Postoperative Hyperamylasemia (POH) is an Early Predictor of Pancreatic Fistula Occurrence and Severity after Distal Pancreatectomy: Results from a European Multicentric Study.

OBJECTIVES: The aim of this international multicentric study is to characterize postoperative hyperamylasemia (POH) after distal pancreatectomy (DP), with particular focus on its relationship with postoperative pancreatic fistula (POPF) occurrence and severity. BACKGROUND: The clinical relevance of POH after DP and its relationship with the occurrence and severity of POPF have not been explored yet. METHODS: All patients undergoing DP for any indication between 2015 and 2021 at three European referral Centers for pancreatic surgery were retrospectively analyzed. Drain fluid amylase (DFA), C-reactive protein (C-RP), and serum amylase were examined from postoperative-day (POD) 1 to 3. Biochemical leak (BL), POPF, POH, and post-pancreatectomy hemorrhage (PPH) were defined and graded according to ISGPS definitions. RESULTS: In total 1192 patients were included. Overall rates of POH and POPF were 18% (n= 210) and 29% (n= 344), respectively. The presence of DFA ≥2000 U/L on POD 1 (OR=2.11, 95% CI 1.68-2.86), C-RP ≥200 mg/L on POD 3 (OR=2.19, 95% CI 1.68-2.86), and POH (OR=1.58, 95% CI 1.14-2.19) were all independent early predictors of POPF (all P< 0.01). The presence of POH almost doubled the rate of POPF (43% vs. 26%, P<0.001), and higher POPF severity presented also higher POH rates (no POPF= 12%; BL= 19%; B POPF= 24%; C POPF= 52%). Among patients developing POPF, patients with POH had higher rates of PPH (22% vs 9%, P= 0.001), sepsis (24% vs 13%; P=0.011), re-operation (21% vs 8%; P< 0.01), and mortality (3% vs 0.3%; P= 0.025). CONCLUSIONS: The occurrence of POH is an early predictor of POPF and its severity after DP. The diagnosis of POH might define patients at higher risk for a complicated course, targeting them for prevention / mitigation strategies against pancreas specific complications.

Molecular testing for personalized therapy is underutilized in patients with borderline resectable and locally advanced pancreatic cancer - real world data from the NORPACT-2 study.

Background: International guidelines currently recommend the use of molecular testing in patients with advanced pancreatic cancer. The rate of actionable molecular alterations is low. The utility of molecular testing in patients with borderline resectable (BRPC) or locally advanced (LAPC) pancreatic cancer in real world clinical practice is unclear.Methods: 188 consecutive patients included in a prospective, population-based study (NORPACT-2) in patients with BRPC and LAPC (2018-2020) were reviewed. Molecular testing was performed at the discretion of the treating oncologist and was not recommended as a routine investigation by the national guidelines. All patients were considered fit to undergo primary chemotherapy and potential surgical resection. The frequency and the results of molecular testing (microsatellite instability (MSI) and/or KRAS status) were assessed.Results: Thirty patients (16%) underwent molecular testing. MSI tumour was detected in one (3.6%) of 28 tested patients. The patient received immunotherapy and subsequently underwent surgical resection. Histological assessment of the resected specimen revealed a complete response. KRAS wild type was detected in one (14.3%) of seven tested patient. Patients who initiated FOLFIRINOX as the primary chemotherapy regimen (p = 0.022), or were being treated at one of the eight hospital trusts (p = 0.001) were more likely to undergo molecular testing.Conclusions: Molecular testing was rarely performed in patients with BRPC or LAPC. Routine molecular testing for all patients with BRPC and LAPC should be considered to increase identification of targetable mutations and improve outcomes.

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.

Surgical and Oncological Outcomes After Preoperative FOLFIRINOX Chemotherapy in Resected Pancreatic Cancer: An International Multicenter Cohort Study.

