Continuous irrigation after pancreatectomy: a systematic review.

PURPOSE: Prevention and management of postoperative pancreatic fistula (POPF) after pancreatic resections is still an unresolved issue. Continuous irrigation of the peripancreatic area is frequently used to treat necrotizing pancreatitis, but its use after elective pancreatic surgery is not well-known. With this systematic review, we sought to evaluate the current knowledge and expertise regarding the use of continuous irrigation in the surgical area to prevent or treat POPF after elective pancreatic resections. METHODS: A systematic search of the literature was conducted according to the PRISMA 2020 guidelines, screening the databases of Pubmed, Scopus, Web of Science, and Ovid MEDLINE. Because of the heterogeneity of the included articles, a statistical inference could not be performed and the literature was reviewed only descriptively. The study was pre-registered online (OSF Registry). RESULTS: Nine studies were included. Three studies provided data regarding the prophylactic use of continuous irrigation after distal and limited pancreatectomies. Here, patients after irrigation showed a lower rate of clinically relevant POPF, related complications, lengths of stay, and mortality. Six other papers reported the use of local lavage to treat clinically relevant POPF and subsequent fluid collections, with successful outcomes. CONCLUSION: In the current literature, only a few publications are focused on the use of continuous irrigation after pancreatic resection to prevent or manage POPF. The included studies showed promising results, and this technique may be useful in patients at high risk of POPF. Further investigations and randomized trials are needed.

Serum albumin at resection predicts in-hospital death, while serum lactate and aPTT on the first postoperative day anticipate anastomotic leakage after Ivor-Lewis-esophagectomy.

BACKGROUND: Anastomotic leakage (AL) is a major complication after esophagectomy, potentiating morbidity and mortality. There are several patient risk factors associated with AL, but high-fidelity postoperative predictors are still under debate. The aim was to identify novel reliable predictors for AL after esophagectomy. METHODS: A high-volume single-center database study, including 138 patients receiving Ivor-Lewis-esophagectomy between 2017 and 2019, was performed. Serum levels of albumin, aPTT, and lactate before and after surgery were extracted to assess their impact on AL and in-hospital mortality. RESULTS: High serum lactate on postoperative day 1 (POD1) could be shown to predict AL after esophagectomy [AL vs. no AL: 1.2 (0.38) vs. 1.0 (0.37); p < 0.001]. Accordingly, also differences of serum lactate level between end (POD0-2) and start of surgery (POD0-1) (p < 0.001) as well as between POD1 and POD0-1 (p < 0.001) were associated with AL. Accordingly, logistic regression identified serum lactate on POD 1 as an independent predictor of AL [HR: 4.37 (95% CI: 1.28-14.86); p = 0.018]. Further, low serum albumin on POD0 [2.6 (0.53) vs. 3.1 (0.56); p = 0.001] and high serum lactate on POD 0-1 [1.1 (0.29) vs. 0.9 (0.30); p = 0.043] were associated with in-hospital death. Strikingly, logistic-regression (HR: 0.111; p = 0.008) and cox-regression analysis (HR: 0.118; p = 0.003) showed low serum albumin as an independently predictor for in-hospital death after esophagectomy. CONCLUSIONS: This study identified high serum lactate as an independent predictor of AL and low serum albumin as a high-fidelity predictor of in-hospital death after esophagectomy. These parameters can facilitate improved postoperative treatment leading to better short-term as well as long-term outcomes.

