Pancreatic ductal adenocarcinoma (PDAC) has still a dismal prognosis, mainly because only 15-20% of all patients present with resectable tumor stages at the time of diagnosis. Due to locally extended ...tumor growth or distant metastases upfront resection is not reasonable in the majority of patients. Considerably, PDAC will be the 2nd most frequent cause of cancer-related deaths within the next 10 years for both men and women. While there is currently no convincing evidence for the use of neoadjuvant therapy in resectable PDAC, there are controversial results from studies investigating neoadjuvant treatment concepts in borderline resectable PDAC (BR-PDAC). However, the definition of BR-PDAC is a topic of debate. While BR-PDAC has originally been defined on merely anatomical criteria, the International Association of Pancreatology (IAP) has recently suggested a broader definition based on a combination of anatomical (A) findings, biological (B) criteria (which reflect tumor aggressiveness), and conditional (C) aspects (which respect host-related condition). In case of BR-PDAC with venous invasion alone, upfront resection is generally recommended whenever technically possible in patients fit for surgery and without evidence for lymph node metastases. In contrast, in case of arterial invasion neoadjuvant therapy is regarded as the treatment of choice. The same accounts for high CA 19-9 levels, suspected or proven lymph node involvement and poor performance status. In locally advanced PDAC (LA-PDAC), neoadjuvant treatment represents the standard of care resulting in proportionally high rates of secondary resection. This "conversion" surgery offers the chance for improved survival times in an otherwise palliative situation. Herein, we summarize the current evidence of different treatment strategies for pancreatic cancer with a focus on conversion surgery and the impact of neoadjuvant treatment in this setting.
To evaluate the impact of clinical and pathological parameters, including resection margin (R) status, on survival in patients undergoing pancreatic surgery after neoadjuvant treatment for initially ...unresectable pancreatic ductal adenocarcinoma (PDAC).
Prognostic factors are well documented for patients with resectable PDAC, but have not been described in detail for patients with initially unresectable PDAC undergoing resection after neoadjuvant therapy.
Prospectively collected data of consecutive patients with initially unresectable pancreatic cancer treated by neoadjuvant treatment and resection were analyzed. The R status was categorized as R0 (tumor-free margin >1 mm), R1 ≤1 mm (tumor-free margin ≤1 mm), and R1 direct (microscopic tumor infiltration at margin). Clinicopathological characteristics and outcomes were compared among these groups and tested for survival prediction.
Between January, 2006 and February, 2017, 280 patients with borderline resectable (n = 18), locally advanced (n = 190), or oligometastatic (n = 72) disease underwent tumor resection after neoadjuvant treatment. Median overall survival from the time of surgery was 25.1 months for R0 (n = 82), 15.3 months for R1 ≤1 mm (n = 99), and 16.1 months for R1 direct (n = 99), with 3-year overall survival rates of 35.0%, 20.7%, and 18.5%, respectively (P = 0.0076). The median duration of the neoadjuvant treatment period was 5.1 months. In multivariable analysis, preoperative CA 19-9 levels, lymph node status, metastasis category, and vascular involvement were all significant prognostic factors for overall survival. The R status was not an independent prognostic factor.
In patients undergoing resection after neoadjuvant therapy for initially unresectable PDAC, preoperative CA 19-9 levels, lymph node involvement, metastasis category, and vascular involvement, but not the R status, were independent prognostic factors of overall survival.
Background
The optimal surgical strategy for pancreatic neuroendocrine tumors (PNETs) is unknown. However, current guidelines recommend a watch-and-wait strategy for small nonfunctional PNETs ...(NF-PNETs). The aim of this study is to investigate the risk stratification and prognostic significance of lymph node metastasis (LNM) of PNETs to guide decision-making for lymphadenectomy.
Patients and Methods
The MEDLINE and Web of Science databases were systematically searched for studies reporting either risk factors of LNM in resected PNETs or survival of patients with LNM. The weighted average incidence of LNM was calculated according to tumor characteristics. Random-effects metaanalyses were performed, and pooled hazard ratios (HR) and their 95% confidence intervals (CI) were calculated to determine the impact of LNM on overall survival (OS). In subgroup analyses, NF-PNETs were assessed.
