Pancreatic duct occlusion with polychloroprene-based glue for the management of postoperative pancreatic fistula after pancreatoduodenectomy-an outdated approach?

Background: Managing postoperative pancreatic fistula (POPF) presents a formidable challenge after pancreatoduodenectomy. Some centers consider pancreatic duct occlusion (PDO) in reoperations following pancreatoduodenectomy as a pancreas-preserving procedure, aiming to control a severe POPF. The aim of the current study was to evaluate the short- and long-term outcomes of employing PDO for the management of the pancreatic stump during relaparotomy for POPF subsequent to pancreatoduodenectomy. Methods: Retrospective review of consecutive patients at Oslo University Hospital undergoing pancreatoduodenectomy and PDO during relaparotomy. Pancreatic stump management during relaparotomy consisted of occlusion of the main pancreatic duct with polychloroprene Faxan-Latex, after resecting the dehiscent jejunal loop previously constituting the pancreaticojejunostomy. Results: Between July 2005 and September 2015, 826 pancreatoduodenectomies were performed. Overall reoperation rate was 13.2% (n = 109). POPF grade B/C developed in 113 (13.7%) patients. PDO during relaparotomy was performed in 17 (2.1%) patients, whereas completion pancreatectomy was performed in 22 (2.7%) patients. Thirteen (76%) of the 17 patients had a persistent POPF after PDO, and the time from PDO until removal of the last abdominal drain was median 35 days. Of the PDO patients, 13 (76%) patients required further drainage procedures (n = 12) or an additional reoperation (n = 1). In-hospital mortality occurred in one patient (5.9%). Five (29%) patients developed new-onset diabetes mellitus, and 16 (94%) patients acquired exocrine pancreatic insufficiency. Conclusions: PDO is a safe and feasible approach for managing severe POPF during reoperation following pancreatoduodenectomy. A significant proportion of patients experience persistent POPF post-procedure, necessitating supplementary drainage interventions. The findings suggest that it is advisable to explore alternative pancreas-preserving methods before opting for PDO in the management of POPF subsequent to pancreatoduodenectomy.

Neoadjuvant FOLFIRINOX versus upfront surgery for resectable pancreatic head cancer (NORPACT-1): a multicentre, randomised, phase 2 trial.