The Effect of Celiac Neurolysis and Splanchnicectomy on Survival in Unresectable Pancreatic Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Intractable pancreatic pain is one of the most common symptoms of patients with pancreatic ductal adenocarcinoma (PDAC). Celiac neurolysis (CN) and splanchnicectomy were already described as effective methods to manage abdominal pain in unresectable PDAC, but their impact on overall survival (OS) has not yet been established. OBJECTIVE: We aimed to investigate the impact of CN and splanchnicectomy on the survival of patients with unresectable pancreatic cancer. METHODS: A systematic review of PubMed and Cochrane Library according to predefined searching terms was conducted in March 2020. Hazard ratios (HR) of OS data were calculated using the Mantel-Haenszel model for random effects or fixed effects. RESULT: Four randomized-controlled trials (RCTs) and 2 non-RCTs with a total of 2,507 patients were identified. The overall pooled HR did not reveal any relevant effect of CN and splanchnicectomy on OS (HR: 1.03; 95% CI: 0.81-1.32), which was also underlined by the sensitivity analysis of RCTs (HR: 1.0; 95% CI: 0.72-1.39) and non-RCTs (HR: 1.07; 95% CI: 0.71-1.63). However, subgroup analyses depending on tumor stage revealed that CN or splanchnicectomy was associated with a worsened OS in AJCC (American Joint Committee on Cancer) stage III patients with unresectable PDAC (HR: 1.22; 95% CI: 1.03-1.45), but nor for AJCC stage IV patients (HR: 1.27; 95% CI: 0.9-1.80). CONCLUSION: Although only few data are currently available, this systematic review with meta-analysis showed that in unresectable PDAC, CN or splanchnicectomy is associated with a worsened survival in stage III PDAC patients, with no effect on stage IV PDAC patients. These data call for caution in the usage of CN or splanchnicectomy in stage III PDAC and for further studies addressing this observation.

Do somatostatin-analogues have the same impact on postoperative morbidity and pancreatic fistula in patients after pancreaticoduodenectomy and distal pancreatectomy? - A systematic review with meta-analysis of randomized-controlled trials.

OBJECTIVE: Postoperative pancreatic fistula/POPF is the most feared complication in pancreatic surgery. Although several systematic reviews investigated the impact of somatostatin analogues on POPF, no stratification was performed regarding type of pancreatic resection (pancreaticoduodenectomy/PD; distal pancreatectomy/DP) and different somatostatin analogues. METHODS: This study was planed according to the Preferred-Reporting-Items-for-Systematic -Review-and-Meta-Analysis/PRISMA-guidelines. After screening databases for randomized controlled trials/RCT, studies were stratified into pancreatic resection techniques and data were pooled in meta-analyses containing subgroups of octreotide, somatostatin, lanreotide, pasireotide and vapreotide. RESULTS: The meta-analysis of studies with a mixed cohort of patients after pancreatic resection revealed a protective effect of somatostatin analogues for morbidity (RR: 0.71, p < .00001) but not for mortality (RR: 1.07, = 0.78) or intra-abdominal abscesses (RR: 1.00, p = 1.00). Moreover, no effect was visible for mortality (RR: 1.57, p = .15), morbidity (RR: 0.87, p = .15) and intra-abdominal abscesses (RR: 0.92, p = .48) after PD. The meta-analysis of patients after PD revealed no impact of somatostatin analogues on POPF (RR: 0.87, p = .19) and clinically relevant POPF (RR: 0.69, p = .30). However, treatment with somatostatin analogues in the mixed cohort showed less POPF (RR: 0.60, p < .00001) and clinically relevant POPF (RR: 0.47, p = .02), which was also the case after DP (RR: 0.41, p = .03). CONCLUSION: Somatostatin analogues did not affect POPF and clinically relevant POPF after PD, but seemed to be associated with less POPF after DP. As no sufficiently powered RCT could be identified by the systematic review, further RCTs are urgently needed to investigate the effect of somatostatin analogues after DP. STUDY REGISTRATION: CRD42018099808.

The quality of pain management in pancreatic cancer: A prospective multi-center study.

BACKGROUND/OBJECTIVES: Pancreatic ductal adenocarcinoma (PDAC) is frequently associated with severe pain. Given the almost inevitably fatal nature of the disease, pain control is crucial. However, data on quality of pain management in PDAC is scarce. METHODS: This is a multi-center, prospective study to evaluate the quality of pain management in PDAC. Insufficient pain treatment (undertreatment) was prevalent if there was an incongruence between the patients level of pain and the potency of analgesic drug therapy. Determinants of pain and undertreatment were identified using multivariable logistic regression. RESULTS: 139 patients with histologically confirmed PDAC were analyzed. The prevalence of pain was 63%, with approximately one third of the patients grading their pain as moderate to severe. Palliative stage (OR: 3.37, 95%CI: 1.23-9.21, p = 0.018) and localization of the primary tumor in the body or tail (OR: 2.57, 95%CI: 1.05-6.31, p = 0.039) were independent determinants of pain. Of those reporting pain, 60% were undertreated and in 89% pain interfered with activities and emotions. Age ≥ 70 years (OR: 3.20, 95%CI: 1.09-9.41, p = 0.035) was an independent predictor of undertreatment. Patients with longer-known PDAC ( ≥ 30 days) showed improved pain management compared to new cases (OR: 0.19, 95%CI: 0.05-0.81, p = 0.025). Treatment by gastroenterologists (OR: 0.22, 95%CI: 0.05-0.89, p = 0.034) was associated with less undertreatment. CONCLUSIONS: The results show a high proportion of PDAC patients with pain, pain interference and undertreatment, whose characteristics could help to identify patients at risk in the future. Several changes in the management of cancer-related pain are necessary to overcome barriers to optimal treatment.