Results
From a total of 5883 articles, 98 retrospective studies with 13,374 patients undergoing resection for PNET were included. In all PNETs, the weighted median rates of LNM were 11.5% for small (≤ 2 cm) PNETs and 15.8% for G1 PNETs. In NF-PNETs, the rates were 11.2% for small PNETs and 10.3% for G1 PNETs. LNM of all PNETs (HR 3.87, 95% CI 3.00–4.99,
P
< 0.001) and NF-PNETs (HR 4.98, 95% CI 2.81–8.83,
P
< 0.001) was associated with worse OS.
Conclusions
LNM is potentially prevalent even in small and well-differentiated PNETs and is associated with worse prognosis. A watch-and-wait strategy for small NF-PNETs should be reappraised, and oncologic resection with lymphadenectomy can be considered. Prospective and controlled studies are needed in the future.
Background
The randomized controlled PROPP trial (DKRS00004191) showed that pylorus-resecting pancreatoduodenectomy (PR) is not superior to the pylorus-preserving procedure (PP) in terms of ...perioperative outcome, specifically in reduction of delayed gastric emptying. Non-superiority of PR was also confirmed in a recent meta-analysis of randomized controlled trials. However, long-term data on morbidity and quality of life after PP compared to PR are sparse. The aim of this study was to investigate long-term outcomes of patients included in the PROPP trial.
Methods
Between February 2013 and June 2016, a total of 188 patients underwent PD and were intraoperatively randomized to either preservation or resection of the pylorus (95 vs. 93 patients). For long-term follow-up, morbidity and quality of life (EORTC QLQ-C30/PAN26) were monitored until January 1, 2018. Statistical analysis was performed on an intention-to-treat basis.
Results
The mean duration of follow-up was 34.3 (± 11.3) months. Sixty-three of the 188 patients had died (PP
n
= 33, PR
n
= 30), 29 patients were lost to follow-up (PP
n
= 17, PR
n
= 12), and the remaining 96 patients were included in long-term follow-up (PP
n
= 45, PR
n
= 51). There was no difference between PP and PR patients regarding endocrine and exocrine pancreatic function, receipt of adjuvant/palliative chemotherapy, cancer recurrence, and other relevant characteristics. Late cholangitis occurred significantly more often in patients following pylorus resection (
P
= 0.042). Reoperations, readmissions to hospital, and quality of life scores except pain were comparable between the two study groups.
Conclusions
Similar to short-term results, long-term follow-up showed no significant differences between pylorus resection compared to pylorus preservation.
Preoperative/Neoadjuvant treatment (NT) is increasingly used in unresectable pancreatic cancer (PDAC). However, ∼40% of patients cannot be resected after NT and reliable preoperative response ...evaluation is currently lacking. We investigated CA 19-9 levels and their dynamics during NT for prediction of resectability and survival.
We screened our institution's database for patients who underwent exploration or resection after NT with gemcitabine-based therapy (GEM) or FOLFIRINOX (FOL). Pre- and post-NT CA 19-9, resection rate and survival were analyzed.
Of 318 patients 165 (51.9%) were resected and 153 (48.1%) received exploration. In the FOL group (n = 103; 32.4%), a post-NT CA 19-9 cutoff at 91.8 U/ml had a sensitivity of 75.0% and a specificity of 76.9% for completing resection with an AUC of 0.783 in the ROC analysis (95% CI: 0.692–0.874; p < 0.001. PPV: 84.2%, NPV: 65.2%). Resected patients above the cutoff did not benefit from resection. Post-NT CA 19-9 <91.8 U/ml (OR 11.63, p < 0.001) and CA 19-9 ratio of <0.4 (OR 5.77, p = 0.001) were independent predictors for resectability in FOL patients.
CA 19-9 levels after neoadjuvant treatment with FOLFIRINOX predict resectability and survival of PDAC more accurately than dynamic values and should be incorporated into response evaluation and surgical decision-making.
Effective chemotherapy protocols are currently changing the treatment options for metastasized pancreatic cancer. Survival benefits after synchronous metastasectomy have been reported for selected ...patients. We set out to assess predictive factors of resectability for synchronous metastases after FOLFIRINOX.