BACKGROUND: In patients undergoing resection for pancreatic cancer, adjuvant modified fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) improves overall survival compared with alternative chemotherapy regimens. We aimed to compare the efficacy and safety of neoadjuvant FOLFIRINOX with the standard strategy of upfront surgery in patients with resectable pancreatic ductal adenocarcinoma. METHODS: NORPACT-1 was a multicentre, randomised, phase 2 trial done in 12 hospitals in Denmark, Finland, Norway, and Sweden. Eligible patients were aged 18 years or older, with a WHO performance status of 0 or 1, and had a resectable tumour of the pancreatic head radiologically strongly suspected to be pancreatic adenocarcinoma. Participants were randomly assigned (3:2 before October, 2018, and 1:1 after) to the neoadjuvant FOLFIRINOX group or upfront surgery group. Patients in the neoadjuvant FOLFIRINOX group received four neoadjuvant cycles of FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, leucovorin 400 mg/m2, and fluorouracil 400 mg/m2 bolus then 2400 mg/m2 over 46 h on day 1 of each 14-day cycle), followed by surgery and adjuvant chemotherapy. Patients in the upfront surgery group underwent surgery and then received adjuvant chemotherapy. Initially, adjuvant chemotherapy was gemcitabine plus capecitabine (gemcitabine 1000 mg/m2 over 30 min on days 1, 8, and 15 of each 28-day cycle and capecitabine 830 mg/m2 twice daily for 3 weeks with 1 week of rest in each 28-day cycle; four cycles in the neoadjuvant FOLFIRINOX group, six cycles in the upfront surgery group). A protocol amendment was subsequently made to permit use of adjuvant modified FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 150 mg/m2, leucovorin 400 mg/m2, and fluorouracil 2400 mg/m2 over 46 h on day 1 of each 14-day cycle; eight cycles in the neoadjuvant FOLFIRINOX group, 12 cycles in the upfront surgery group). Randomisation was performed with a computerised algorithm that stratified for each participating centre and used a concealed block size of two to six. Patients, investigators, and study team members were not masked to treatment allocation. The primary endpoint was overall survival at 18 months. Analyses were done in the intention-to-treat (ITT) and per-protocol populations. Safety was assessed in all patients who were randomly assigned and received at least one cycle of neoadjuvant or adjuvant therapy. This trial is registered with ClinicalTrials.gov, NCT02919787, and EudraCT, 2015-001635-21, and is ongoing. FINDINGS: Between Feb 8, 2017, and April 21, 2021, 77 patients were randomly assigned to receive neoadjuvant FOLFIRINOX and 63 to undergo upfront surgery. All patients were included in the ITT analysis. For the per-protocol analysis, 17 (22%) patients were excluded from the neoadjuvant FOLFIRINOX group (ten did not receive neoadjuvant therapy, four did not have pancreatic ductal adenocarcinoma, and three received another neoadjuvant regimen), and eight (13%) were excluded from the upfront surgery group (seven did not have pancreatic ductal adenocarcinoma and one did not undergo surgical exploration). 61 (79%) of 77 patients in the neoadjuvant FOLFIRINOX group received neoadjuvant therapy. The proportion of patients alive at 18 months by ITT was 60% (95% CI 49-71) in the neoadjuvant FOLFIRINOX group versus 73% (62-84) in the upfront surgery group (p=0·032), and median overall survival by ITT was 25·1 months (95% CI 17·2-34·9) versus 38·5 months (27·6-not reached; hazard ratio [HR] 1·52 [95% CI 1·00-2·33], log-rank p=0·050). The proportion of patients alive at 18 months in per-protocol analysis was 57% (95% CI 46-67) in the neoadjuvant FOLFIRINOX group versus 70% (55-83) in the upfront surgery group (p=0·14), and median overall survival in per-protocol population was 23·0 months (95% CI 16·2-34·9) versus 34·4 months (19·4-not reached; HR 1·46 [95% CI 0·99-2·17], log-rank p=0·058). In the safety population, 42 (58%) of 73 patients in the neoadjuvant FOLFIRINOX group and 19 (40%) of 47 patients in the upfront surgery group had at least one grade 3 or worse adverse event. 63 (82%) of 77 patients in the neoadjuvant group and 56 (89%) of 63 patients in the upfront surgery group had resection (p=0·24). One sudden death of unknown cause and one COVID-19-related death occurred after the first cycle of neoadjuvant FOLFIRINOX. Adjuvant chemotherapy was initiated in 51 (86%) of 59 patients with resected pancreatic ductal adenocarcinoma in the neoadjuvant FOLFIRINOX group and 44 (90%) of 49 patients with resected pancreatic ductal adenocarcinoma in the upfront surgery group (p=0·56). Adjuvant modified FOLFIRINOX was given to 13 (25%) patients in the neoadjuvant FOLFIRINOX group and 19 (43%) patients in the upfront surgery group. During adjuvant chemotherapy, neutropenia (11 [22%] patients in the neoadjuvant FOLFIRINOX group and five [11%] in the upfront surgery group) was the most common grade 3 or worse adverse event. INTERPRETATION: This phase 2 trial did not show a survival benefit from neoadjuvant FOLFIRINOX in resectable pancreatic ductal adenocarcinoma compared with upfront surgery. Implementation of neoadjuvant FOLFIRINOX was challenging. Future trials on treatment sequencing in resectable pancreatic ductal adenocarcinoma should be biomarker driven. FUNDING: Norwegian Cancer Society, South Eastern Norwegian Health Authority, The Sjöberg Foundation, and Helsinki University Hospital Research Grants.

Performance and safety of diagnostic EUS FNA/FNB and therapeutic ERCP in patients with borderline resectable and locally advanced pancreatic cancer - results from a population-based, prospective cohort study.

