Surgery for intraductal papillary mucinous neoplasms in young patients: High-risk population.

BACKGROUND: Intraductal papillary mucinous neoplasms of the pancreas are uncommon in young individuals. Management of these patients is challenging because the risk of malignancy and recurrence after surgery remains unclear. The aim of the present study was to assess the long-term risk for intraductal papillary mucinous neoplasm recurrence after surgery for intraductal papillary mucinous neoplasms in patients ≤50 years of age. METHODS: Perioperative and long-term follow-up data of patients who had undergone surgery for intraductal papillary mucinous neoplasms between 2004 and 2020 were extracted from a prospective unicentric database and retrospectively analyzed. RESULTS: Seventy-eight patients underwent surgical treatment for benign intraductal papillary mucinous neoplasms (low-grade n = 22 and intermediate-grade n = 21) and malignant intraductal papillary mucinous neoplasms (high-grade n = 16 and intraductal papillary mucinous neoplasm-associated carcinoma n = 19). Severe postoperative morbidity (Clavien-Dindo ≥III) was found in 14 patients (18%). The median length of hospital stay was 10 days. No perioperative mortality was observed. The median length of follow-up was 72 months. Recurrence of intraductal papillary mucinous neoplasm-associated carcinoma was found in 6 patients (19%) with malignant intraductal papillary mucinous neoplasm and 1 patient (3%) with benign intraductal papillary mucinous neoplasm. CONCLUSION: Surgery for intraductal papillary mucinous neoplasm is safe and can be performed with low morbidity and potentially no mortality in young patients. Given the high rate of malignancy (45%), these patients with intraductal papillary mucinous neoplasms represent a high-risk population, and prophylactic surgical treatment should be considered in these patients with long life expectancies. Regular clinical and radiologic follow-up examinations are important to rule out disease recurrence, which is high, especially in patients with intraductal papillary mucinous neoplasm-associated carcinoma.

Enucleation for low-grade branch duct intraductal papillary mucinous neoplasms: Long-term follow-up.

BACKGROUND: Pancreatic enucleation allows resection of branch-duct intraductal papillary mucinous neoplasms with full parenchyma preservation. The aim of this study was to assess intraductal papillary mucinous neoplasms recurrence and functional outcomes during long-term follow-up after enucleation. METHODS: Patient characteristics, as well as radiologic and clinicopathologic follow-up data of patients who underwent enucleation for branch-duct intraductal papillary mucinous neoplasms between 2004 and 2014, were analyzed. Quality of life was assessed using the EORTC QLQ-C30 and QLQ-PAN26 questionnaires. RESULTS: Seventy-four patients underwent enucleation for low-grade branch-duct intraductal papillary mucinous neoplasms in 71 and high-grade branch-duct intraductal papillary mucinous neoplasms in 3 patients. Long-term follow-up data were available for 66 patients (89%; median follow-up: 87 months). Radiologic imaging (n = 56) showed intraductal papillary mucinous neoplasm recurrence in 10 patients (18%) including local recurrence at the site of enucleation in 3 patients (5%) and new onset intraductal papillary mucinous neoplasms manifestation in 7 patients (13%) at a distant site in the pancreatic remnant. Four patients (6%) underwent reoperation. Two of these patients had intraductal papillary mucinous neoplasm-associated carcinoma, one of them at the enucleation site. During the follow-up period, no intraductal papillary mucinous neoplasm-related deaths occurred and no new onsets of insulin-dependent diabetes mellitus were observed. QLQ-C30 revealed a global health status of 66.0% and overall functioning and symptom scores of 81.0% and 22.8%, respectively. Additionally, QLQ-PAN26 showed an overall symptom score of 26.5%. CONCLUSION: Enucleation is an organ-preserving surgical treatment option for low-grade branch-duct intraductal papillary mucinous neoplasms with low local recurrence risk and excellent functional long-term outcome. However, postoperative life-long follow-up must be performed as for any type of partial pancreatectomy for intraductal papillary mucinous neoplasms due to the risk of recurrence and potential malignancy.

IPMN-associated pancreatic cancer: Survival, prognostic staging and impact of adjuvant chemotherapy.

BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN)-associated carcinoma is a subtype of pancreatic cancer for which prognostic factors, the validity of the AJCC/UICC staging system and the role of adjuvant chemotherapy remain unknown. MATERIALS AND METHODS: Clinicopathological, treatment and follow-up data of patients with IPMN-associated carcinoma undergoing resection between 2002 and 2018 were analyzed. Uni- and multivariable survival analyses were performed to identify prognostic factors. RESULTS: Of 424 patients undergoing resection for IPMN-associated carcinoma, 77% patients had pancreatic ductal adenocarcinoma (IPMN-PDAC) and 23% had colloid carcinoma (IPMN-CC). Compared to IPMN-CC, IPMN-PDAC was diagnosed at more advanced tumor stages, more frequently involved lymph nodes, more frequently showed poor differentiation and were associated with higher rates of R1 resections. Resected IPMN-PDAC showed markedly shorter median overall survival than IPMN-CC (26.7 months vs. 91.3 months). The current AJCC/UICC staging system was validated for IPMN-associated carcinoma and for both of its subtypes. In multivariable analysis age ≥70 years, diabetes mellitus, high levels of Ca 19-9, IPMN-PDAC subtype, G3 tumors and higher AJCC/UICC stage were independently associated with shorter survival. Adjuvant therapy was not associated with improved survival in IPMN-associated carcinoma. Overall survival was comparable in patients receiving vs. not receiving adjuvant therapy. CONCLUSIONS: Survival after resection of IPMN-associated carcinoma depends on tumor stage, on histologic tumor subtype, grading, and Ca 19-9 levels. The current 8th edition of the AJCC/UICC staging system is applicable for IPMN-associated carcinoma and for both of its subtypes IPMN-PDAC and IPMN-CC. The role of adjuvant therapy for IPMN-associated carcinoma remains unclear.

