Patients with resected, histologically re-confirmed pancreatic ductal adenocarcinoma (PDAC) can achieve long-term survival despite T3 tumour or nodal involvement. The Finnish Register Study 2000-2013.

BACKGROUND: Long-term survival of patients with operated pancreatic ductal adenocarcinoma (PDAC) has been associated with resection status, disease stage and centralisation. However, no previous reports are available about long-term survivors of PDAC with confirmed histology covering an entire nation. Our aim was to analyze retrospectively confirmed long-term survivors of PDAC operated on in Finland 2000-2008. METHOD: PDAC patients operated between 2000 and 2008 were selected from Finnish patient registers and archives. Histological slides of patients with over four-year survival were re-evaluated by an expert pancreatic pathologist. From the confirmed PDAC patients, demographic, oncologic and operative parameters were recorded. The cut-point of survival was 31.12.2013. RESULTS: Out of the 598 patients operated on and originally diagnosed with PDAC, 52 of the long-term survivors (LTS) were confirmed as having had true PDAC. The four-year survival rate in high volume centres (HVC) was 13.0% and 6.7% elsewhere (p = 0.017). Five-year survival rate was 7.2%. After multivariate analysis only the size of the tumour persisted as prognostic factor for over four-year survival. Among LTSs, 50% of patients had stage IIB tumour and 40% had a R1 resection without difference with patients with shorter survival. The use of adjuvant therapy did not differ between the groups. CONCLUSION: This is the largest single-nationwide cohort of long-term survivors with confirmed PDAC. Comprehensive pathological evaluation is mandatory for an adequate PDAC diagnosis and true survival analysis. Long-term survival can be achieved even in T3 patients with nodal involvement and may be explained by favorable tumour biology.

Perioperative Hydrocortisone Reduces Major Complications After Pancreaticoduodenectomy: A Randomized Controlled Trial.

OBJECTIVES: The aim of this study was to study whether post-pancreaticoduodenectomy complications (PPDC) in high-risk patients can be reduced with hydrocortisone. BACKGROUND: Soft pancreas is a well-known risk factor for PPDC. Previously, we have shown that patients with >40% acini in the pancreatic transection line are most prone to PPDC. Recent studies have demonstrated that surgical trauma leads to inflammation of the pancreatic remnant, which precedes PPDC. METHODS: On the basis of power analysis, randomized controlled trial (RCT) (Clinicaltrials.gov NCT01460615), 155 patients (February 2011-May 2015) scheduled for pancreaticoduodenectomy were randomized to intravenous (i.v.) treatment with hydrocortisone 100 mg or placebo. All patients received the first dose at the induction of anesthesia. During the operation, the percentage of acini was calculated from pancreatic transection line frozen samples by a pathologist. As planned, only the high-risk patients with >40% acini (n = 62) continued in the study to receive in total 8 doses of randomization-based hydrocortisone/placebo every 8 hours. Primary endpoints were urine trypsinogen positive days and overall complications (Clavien-Dindo III-IV). Postoperative pancreatic fistulas (POPFs), postpancreatectomy hemorrhage (PPH), and delayed gastric emptying (DGE) were also graded. RESULTS: Hydrocortisone treatment did not alter trypsinogen release (2 or more positive days 46% vs 50%), but it significantly reduced overall complications compared with placebo in the high-risk patients (18% vs 41%; P < 0.05; Clavien-Dindo III-IV). Also, clinically significant POPF (11% vs 27%), PPH (14% vs 24%), and DGE (29% vs 44%) tended to be lower in the hydrocortisone group. Ninety-day mortality was zero. CONCLUSIONS: This RCT shows that in high-risk patients, overall PPDC can be significantly reduced with hydrocortisone treatment. Inflammation may be an important mediator of PPDC.

Tumor-like Chronic Pancreatitis Is Often Autoimmune Pancreatitis.