Objective: Endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS FNA/FNB) and potential endoscopic retrograde cholangiopancreatography (ERCP) for biliary decompression are indicated in patients with pancreatic cancer before initation of primary chemotherapy. This study aims to investigate the performance and safety of these two procedures in patients with borderline resectable (BRPC) or locally advanced pancreatic cancer (LAPC). Methods: Endoscopy and pathology reports, and hospital records of consecutive patients with a radiological diagnosis of BRPC/LAPC included in a population based, protocol-driven study (NORPACT-2) were reviewed. Results: Of 251 patients, 223 (88.9%) underwent EUS-FNA/FNB, and 133 (53%) underwent ERCP. Repeated EUS attempts were performed in 33 (14.8%), eight (3.6%), and four (1.8%) patients. FNA was performed in 155 procedures, FNB in 30, and combined EUS-FNA/FNB in 83. Diagnostic accuracy was 86.1% for first EUS-FNA/FNB. The cumulative diagnostic accuracy for all attempts was 96%. False positive rate for malignancy was 0.9%. Of a total of 149 ERCP procedures, 122 (81.9%) were successful, and 27 (18.1%) were unsuccessful. Success rate of first ERCP attempt was 80.5% (107/133). Sixteen patients (12%) underwent a second attempt with a success rate of 93.8% (15 of 16). Combined EUS and ERCP was performed in 41 patients. Complications occurred in eight procedures (3%) after EUS-FNA/FNB, 23 procedures (15.3%) after ERCP, and four (9.8%) patients after combined EUS-FNA/FNB and ERCP. Conclusion: EUS-FNA/FNB and ERCP with biliary stenting in patients with BRPC/LAPC demonstrated acceptable performance and safety. Repeat procedures were performed with high success rates. Same session EUS-FNA/FNB and ERCP for biliary decompression is safe.

Pancreatoduodenectomy after Roux-en-Y gastric bypass surgery: Single-center experience and literature review.

BACKGROUND AND OBJECTIVE: Bariatric surgery with Roux-en-Y gastric bypass (RYGB) is widely used to treat morbid obesity and present diagnostic and therapeutic challenges in patients with pancreatic and periampullary tumors. The aim of this study was to describe diagnostic tools and challenges in performing pancreatoduodenectomy (PD) on patients with altered anatomy after RYGB. METHODS: Patients undergoing PD after RYGB from April 2015 to June 2022 at a tertiary referral center were identified. Preoperative workup, operative techniques, and outcomes were reviewed. A literature search was performed to identify articles reporting PD in post-RYGB patients. RESULTS: Of a total of 788 PDs, six patients had previous RYGB. The majority were women (n = 5), and median age was 59 years. The patients most commonly presented with pain (50%) and jaundice (50%) with a median of 5.5 years after RYGB. The gastric remnant was resected in all cases, and reconstruction of the pancreatobiliary drainage was achieved using the distal part of the pre-existing pancreatobiliary limb in all patients. Median follow-up was 60 months. The Clavien-Dindo grade ⩾3 complications occurred in two patients (33.3%), and 90 days mortality occurred in one patient (16.6%). The literature search revealed 9 articles reporting a total of 122 cases, specifically addressing PD after RYGB. CONCLUSIONS: Reconstruction after PD in post-RYGB patients may be challenging. Resection of the gastric remnant and use of the pre-existing biliopancreatic limb may be a safe strategy, but surgeons should be prepared for other reconstruction options for creation of a new pancreatobiliary limb.

Neoadjuvant chemotherapy is associated with an altered metabolic profile and increased cancer stemness in patients with pancreatic ductal adenocarcinoma.

The modest clinical benefits of neoadjuvant chemotherapy (NAT) in pancreatic ductal adenocarcinoma (PDAC) are associated with a lack of robust data on treatment-induced changes in the tumor. To this end, comparative proteomic profiling of tumor tissue samples from treatment-naïve (TN, n = 20) and NAT-treated (n = 22) PDACs was performed. Differentially expressed proteins were identified and correlation with overall survival (OS) was performed. Tumors were also examined for histopathological changes and expression of cancer stem cell (CSC) markers. Serum from 33 matched patients was analyzed for metabolic markers. Cytotoxicity, proliferation, and expression of CSC markers were assessed in chemoresistant Panc-1 and Mia PaCa-2 cells. Of the 2265 proteins identified, 227 and 144 proteins showed significantly altered expression and differential phosphorylation, respectively, in NAT compared with TN samples. The majority of these were metabolism-related proteins, and 14 of these correlated moderately with OS. NAT-treated tumors and chemoresistant cancer cells showed increased expression of CSC markers. Serum ALDH1A1 was higher in NAT compared with TN. Differentially phosphorylated proteins were mainly involved in cytoskeleton organization, cell locomotion, motility, and migration, and 17 of these showed a strong positive correlation with OS. This study provides evidence of the effects of NAT on PDAC metabolism at both the tumor and the systemic levels. NAT-treated tumors showed significantly lower expression of metabolic proteins, and patients who underwent NAT showed reduced serum lactate and high-density lipoprotein-cholesterol. Lastly, cancer cells that survived cytotoxic treatment expressed higher CSC markers, both in vivo and in vitro.