BACKGROUND: Preoperative FOLFIRINOX chemotherapy is increasingly administered to patients with borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC) to improve overall survival (OS). Multicenter studies reporting on the impact from the number of preoperative cycles and the use of adjuvant chemotherapy in relation to outcomes in this setting are lacking. This study aimed to assess the outcome of pancreatectomy after preoperative FOLFIRINOX, including predictors of OS. METHODS: This international multicenter retrospective cohort study included patients from 31 centers in 19 European countries and the United States undergoing pancreatectomy after preoperative FOLFIRINOX chemotherapy (2012-2016). The primary end point was OS from diagnosis. Survival was assessed using Kaplan-Meier analysis and Cox regression. RESULTS: The study included 423 patients who underwent pancreatectomy after a median of six (IQR 5-8) preoperative cycles of FOLFIRINOX. Postoperative major morbidity occurred for 88 (20.8%) patients and 90-day mortality for 12 (2.8%) patients. An R0 resection was achieved for 243 (57.4%) patients, and 259 (61.2%) patients received adjuvant chemotherapy. The median OS was 38 months (95% confidence interval [CI] 34-42 months) for BRPC and 33 months (95% CI 27-45 months) for LAPC. Overall survival was significantly associated with R0 resection (hazard ratio [HR] 1.63; 95% CI 1.20-2.20) and tumor differentiation (HR 1.43; 95% CI 1.08-1.91). Neither the number of preoperative chemotherapy cycles nor the use adjuvant chemotherapy was associated with OS. CONCLUSIONS: This international multicenter study found that pancreatectomy after FOLFIRINOX chemotherapy is associated with favorable outcomes for patients with BRPC and those with LAPC. Future studies should confirm that the number of neoadjuvant cycles and the use adjuvant chemotherapy have no relation to OS after resection.

Management of Coeliac and Hepatic Artery Aneurysms: An Experience of 84 Cases.

OBJECTIVE: To report outcomes following open or endovascular treatment of true hepatic and coeliac artery aneurysms at a single referral centre. METHODS: This was a retrospective cohort study of consecutive patients treated for true hepatic and coeliac artery aneurysms between May 2002 and December 2021. Outcome measures included complications, graft patency, and survival rate. RESULTS: Overall, 84 patients were included with a median age of 63 years (interquartile range 55, 79). The majority (76%) of the patients were men. Frequent comorbidities included a history of tobacco (69%), hypertension (65%), hyperlipidaemia (32%), and diabetes (15%). Multiple synchronous aneurysms were detected in 22 patients (26%). There were 33 (39%) symptomatic aneurysms (abdominal pain without rupture [n = 18], rupture [n = 10], and sepsis [n = 5]). Seventeen patients (20%) had mycotic aetiology. Fifty patients (60%) underwent endovascular treatment with either covered stent placement (n = 29) or coil embolisation (n = 21), and 34 patients (40%) were treated with open surgery using allogenic iliac artery (n = 15), autologous saphenous vein (n = 15), GoreTex graft (n = 2), or ligation (n = 2). The complication rate was 32% in the open group and 18% in the endovascular group (p = .048). The overall 90 day post-operative mortality rate was 1.2%, five year primary patency was 90.0%, five year survival rate was 81.2%, and mean follow up was 6.9 ± 4.2 years. CONCLUSION: Endovascular treatment is the preferred approach whenever technically possible. Despite higher post-operative morbidity, an open approach with vascular reconstruction using autologous or allogenic vascular grafts yields acceptable long term results.

Clinical Outcomes After Total Pancreatectomy: A Prospective Multicenter Pan-European Snapshot Study.

