI). Overall survival was investigated by Kaplan‒Meier analysis. RESULTS: A total of 55 patients with SD were identified and matched with 110 ES patients. After the primary intervention, ES patients experienced more complications (ES: 17.3% vs. SD: 3.6%; P=0.013). The overall complication burden after pancreatic resection was higher in ES patients than in SD patients (CCI: 27.2 vs. 19.9; P=0.022). Additionally, bacterial contamination of the bile was more frequent in ES patients compared to SD individuals (94.3% vs. 7.1%; P<0.001) with similar bacteria in 83.3% of postoperative abdominal infections in ES patients. While overall survival did not differ between the two groups, patients with postinterventional complications after ES had an impaired survival compared to those without complications (11.3 mo vs. 20.4 mo; P=0.03). CONCLUSION: SD for obstructive jaundice in resectable pancreatic cancer is associated with a lower overall complication burden. Additionally, patients with complications after ES experience worse overall survival. These findings indicate to rethink our standards of treatment of obstructive jaundice in patients with pancreatic cancer.

Spatially Resolved Multi-Omics Single-Cell Analyses Inform Mechanisms of Immune Dysfunction in Pancreatic Cancer.

BACKGROUND & AIMS: As pancreatic ductal adenocarcinoma (PDAC) continues to be recalcitrant to therapeutic interventions, including poor response to immunotherapy, albeit effective in other solid malignancies, a more nuanced understanding of the immune microenvironment in PDAC is urgently needed. We aimed to unveil a detailed view of the immune micromilieu in PDAC using a spatially resolved multimodal single-cell approach. METHODS: We applied single-cell RNA sequencing, spatial transcriptomics, multiplex immunohistochemistry, and mass cytometry to profile the immune compartment in treatment-naïve PDAC tumors and matched adjacent normal pancreatic tissue, as well as in the systemic circulation. We determined prognostic associations of immune signatures and performed a meta-analysis of the immune microenvironment in PDAC and lung adenocarcinoma on single-cell level. RESULTS: We provided a spatially resolved fine map of the immune landscape in PDAC. We substantiated the exhausted phenotype of CD8 T cells and immunosuppressive features of myeloid cells, and highlighted immune subsets with potentially underappreciated roles in PDAC that diverged from immune populations within adjacent normal areas, particularly CD4 T cell subsets and natural killer T cells that are terminally exhausted and acquire a regulatory phenotype. Differential analysis of immune phenotypes in PDAC and lung adenocarcinoma revealed the presence of extraordinarily immunosuppressive subtypes in PDAC, along with a distinctive immune checkpoint composition. CONCLUSIONS: Our study sheds light on the multilayered immune dysfunction in PDAC and presents a holistic view of the immune landscape in PDAC and lung adenocarcinoma, providing a comprehensive resource for functional studies and the exploration of therapeutically actionable targets in PDAC.

Risk Factors for Rectal Stump Leakage After Discontinuity Resection: Stump Length Matters Most.