Clinical presentation and prognosis of adenosquamous carcinoma of the pancreas - Matched-pair analysis with pancreatic ductal adenocarcinoma.

INTRODUCTION: Adenosquamous carcinoma of the pancreas (ASCP) is a rare subtype of pancreatic adenocarcinoma. The aim of this study was to investigate the characteristics and outcomes of ASCP in comparison to pancreatic ductal adenocarcinoma (PDAC). MATERIALS AND METHODS: All patients with ASCP treated between December 2001 and December 2017 were identified from a prospective database. Clinicopathological and follow-up data were analyzed. A nested case-control-study with matched-pair analysis was performed to compare overall survival of ASCP and PDAC. RESULTS: Of 4009 patients undergoing surgery for pancreatic adenocarcinoma 91 patients had ASCP. Compared to PDAC ASCP were larger (4.0 vs. 3.2 cm; p < 0.0001), more frequently involved lymph nodes (88% vs. 78%; p = 0.0216), more frequently showed poor differentiation (G3: 79% vs. 36%; p < 0.0001) and more frequently were located in the pancreatic tail (19% vs. 10%; p = 0.0179). Overall median post-resection-survival was shorter in ASCP (10.8 vs. 20.5 months in PDAC; p = 0.0085), but 5-year survival rates were comparable (18.2% vs. 17.5%). After matching for the unevenly distributed prognostic factors survival after resection of ASCP and PDAC was comparable (p = 0.8301). Localization in the head or several parts of the pancreas, high CA 19-9 levels, and M1 disease were independent predictors of survival in patients with ASCP. CONCLUSION: ASCP is more aggressive with poorer differentiation and higher rates of lymph node metastases compared to PDAC. In spite of a shorter median survival, 5-year survival rates after surgical resection of about 18% can be expected in ASCP and support resection as part of a multimodal therapy as the treatment of choice in this rare cancer.

Enucleation for benign or borderline tumors of the pancreas: comparing open and minimally invasive surgery.

BACKGROUND: The feasibility and safety of minimally invasive enucleation (ME) for benign or borderline pancreatic tumors is still unclear. The aim of this study was to compare outcomes between ME and open enucleation (OE). METHODS: All patients undergoing pancreatic enucleation between October 2001 and January 2020 were analyzed from a prospective database. Consecutive patients undergoing ME were compared with patients undergoing OE in a matched-pair analysis (1:2). RESULTS: Of 358 patients, undergoing enucleation, 120 matched patients (ME n = 40, OE n = 80) were included. Patients undergoing ME had less blood loss (median 50 vs. 100 ml, P = 0.025) and had a higher proportion of patients discharged by 7 days, than patients undergoing OE (38% vs. 18%, P = 0.016). The rates of clinically relevant postoperative pancreatic fistula (POPF) and major complications (Clavien grade ≥ 3) were similar between both groups. Risk factor analysis for POPF B/C showed no significant parameters associated with POPF, including tumor size and proximity to the main pancreatic duct. CONCLUSION: Compared with conventional OE, ME reduces the amount of bleeding and allows earlier postoperative discharge, without increasing the incidence of major complications. Thus, minimally invasive enucleation should be considered for benign tumors of the pancreas when technically and oncologically feasible.

Abdominal drainage versus no drainage after distal pancreatectomy: study protocol for a randomized controlled trial.

