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.

Resection rates and intention-to-treat outcomes in borderline and locally advanced pancreatic cancer: real-world data from a population-based, prospective cohort study (NORPACT-2).

BACKGROUND: Systemic chemotherapy is the initial treatment strategy for borderline resectable and locally advanced pancreatic cancer to facilitate curative resection. The aim of this study was to investigate the resection rates and overall survival in patients with borderline resectable pancreatic cancer and locally advanced pancreatic cancer. METHODS: Consecutive patients with borderline resectable pancreatic cancer/locally advanced pancreatic cancer discussed by Oslo University Hospital multidisciplinary team between 2018 and 2020, serving a population of 3.1 million within a geographically defined area in south-eastern Norway, were included in this prospective Norwegian Pancreatic Cancer Trial-2 study, according to intention-to-treat principles. The total number of patients with pancreatic cancer was sought from the Cancer Registry of Norway. RESULTS: A total of 1178 patients were diagnosed with pancreatic cancer, of whom 618 were referred to Oslo University Hospital. After multidisciplinary team evaluation, 230 patients were considered to have borderline resectable pancreatic cancer/locally advanced pancreatic cancer. The final study group consisted of 188 patients (borderline resectable pancreatic cancer n = 96, locally advanced pancreatic cancer n = 92) who were fit to receive primary chemotherapy. Resection rates were 46.9% (45 of 96) for borderline resectable pancreatic cancer and 13% (12 of 92) for locally advanced pancreatic cancer (P <0.001). Median overall survival was 14.6 months (borderline resectable pancreatic cancer 16.4 months; locally advanced pancreatic cancer 13.7 months, (P = 0.2)). Adjusted for immortal time bias, median overall survival for patients undergoing resection versus only chemotherapy was 24.4 months versus 10.1 months (P <0.001) for borderline resectable pancreatic cancer and 28.4 months versus 12.6 months for locally advanced pancreatic cancer (P = 0.001). CONCLUSION: Resection rates and survival in patients with borderline resectable pancreatic cancer and locally advanced pancreatic cancer treated at a high-volume centre in a universal healthcare system compare well with those treated at international expert centres.Registration number: NCT04423731 (http://www.clinicaltrials.gov).

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.

Management of gastric conduit retention following hybrid and minimally invasive esophagectomy for esophageal cancer: Two retrospective case series.

INTRODUCTION: Following esophagectomy about 5% of patients experience long-term gastric conduit retention. We report two patients with surgical correction for this problematic condition. This case series is a retrospective, non-consecutive single center report. PRESENTATION OF CASES: A slender female aged 76 (patient 1) and an obese man aged 69 (patient 2) with esophageal cancer, underwent hybrid and total minimally invasive Ivor-Lewis esophagectomy, respectively. The conduit was tubularized, and the stapled anastomosis located above carina. The crura were divided in patient 1. Contrast enema revealed a straight (patient 1) or redundant (patient 2) thoracic conduit. Conduit retention in patient 1 began after 47 months. After 61 months reoperation was performed with open thoracoabdominal access for mobilization, abdominal reduction and diaphragmatic suture fixation of the herniated conduit. Symptoms improved and oral nutrition is still sufficient after 8 months.Patient 2 had clinically significant retention after 15 months, despite using pyloric Botox injection and expandable metal stenting. At laparoscopic reoperation after 27 months a partial conduit mobilization and refixation were unsuccessful, but an accidental colonic hiatal hernia was taken down. After 28 months a second reoperation was performed, similar to patient 1. Fifteen months afterwards the patient still ate sufficiently, but a limited double reherniation had occurred. DISCUSSION: Long-term retention post-esophagectomy often start with an initial redundant conduit, that can increase from food-induced stretching and declive emptying against gravity. A wide hiatal opening probably also predispose to conduital herniation. CONCLUSIONS: Conduit retention improved after mobilization, reduction and its hiatal fixation. A too wide or narrow hiatal opening must be avoided to prevent herniation.