Minimally Invasive Pancreatoduodenectomy: Contemporary Practice, Evidence, and Knowledge Gaps.

Minimally invasive pancreatoduodenectomy has gained popularity throughout the last decade. For laparoscopic pancreatoduodenectomy, some high-level evidence exists, but with conflicting results. There are currently no published randomized controlled trials comparing robotic and open pancreatoduodenectomy. Comparative long-term data for patients with pancreatic ductal adenocarcinoma is lacking to date. Based on the existing evidence, current observed benefits of minimally invasive pancreatoduodenectomy over open pancreatoduodenectomy seem scarce, but retrospective data indicate the safety of these procedures in selected patients. As familiarity with the robotic platform increases, studies have shown an expansion in indications, also including patients with vascular involvement and even indicating favorable results in patients with obesity and high-risk morphometric features. Several ongoing randomized controlled trials aim to investigate potential differences in short- and long-term outcomes between minimally invasive and open pancreatoduodenectomy. Their results are much awaited.

Short-Course or Total Neoadjuvant Chemotherapy in Resectable and Borderline Resectable Pancreatic Cancer - Current Status and Future Perspectives.

Neoadjuvant therapy improves overall survival compared with a surgery-first approach in patients with borderline resectable pancreatic cancer (BRPC). Evidence of higher quality is required to determine whether neoadjuvant therapy has potential benefits and improves survival for patients with resectable pancreatic cancer (RPC). Most randomized controlled trials (RCTs) have explored short-course neoadjuvant chemotherapy (SNT), but total neoadjuvant chemotherapy (TNT) is now the experimental arm of ongoing RCTs. This article reviews the current status of SNT and TNT in RPC and BRPC, and provides perspectives of future challenges and research directions in this field.

Echinococcosis in a non-endemic country - 20-years' surgical experience from a Norwegian tertiary referral Centre.

BACKGROUND: In Scandinavia, the incidence of cystic echinococcosis (CE) and alveolar echinococcosis (AE) is low and almost exclusively an imported disease following the trends of immigration. The aim of the study was to review available data on clinical management and outcome for patients treated at Oslo University Hospital, a referral centre for echinococcosis in Norway, with special emphasis on surgical treatment. METHODS: All patients admitted with echinococcosis between January 2000 and December 2020 were identified. Medical records were reviewed retrospectively concerning patient demographics, treatment strategy, surgical procedures, complications and outcomes. RESULTS: A total of 92 patients with median age 37 years (range 4-85) were identified. Sixty-eight patients (74%) were symptomatic. All patients, except for two, were immigrants to Norway and born in endemic areas. Ninety patients were diagnosed with CE and two with AE. Location of the cysts was most commonly in the liver (86%) followed by peritoneum, lungs, and spleen. All patients with active cysts were treated with albendazole. Surgical treatment was performed in 51 (56%) patients. The most common reason for abstaining from surgical treatment was that the diagnostic work-up revealed inactive cysts or interventional radiology was performed. Of the 51 patients who underwent surgery, a radical procedure was performed in 32 (64%) cases, a conservative procedure in 12 (24%), and a combination in six (12%). Clavien Dindo grade ≥3 complications occurred in 30%, and 90-day mortality was 2%. Bile leakage occurred in seven patients and was treated successfully with endoscopic retrograde cholangiopancreatography with biliary stent placement in all patients. CONCLUSION: In a low-endemic area like Norway, management of echinococcus includes medical therapy, surgery, and/or interventional radiology. Surgical intervention seems to be effective, and is associated with acceptable morbidity rates.