BACKGROUND: Discontinuity resection is commonly conducted to avoid anastomotic leakage in high-risk patients but potentially results in rectal stump leakage. Although risk factors for anastomotic leakage have been widely studied, data on rectal stump leakage rates and underlying risk factors are scarce. OBJECTIVE: To determine rectal stump leakage rates following Hartmann's procedure and to identify patient-and surgery-associated risk factors. DESIGN: A retrospective study with univariate and multivariate analyses was performed to identify risk factors of rectal stump leakage. A subgroup analysis of scheduled operations was performed. SETTINGS: The study was conducted at Heidelberg University Hospital, Germany. PATIENTS: Patients were included who underwent discontinuity resection with rectal stump formation between 2010 and 2020. MAIN OUTCOME MEASURES: The main outcome measures included rectal stump leakage rates, 30-day mortality, length of hospitalization, and necessity for further invasive treatment. RESULTS: Rectal stump leakage occurred in 11.78% of patients. Rectal stump leakage rates varied considerably depending on the surgical procedure performed and were highest following subtotal pelvic exenteration (34%). Diagnosis of rectal stump leakage peaked on postoperative day 7. A short rectal stump ( p = 0.001), previous pelvic radiotherapy ( p = 0.04), chemotherapy ( p = 0.004), and previous laparotomy ( p = 0.03) were independent risk factors for rectal stump leakage in the entire patient collective. In patients undergoing scheduled surgery, a short rectal stump was the only independent risk factor ( p = 0.003). Rectal stump leakage was not associated with increased 30-day mortality but prolonged length of hospitalization and frequently necessitated further invasive treatment. LIMITATIONS: Study results are limited by the retrospective design, a high number of emergency operations, and the mere inclusion of symptomatic leakages. CONCLUSIONS: Rectal stump leakage is a relevant complication after discontinuity resection. Risk factors should be considered during surgical decision-making when both discontinuity resection and abdominoperineal resection are feasible. See Video Abstract. FACTORES DE RIESGO PARA LA FUGA DEL MUN RECTAL DESPUS DE UNA RESECCIN POR DISCONTINUIDAD LA LONGITUD DEL MUN ES LO MS IMPORTANTE: ANTECEDENTES:La resección de discontinuidad se realiza comúnmente para evitar la fuga anastomótica en pacientes de alto riesgo, pero potencialmente da como resultado una fuga del muñón rectal. Si bien los factores de riesgo de fuga anastomótica se han estudiado ampliamente, los datos sobre las tasas de fuga del muñón rectal y los factores de riesgo subyacentes son escasos.OBJETIVO:Determinar las tasas de fuga del muñón rectal después del procedimiento de Hartmann e identificar los factores de riesgo asociados con el paciente y la cirugía.DISEÑO:Se realizó un estudio retrospectivo con análisis univariado y multivariado para identificar los factores de riesgo de fuga del muñón rectal. Se llevó a cabo un análisis de subgrupos de las operaciones programadas.AJUSTES:El estudio se realizó en el Hospital Universitario de Heidelberg, Alemania.PACIENTES:Se incluyeron pacientes que se sometieron a resección de discontinuidad con formación de muñón rectal entre 2010 y 2020.MEDIDAS DE RESULTADO PRINCIPALES:Las principales medidas de resultado incluyeron las tasas de fuga del muñón rectal, la mortalidad a los 30 días, la duración de la hospitalización y la necesidad de un tratamiento invasivo adicional.RESULTADOS:La fuga del muñón rectal ocurrió en el 11,78% de los pacientes. Las tasas de fuga del muñón rectal variaron considerablemente según el procedimiento quirúrgico realizado y fueron más altas después de la exenteración pélvica subtotal (34%). El diagnóstico de fuga del muñón rectal alcanzó su punto máximo en el día 7 del postoperatorio. Un muñón rectal corto (p = 0,001), radioterapia pélvica previa (p = 0,04), quimioterapia (p = 0,004) y laparotomía previa (p = 0,03) fueron factores de riesgo independientes de fuga rectal. Fuga del muñón en todo el colectivo de pacientes. En los pacientes sometidos a cirugía programada, el muñón rectal corto fue el único factor de riesgo independiente (p = 0,003). La fuga del muñón rectal no se asoció con un aumento de la mortalidad a los 30 días, pero con una duración prolongada de la hospitalización y con frecuencia requirió un tratamiento invasivo adicional.LIMITACIONES:Los resultados del estudio están limitados por el diseño retrospectivo, un alto número de operaciones de emergencia y la mera inclusión de fugas sintomáticas.CONCLUSIONES:La fuga del muñón rectal es una complicación relevante tras la resección por discontinuidad. Se deben considerar los factores de riesgo durante la toma de decisiones quirúrgicas cuando son factibles tanto la resección por discontinuidad como la resección abdominoperineal. (Traducción-Yesenia Rojas-Khalil ).

Tranexamic Acid Administration During Liver Transplantation Is Not Associated With Lower Blood Loss or With Reduced Utilization of Red Blood Cell Transfusion.