OBJECTIVE: To assess outcomes among patients undergoing total pancreatectomy (TP) including predictors for complications and in-hospital mortality. BACKGROUND: Current studies on TP mostly originate from high-volume centers and span long time periods and therefore may not reflect daily practice. METHODS: This prospective pan-European snapshot study included patients who underwent elective (primary or completion) TP in 43 centers in 16 European countries (June 2018-June 2019). Subgroup analysis included cutoff values for annual volume of pancreatoduodenectomies (<60 vs ≥60).Predictors for major complications and in-hospital mortality were assessed in multivariable logistic regression. RESULTS: In total, 277 patients underwent TP, mostly for malignant disease (73%). Major postoperative complications occurred in 70 patients (25%). Median hospital stay was 12 days (IQR 9-18) and 40 patients were readmitted (15%). In-hospital mortality was 5% and 90-day mortality 8%. In the subgroup analysis, in-hospital mortality was lower in patients operated in centers with ≥60 pancreatoduodenectomies compared <60 (4% vs 10%, P = 0.046). In multivariable analysis, annual volume <60 pancreatoduodenectomies (OR 3.78, 95% CI 1.18-12.16, P = 0.026), age (OR 1.07, 95% CI 1.01-1.14, P = 0.046), and estimated blood loss ≥2L (OR 11.89, 95% CI 2.64-53.61, P = 0.001) were associated with in-hospital mortality. ASA ≥3 (OR 2.87, 95% CI 1.56-5.26, P = 0.001) and estimated blood loss ≥2L (OR 3.52, 95% CI 1.25-9.90, P = 0.017) were associated with major complications. CONCLUSION: This pan-European prospective snapshot study found a 5% inhospital mortality after TP. The identified predictors for mortality, including low-volume centers, age, and increased blood loss, may be used to improve outcomes.

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.

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.

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.

Survival after liver resection and liver transplantation for colorectal liver metastases: a comparative analysis stratified by metabolic tumor volume assessed by 18F-FDG PET/CT.

BACKGROUND: Many patients undergoing resection for colorectal liver metastases (CRLM) recur with poor survival. Overall survival (OS) following liver transplantation (LT) for CRLM is reported to be about 80% at 5 years. In this study, survival following resection versus transplantation for CRLM in patients with moderate (6-70 cm3) metabolic tumor volume (MTV) from the preoperative positron emission tomography (PET) was compared. METHODS: Disease-free survival (DFS), OS and post recurrence survival (PRS) following resection (n = 18) and LT (n = 12) was compared by using the Kaplan Meier method and log rank test for patients with moderate MTV. RESULTS: Patients undergoing LT had unresectable metastases, significantly lower age, higher tumor burden score and number of liver metastases, longer time from diagnosis to surgery, and more patients received neoadjuvant chemotherapy. OS at 5 years was 39% in the resection group and 83% in the LT group (P = 0.012). PRS was significantly improved in patients treated with LT compared to resection with 71% alive at 5 years from recurrence compared to 17% in the resection group (P = 0.017). CONCLUSION: LT for selected patients seems to be superior to resection as treatment for CRLM for patients with moderate MTV.

Tailored surgery in chronic pancreatitis after implementation of a multidisciplinary team assessment; a prospective observational study.

INTRODUCTION: Optimal management of chronic pancreatitis involves several specialties. Selection of patients for surgery may benefit from evaluation by a multidisciplinary team (MDT), similar to cancer care. The aim of this study was to evaluate outcomes in patients selected for surgery after MDT decision. METHODS: A prospective, observational study of consecutive patients operated for pain due to chronic pancreatitis after implementation of a MDT. The main outcome was Quality of life (QoL) assessed by EORTC-QLQ C30 and pain relief in patients followed >3 months. Complications were registered and predictive factors for pain relief analyzed. RESULTS: Of 269 patients evaluated by the MDT, 60 (22%) underwent surgery. Postoperative surgical complications occurred in five patients (8.3%) and reoperation within 30 days in two. There was no 90-days mortality. Complete or partial pain relief was achieved in 44 of 50 patients followed >3 months (88%). Preoperative duration of pain predicted lower probability of success. Postoperative improvement in QoL was most prominent for pain, appetite and nausea. CONCLUSIONS: After MDT evaluation, one in five patients was selected for surgery. Pain relief was obtained in a majority of patients with improved QoL. A tailored approach through a MDT seems warranted and efficient.

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).

Tumour exosome integrins determine organotropic metastasis.