Respect - A multicenter retrospective study on preoperative chemotherapy in locally advanced and borderline resectable pancreatic cancer.

BACKGROUND: Neoadjuvant chemotherapy has become a powerful tool to convert borderline resectable (BRPC) and locally advanced pancreatic cancers (LAPC) into a resectable scenario. However, data analyzing the optimal type of therapy are scarce. In the present multicenter retrospective study, we evaluated the influence of FOLFIRINOX (FFX) and gemcitabine (GEM)-based neoadjuvant therapy on patient prognosis. METHODS: Data on 239 patients from 7 centers across Europe was gathered using an online database. Patients having received their first cycle of chemotherapy for BRPC/LAPC before 06/2017, with a minimum follow-up of 12 months, were included in the intention-to-treat analysis. RESULTS: Patients treated with neoadjuvant FFX (n = 135) or gemcitabine + nab-paclitaxel (GNP) (n = 38) had significantly improved radiological response according to RECIST criteria as compared to single-agent GEM (n = 16), with a partial/complete response of 59.3%, 55.3% and 6.25% respectively (p = 0.001). Treatment with FFX (n = 135) and GNP (n = 38) resulted in higher resection rates compared to GEM (73.3%, 81.6% and 43.8%; p = 0.01 and p = 0.005). Regardless of regimen, patients who were resected had significantly prolonged overall survival compared to non-resected patients (p < 0.01). Complete pathological responses (ypT0 ypN0) were predominantly observed with FFX (p = 0.01). Adjuvant GNP in addition to successful neoadjuvant therapy and surgery resulted in a trend towards improved median survival as compared to postoperative observation (47.0 vs. 30.1 months, p = 0.06). CONCLUSIONS: Representing one of the largest studies published so far, our results reveal that patients with BRPC/LAPC should be offered either FFX or GNP to improve chances of resection and with this also survival.

Genetically induced vs. classical animal models of chronic pancreatitis: a critical comparison.

Chronic pancreatitis (CP) is an utmost complex disease that is pathogenetically linked to pancreas-intrinsic ( e.g., duct obstruction), environmental-toxic ( e.g., alcohol, smoking), and genetic factors. Studying such a complex disease naturally requires validated experimental models. In the past 2 decades, the various animal models of CP usually addressed either the pancreas-intrinsic ( e.g., the caerulein model), the environmental-toxic ( e.g., diet-induced models), or the genetic component of CP. As such, these models were far from mirroring CP in its full spectrum, and the correct choice of models was vital for valid scientific conclusions on CP. The quest for mechanistic, genetic models gave rise to models based on gene modification and transgene insertion, such as the PRSS1 and the IL-1ß/IL-1ß models. Recently, we witnessed the development of highly exciting models that rely on the importance of autophagy in CP, that is, the murine pancreas-specific Atg5 and LAMP2 knockout models. Today, critical comparison of these several models is more important than ever for guiding research on CP in an efficient direction. The present review outlines the characteristics of the new genetic models in comparison with the well-known classic models for CP, notes the caveats in the choice of models, and also indicates novel directions for model development.-Klauss, S., Schorn, S., Teller, S., Steenfadt, H., Friess, H., Ceyhan, G. O., Demir, I. K. Genetically induced vs. classical animal models of chronic pancreatitis: a critical comparison.

Mortality and postoperative complications after different types of surgical reconstruction following pancreaticoduodenectomy-a systematic review with meta-analysis.