BACKGROUND: Current clinical guidelines recommend antifibrinolytic treatment for liver transplantation to reduce blood loss and transfusion utilization. However, the clinical relevance of fibrinolysis during liver transplantation is questionable, a benefit of tranexamic acid (TXA) in this context is not supported by sufficient evidence, and adverse effects are also conceivable. Therefore, we tested the hypothesis that use of TXA is associated with reduced blood loss. METHODS: We performed a retrospective cohort study on patients who underwent liver transplantation between 2004 and 2017 at Heidelberg University Hospital, Heidelberg, Germany. Univariable and multivariable linear regression analyses were used to determine the association between TXA administration and the primary end point intraoperative blood loss and the secondary end point intra- and postoperative red blood cell (RBC) transfusions. For further secondary outcome analyses, the time to the first occurrence of a composite end point of hepatic artery thrombosis, portal vein thrombosis, and thrombosis of the inferior vena cava were analyzed using a univariable and multivariable Cox proportional hazards model. RESULTS: Data from 779 transplantations were included in the final analysis. The median intraoperative blood loss was 3000 mL (1600-5500 mL). Intraoperative TXA administration occurred in 262 patients (33.6%) with an average dose of 1.4 ± 0.7 g and was not associated with intraoperative blood loss (regression coefficient B, -0.020 [-0.051 to 0.012], P = .226) or any of the secondary end points (intraoperative RBC transfusion; regression coefficient B, 0.023 [-0.006 to 0.053], P = .116), postoperative RBC transfusion (regression coefficient B, 0.007 [-0.032 to 0.046], P = .717), and occurrence of thrombosis (hazard ratio [HR], 1.110 [0.903-1.365], P = .321). CONCLUSIONS: Our data do not support the use of TXA during liver transplantation. Physicians should exercise caution and consider individual factors when deciding whether or not to administer TXA.

Thoracic Epidural Analgesia Is Not Associated With Improved Survival After Pancreatic Surgery: Long-Term Follow-Up of the Randomized Controlled PAKMAN Trial.

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.

Patient reported outcomes of duodenum-preserving pancreatic head resection in chronic pancreatitis: high effectivity is impaired by prolonged non-surgical management.

BACKGROUND: Chronic pancreatitis (CP) causes suffering and socioeconomic burden. This study evaluated perioperative results and patient-reported outcomes (PRO) in CP patients treated with duodenum-preserving pancreatic head resection (DPPHR). METHODS: Data were analyzed of CP patients undergoing DPPHR between 01/2001-10/2014. PROs were measured using a specifically designed questionnaire and the EORTC QLQ-C30/PAN26. Associations between treatment variables and PROs were examined. RESULTS: Of 332 patients who received DPPHR, most (n = 251, 75.6%) underwent the Berne modification. Surgical morbidity was 21.5% (n = 71) and 90-day mortality 1.5% (n = 5). Median follow-up was 79.9 months, 5-year survival 90.5%, and 1.8% of patients developed pancreatic cancer. Of 283 patients alive, 178 (62.9%) returned questionnaires. Referral for surgery was self-initiated (38.0% of cases), by gastroenterologists (27.5%) and by general practitioners (21.1%). QoL improved in 78.7% of patients, remained stable in 12.1%, and worsened in 9.1%. Median Izbicki scores decreased from 90 to 5 points after surgery (p < 0.0001). Time from diagnosis to DPPHR was an independent, proportional predictor of a higher postoperative Izbicki score (p = 0.04). CONCLUSION: DPPHR is an effective, safe treatment for CP. A delay in surgery decreases surgical effectivity, hence CP patients should be referred to surgery early to ensure satisfactory outcomes.

DNA-methylation signature accurately differentiates pancreatic cancer from chronic pancreatitis in tissue and plasma.

OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy. Differentiation from chronic pancreatitis (CP) is currently inaccurate in about one-third of cases. Misdiagnoses in both directions, however, have severe consequences for patients. We set out to identify molecular markers for a clear distinction between PDAC and CP. DESIGN: Genome-wide variations of DNA-methylation, messenger RNA and microRNA level as well as combinations thereof were analysed in 345 tissue samples for marker identification. To improve diagnostic performance, we established a random-forest machine-learning approach. Results were validated on another 48 samples and further corroborated in 16 liquid biopsy samples. RESULTS: Machine-learning succeeded in defining markers to differentiate between patients with PDAC and CP, while low-dimensional embedding and cluster analysis failed to do so. DNA-methylation yielded the best diagnostic accuracy by far, dwarfing the importance of transcript levels. Identified changes were confirmed with data taken from public repositories and validated in independent sample sets. A signature of six DNA-methylation sites in a CpG-island of the protein kinase C beta type gene achieved a validated diagnostic accuracy of 100% in tissue and in circulating free DNA isolated from patient plasma. CONCLUSION: The success of machine-learning to identify an effective marker signature documents the power of this approach. The high diagnostic accuracy of discriminating PDAC from CP could have tremendous consequences for treatment success, once the result from still a limited number of liquid biopsy samples would be confirmed in a larger cohort of patients with suspected pancreatic cancer.