Proteome Analysis of Pancreatic Tumors Implicates Extracellular Matrix in Patient Outcome.

Pancreatic cancer remains a disease with unmet clinical needs and inadequate diagnostic, prognostic, and predictive biomarkers. In-depth characterization of the disease proteome is limited. This study thus aims to define and describe protein networks underlying pancreatic cancer and identify protein centric subtypes with clinical relevance. Mass spectrometry-based proteomics was used to identify and quantify the proteome in tumor tissue, tumor-adjacent tissue, and patient-derived xenografts (PDX)-derived cell lines from patients with pancreatic cancer, and tissues from patients with chronic pancreatitis. We identified, quantified, and characterized 11,634 proteins from 72 pancreatic tissue samples. Network focused analysis of the proteomics data led to identification of a tumor epithelium-specific module and an extracellular matrix (ECM)-associated module that discriminated pancreatic tumor tissue from both tumor adjacent tissue and pancreatitis tissue. On the basis of the ECM module, we defined an ECM-high and an ECM-low subgroup, where the ECM-high subgroup was associated with poor prognosis (median survival months: 15.3 vs. 22.9 months; log-rank test, P = 0.02). The ECM-high tumors were characterized by elevated epithelial-mesenchymal transition and glycolytic activities, and low oxidative phosphorylation, E2F, and DNA repair pathway activities. This study offers novel insights into the protein network underlying pancreatic cancer opening up for proteome precision medicine development. Significance: Pancreatic cancer lacks reliable biomarkers for prognostication and treatment of patients. We analyzed the proteome of pancreatic tumors, nonmalignant tissues of the pancreas and PDX-derived cell lines, and identified proteins that discriminate between patients with good and poor survival. The proteomics data also unraveled potential novel drug targets.

Prognostic Impact of Resection Margin Status in Distal Pancreatectomy for Ductal Adenocarcinoma.

BACKGROUND: Resection margin status is considered one of the few surgeon-controlled parameters affecting prognosis in pancreatic ductal adenocarcinoma (PDAC). While studies mostly focus on resection margins in pancreatoduodenectomy, little is known about their role in distal pancreatectomy (DP). This study aimed to investigate resection margins in DP for PDAC. METHODS: Patients who underwent DP for PDAC between October 2004 and February 2020 were included (n = 124). Resection margins and associated parameters were studied in two consecutive time periods during which different pathology examination protocols were used: non-standardized (period 1: 2004-2014) and standardized (period 2: 2015-2020). Microscopic margin involvement (R1) was defined as ≤1 mm clearance. RESULTS: Laparoscopic and open resections were performed in 117 (94.4%) and 7 (5.6%) patients, respectively. The R1 rate for the entire cohort was 73.4%, increasing from 60.4% in period 1 to 83.1% in period 2 (p = 0.005). A significantly higher R1 rate was observed for the posterior margin (35.8 vs. 70.4%, p < 0.001) and anterior pancreatic surface (based on a 0 mm clearance; 18.9 vs. 35.4%, p = 0.045). Pathology examination period, poorly differentiated PDAC, and vascular invasion were associated with R1 in the multivariable model. Extended DP, positive anterior pancreatic surface, lymph node ratio, perineural invasion, and adjuvant chemotherapy, but not R1, were significant prognostic factors for overall survival in the entire cohort. CONCLUSIONS: Pathology examination is a key determinant of resection margin status following DP for PDAC. A high R1 rate is to be expected when pathology examination is meticulous and standardized. Involvement of the anterior pancreatic surface affects prognosis.

Implementation and training with laparoscopic distal pancreatectomy: 23-year experience from a high-volume center.