BACKGROUND: Pancreaticoduodenectomy/PD is a technically demanding pancreatic resection. Options of surgical reconstruction include (1) the child reconstruction defined as pancreatojejunostomy/PJ followed by hepaticojejunostomy/HJ and the gastrojejunostomy/GJ "the standard/s-Child," (2) the s-child reconstruction with an additional Braun enteroenterostomy "BE-Child," or (3) Isolated-Roux-En-Y-pancreaticojejunostomy "Iso-Roux-En-Y," in which the pancreas anastomosis is reconstructed in a separate loop after the GJ. Yet, the impact of these reconstruction methods on patients' outcome has not been sufficiently compared in a systematic manner. METHODS: A systematic review and meta-analysis were conducted according to the Preferred-Reporting-Items-for-Systematic-review-and-Meta-Analysis/PRISMA-guidelines by screening Pubmed/Medline, Scopus, Cochrane Library and Web-of-Science. Articles meeting predefined criteria were extracted and meta-analysis was performed. RESULTS: Nineteen studies were identified comparing BE-Child or Isolated-Roux-En-Y vs. s-Child. Compared to s-Child neither BE-Child (p = 0.43) nor Iso-Roux-En-Y (p = 0.94) displayed an impact on postoperative mortality, whereas BE-Child showed less postoperative complications (p = 0.02). BE-Child (p = 0.15) and Iso-Roux-En-Y (p = 0.61) did not affect postoperative pancreatic fistula/POPF in general, but BE-Child was associated with a decrease of clinically relevant POPF (p = 0.005), clinically relevant delayed gastric emptying/DGE B/C (p = 0.004), bile leaks (p = 0.01), and hospital stay (p = 0.06). BE-Child entailed also an increased operation time (p = 0.0002) with no impact on DGE A/B/C, hemorrhage, surgical site infections and pulmonary complications. CONCLUSION: BE-Child is associated with a decreased risk for postoperative complications, particularly a decreased risk for clinically relevant DGE, POPF, and bile leaks, whereas Iso-Roux-En-Y does not seem to affect the clinical course after PD. Therefore, BE seems to be a valuable surgical method to improve patients' outcome after PD.

R0 Versus R1 Resection Matters after Pancreaticoduodenectomy, and Less after Distal or Total Pancreatectomy for Pancreatic Cancer.

OBJECTIVE: The aim of this study was to decipher the true importance of R0 versus R1 resection for survival in pancreatic ductal adenocarcinoma (PDAC). SUMMARY OF BACKGROUND DATA: PDAC is characterized by poor survival, even after curative resection. In many studies, R0 versus R1 does not result in different prognosis and does not affect the postoperative management. METHODS: Pubmed, Embase, and Cochrane databases were screened for prognostic studies on the association between resection status and survival. Hazard ratios (HRs) were pooled in a meta-analysis. Furthermore, our prospective database was retrospectively screened for curative PDAC resections according to inclusion criteria (n = 254 patients) between July 2007 and October 2014. RESULTS: In the meta-analysis, R1 was associated with a decreased overall survival [HR 1.45 (95% confidence interval, 95% CI 1.37-1.52)] and disease-free survival [HR 1.44 (1.30-1.59)] in PDAC when compared with R0. Importantly, this effect held true only for pancreatic head resection both in the meta-analysis [R0 ≥0 mm: HR 1.21 (1.05-1.39) vs R0 ≥1 mm: HR 1.66 (1.46-1.89)] and in our cohort (R0 ≥0 mm: 31.8 vs 14.5 months, P < 0.001; R0 ≥1 mm, 41.2 vs 16.8 months; P < 0.001). Moreover, R1 resections were associated with advanced tumor disease, that is, larger tumor size, lymph node metastases, and extended resections. Multivariable Cox proportional hazard model suggested G3, pN1, tumor size, and R1 (0 mm/1 mm) as independent predictors of overall survival. CONCLUSION: Resection margin is not a valid prognostic marker in publications before 2010 due to heterogeneity of cohorts and lack of standardized histopathological examination. Within standardized pathology protocols, R-status' prognostic validity may be primarily confined to pancreatic head cancers.

The impact of surgically placed, intraperitoneal drainage on morbidity and mortality after pancreas resection- A systematic review & meta-analysis.