BACKGROUND: Distinguishing between pancreatic cancer and chronic pancreatitis (CP) is often difficult. Certain (5-6%) CP cases are autoimmune in nature, and these patients respond to corticosteroid treatment, making surgery avoidable. Our aim was to evaluate the incidence of autoimmune pancreatitis (AIP) among patients operated on for a pancreatic mass with a final histology of CP. PATIENTS AND METHODS: A total of 33 patients were operated on at the Tampere or Helsinki University Hospital for suspicion of cancer, but with final histopathological diagnosis of CP. The median age was 58 (31-81) years; 26 patients (79%) were male. There were 28 pancreaticoduodenectomes and five left pancreatic resections. Surgical specimens were re-evaluated by experienced pathologists, with representative samples chosen for immunohistochemistry Each sample was scored as positive or negative for immunoglobulin G4 (IgG4) independently by two pathologists. Honolulu consensus criteria served for AIP sub-typing. RESULTS: Out of the 33 specimens, 10 (30%) were positive for IgG4. Histopathological re-evaluation of these revealed all to be type 1 AIP. CONCLUSION: The proportion of AIP, according to IgG4-positive immunohistochemistry and histological re-evaluation, was much higher than expected. This suggests that by focusing on diagnosis of AIP preoperatively, certain patients might be treated with corticosteroids and possibly avoid unnecessary surgery.

Spyglass single-operator peroral cholangioscopy seems promising in the evaluation of primary sclerosing cholangitis-related biliary strictures.

UNLABELLED: Early diagnosis of dysplastic changes and exclusion of cholangiocarcinoma (CCA) in patients with primary sclerosing cholangitis (PSC) remain a major clinical challenge. Although SpyGlass single-operator cholangioscopy (SOC) appears effective in diagnostics of indeterminate biliary strictures, there are only few studies on its safety in PSC-related strictures. OBJECTIVE: The aim of this study was to assess the clinical feasibility of SOC and directed biopsies, flow cytometry, and brush cytology in PSC patients. MATERIALS AND METHODS: Eleven consecutive patients (median age 45 years, 5 females) undergoing SOC for progression of PSC in a single tertiary center were included in a prospective observational study. RESULTS: Brush sample and directed biopsies were successfully acquired from strictures in all cases. Samples were adequate for cytological and histological diagnosis in 9 (82%) and 10 patients (91%), respectively. There were two cases of pancreatitis. In one patient, flow cytometry showed aneuploidy, which resulted in closer follow-up. CONCLUSIONS: SpyGlass SOC and directed biopsies seem to offer a feasible and promising method in evaluation of PSC-related strictures. However, the long-term prognostic value it adds to cytology and flow cytometry remains to be assessed in future trials.

Cyst fluid SPINK1 may help to differentiate benign and potentially malignant cystic pancreatic lesions.

OBJECTIVE: Differential diagnosis between benign and potentially malignant cystic pancreatic lesions may be difficult. Previously we have compared cyst fluid serine protease inhibitor Kazal type I (SPINK1) with some traditionally used tumour markers (amylase, CEA, Ca19-9) and found that it may be a new promising maker in the differential diagnosis of cystic pancreatic lesions. In the present study, we focused on cyst fluid SPINK1 levels in benign and potentially malignant cystic pancreatic lesions. DESIGN: Sixty-one patients operated on for cystic pancreatic lesion in Tampere University Hospital, Finland and in Verona University Hospital, Italy, were included. Cyst fluid was aspirated during surgery, stored at -70 °C, and analysed with immunofluorometric assay for SPINK1. The final diagnosis was acute pancreatitis with fluid collection (Acute FC) in 4 patients, chronic pseudocyst (PS) in 17 patients, serous cystadenoma (SCA) in 7 patients, mucinous cystadenoma (MCA) in 21 patients and intraductal papillary-mucinous neoplasm (IPMN) in 12 patients (9 main/mixed duct type and 3 branch duct type). RESULTS: The acute FC patients had high SPINK1 levels. Among chronic cysts, SPINK1 levels were significantly higher in patients with potentially malignant cysts (main/mixed duct IPMN and MCA) than with benign cysts (side branch IPMN and SCA), (median and range, [480 (13-3602) vs. 18 (0.1-278) µg/L]; p < 0.0001). In the subcohort of 24 patients with <3 cm chronic cyst, cyst fluid SPINK 1 levels were significantly lower in SCA or side branch IPMN (3 [2-116] µg/L) than in main duct IPMN or MCA (638 [66-3602] µg/L; p = 0.018). The best sensitivity and specificity to differentiate any size MCA or main/mixed type IPMN from SCA or side branch IPMN were 85% and 84% (AUC 0.94; cut-off value 118 µg/L). The best sensitivity and specificity to differentiate <3 cm MCA or main duct IPMN from SCA or side branch IPMN were 93% and 89% (AUC 0.98; cut-off value 146 µg/L). CONCLUSIONS: Cyst fluid SPINK1 may be a possible marker in the differential diagnosis of benign and potentially malignant cystic pancreatic lesions.

