Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis, with a median survival time of 10-12 months. Clinically, these poor outcomes are attributed to several factors, including late stage at the time of diagnosis impeding resectability, as well as multi-drug resistance. Despite the high prevalence of drug-resistant phenotypes, nearly all patients are offered chemotherapy leading to modest improvements in postoperative survival. However, chemotherapy is all too often associated with toxicity, and many patients elect for palliative care. In cases of inoperable disease, cytotoxic therapies are less efficacious but still carry the same risk of serious adverse effects, and clinical outcomes remain particularly poor. Here we discuss the current state of pancreatic cancer therapy, both surgical and medical, and emerging factors limiting the efficacy of both. Combined, this review highlights an unmet clinical need to improve our understanding of the mechanisms underlying the poor therapeutic responses seen in patients with PDAC, in hopes of increasing drug efficacy, extending patient survival, and improving quality of life.

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The Current Treatment Paradigm for Pancreatic Ductal Adenocarcinoma and Barriers to Therapeutic Efficacy.

Non-metastatic pancreatic adenocarcinoma (PDAC) is associated with a high rate of recurrence and lethality. In addition, less than half of all patients are able to complete systemic therapy after curative-intent pancreatectomy. With its well-known potential benefits, this report highlights the current prospective data relevant to the use of neoadjuvant systemic therapy in resectable PDAC. Recently, there have been numerous reports, many of which consist of long-awaited multi-intuitional trial data evaluating the use of neoadjuvant systemic chemotherapy in non-metastatic PDAC as well as the use of combination chemotherapy regimens in the adjuvant setting. Currently, recommended guidelines for neoadjuvant systemic therapy only exist for borderline-resectable and locally-advanced disease. Given the plethora of new data, there has been a shift in the paradigm of how resectable pancreatic cancer is treated at certain centers across the world. This review highlights the relevant available data from recent sentinel prospective trials and how they relate to the systemic treatment of resectable PDAC in the neoadjuvant setting.

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Neoadjuvant Therapy for Resectable Pancreatic Cancer: An Evolving Paradigm Shift.

Intraoperative bile analysis during pancreatoduodenectomy (PD) is performed routinely at specialized centers worldwide. However, it remains controversial if and how intraoperative bacterobilia during PD affects morbidity and its management. The aim of the study was a systematic review and meta-analysis of intraoperative bacterobilia and its impact on patient outcome after PD. Five relevant outcomes of interest were defined, and a systematic review of the literature with meta-analysis was performed according to the PRISMA guidelines. A total of 28 studies (8523 patients) were included. The median incidence of bacterobilia was 58% (interquartile range 51–67%). The most frequently isolated bacteria were Enterococcus species (51%), Klebsiella species (28%), and Escherichia coli (27%). Preoperative biliary drainage was significantly associated with bacterobilia (86 vs. 25%; RR 3.27; 95% confidence interval (CI) 2.42–4.42; p < 0.001). The incidence of surgical site infections (SSI) was significantly increased in cases with bacterobilia (RR 2.84; 95% CI 2.17–3.73; p < 0.001). Postoperative pancreatic fistula, overall postoperative morbidity, and mortality were not significantly influenced. Identical bacteria in bile and the infectious sources were found in 48% (interquartile range 34–59%) of the cases. Bacterobilia is detected during almost every second PD and is associated with an increased rate of SSI. The microbiome from intraoperative bile and postoperative infectious sources match in ~50% of patients, providing the option of early administration of calculated antibiotics and the determination of resistance patterns.

Prognostic Impact of Bacterobilia on Morbidity and Postoperative Management After Pancreatoduodenectomy: A Systematic Review and Meta-analysis.

Preoperative biliary drainage of severely obstructive jaundiced patients decreases overall postoperative complications after pancreaticoduodenectomy: A retrospective and propensity score-matched analysis.

BACKGROUND Jaundice or preoperative cholestasis (PC) are typical symptoms of pancreatic masses. Approximately 50% of patients undergo preoperative biliary drainage (PBD) placement. PBD is a common cause of bacterobilia (BB) and is a known surgical site infection risk factor. An adjustment of preoperative antibiotic prophylaxis (PAP) may be reasonable according to the profile of BB. For this, we examined the microbiological findings in routine series of patients. AIM To investigate the incidence and profile of biliary bacterial colonization in patients undergoing pancreatic head resections. METHODS In the period from January 2009 to December 2015, 285 consecutive pancreatic head resections were performed. Indications for surgery were malignancy (71%), chronic pancreatitis (18%), and others (11%). A PBD was in 51% and PC was in 42%. The standard PAP was ampicillin/sulbactam. Intraoperatively, a smear was taken from the hepatic duct. An analysis of the isolated species and resistograms was performed. Patients were categorized according to the presence or absence of PC (PC+/PC-) and PBD (PBD+/PBD-) into four groups. Antibiotic efficiency was analyzed for standard PAP and possible alternatives. RESULTS BB was present in 150 patients (53%). BB was significantly more frequent in PBD+ (n =120) than in PBD- (n = 30), P < 0.01. BB was present both in patients with PC and without PC: (PBD-/PC-: 18%, PBD-/PC+: 30%, PBD+/PC-: 88%, PBD+/PC+: 80%). BB was more frequent in malignancy (56%) than in chronic pancreatitis (45%). PBD, however, was the only independent risk factor in multivariate analysis. In total, 357 pathogens (342 bacteria and 15 fungi) were detected. The five most common groups (n = 256, 74.8%) were Enterococcus spp. (28.4%), Streptococcus spp. (16.9%), Klebsiella spp. (12.6%), Escherichia coli (10.5%), and Enterobacter spp. (6.4%). A polymicrobial BB (PBD+: 77% vs PBD-: 40%, P < 0.01) and a more frequent detection of Enterococcus (P < 0.05) was significantly associated with PBD+. In PBD+, the efficiency of imipenem and piperacillin/tazobactam was significantly higher than that of the standard PAP (P < 0.01). CONCLUSION PBD-/PC- and PBD-/PC+ were associated with a low rate of BB, while PBD+ was always associated with a high rate of BB. In PBD+ patients, BB was polymicrobial and more often associated with Enterococcus. In PBD+, the spectrum of potential bacteria may not be covered by standard PAP. A more potent alternative for prophylactic application, however, was not found.

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F Scheufele

Papers

Präoperative Galleableitung bei malignem Verschlussikterus sinnvoll