P-suPAR may reflect the inflammatory response after pancreatic surgery.

BACKGROUND: Several different scoring systems have been developed to predict post-pancreatectomy complications. Currently used inflammatory markers are of only limited value in predicting complications after pancreatic surgery. Plasma soluble urokinase plasminogen activator receptor (P-suPAR) is a prognostic biomarker associated with different inflammatory conditions. The aim of this study was to investigate P-suPAR levels before and after pancreatic surgery. METHODS: One hundred and seventy-six patients evaluated for pancreatic surgery due to suspected malignant or premalignant lesion were recruited for this study at Tampere University Hospital between 2016 and 2021. P-suPAR was analyzed before the planned operation and on postoperative days (PODs) one and three. RESULTS: One hundred and thirty-three patients [median age 67 (range 33-84) years, 50 % male] underwent a pancreatic surgery procedure. Compared to preoperative values [median 3.7 (IQR 3.1-4.7) ng/mL], P-suPAR was significantly lower on PODs 1 [3.2 (2.5-3.9) ng/mL; p < 0.001] and 3 [3.2 (2.7-4.1) ng/mL; p < 0.001]. P-suPAR on POD 1 was significantly lower in patients with postoperative pancreatic fistula (POPF) [2.6 (2.1-3.4) ng/mL] than in patients with no POPF [3.2 (2.6-3.8) ng/mL; p = 0.007]. Similar decreases in P-suPAR values were seen in patients with postoperative acute pancreatitis (POAP) and surgical site infection (SSI). CONCLUSIONS: After pancreatic surgery, P-suPAR level on POD 1 is significantly lower in patients with POPF, POAP or SSI. P-suPAR is decreased after pancreatic resection in all patients. This type of postoperative P-suPAR profile has not previously been described, and may reflect the compensatory anti-inflammatory reaction following the initial systemic inflammatory reaction caused by surgical trauma.

Unconventional treatment of inoperable biliary IPMN with an oesophageal stent in the common bile duct: case report.

Biliary intraductal papillary mucinous neoplasm (IPMN) is a rare biliary neoplasia preferably treated with oncologic resection. Endoscopic radio frequency (RF) ablation may be used as a palliative measure. We present a rare case, where heavy co-morbidities prevented surgery. Continuous mucus production caused recurrent episodes of severe cholangitis. Several ERCPs (endoscopic retrograde cholangio pancretography) were necessary due to recurrent biliary obstruction. RF ablation was not effective in the dilated common bile duct without a stricture. Standard biliary stents failed due to either migration or occlusion. When other options failed, an exceptional decision was made: a covered large diameter oesophageal stent was inserted in ERCP into the bile duct to secure bile flow and stop mucus production. Digital cholangioscopy was crucial adjunct to standard ERCP in endoscopic management. The palliative treatment method was successful: there were no stent-related adverse events or readmissions for cholangitis. The follow-up in the palliative care lasted until patient's last 10 months of lifetime.

Initial management of suspected biliary injury after laparoscopic cholecystectomy.

Although rare, iatrogenic bile duct injury (BDI) after laparoscopic cholecystectomy may be devastating to the patient. The cornerstones for the initial management of BDI are early recognition, followed by modern imaging and evaluation of injury severity. Tertiary hepato-biliary centre care with a multi-disciplinary approach is crucial. The diagnostics of BDI commences with a multi-phase abdominal computed tomography scan, and when the biloma is drained or a surgical drain is put in place, the diagnosis is set with the help of bile drain output. To visualize the leak site and biliary anatomy, the diagnostics is supplemented with contrast enhanced magnetic resonance imaging. The location and severity of the bile duct lesion and concomitant injuries to the hepatic vascular system are evaluated. Most often, a combination of percutaneous and endoscopic methods is used for control of contamination and bile leak. Generally, the next step is endoscopic retrograde cholangiography (ERC) for downstream control of the bile leak. ERC with insertion of a stent is the treatment of choice in most mild bile leaks. The surgical option of re-operation and its timing should be discussed in cases where an endoscopic and percutaneous approach is not sufficient. The patient's failure to recover properly in the first days after laparoscopic cholecystectomy should immediately raise suspicion of BDI and this merits immediate investigation. Early consultation and referral to a dedicated hepato-biliary unit are essential for the best outcome.

Long-term (10-year) outcomes and prognostic factors in resected intraductal papillary mucinous neoplasm tumors in Finland: A nationwide retrospective study.