Ever since Stephen Paget's 1889 hypothesis, metastatic organotropism has remained one of cancer's greatest mysteries. Here we demonstrate that exosomes from mouse and human lung-, liver- and brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells. We show that tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche. Treatment with exosomes from lung-tropic models redirected the metastasis of bone-tropic tumour cells. Exosome proteomics revealed distinct integrin expression patterns, in which the exosomal integrins α6ß4 and α6ß1 were associated with lung metastasis, while exosomal integrin αvß5 was linked to liver metastasis. Targeting the integrins α6ß4 and αvß5 decreased exosome uptake, as well as lung and liver metastasis, respectively. We demonstrate that exosome integrin uptake by resident cells activates Src phosphorylation and pro-inflammatory S100 gene expression. Finally, our clinical data indicate that exosomal integrins could be used to predict organ-specific metastasis.

Graft type for superior mesenteric and portal vein reconstruction in pancreatic surgery - A systematic review.

BACKGROUND: Contemporary practice for superior mesenteric/portal vein (SMV-PV) reconstruction during pancreatectomy with vein resection involves biological (autograft, allograft, xenograft) or synthetic grafts as a conduit or patch. The aim of this study was to systematically review the safety and feasibility of the different grafts used for SMV-PV reconstruction. METHODS: A systematic search was performed in PubMed and Embase according to the PRISMA guidelines (January 2000-March 2020). Studies reporting on ≥ 5 patients undergoing reconstruction of the SMV-PV with grafts during pancreatectomy were included. Primary outcome was rate of graft thrombosis. RESULTS: Thirty-four studies with 603 patients were included. Four graft types were identified (autologous vein, autologous parietal peritoneum/falciform ligament, allogeneic cadaveric vein/artery, synthetic grafts). Early and overall graft thrombosis rate was 7.5% and 22.2% for synthetic graft, 5.6% and 11.7% for autologous vein graft, 6.7% and 8.9% for autologous parietal peritoneum/falciform ligament, and 2.5% and 6.2% for allograft. Donor site complications were reported for harvesting of the femoral, saphenous, and external iliac vein. No cases of graft infection were reported for synthetic grafts. CONCLUSION: In selected patients, autologous, allogenic or synthetic grafts for SMV-PV reconstruction are safe and feasible. Synthetic grafts seems to have a higher incidence of graft thrombosis.

Laparoscopic distal pancreatectomy in patients with poor physical status.

BACKGROUND: Laparoscopic distal pancreatectomy (LDP) is advantageous over open surgery in the treatment of benign pancreatic lesions and low-grade malignancies. Yet the evidence on the relationship between comorbidities and the outcomes of LDP remains scarce. METHODS: Patients who had undergone LDP for all indications between April 1997 and December 2019 were included. Preoperative physical status was defined according to the American Society of Anesthesiology (ASA) criteria. Perioperative outcomes were compared between the patients with high (ASA III-IV) and low/moderate anesthetic risk (ASA I-II). RESULTS: A total of 605 patients were eligible for analysis including 190 with ASA III-IV and 415 with ASA I-II. The former was associated with older age, male gender, preexisting medical conditions, greater total number of comorbidities and red blood cell transfusion. The rate of medical complications was significantly higher in high-risk patients. Multivariable analysis identified ASA III-IV and operative time as independent predictors for medical complications. Overall/severe morbidity, surgical complications and mortality rates were similar. CONCLUSIONS: Poor physical status defined as ASA grades III-IV predicts medical complications, but has a limited impact on surgical complications and severe morbidity of LDP. Thus, it should not be considered as a contraindication for LDP.

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.

Circulating Tumor Cells are an Independent Predictor of Shorter Survival in Patients Undergoing Resection for Pancreatic and Periampullary Adenocarcinoma.