Consecutive patients with metastatic pancreatic cancer undergoing surgery after FOLFIRINOX between 2011 and 2017 were identified from a prospectively collected database. Surgery following chemotherapy was indicated in patients with no more than six metastatic lesions, no progression detected on CT, and technically resectable disease. Patients who received synchronous metastasectomy were compared with patients who received explorative laparotomy or palliative surgery in terms of predictors of resectability and overall survival. In patients undergoing resection, prognostic factors were examined.
Of 101 patients scheduled for surgery after FOLFIRINOX, synchronous metastasectomy was performed in 43 cases (43%) and non-resection surgery in 58 cases (57%). The shrinkage rate of the primary tumor on CT (P = 0.04) and the postchemotherapy serum CA19-9 concentration (P = 0.02) were associated with resectability. The median overall survival of the patients undergoing metastasectomy was longer than that of the patients without resection (21.9 months vs 16.4 months, P = 0.006). Postchemotherapy serum CA19-9 value (P = 0.04) and lymph node ratio (P = 0.01) were prognostic factors in the patients undergoing metastasectomy.
In selected patients who satisfied our surgical criteria, shrinkage rate of primary tumor and postchemotherapy serum CA19-9 level, which predict resectability of metastasized pancreatic cancer, should be considered in decision making to avoid unnecessary surgery.
Purpose
Tracheostomy is one of the most frequently performed procedures in intensive care medicine. The two main approaches are open surgical tracheostomy (ST) and percutaneous dilatational ...tracheostomy (PDT). This systematic review summarizes and analyzes the existing evidence regarding perioperative and postoperative parameters of safety.
Methods
A systematic literature search was conducted in the Cochrane Library, EMBASE, LILACS, and MEDLINE to identify all randomized controlled trials (RCTs) comparing complications of ST and PDT and to define the strategy with the lower risk of potentially life-threatening events. Risk of bias was assessed using the criteria outlined in the Cochrane Handbook.
Results
Twenty-four citations comprising 1795 procedures (PDT:
n
= 926; ST:
n
= 869) were found suitable for systematic review. No significant difference in the risk of a potentially life-threatening event (risk difference (RD) 0.01, 95% CI − 0.03 to 0.05,
P
= 0.62,
I
2
= 47%) was found between PDT and ST. There was no difference in mortality (RD − 0.00, 95% CI − 0.01 to 0.01,
P
= 0.88,
I
2
= 0%). An increased rate of technical difficulties was shown for PDT (RD 0.04, 95% CI 0.01, 0.08,
P
= 0.01,
I
2
= 60%). Stomal infection occurred more often with ST (RD − 0.05, 95% CI − 0.08 to − 0.02,
P
= 0.003,
I
2
= 60%). Both techniques can be safely performed on the ICU. Meta-analysis of the duration of procedure was not possible owing to high heterogeneity (
I
2
= 99%).
Conclusion
ST and PDT are safe techniques with low incidence of complications. Both techniques can be performed successfully in an ICU setting. ST can be performed on every patient whereas PDT is restricted by several contraindications like abnormal anatomy, previous surgery, coagulopathies, or difficult airway of the patient.