BACKGROUND: Although routinely used, the benefit of surgically placed intraperitoneal drains after pancreas resection is still under debate. To assess the true impact of intraperitoneal drains in pancreas resection, a systematic review with meta-analysis was performed. METHODS: For this, the Preferred-Reporting-Items-for-Systematic-review-and-Meta-Analysis/PRISMA-guidelines were conducted and Pubmed/Medline, Embase, Scopus and The Cochrane Library were screened for relevant studies. RESULTS: 8 retrospective and 3 prospective studies were included in the systematic review. No difference was found between patients with or without intraperitoneal drains in mortality (Risk-ratio/RR 0.74, 95%-Confidence-interval/CI: 0.47-1.18, p = 0.20), in Grade B/C-postoperative pancreatic fistulas/POPF (RR 1.31, 95%-CI: 0.74-2.32, p = 0.35), in intraabdominal abscesses (RR 0.92, 95%-CI: 0.65-1.30, p = 0.64), in surgical site infection (RR 1.20, 95%-CI: 0.85-1.70, p = 0.30), in delayed gastric emptying (RR 1.11, 95%-CI: 0.65-1.90, p = 0.71), in postoperative haemorrhages (RR 0.92 95%-CI: 0.63-1.33, p = 0.65), in reoperations (RR 1.15, 95%-CI: 0.87-1.52, p = 0.33), or in radiological reinterventions (RR 0.95, 95%-CI: 0.69-1.31, p = 0.76). The risk for overall morbidity (RR 1.16, 95%-CI: 1.04-1.29, p = 0.008), of any POPF (RR 2.15, 95%-CI: 1.52-3.04, p < 0.0001) and of readmissions (RR 1.23, 95%-CI: 1.04-1.45, p = 0.01) was increased for patients with intraperitoneal drain compared to patients without following pancreatic resection. CONCLUSION: Regarding the controversial results of the recent prospective, randomized trials this meta-analysis revealed no difference in mortality but an increased risk for postoperative morbidity, POPF and readmissions of patients with intraperitoneal drains after pancreatic resection. Therefore, the indication for intraperitoneal drains should be critically weighed in patients undergoing pancreatic resections.

Nerve growth factor & TrkA as novel therapeutic targets in cancer.

In the past 20years, nerve growth factor (NGF) and its receptors TrkA & p75NTR were recognized to be overexpressed in the overwhelming majority of human solid cancers. Recent studies discovered the presence of overactive TrkA signaling due to TrkA rearrangements or TrkA fusion products in frequent cancers like colorectal cancer, thyroid cancer, or acute myeloid leukemia. Thus, targeting TrkA/NGF via selective small-molecule-inhibitors or antibodies has gained enormous attention in the drug discovery sector. Clinical studies on the anti-cancer impact of NGF-blocking antibodies are likely to be accelerated after the recent removal of clinical holds on these agents by regulatory authorities. Based on these current developments, the present review provides not only a broad overview of the biological effects of NGF-TrkA-p75NTR on cancer cells and their microenvironment, but also explains why NGF and its receptors are going to evoke major interest as promising therapeutic anti-cancer targets in the coming decade.

Activated Schwann cells in pancreatic cancer are linked to analgesia via suppression of spinal astroglia and microglia.

OBJECTIVE: The impact of glia cells during GI carcinogenesis and in cancer pain is unknown. Here, we demonstrate a novel mechanism how Schwann cells (SCs) become activated in the pancreatic cancer (PCa) microenvironment and influence spinal activity and pain sensation. DESIGN: Human SCs were exposed to hypoxia, to pancreatic cancer cells (PCCs) and/or to T-lymphocytes. Both SC and intrapancreatic nerves of patients with PCa with known pain severity were assessed for glial intermediate filament and hypoxia marker expression, proliferation and for transcriptional alterations of pain-related targets. In conditional PCa mouse models with selective in vivo blockade of interleukin (IL)-6 signalling (Ptf1a-Cre;LSL-Kras(G12D)/KC interbred with IL6(-/-) or sgp130(tg) mice), SC reactivity, abdominal mechanosensitivity and spinal glial/neuronal activity were quantified. RESULTS: Tumour hypoxia, PCC and/or T-lymphocytes activated SC via IL-6-signalling in vitro. Blockade of the IL-6-signalling suppressed SC activation around PCa precursor lesions (pancreatic intraepithelial neoplasia (PanIN)) in KC;IL6(-/-) (32.06%±5.25% of PanINs) and KC;sgp130(tg) (55.84%±5.51%) mouse models compared with KC mice (78.27%±3.91%). Activated SCs were associated with less pain in human PCa and with decreased abdominal mechanosensitivity in KC mice (von Frey score of KC: 3.9±0.5 vs KC;IL6(-/-) mice: 5.9±0.9; and KC;sgp130(tg): 10.21±1.4) parallel to attenuation of spinal astroglial and/or microglial activity. Activated SC exhibited a transcriptomic profile with anti-inflammatory and anti-nociceptive features. CONCLUSIONS: Activated SC in PCa recapitulate the hallmarks of 'reactive gliosis' and contribute to analgesia due to suppression of spinal glia. Our findings propose a mechanism for how cancer might remain pain-free via the SC-central glia interplay during cancer progression.