Oncological Outcome of Conversion Surgery After Preoperative Chemotherapy for Metastatic Pancreatic Cancer.

OBJECTIVE: To investigate the outcome of conversion surgery in patients with metastatic pancreatic cancer (mPDAC) and to identify patients who may benefit from this approach. BACKGROUND: The role of conversion surgery in patients with mPDAC and exceptional response to chemotherapy remains unclear. METHODS: Patients who underwent surgical exploration for mPDAC following chemotherapy between 2006 and 2019 were included. Data on demographics, oncologic treatment, pathology, and postoperative outcomes were analyzed. Univariate and multivariate survival analyses were performed. RESULTS: Some 173 patients received preoperative chemotherapy and underwent surgical exploration. Ninety-three patients underwent resection of the primary tumor and metastatic sites, 80 patients underwent exploration only. In the resection subgroup, 45 patients had complete pathological response of metastases (ypM0) and 48 patients had residual metastases (ypM1). ypM0 status was associated with lower carcinoembryonic antigen levels and lower ypN stage. Overall survival after resection was 25.5 months in ypM0, 10.7 months in ypM1, and 8.1 months in patients without resection ( P <0.001). Additional adjuvant chemotherapy was significantly associated with prolonged survival in resected patients (29.0 vs 14.8 mo, P =0.024) as well as in ypM0 (29.1 vs 19.2 mo, P =0.047). Multivariable analysis identified conversion surgery, carbohydrate antigen 19-9 (CA19-9) and time of resection as independent prognostic markers for the entire cohort. CA19-9, ypM0 and adjuvant treatment were independent predictors of survival in the resection subgroup. CONCLUSION: In patients with mPDAC and ypM0 status after chemotherapy, surgical resection is associated with encouraging survival. mPDAC patients with exceptional response to chemotherapy may be candidates for exploration and for resection in ypM0. Adjuvant chemotherapy may provide an additional survival advantage.

Distal Bile Duct Cancer: Radical (R0 > 1 mm) Resection Achieves Favorable Survival.

OBJECTIVE: Evaluation of the outcome after resection for distal bile duct cancer (DBC) with focus on the impact of microscopic histopathological resection status R0 (>1 mm) versus R1 (≤1 mm) vs R1 (direct). SUMMARY BACKGROUND DATA: DBC is a rare disease for which oncologic resection offers the only chance of cure. METHODS: Prospectively collected data of consecutive patients undergoing pancreaticoduodenectomy for DBC were analyzed. Histopathological resection status was classified according to the Leeds protocol for pancreatic ductal adeno carcinoma (PDAC) (PDAC; R0 >1 mm margin clearance vs R1 ≤1 mm vs R1 direct margin involvement). RESULTS: A total of 196 patients underwent pancreaticoduodenectomy for DBC. Microscopic complete tumor clearance (R0>1 mm) was achieved in 113 patients (58%). Median overall survival (OS) of the entire cohort was 37 months (5- and 10-year OS rate: 40% and 31%, respectively). After R0 resection, median OS increased to 78 months with a 5-year OS rate of 52%. Negative prognostic factors were age >70 years ( P < 0.0001, hazard ratio (HR) 2.48), intraoperative blood loss >1000 mL ( P = 0.0009, HR 1.99), pN1 and pN2 status ( P = 0.0052 and P = 0.0006, HR 2.14 and 2.62, respectively) and American Society of Anesthesiologists score >II ( P = 0.0259, HR 1.61). CONCLUSIONS: This is the largest European single-center study of surgical treatment for DBC and the first to investigate the prognostic impact of the revised PDAC resection status definition in DBC. The results show that this definition is valid in DBC and that "true" R0 resection (>1 mm) is a key factor for excellent survival. In contrast to PDAC, there was no survival difference between R1 (≤1 mm) and R1 (direct).