BACKGROUND: Distal pancreatectomy is the most common procedure in minimally-invasive pancreatic surgery. Data in the literature suggest that the learning curve flattens after performing up to 30 procedures. However, the exact number remains unclear. METHODS: The implementation and training with laparoscopic distal pancreatectomy (LDP) in a high-volume center were studied between 1997 and 2020. Perioperative outcomes and factors related to conversion were assessed. The individual experiences of four different surgeons (pioneer and adopters) performing LDP on a regular basis were examined. RESULTS: Six hundred forty LDPs were done accounting for 95% of all distal pancreatectomies performed throughout the study period. Conversion was needed in 14 (2.2%) patients due to intraoperative bleeding or tumor adherence to the major vasculature. Overall morbidity and mortality rates were 35 and 0.6%, respectively. Intra- and postoperative outcomes did not change for any of the surgeons within their first 40 cases. Operative time significantly decreased after the first 80 cases for the pioneer surgeon and did not change afterwards although the proportion of ductal adenocarcinoma increased. Tumor size increased after the first 80 cases for the first adopter without affecting the operative time. CONCLUSIONS: In this nearly unselected cohort, no significant changes in surgical outcomes were observed throughout the first 40 LDPs for different surgeons. The exact number of procedures required to overcome the learning curve is difficult to determine as it seems to depend on patient selection policy and specifics of surgical training at the corresponding center.

Early detection of anastomotic leakage after pancreatoduodenectomy with microdialysis catheters: an observational Study.

BACKGROUND: Microdialysis catheters can detect focal inflammation and ischemia, and thereby have a potential for early detection of anastomotic leakages after pancreatoduodenectomy. The aim was to investigate whether microdialysis catheters placed near the pancreaticojejunostomy can detect leakage earlier than the current standard of care. METHODS: Thirty-five patients with a median age 69 years were included. Two microdialysis catheters were placed at the end of surgery; one at the pancreaticojejunostomy, and one at the hepaticojejunostomy. Concentrations of glucose, lactate, pyruvate, and glycerol were analyzed hourly in the microdialysate during the first 24 h, and every 2-4 h thereafter. RESULTS: Seven patients with postoperative pancreatic fistulae (POPF) had significantly higher glycerol levels (P < 0.01) in the microdialysate already in the first postoperative samples. Glycerol concentrations >400 µmol/L during the first 12 postoperative hours detected patients with POPF with a sensitivity of 100% and a specificity of 93% (P < 0.001). After 24 h, lactate and lactate-to-pyruvate ratio were significantly higher (P < 0.05) and glucose was significantly lower (P < 0.05) in patients with POPF. CONCLUSION: High levels of glycerol in microdialysate was an early detector of POPF. The subsequent inflammation was detected as increase in lactate and lactate-to-pyruvate ratio and a decrease in glucose (NCT03627559).

A young woman who did not awake after extensive surgery. / En ung kvinne som ikke våknet etter omfattende operasjon.

BACKGROUND: Cystic echinococcosis (CE) caused by Echinococcus granulosus, significantly impacts health globally, but is a rare disease in Norway. CE is treated with a combination of anthelmintics and surgery, or percutaneous drainage. CASE PRESENTATION: A woman in her thirties underwent extensive surgery due to disseminated CE in the abdominal cavity and liver. Due to intraoperative cyst rupture with contamination of the abdominal cavity, peritoneal lavage with hypertonic saline (20 % NaCl), a scolicidal agent, was performed for ten minutes before irrigation with physiological saline. Immediately after surgery, the patient was haemodynamically unstable and did not awake. Blood level of sodium was found to be severely increased at 188 mmol/L (ref 137−144 mmol/L). Hypotonic fluids (5 % glucose) were immediately administered intravenously to correct the acute hypernatraemia. CT scan of the head did not show signs of bleeding or oedema. The sodium level was normalised on postoperative day three and the patient was discharged without any neurological sequelae. INTERPRETATION: Our patient developed iatrogenic acute severe hypernatraemia following abdominal lavage with hypertonic saline. Acute severe hypernatraemia is potentially lethal. Hypertonic saline must be used intraoperatively with great caution. Regular blood tests to detect hypernatraemia and monitor other electrolyte disturbances should be mandatory.

Gastro- or Duodenojejunostomy Leaks After Pancreatoduodenectomy: Single Center Experience and Narrative Literature Review.