BACKGROUND: The degree of dysplasia is the most important prognostic factor for patients with resected intraductal papillary mucinous neoplasms. Intraductal papillary mucinous neoplasms are predominantly premalignant conditions; in most cases, surveillance is an adequate treatment. If worrisome features are present, surgery should be considered. However, there is limited data on the long-term prognosis of resected intraductal papillary mucinous neoplasms. We aimed to ascertain the nationwide survival of patients with resected intraductal papillary mucinous neoplasms and identify factors associated with survival. METHODS: This is a retrospective nationwide cohort study. All intraductal papillary mucinous neoplasms operated on in Finland between 2000 and 2008 were identified. Patient records were evaluated, and original radiologic data and histologic samples were re-evaluated. Survival data were collected after a 10-year follow-up period. RESULTS: Out of 2,024 pancreatic resections, 88 were performed for intraductal papillary mucinous neoplasm. The median age of the patients was 65 years. Histologic diagnoses were main duct intraductal papillary mucinous neoplasm 47/88 (53,4%), mixed-type intraductal papillary mucinous neoplasm 27/88 (30.7%), and branchduct intraductal papillary mucinous neoplasm 14/88 (15.9%). Of the tumors, 40/88 (45.5%) were low-grade dysplasia, 9/88 (10.2%) high-grade, and 39/88 (44.3%) were invasive cancer. The median survival was 121 (range 0-252) months. Ten-year survival was 72.5%, 66.7%, and 23.1% in the low-grade dysplasia, high-grade dysplasia, invasive cancer groups, respectively. Ten-year mortality for pancreatic cancer was 5%, 9.1%, and 71.8% in the low-grade dysplasia, high-grade dysplasia, invasive cancer groups, respectively. CONCLUSION: Overall, 44.3% of the patients had a malignant tumor, and three-quarters (74.5%) of the main duct intraductal papillary mucinous neoplasms were malignant or high-grade dysplasia at the time of surgery. Ten-year survival was significantly better in patients operated on at the stage of a premalignant tumor (low-grade dysplasia + high-grade dysplasia) than in patients operated on at the stage of a malignant tumor.

Bile-volatile organic compounds in the diagnostics of pancreatic cancer and biliary obstruction: A prospective proof-of-concept study.

Objectives: Detection of volatile organic compounds (VOCs) from bodily fluids with field asymmetric waveform ion mobility spectrometry (FAIMS) and related methods has been studied in various settings. Preliminary results suggest that it is possible to detect prostate, colorectal, ovarian and pancreatic cancer from urine samples. In this study, our primary aim was to differentiate pancreatic cancer from pancreatitis and benign tumours of the pancreas by using bile samples obtained during endoscopic retrograde cholangiopancreatography (ERCP). Secondarily, we aimed to differentiate all pancreatic region malignancies from all other kinds of benign causes of biliary obstruction. Methods: A bile sample was successfully aspirated from 94 patients during ERCP in Tampere University Hospital. Hospital and patient records were prospectively followed up for at least two years after ERCP. Bile samples were analysed using a Lonestar chemical analyser (Owlstone, UK) using an ATLAS sampling system and a split-flow box. Diagnoses and corresponding data from the analyses were matched and divided into two subcategories for comparison. Statistical analysis was performed using linear discriminant analysis, support vector machines, and 5-fold cross-validation. Results: Pancreatic cancers (n=8) were differentiated from benign pancreatic lesions (n=9) with a sensitivity of 100%, specificity of 77.8%, and correct rate of 88%. All pancreatic region cancers (n=19) were differentiated from all other kinds of benign causes of biliary obstruction (n=75) with corresponding values of 21.1%, 94.7%, and 80.7%. The sample size was too small to try to differentiate pancreatic cancers from adjacent cancers. Conclusion: Analysing bile VOCs using FAIMS shows promising capability in detecting pancreatic cancer and other cancers in the pancreatic area.

Preoperative measures predicting outcome after pancreatic resection in aged patients.

BACKGROUND AND OBJECTIVE: High-risk surgery on aged patients raises challenging ethical and clinical issues. The aim of this study was to analyze the preoperative factors associated with severe complications and returning home after pancreatic resection among patients aged ⩾ 75 years. PATIENTS AND METHODS: Patients aged ⩾ 75 years undergoing pancreatic resection in 2012-2019 were retrospectively searched from the hospital database. Preoperative indices (Clinical Frailty Scale, Skeletal Muscle Index, Geriatric Nutritional Risk Index, Charlson Comorbidity Index, and National Surgical Quality Improvement Program risk for severe complications) were determined. Postoperative outcome was evaluated by incidence of Clavien-Dindo 3b-5 complications, rate of returning home, and 1-year survival. RESULTS: A total of 95 patients were included. American Society of Anesthesiologists Class 3-4 covered 50%, Clinical Frailty Scale > 3 22%, Charlson Comorbidity Index > 6 53%, and a sarcopenic Skeletal Muscle Index 51% of these patients. The National Surgical Quality Improvement Program risk for severe complications was higher than average among 21% of patients. Geriatric Nutritional Risk Index showed high risk among 3% of them. In total, 19 patients (20%) experienced a severe (Clavien-Dindo 3b-5) complication. However, 30- and 90-day mortality was 2.1%. Preoperative indices were not associated with severe complications. Most patients (79%) had returned home within 8 weeks of surgery. Not returning home was associated with severe complications (p = 0.010). CONCLUSIONS: The short-term outcome after pancreatic resection of fit older patients is similar to that of younger, unselected patient groups. In these selected patients, the commonly used preoperative indexes were not associated with severe complications or returning home.