Ewing's sarcoma family of tumors in Finland during 1990-2009: a population-based study.

BACKGROUND: Ewing's sarcoma family of tumors (ESFTs) are rare bone and soft tissue tumors characterized by specific genetic alterations. Our aim was to carry out a nationwide analysis of ESFT, to survey the treatments used and to report the five-year disease specific and event-free survival rates (EFS and DSS). MATERIAL AND METHODS: The study data was gathered from the Finnish National Cancer Registry and all five University Hospitals and consisted of 76 bone and soft tissue ESFT patients diagnosed during 1990-2009. Their medical records were reviewed and data on their disease, treatments, complications and outcome were analyzed. RESULTS: The five-year EFS and DSS of patients with localized disease at diagnosis (n = 57) were 70% and 60%, respectively. Factors contributing to DSS and EFS were the axial vs. peripheral site of primary tumor and adequate surgical resection of the primary tumor. DSS was also affected by patient's age at diagnosis and the treatment employed. The five-year DSS of patients with metastatic disease at diagnosis (n = 19) was 33% and both preoperative and high dose chemotherapy were associated with improved survival. CONCLUSION: Population-based studies including both bone and soft tissue ESFTs are few. In this nationwide, population-based study on Finnish bone and soft tissue ESFT patients, we find their treatment successful and results comparable to those previously published. Absence of metastases, young age at diagnosis and a peripheral primary tumor site were associated with a better prognosis. It seems that surgical resection of the primary tumor should be performed whenever adequate resection margins can be achieved. The role of high dose chemotherapy merits further studies in this setting.

The risk for immediate postoperative complications after pancreaticoduodenectomy is increased by high frequency of acinar cells and decreased by prevalent fibrosis of the cut edge of pancreas.

OBJECTIVES: Soft pancreas is considered as a factor for pancreatitis after pancreaticoduodenectomy, which in turn constitutes a high risk for local complications. The aim was to analyze the proportion of different cell types in the cut edge of pancreas (CEP) in relation to postoperative pancreatitis and other complications after pancreaticoduodenectomy. METHODS: Data from postoperative follow-up was collected on 40 patients who had undergone pancreaticoduodenectomy. Positive urine trypsinogen-2, an early detector of pancreatitis, was checked on days 1 to 6 after operation. Drain amylase was measured on postoperative day 3. Anastomotic leakages, delayed gastric emptying, and other complications were registered. The areas of different cell types were calculated from the entire hematoxylin-eosin-stained section of CEP. RESULTS: High frequency of acinar cells in the CEP significantly increased positive urine trypsinogen-2 days, drain amylase values, and delayed gastric emptying. In a subgroup of patients with more than 40% acini in the CEP, there were significantly more postoperative complications. Increased fibrosis correlated with a small number of positive urine trypsinogen-2 days and postoperative complications. CONCLUSIONS: A large number of acinar cells in the CEP increases, whereas extensive fibrosis in the CEP decreases, the risk for postoperative complications after pancreaticoduodenectomy. These results emphasize the importance of acini in the development of postoperative complications.