BACKGROUND AND METHODS: Gastro- or duodenojejunostomy leaks after pancreatoduodenectomy is rare. This study aims to analyze the incidence, management, and outcome of gastro- or duodenojejunostomy leaks after pancreatoduodenectomy based on a single center experience from 2004 to 2020 with a narrative literature review. RESULTS: Of a total of 1494 pancreatoduodenectomies, eight patients with gastrojejunostomy (n=1) or duodenojejunostomy (n=7) leak were identified from the institutional pancreatic database. All leaks were treated operatively. In two patients dismantling of the duodenojejunostomy, distal gastrectomy, and closure of the pyloric and jejunal side, a percutaneous endoscopic gastrostomy and a feeding jejunostomy ultimately had to be performed after an unsuccessful attempt of gastrojejunostomy and suture of the duodenojejunostomy, respectively. The literature search revealed three more studies specifically addressing this complication after pancreatoduodenectomy (36 patients of a total of 4739 pancreatoduodenectomies). Based on an analysis of the current study and the literature review, the overall incidence of gastro- or duodenojejunostomy leaks after pancreatoduodenectomy was 0.71 % (44/6233 pancreatoduodenectomies). The occurrence of a gastro- or duodenojejunostomy leak was associated with a concomitant postoperative pancreatic fistula in 50 % of the cases, an increased length of hospital stay, and a mortality rate of 15.9 %. Surgical treatment was performed in 84 % of the cases. CONCLUSION: Gastro- or duodenojejunostomy leak is a rare complication after pancreatoduodenectomy. Prompt diagnosis and early repair is important. In most cases, a surgical intervention is necessary for a good outcome. Under salvage conditions, a bailout strategy may be to temporarily dismantle the gastro- or duodenojejunal anastomosis.

Preoperative CTC-Detection by CellSearch® Is Associated with Early Distant Metastasis and Impaired Survival in Resected Pancreatic Cancer.

In patients with presumed pancreatic ductal adenocarcinoma (PDAC), biomarkers that may open for personalised, risk-adapted treatment are lacking. The study analysed the impact of CTCs-presence on the patterns of recurrence and survival in 98 patients resected for PDAC with 5-10 years of follow-up. Preoperative samples were analysed by the CellSearch® system for EpCAM+/DAPI+/CK+/CD45-CTCs. CTCs were detected in 7 of the 98 patients. CTCs predicted a significantly shorter median disease-free survival (DFS) of 3.3 vs. 9.2 months and a median cancer specific survival (CSS)of 6.3 vs. 18.5 months. Relapse status was confirmed by imaging for 87 patients. Of these, 58 patients developed distant metastases (DM) and 29 developed isolated local recurrence (ILR) as the first sign of cancer relapse. All patients with CTCs experienced DM. pN-status and histological grade >2 were other independent risk factors for DM, but only CTCs predicted significantly shorter cancer-specific, disease-free and post-recurrence survival. Preoperative parameters did not affect clinical outcome. We conclude that CTC presence in resected PDAC patients predicted early distant metastasis and impaired survival. Preoperative CTCs alone or in combination with histopathological factors may guide initial treatment decisions in patients with resectable PDAC in the future.

Laparoscopic Distal Pancreatectomy Following Prior Upper Abdominal Surgery (Pancreatectomy and Prior Surgery).

BACKGROUND AND PURPOSE: Previous abdominal surgery can be a risk factor for perioperative complications in patients undergoing laparoscopic procedures. Today, distal pancreatectomy is increasingly performed laparoscopically. This study investigates the consequences of prior upper abdominal surgery (PUAS) for laparoscopic distal pancreatectomy (LDP). METHODS: Patients who had undergone LDP from April 1997 to January 2020 were included. Based on the history and type of PUAS, these were categorized into three groups: minimally invasive (I), open (II), and no PUAS (III). To reduce possible confounding factors, the groups were matched in 1:2:4 fashion based on age, sex, body mass index (BMI) and American Society of Anesthesiology grade. RESULTS: After matching, 30, 60, and 120 patients were included in the minimally invasive, open and no PUAS groups, respectively. No statistically significant differences were found in terms of intraoperative outcomes. Postoperative morbidity, mortality and length of hospital stay were similar. Open PUAS was associated with higher Comprehensive Complication Index (33.7 vs 20.9 vs 26.2, p = 0.03) and greater proportion of patients with ≥ 2 complications (16.7 vs 0 vs 6.7%, p = 0.02) compared with minimally invasive and no PUAS. Male sex, overweight (BMI 25-29.9 kg/m2), diagnosis of neuroendocrine neoplasia, and open PUAS were risk factors for severe morbidity in the univariable analysis. Only open PUAS was statistically significant in the multivariable model. CONCLUSIONS: PUAS does not impair the feasibility and safety of LDP as its perioperative outcomes are largely comparable to those in patients without PUAS. However, open PUAS increases the burden and severity of postoperative complications.