Systematic review registration
PROSPERO CRD42015021967
Background Postoperative pancreatic fistula represents the most important complication after distal pancreatectomy. The aim of this study was to evaluate the use of a preoperative endoscopic ...injection of botulinum toxin into the sphincter of Oddi to prevent postoperative pancreatic fistula (German Clinical Trials Register number: DRKS00007885). Methods This was an investigator-initiated, prospective clinical phase I/II trial with an exploratory study design. We included patients who underwent preoperative endoscopic sphincter botulinum toxin injection (100 units of Botox). End points were the feasibility, safety, and postoperative outcomes, including postoperative pancreatic fistula within 30 days after distal pancreatectomy. Botulinum toxin patients were compared with a control collective of patients undergoing distal pancreatectomy without botulinum toxin injection by case-control matching in a 1:1 ratio. Results Between February 2015 and February 2016, 29 patients were included. All patients underwent successful sphincter of Oddi botulinum toxin injection within a median of 6 (range 0–10) days before operation. One patient had an asymptomatic, self-limiting (48 hours) increase in serum amylase and lipase after injection. Distal pancreatectomy was performed in 24/29 patients; 5 patients were not resectable. Of the patients receiving botulinum toxin, 7 (29%) had increased amylase levels in drainage fluid on postoperative day 3 (the International Study Group of Pancreatic Surgery definition of postoperative pancreatic fistula grade A) without symptoms or need for reintervention. Importantly, no clinically relevant fistulas (International Study Group of Pancreatic Surgery grades B/C) were observed in botulinum toxin patients compared to 33% postoperative pancreatic fistula grade B/C in case-control patients ( P < .004). Conclusion Preoperative sphincter of Oddi botulinum toxin injection is a novel and safe approach to decrease the incidence of clinically relevant postoperative pancreatic fistula after distal pancreatectomy. The results of the present trial suggest its efficacy in the prevention of clinically relevant postoperative pancreatic fistula and are validated currently in the German Federal Government–sponsored, multicenter, randomized controlled PREBOT trial.
Introduction
Bile leakage represents a major cause of morbidity following hepatic resection. Although most patients can be managed non-operatively, this complication requires diagnostics and ...therapeutic interventions. Preoperative endoscopic injection of botulinum toxin (BTX) into the sphincter of Oddi represents an innovative approach to prevent bile leakage. The aim of the PREBOT-II trial is to generate the first randomised controlled trial data on the safety, feasibility and efficacy of preoperative endoscopic BTX injection into the sphincter of Oddi to prevent bile leakage following hepatic resection.
Methods and analysis
The PREBOT-II trial is an investigator-initiated, exploratory, multicentre, randomised, controlled, open-label, phase II clinical trial with two parallel study groups. 70 patients scheduled for hepatic resection will be randomised to either the intervention or the control group. Patients of the intervention group will undergo preoperative endoscopic injection of BTX into the sphincter of Oddi 3–10 days before surgery, whereas in the control group only hepatic resection will be performed. The primary endpoint is the occurrence of a postoperative bile leakage within 30 days after hepatic resection according to the definition of the International Study Group of Liver Surgery. The secondary endpoints comprise further postoperative morbidity parameters such as severity of postoperative bile leakage, post-hepatectomy haemorrhage or liver failure, mortality and quality of life up to 3 months after hepatic resection. Safety and feasibility of the procedure will also be recorded.
Ethics, funding and dissemination
The PREBOT-II trial has been approved by the German Federal Institute for Drugs and Medical Devices (reference number 4044932) and the Ethics Committee of Heidelberg University (reference number AFmu-558/2021). This trial is supported by the German Federal Ministry of Education and Research. The results will be presented at national and international conferences and published in a peer-reviewed journal.
Trial registration number
DRKS00024061, EudraCT: 2020-006001-35.
Background Since the introduction of the duodenum-preserving pancreatic head resection for operative treatment of chronic pancreatitis, various modifications of the original Beger procedure have ...emerged. A randomized controlled trial comparing the Beger procedure and the Berne modification indicated that the latter is an equivalent alternative, but a comparison of the long-term results of both procedures has not yet been published. Methods Between December 2002 and January 2005, 65 patients were randomized intraoperatively to the Beger or the Berne procedure. For this 10-year follow-up, patients were contacted by phone and in writing to evaluate patient-relevant outcome parameters. Statistical analysis was made on an intention-to-treat basis. Results Median follow-up was 129 (111–137) months. Forty of 65 patients were available for follow-up; 11 of the original study cohort had died, and 14 were otherwise lost to follow-up. Quality of life, pain, occupational disability, exocrine and endocrine pancreatic function, endoscopic interventions, and redo operations were comparable in both groups. More than half of the patients were completely free of pain, and the majority in both groups judged that the index operation had improved their quality of life. Conclusion Ten-year follow-up showed no differences in patient-relevant outcome parameters between the Beger and Berne procedures for treatment of chronic pancreatitis. Because short-term results have shown the Berne modification is superior in terms of operation time and duration of hospital stay, it should be preferred whenever possible, depending on the individual surgeon's expertise and the intraoperative findings.
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