Portal Vein Resection in Pancreatic Cancer Surgery: Risk of Thrombosis and Radicality Determine Survival.

OBJECTIVE: To evaluate the outcomes of pancreatic cancer [pancreatic ductal adenocarcinoma (PDAC)] surgery with concomitant portal vein resection (PVR), focusing on the PVR type according to the International Study Group of Pancreatic Surgery (ISGPS). BACKGROUND: Surgery offers the only chance for cure in PDAC. PVR is often performed for borderline or locally advanced tumors. METHODS: Consecutive patients with PDAC operated between January 2006 and January 2018 were included. Clinicopathologic characteristics and outcomes were analyzed and tested for survival prediction. RESULTS: Of 2265 PDAC resections, 1571 (69.4%) were standard resections and 694 (30.6%) were resections with PVR, including 149 (21.5%) tangential resections with venorrhaphy (ISGPS type 1), 21 (3.0%) resections with patch reconstruction (type 2), 491 (70.7%) end-to-end anastomoses (type 3), and 33 (4.8%) resections with graft interposition (type 4). The 90-day mortality rate was 2.6% after standard resection and 6.3% after resection with PVR ( P <0.0001). Postoperative portal vein thrombosis and pancreas-specific surgical complications most frequently occurred after PVR with graft interposition (21.2% and 48.5%, respectively). In multivariable analysis, age 70 years and above, ASA stages 3/4, increased preoperative serum carbohydrate antigen 19-9, neoadjuvant treatment, total pancreatectomy, PVR, higher UICC stage, and R+ resections were significant negative prognostic factors for overall survival. Radical R0 (>1 mm) resection resulted in 23.3 months of median survival. CONCLUSIONS: This is the largest single-center, comparative cohort study of PVR in PDAC surgery, showing that postoperative morbidity correlates with the reconstruction type. When radical resection is achieved, thrombosis risk is outweighed by beneficial overall survival times of nearly 2 years.

Distal Pancreatectomy With En Bloc Celiac Axis Resection (DP-CAR) for Locally Advanced Pancreatic Cancer: A Safe and Effective Procedure.

OBJECTIVE: To determine perioperative and oncologic outcomes after distal pancreatectomy with en bloc resection of the celiac axis (DP-CAR). BACKGROUND: DP-CAR can be used in a selective group of patients to resect locally advanced pancreatic cancer involving the celiac axis or common hepatic artery without arterial reconstruction by preserving retrograde blood flow via the gastroduodenal artery to the liver and stomach. METHODS: We analyzed all consecutive patients who had undergone DP-CAR between May 2003 and April 2022 at a tertiary hospital specialized in pancreatic surgery and present one of the largest single-center studies. RESULTS: A total of 71 patients underwent DP-CAR. Additional venous resection (VR) of the mesenterico-portal axis was performed in 31 patients (44%) and multivisceral resection (MVR) in 42 patients (59%). Margin-free (R0) resection was achieved in 40 patients (56%). The overall 90-day mortality rate was 8.4% for the entire patient cohort. After a cumulated experience of 16 cases, the 90-day mortality dropped to 3.6% in the following 55 patients. Extended procedures with (+) additional MVR with or without (+/-) VR resulted in higher major morbidity (Clavien-Dindo ≥IIIB; standard DP-CAR: 19%; DP-CAR + MVR +/- VR: 36%) and higher 90-day mortality (standard DP-CAR: 0%; DP-CAR + MVR +/- VR: 11%). Median overall survival after DP-CAR was 28 months. CONCLUSIONS: DP-CAR is a safe and effective procedure but requires experience. Frequently, surgical resection has to be extended with MVR and VR to accomplish tumor resection, which results in promising oncologic outcomes. However, extended resections were associated with increased morbidity and mortality.

Celiac Axis Stenosis is an Underestimated Risk Factor for Increased Morbidity After Pancreatoduodenectomy.