The neurotrophic factor neurturin contributes toward an aggressive cancer cell phenotype, neuropathic pain and neuronal plasticity in pancreatic cancer.

UNLABELLED: Neurotrophic factors possess an emerging role in the pathophysiology of several gastrointestinal disorders, regulating innervation, pain sensation and disease-associated neuroplasticity. Here, we aimed at characterizing the role of the neurotrophic factor neurturin (NRTN) and its receptor glial-cell-line-derived neurotrophic factor receptor alpha-2 (GFRα-2) in pancreatic cancer (PCa) and pancreatic neuropathy. For this purpose, NRTN and GFRα-2 were studied in normal human pancreas and PCa tissues via immunohistochemistry, quantitative reverse transcription-polymerase chain reaction, immunoblotting and correlated to abdominal pain. The impact of NRTN/GFRα-2 on PCa cell (PCC) biology was investigated via exposure to hypoxia, 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide viability and matrigel invasion assays in native and specific small interfering RNA-silenced PCCs. To assess the influence of NRTN on pancreatic neuroplasticity and neural invasion (NI), its impact was explored via an in vitro 'neuroplasticity assay' and a 3D neural migration assay. NRTN and GFRα-2 demonstrated a site-specific upregulation in PCa, predominantly in nerves, PCCs and extracellular matrix. Patients with severe pain demonstrated higher intraneural GFRα-2 immunoreactivity than patients with no pain. PCa tissue and PCCs contained increased amounts of NRTN, which was suppressed under hypoxia. NRTN promoted PCC invasiveness, and silencing of NRTN limited both PCC proliferation and invasion. Depletion of NRTN from PCa tissue extracts and PCC supernatants decreased axonal sprouting in neuronal cultures but did not influence glial density. Silencing of NRTN in PCCs boosted NI. We conclude that increased NRTN/GFRα-2 in PCa seems to promote an aggressive PCC phenotype and neuroplasticity in PCa. Accelerated NI following NRTN suppression constitutes a novel explanation for the attraction of PCC to nerves in the hypoxic PCa tumor microenvironment. SUMMARY: PCa is characterized by intrapancreatic neuroplasticity and NI. Here, we show that PCC produce the neurotrophic factor NRTN, which reinforces their biological properties, triggers neuroplastic alterations, NI and influences pain sensation via the GFRα-2 receptor.

Lymph node examination and survival in resected pancreatic ductal adenocarcinoma: retrospective study.

BACKGROUND: The minimum number of examined lymph nodes (ELN) required for adequate staging and best prediction of survival has not been established in pancreatic ductal adenocarcinoma (PDAC). The aim of the study was to investigate the influence of ELN on staging and survival in PDAC. METHODS: Patients undergoing partial or total pancreatectomy for PDAC at two European university hospitals between 2007 and 2018 were retrospectively reviewed. Multivariate Cox regression model and survival analyses were performed to verify adequate staging. RESULTS: Overall 341 (73 per cent) patients showed lymph node metastasis (N1/N2), whereas 125 (27 per cent) patients had no lymph node involvement (N0). With increasing number of ELN, the proportion of positive lymph nodes increased. The minimum number of ELN needed to detect lymph node involvement was 21. In multivariate analysis, examination of <21 lymph nodes was a significant negative predictor for survival. Examination of ≥21 ELN reversed this effect and ruled out possible misclassification. CONCLUSION: The number of ELN affects survival in PDAC. Possible misclassification was identified when <21 lymph nodes were examined. Therefore, at least 21 lymph nodes must be examined to avoid false lymph node classification in all types of resection.

Arterial Resection for Pancreatic Cancer: Feasibility and Current Standing in a High-Volume Center.