BACKGROUND: The placement of prophylactic intra-abdominal drains has been common practice in abdominal operations including pancreatic surgery. The PANDRA trial showed that the omission of drains following pancreatic head resection was non-inferior to intra-abdominal drainage in terms of postoperative reinterventions and superior in terms of clinically relevant pancreatic fistula rate and fistula-associated complications. The aim of the present PANDRA II trial is to evaluate the clinical outcome with versus without prophylactic drain placement after distal pancreatectomy. METHODS: The PANDRA II trial is a mono-center, randomized controlled, non-inferiority trial with two parallel study groups. In the control group at least one passive intra-abdominal drain is placed at the pancreatic resection margin. In the experimental group no drains are placed. The primary endpoint of this trial will be the Comprehensive Complication Index (CCI) measuring all postoperative complications within 90 days. Secondary endpoints are in-hospital mortality and morbidity, including the rates of postoperative pancreatic fistula, chyle leak, postpancreatectomy hemorrhage, delayed gastric emptying, reinterventions and reoperations, surgical site infection, and abdominal fascia dehiscence. Moreover, length of hospital stay, duration of intensive care unit stay, and the rate of readmission after discharge from hospital (up to day 90 after surgery) are assessed. We will need to analyze 252 patients to test the hypothesis that no drainage is non-inferior to drain placement in terms of the CCI (δ 7.5 points) in a one-sided t test with a one-sided level of significance of 2.5% and a power of 80%. DISCUSSION: The results of the PANDRA II trial will help to evaluate the effect of an omission of prophylactic intraperitoneal drainage on the rate of complications after open or minimally invasive distal pancreatectomy. TRIAL REGISTRATION: German Clinical Trials Register (DRKS), DRKS00013763 . Registered on 6 March 2018.

Extended Pancreatectomy: Does It Have a Role in the Contemporary Management of Pancreatic Adenocarcinoma?

BACKGROUND: Pancreatic cancer is a low-incident but highly mortal disease. Surgery is still the preferred treatment option for resectable pancreatic cancer as it offers the only realistic chance for cure. As many patients present with locally advanced disease, which is generally considered as not amenable to surgical treatment, it is important to know the limits of surgical therapy in this disease. METHODS: In this review, the indication and outcomes of extended pancreatectomies as well as the alternative treatment options for locally advanced pancreatic cancer are described. Furthermore, controversies as well as ongoing and future directions for the treatment options of locally advanced pancreatic cancer are discussed. RESULTS: Extended pancreatectomy can be performed with higher morbidity and mortality rates in patients with locally advanced pancreatic cancer compared to patients undergoing formal pancreatic resections. These procedures offer significant advantages with respect to both perioperative results and to long-term outcome when compared to chemotherapy. CONCLUSION: Due to the higher morbidity and mortality rates, these operations should be limited to specialist units with great experience in pancreatic surgery as well as experience in peri- and post-operative management of patients with pancreatic diseases.

Enucleation: A treatment alternative for branch duct intraductal papillary mucinous neoplasms.

BACKGROUND: Small, asymptomatic, branch-duct intraductal papillary mucinous neoplasms of the pancreas are often kept under surveillance despite their malignant potential. The management of branch-duct intraductal papillary mucinous neoplasm is controversial with regard to indications and extent of any operative intervention. The present study aimed to evaluate enucleation as an alternative operative approach for branch-duct intraductal papillary mucinous neoplasms to exclude and prevent malignancy. METHODS: For branch-duct intraductal papillary mucinous neoplasms of <30 mm in diameter and an acceptable distance from the main pancreatic duct, enucleation was considered as the operative approach of choice. All patients scheduled for enucleation of branch-duct intraductal papillary mucinous neoplasm on the basis of these features between January 2004 and September 2014 were analyzed. Among these, patients with successful enucleation were compared with those who were scheduled for enucleation but converted intraoperatively to pancreatic resection (intention-to-treat analysis). End points were hospital morbidity and mortality as well as histopathology and functional outcome at a mean follow-up of 32 months. RESULTS: In the study, 115 patients with presumed branch-duct intraductal papillary mucinous neoplasm and the intention to perform pancreatic enucleation were included; 87 enucleations were performed in 74 patients. In 41 patients, enucleation was converted to a pancreatic resection (procedure-specific success rate 64%); indications for conversion included location or size (46%), presence of multicystic lesions (39%), or involvement of the main pancreatic duct (15%). Of the 74 patients with enucleation, 64 branch-duct intraductal papillary mucinous neoplasms revealed low- (85%), 11% moderate dysplasia-, and 4% high-grade dysplasia on histology. Among converted resections, 6 intraductal papillary mucinous neoplasms revealed high-grade dysplasia or invasive carcinoma (15%). Intention-to-treat analysis with patients converted to pancreatic resection showed that enucleations resulted in less blood loss (100 vs 400 mL) and a shorter operation time (146 vs 255 minutes; P < .001 each). Postoperative morbidity including postoperative pancreatic fistula was similar in both groups. No mortality occurred after enucleation; after formal resection, 1 patient died due to multiorgan failure. Both hospital stay (10 vs 14 days) and rates of postoperative endocrine and exocrine dysfunction rates were less after enucleation (P < .02 each). Intraductal papillary mucinous neoplasm-specific recurrence rates (3% vs 6%) were similar in both groups. CONCLUSION: Enucleation is a safe procedure that can be performed successfully in a high proportion of branch-duct intraductal papillary mucinous neoplasms and should be considered instead of standard resections as an important function-preserving alternative. Limitations may occur due to malignancy, size, localization, multilocularity, or main-duct involvement requiring conversion to a formal, anatomic resection. Beside the advantages in the short-term course, functional outcome seems to be superior after enucleation, and intraductal papillary mucinous neoplasm-specific recurrence rates are not increased compared with standard resections, at least at a mean follow-up of 32 months.