OBJECTIVE: To assesses the prevalence and severity of CAS in patients undergoing PD/total pancreatectomy and its association with major postoperative complications after PD. SUMMARY OF BACKGROUND DATA: CAS may increase the risk of ischemic complications after PD. However, the prevalence of CAS and its relevance to major morbidity remain unknown. METHODS: All patients with a preoperative computed tomography with arterial phase undergoing partial PD or TP between 2014 and 2017 were identified from a prospective database. CAS was assessed based on computed tomography and graded according to its severity: no stenosis (<30%), grade A (30%-<50%), grade B (50%-≤80%), and grade C (>80%). Postoperative complications were assessed and uni- and multivariable risk analyses were performed. RESULTS: Of 989 patients, 273 (27.5%) had CAS: 177 (17.9%) with grade A, 83 (8.4%) with grade B, and 13 (1.3%) with grade C. Postoperative morbidity and 90-day mortality occurred in 278 (28.1%) patients and 41 (4.1%) patients, respectively. CAS was associated with clinically relevant pancreatic fistula ( P =0.019), liver perfusion failure ( P =0.003), gastric ischemia ( P =0.001), clinically relevant biliary leakage ( P =0.006), and intensive care unit ( P =0.016) and hospital stay ( P =0.001). Multivariable analyses confirmed grade B and C CAS as independent risk factors for liver perfusion failure; in addition, grade C CAS was an independent risk factor for clinically relevant pancreatic fistula and gastric complications. CONCLUSIONS: CAS is common in patients undergoing PD. Higher grade of CAS is associated with an increased risk for clinically relevant complications, including liver perfusion failure and postoperative pancreatic fistula. Precise radiological assessment may help to identify CAS. Future studies should investigate measures to mitigate CAS-associated risks.

Completion Pancreatectomy After Pancreatoduodenectomy: Who Needs It?

OBJECTIVE: The objective of this study was to identify the indications for and report the outcomes of completion pancreatectomy (CPLP) in the postoperative course after pancreatoduodenectomy (PD). BACKGROUND: CPLP may be considered or even inevitable for damage control after PD. METHODS: A prospectively maintained database of all patients undergoing PD between 2001 and 2019 was searched for patients who underwent CPLP in the postoperative course after PD. Baseline characteristics, perioperative details, and outcomes of CPLP patients were analyzed and specific indications for CPLP were identified. RESULTS: A total of 3953 consecutive patients underwent PD during the observation period. CPLP was performed in 120 patients (3%) after a median of 10 days following PD. The main indications for CPLP included postpancreatectomy acute necrotizing pancreatitis [n=47 (39%)] and postoperative pancreatic fistula complicated by hemorrhage [n=41 (34%)] or associated with uncontrollable leakage of the pancreatoenteric anastomosis [n=23 (19%)]. The overall 90-day mortality rate of all 3953 patients was 3.5% and 37% for patients undergoing CPLP. CONCLUSIONS: Our finding that only very few patients (3%) need CPLP suggests that conservative, interventional, and organ-preserving surgical measures are the mainstay of complication management after PD. Postpancreatectomy acute necrotizing pancreatitis, uncontrollable postoperative pancreatic fistula, and fistula-associated hemorrhage are highly dangerous and represent the main indications for CPLP after PD.

A Simple Classification of Pancreatic Duct Size and Texture Predicts Postoperative Pancreatic Fistula: A classification of the International Study Group of Pancreatic Surgery.

OBJECTIVE: The aim of this study was to develop a classification system for pancreas-associated risk factors in pancreatoduodenectomy (PD). SUMMARY BACKGROUND DATA: Postoperative pancreatic fistula (POPF) is the most relevant PD-associated complication. A simple standardized surgical reporting system based on pancreas-associated risk factors is lacking. METHODS: A systematic literature search was conducted to identify studies investigating clinically relevant (CR) POPF (CR-POPF) and pancreas-associated risk factors after PD. A meta-analysis of CR-POPF rate for texture of the pancreas (soft vs not-soft) and main pancreatic duct (MPD) diameter was performed using the Mantel-Haenszel method. Based on the results, the International Study Group of Pancreatic Surgery (ISGPS) proposes the following classification: A, not-soft (hard) texture and MPD >3 mm; B, not-soft (hard) texture and MPD ≤3 mm; C, soft texture and MPD >3 mm; D, soft texture and MPD ≤3 mm. The classification was evaluated in a multi-institutional, international cohort. RESULTS: Of the 2917 articles identified, 108 studies were included in the analyses. Soft pancreatic texture was significantly associated with the development of CR-POPF [odds ratio (OR) 4.24, 95% confidence interval (CI) 3.67-4.89, P < 0.01) following PD. Similarly, MPD diameter ≤3 mm significantly increased CR-POPF risk compared with >3 mm diameter MPDs (OR 3.66, 95% CI 2.62-5.12, P < 0.01). The proposed 4-stage system was confirmed in an independent cohort of 5533 patients with CR-POPF rates of 3.5%, 6.2%, 16.6%, and 23.2% for type A-D, respectively ( P < 0.001). CONCLUSION: For future pancreatic surgical outcomes studies, the ISGPS recommends reporting these risk factors according to the proposed classification system for better comparability of results.