Background: Arterial resection (AR) during pancreatectomy for curative R0 resection of pancreatic ductal adenocarcinoma (PDAC) remains a controversial procedure with high morbidity. Objective: To investigate the feasibility and oncological outcomes of pancreatectomy combined with AR at a high-volume center for pancreatic surgery. Methods: We retrospectively analyzed our experience in PDAC patients, who underwent pancreatic resection with AR and/or venous resection (VR) between 2007 and 2021. Results: In total 259 PDAC patients with borderline resectable (n = 138) or locally advanced (n = 121) PDAC underwent vascular resection during tumor resection. From these, 23 patients had AR (n = 4 due to intraoperative injury, n = 19 due to suspected arterial infiltration). However, 12 out of 23 patients (52.2%) underwent simultaneous VR including 1 case with intraoperative arterial injury. In comparison, 11 patients (47.8%) underwent AR only including 3 intraoperative arterial injury patients. Although the operation time and bleeding rate of patients with AR were respectively longer and higher than in VR, no significant difference was detected in postoperative complications between VR and AR (P = 0.11). The final histopathological findings of PDAC patients were similar, including M stage, regional lymph node metastases, and R0 margin resection. The mortality of the entire cohort was 6.2% (16/259), with a tendency to increase mortality in the AR cohort, yet without statistical significance (VR: 5% vs AR: 21.1%; P = 0.05). Although 19 (82.6%) patients had PDAC in the final histopathology, only 6 were confirmed to have infiltrated arteria. The microscopic distribution of PDAC in these infiltrated arterial walls on hematoxylin-eosin staining was classified into 3 patterns. Strikingly, the perivascular nerves frequently exhibited perineural invasion. Conclusions: AR can be performed in high-volume centers for pancreatic surgery with an acceptable morbidity, which is comparable to that of VR. However, the likelihood of arterial infiltration seems to be rather overestimated, and as such, AR might be avoidable or replaced by less invasive techniques such as divestment during PDAC surgery.

[Treatment of acute pancreatitis from the viewpoint of surgery]. / Die Behandlung der akuten Pankreatitis aus Sicht der Chirurgie.

The role of surgery in the treatment of acute pancreatitis has clearly changed over the years. In the 1990s a clear reduction in hospital mortality was achieved through surgery, whereas the value of surgery (open, in general) has slipped into the background due to the improvement in intensive care medicine in general and the development of minimally invasive treatment options. Nowadays, patients with acute pancreatitis are only operated on after exhaustion of intensive medical care treatment and minimally invasive interventions or when complications occur that cannot be treated in any other way (e.g. hollow organ perforation). This article provides an overview of the currently used treatment measures.

Drain use in pancreatic surgery: Results from an international survey among experts in the field.

BACKGROUND: Drain use in pancreatic surgery remains controversial. This survey sought to evaluate habits, experiences, and opinions of experts in the field on the use of drains to provide interesting insights for pancreatic surgeons worldwide. METHODS: An online survey designed via Google Forms was sent in December 2020 to experienced surgeons of the International Study Group for Pancreatic Surgery. RESULTS: Forty-two surgeons (42/63, 67%) completed the survey. During their career, 74% (31/42) performed personally >500 pancreatic resections; of these, 9 (21%) >1,500. Sixty-nine percent of the respondents (29/42) declared to always use drains during pancreatic resections and 17% (7/42) in >50% of the operations. For these participants, the use of drains does not increase but reduces the risk of pancreatic fistula and other complications, and more importantly, helps to detect them earlier and manage them better. By contrast, 2 surgeons (5%) declared to never apply drains, whereas other 4 (10%) use drains only in selective cases, deeming that drains increase the risk of infection and other complications. When applied, drains are managed very heterogeneously as for the type of drains, enzyme testing, and removal schedules. Four participants declared to practice continuous irrigation. Twenty-two surgeons (55%) remove drains routinely within the third postoperative day, other 11 (27.5%) only in selected cases, whereas 7 (17.5%) normally keep drains longer. CONCLUSION: Despite plenty of publications on this topic, drain management in pancreatic surgery remains very heterogeneous. Safety and the surgeon´s personal experience seem to play a determining role.

Bacterial content of the human pancreatic duct: An observational study.