Cytokeratin-positive cells in the bone marrow from patients with pancreatic, periampullary malignancy and benign pancreatic disease show no prognostic information.

BACKGROUND: Pancreatic and periampullary carcinoma are aggressive tumours where preoperative assessment is challenging. Disseminated tumour cells (DTC) in the bone marrow (BM) are associated with impaired prognosis in a variety of epithelial cancers. In a cohort of patients with presumed resectable pancreatic and periampullary carcinoma, we evaluated the frequency and the potential prognostic impact of the preoperative presence of DTC, defined as cytokeratin-positive cells detected by immunocytochemistry (ICC). METHODS: Preoperative BM samples from 242 patients selected for surgical resection of presumed resectable pancreatic and periampullary carcinoma from 09/2009 to 12/2014, were analysed for presence of CK-positive cells by ICC. The median observation time was 21.5 months. Overall survival (OS) and disease-free survival (DFS) were calculated by Kaplan-Meier and Cox regression analysis. RESULTS: Successful resections of malignant tumours were performed in 179 of the cases, 30 patients resected had benign pancreatic disease based on postoperative histology, and 33 were deemed inoperable intraoperatively due to advanced disease. Overall survival for patients with resected carcinoma was 21.1 months (95% CI: 18.0-24.1), for those with benign disease OS was 101 months (95% CI: 69.4-132) and for those with advanced disease OS was 8.8 months (95% CI: 4.3-13.3). The proportion of patients with detected CK-positive cells was 6/168 (3.6%) in resected malignant cases, 2/31 (6.5%) in advanced disease and 4/29 (13.8%) in benign disease. The presence of CK-positive cells was not correlated to OS or DFS, neither in the entire cohort nor in the subgroup negative for circulating tumour cells (CTC). CONCLUSIONS: The results indicate that CK-positive cells may be present in both patients with malignant and benign diseases of the pancreas. Detection of CK-positive cells was not associated with differences in prognosis for the entire cohort or any of the subgroups analysed. TRIAL REGISTRATION: clinicaltrials.gov ( NCT01919151 ).

Preoperative 18F-FDG PET/computed tomography predicts survival following resection for colorectal liver metastases.

OBJECTIVE: The liver is the most frequent metastatic site from colorectal cancer and about 20% of these patients are treated by surgical resection. However, the 5-year disease-free survival (DFS) following resection is only about 25% and 5-year overall survival (OS) about 38%. The aim of the study was to evaluate the ability of metabolic and volumetric measurements from fluorine-18-fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) prior to resection for colorectal liver metastases (CLM) to predict survival. PATIENTS AND METHODS: Preoperative F-FDG PET/CT examinations were assessed. Metabolic tumor volume (MTV), total lesion glycolysis (TLG), maximum, mean and peak standardized uptake values and tumor to background ratio, were obtained for all CLM. Cutoff values were determined for each of these parameters by using receiver operating characteristic analysis dividing the patients into two groups. DFS, liver recurrence-free survival (LRFS), OS and cancer-specific survival (CSS) for patients over and under the cutoff value were compared by using the Kaplan-Meier method and log-rank test. RESULTS: Twenty-seven patients who underwent F-FDG PET/CT prior to resection for CLM were included. Low values of total MTV and TLG were significantly correlated to improved 5-year LRFS (P = 0.016 and 0.006) and CSS (P = 0.034 and 0.008). Patients who developed liver recurrence had significantly higher total MTV and TLG compared to patients without liver recurrence (P = 0.042 and 0.047). CONCLUSION: Low values of total MTV and TLG were significantly correlated to improved LRFS and CSS and may improve the risk stratification of patients considered for resection for CLM.