OBJECTIVE: We evaluated the prognostic impact of circulating tumor cells (CTCs) for patients with presumed resectable pancreatic and periampullary cancers. SUMMARY OF BACKGROUND DATA: Initial treatment decisions for this group are currently taken without a reliable prognostic marker. The CellSearch system allows standardized CTC-testing and has shown excellent specificity and prognostic value in other applications. METHODS: Preoperative blood samples from 242 patients between September 2009 and December 2014 were analyzed. One hundred seventy-nine patients underwent tumor resection, of whom 30 with stage-I tumors and duodenal cancer were assigned to the low-risk group, and the others to the high-risk group. Further 33 had advanced disease, 30 benign histology. Observation ended in December 2016. Cancer-specific survival (CSS) and disease-free survival (DFS) were calculated by log-rank and Cox regression. RESULTS: CTCs (CTC-positive; ≥1 CTC/7.5 mL) were detected in 6.8% (10/147) of the high-risk patients and 6.2% (2/33) with advanced disease. No CTCs (CTC-negative) were detected in the low-risk patients or benign disease. In high-risk patients, median CSS for CTC-positive versus CTC-negative was 8.1 versus 20.0 months (P < 0.0001), and DFS 4.0 versus 10.5 months (P < 0.001). Median CSS in advanced disease was 7.7 months. Univariate hazard ratio (HR) of CTC-positivity was 3.4 (P < 0.001). In multivariable analysis, CTC-status remained independent (HR: 2.4, P = 0.009) when corrected for histological type (HR: 2.7, P = 0.030), nodal status (HR: 1.7, P = 0.016), and vascular infiltration (HR: 1.7, P = 0.001). CONCLUSION: Patients testing CTC-positive preoperatively showed a detrimental outcome despite successful tumor resections. Although the low CTC-rate seems a limiting factor, results indicate high specificity. Thus, preoperative analysis of CTCs by this test may guide treatment decisions and warrants further testing in clinical trials.

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 ).

Portal vein stent placement after hepatobiliary and pancreatic surgery.

PURPOSE: To evaluate the long-term outcomes of percutaneous transhepatic stent placement for portal vein (PV) stenosis after liver transplantation (LT) and hepato-pancreato-biliary (HPB) surgery. METHODS: Retrospective study of 455 patients who underwent LT and 522 patients who underwent resection of the pancreatic head between June 2011 and February 2016. Technical success, clinical success, patency, and complications were evaluated for both groups. RESULTS: A total of 23 patients were confirmed to have postoperative PV stenosis and were treated with percutaneous transhepatic PV stent placement. The technical success rate was 100%, the clinical success rate was 80%, and the long-term stent patency was 91.3% for the entire study population. Two procedure-related hemorrhages and two early stent thromboses occurred in the HPB group while no complications occurred in the LT group. A literature review of selected studies reporting PV stent placement for the treatment of PV stenosis after HPB surgery and LT showed a technical success rate of 78-100%, a clinical success rate of 72-100%, and a long-term patency of 57-100%, whereas the procedure-related complication rate varied from 0-33.3%. CONCLUSIONS: Percutaneous transhepatic PV stent is a safe and effective treatment for postoperative PV stenosis/occlusion in patients undergoing LT regardless of symptoms. Due to increased risk of complications, the indication for percutaneous PV stent placement after HPB surgery should be limited to patients with clinical symptoms after an individual assessment.

Pancreatoduodenectomy with venous resection for ductal adenocarcinoma rarely achieves complete (R0) resection.

BACKGROUND: Pancreatoduodenectomy with venous resection is considered standard of care for patients with tumour involvement of the superior mesenteric/portal vein (SMV/PV) and deemed justified if an R0-resection can be achieved. The aim of this study was to provide a detailed pathology assessment of the site and extent of margin involvement in specimens resulting from pancreatoduodenectomy with venous resection. METHODS: Retrospective observational study including patients undergoing pancreatoduodenectomy with or without venous resection for pancreatic ductal adenocarcinoma between 2015 and 2017. Detailed histopathological mapping of the tumour and its relationship to the margins was undertaken. RESULTS: 98 patients met the inclusion criteria. An R0-resection, based on 1 mm clearance, was achieved in 16 of 73 patients without venous resection and in 1 of 25 patients with venous resection (p = 0.063). The surface of the SMV-groove was the most frequently involved margin (23 of 25 patients with venous resection, 37 of 73 patients without venous resection; p < 0.001). The broad invasive tumour front as well as the absence of peripancreatic fat at the SMV-groove were the reasons for these findings. CONLUSION: An R0-resection following pancreatoduodenectomy with venous resection for ductal adenocarcinoma can rarely be achieved due to microscopical involvement of the SMV-groove.