Background: Pancreatic fistula/PF is a challenging surgical complication. We could recently show that intestinal bacteria such as Enterobacterales colonize the PF fluid even after a "sterile" operation like distal pancreatectomy/DP. Therefore, we explored the bacterial flora of the human pancreatic duct in a patient collective undergoing pancreatic surgery. Methods: In this observational study, upon transection of the pancreas during surgery, a swab was inserted into the main duct, and the micro-organismal content was correlated with clinical characteristics. Results: Between February 2017 and February 2020, an intraoperative swab from the pancreatic duct was obtained from a total of 54 patients who underwent pancreatico-duodenectomy/PD or DP. The swabs were sterile in 39 cases (72.2%), detected intestinal bacteria in 10 cases (18.5%), and other bacteria in 5 cases (9.3%). There was no correlation of the micro-organismal content of the pancreatic duct swab with bacteria detected in the PF fluid or bile. Preoperative ERCP was associated with a higher frequency of bacterial colonization of the pancreatic duct (33.3% vs. 6.7%, p = 0.005). There was no correlation of the pancreatic duct swabs with postoperative complications. Discussion: The human main pancreatic duct is usually sterile, and its bacterial colonization does not correlate with the occurrence of PF. Therefore, the mechanisms leading to infection of PF warrant in-depth, mechanistic investigation.

Diabetes mellitus in intraductal papillary mucinous neoplasms: A systematic review and meta-analysis.

BACKGROUND: Our current knowledge of diabetes mellitus in intraductal papillary mucinous neoplasm is very limited and its prevalence and predictive value for malignant transformation are not clear. This study sought to systematically review the literature to define the prevalence of diabetes mellitus in intraductal papillary mucinous neoplasm and to evaluate the association of diabetes mellitus with the progression to high-grade dysplasia or invasive cancer. METHODS: A PubMed/Medline systematic search was performed to identify studies reporting data on preoperative diabetes mellitus in intraductal papillary mucinous neoplasm. Articles meeting the predefined inclusion criteria were analyzed and a meta-analysis was performed. The study was preregistered (PROSPERO ID: CRD42020153581). RESULTS: From the initially detected 827 studies, 27 studies including resected patients with histologically confirmed intraductal papillary mucinous neoplasm were included. The global prevalence of preoperative diabetes mellitus was 25% (1,112 of 4,412); whereas new-onset/worsening diabetes mellitus was reported in 6% of patients (68 of 1,202). The meta-analysis revealed that patients with pre-existing diabetes mellitus had an increased risk of harboring a main pancreatic duct involvement (risk ratio 1.43, 95% confidence interval: 1.21-1.69, P < .001), high-grade dysplasia (risk ratio 1.27, 95% confidence interval: 1.01-1.59, P = .04), and invasive cancer (risk ratio 1.61, 95% confidence interval: 1.33-1.95, P < .001). CONCLUSION: The prevalence of diabetes mellitus in intraductal papillary mucinous neoplasm is high, and diabetic patients demonstrate an increased risk of a more aggressive disease. Therefore, diabetes mellitus should be increasingly considered in the stratification of patients with intraductal papillary mucinous neoplasm. Further investigations to determine the mechanisms behind the association with progression should be carried out.

INR and not bilirubin levels predict postoperative morbidity in patients with malignant obstructive jaundice.

BACKGROUND: There are no established predictors for deciding between upfront surgery and PBD in pancreatic head malignancy. Once PBD is present, the ideal drainage-time remains elusive. The aim was, to identify predictors in jaundiced patients and ideal PBD-duration. METHODS: Analysis of 304 patients with pancreatic head malignancy (56% with PBD, n = 170) undergoing pancreaticoduodenectomy was performed. Postoperative morbidity and survival were analyzed. RESULTS: Postoperative complications increased after PBD (98.2% vs. 88.8%; p < 0.001). Patients with PBD received more postoperative antibiotics (42.4% vs. 21.6%; p < 0.001) and wound infections were increased (21.4% vs. 9.4%; p = 0.006). INR predicted postoperative morbidity (p = 0.026), whereas serum-bilirubin (p = 0.708), leucocytes (p = 0.158) and MELD-score (p = 0.444) had no impact. Complications were not different between long (>4 weeks) and short (<4 weeks) PBD-duration (p = 0.608). No life-threatening complications (CDIV + V) occurred after long drainage (0.0% vs. 8.9%; p = 0.028) and long-term survival was not compromised. CONCLUSIONS: INR is a suitable predictor for postoperative outcome, while serum-bilirubin levels had no predictive value. The INR can help deciding between PBD and upfront surgery. If PBD is inevitable, drainage duration of >4 weeks reduced major complications. CATEGORY: Clinical study.