Extensive Peritonectomy is an Independent Risk Factor for Cisplatin HIPEC-Induced Acute Kidney Injury.

BACKGROUND: Cisplatin (CDDP)-containing hyperthermic intraperitoneal chemotherapy (HIPEC) is frequently applied in selected patients with peritoneal malignancies derived from ovarian cancer, gastric cancer, and primary peritoneal mesothelioma. HIPEC with CDDP increases perioperative morbidity, in particular by inducing acute kidney injury (AKI). Factors contributing to occurrence of AKI after intraperitoneal perfusion with CDDP have not been sufficiently evaluated. PATIENTS AND METHODS: Data from 63 patients treated with a CDDP-containing HIPEC regimen were retrospectively analyzed concerning demographics, underlying disease, surgery, and HIPEC details to evaluate risk factors of AKI. A preclinical rat perfusion model was applied to assess the influence of temperature, concentration, perfusate volume, perfusion flow rate, and extent of peritonectomy on drug absorption upon intraperitoneal CDDP perfusion. RESULTS: AKI occurred in 66.1% of patients undergoing CDDP-containing HIPEC, with total intraoperative fluid influx being a negative and the extent of parietal peritonectomy being a positive independent predictor of postoperative AKI. In a preclinical model, bilateral anterior parietal peritonectomy significantly increased systemic CDDP absorption by 1.6 to 2-fold. CDDP plasma levels in animals were significantly higher after both perfusion with increased CDDP perfusate concentrations and bilateral anterior parietal peritonectomy. CONCLUSION: CDDP-containing HIPEC is associated with relevant morbidity owing to its systemic toxicity. Extent of parietal peritonectomy is an independent predictor of AKI. CDDP dose reduction should be considered in case of extensive parietal peritonectomy. Cytostatic drug concentrations in HIPEC perfusate should be paid more attention to than total dose per body surface area. Further clinical studies are needed to confirm the presented preclinical findings.

Induction Chemotherapy with FOLFIRINOX for Locally Advanced Pancreatic Cancer: A Simple Scoring System to Predict Effect and Prognosis.

BACKGROUND: Effective chemotherapy (CTx) protocols as induction treatment provide increasing opportunities for surgical resection of locally advanced pancreatic cancer (LAPC). Although improved survival after resection of LAPC with CTx has been reported for selected patients, reliable recommendations on the indication for conversion surgery after induction treatment are currently lacking. We investigated the factors predictive of prognosis in resected LAPC after FOLFIRINOX. METHODS: Consecutive patients with LAPC undergoing curative resection after FOLFIRINOX between 2011 and 2018 were identified from a prospectively maintained database. Relevant clinical parameters and CT findings were examined. A scoring system was developed based on the ratio of hazard ratios for overall survival of all significant predictors. RESULTS: A total of 62 patients with LAPC who underwent oncologic resection after FOLFIRINOX were analyzed. Tumor shrinkage, tumor density, and postchemotherapy CA19-9 serum levels were independently associated with overall survival (multivariate analysis: HR = 0.31, 0.17, and 0.18, respectively). One, two, and two points were allocated to these three factors in the proposed scoring system, respectively. The median overall survival of patients with a score from 0 to 2 was significantly shorter than that of patients with a score from 3 to 5 (22.1 months vs. 53.2 months, P < 0.001). CONCLUSIONS: Tumor density is a novel predictive marker for the prognosis of patients with resected LAPC after FOLFIRINOX. A simple scoring model incorporating tumor density, the tumor shrinkage rate, and CA 19-9 levels identifies patients with a low score, who may be candidates for additional treatment.