The European evidence-based guidelines on pancreatic cystic neoplasms (PCN) in clinical practice: The development of relative and absolute indications for surgery during prospective IPMN surveillance.

INTRODUCTION: The European evidence-based guidelines on PCN recommend surveillance for IPMN patients who are fit for surgery but who have no indication for immediate surgery. Our aim was to demonstrate the feasibility of the new guidelines in clinical practice. METHODS: This is a prospective cohort study of patients included in the IPMN register in Tampere University Hospital, Finland. IPMN was diagnosed from January 1, 2013 to December 31, 2018. Patients were analyzed for surveillance and indications for surgery according to the European guidelines on PCN. RESULTS: Out of 128 patients in register 23 was decided to operate upfront and 105 patients were included in the surveillance programme. Invasive carcinoma was found in 4/23 of operated patients. Median follow-up time was 26 months (6-69). Median size of the cyst at the beginning and end of the surveillance was 16 mm (4-58 mm). During surveillance 0/105 (0.0%) patients had or developed an absolute indication for surgery. Relative indication for surgery was present in 8/105 (7.6%) patients in the beginning surveillance and 9/105 (8.6%) patients developed at least one relative indication for surgery during surveillance. From the surveillance cohort 2/105 patients were operated. Surveillance was abandoned in 15/105 (14.1%) patients all due to poor general condition or other medical conditions. CONCLUSIONS: In clinical practice, surveillance of IPMN according to the European guidelines on PCN is feasible. Among our patients 16% were detected to have relative indications for surgery during the median 26 (range 3-135) months of surveillance. Nearly 15% became surgically unfit during surveillance period.

Perioperative hydrocortisone treatment reduces postoperative pancreatic fistula rate after open distal pancreatectomy. A randomized placebo-controlled trial.

BACKGROUND: Postoperative pancreatic fistula (POPF) is the most common complication after distal pancreatectomy (DP). In a recent RCT on pancreaticoduodenectomy (PD), perioperative hydrocortisone (HC) treatment reduced Clavien-Dindo (C-D) III-V complications. The aim of this study was to investigate whether perioperative HC treatment reduces the overall complications and clinically significant POPF after distal pancreatectomy (DP). METHODS: Fourty consecutive patients undergoing DP were randomized to receive intravenous HC 100mg/placebo every eight hours until the second postoperative day. Thirty-one patients were completed with DP and received HC/placebo every 8 h for two days postoperatively. The primary endpoint was overall complications (C-D III-V) and the secondary endpoint was the development of clinically significant POPF. RESULTS: Pancreatic duct diameter, operative time and blood loss were similar in the groups. Ninety-day mortality was zero. With HC treatment the rates of C-D III-V complications tended to be lower compared to the placebo group (5.9% vs 21.4%, p = 0.034). The rate of grade B/C POPF was significantly reduced with HC treatment compared to the placebo group (5.9% vs. 42.9%, p = 0.028). CONCLUSION: Perioperative HC treatment may have a favourable effect on overall major complications after open DP. HC treatment reduces the incidence of clinically significant POPF after open DP.

Characteristics and long-term survival of resected pancreatic cystic neoplasms in Finland. The first nationwide retrospective cohort analysis.

BACKGROUND: Pancreatic cystic neoplasms (PCN) are being found increasingly in imaging studies. Even though the characteristics of PCN lesions have been studied extensively in single and multicentre settings, nationwide data is lacking. The aim of this study was to determine the nationwide epidemiologic characteristics and long-term survival of all resected PCNs. METHODS: For this retrospective cohort analysis, all PCNs operated on in Finland during the period 2000-2008 were identified. Data was collected from all patients: on demographics, comorbidities, symptoms, radiological findings, surgical procedures, complications, histopathological diagnoses and survival. Incomplete pathology reports and any uncertain diagnoses were re-assessed. Survival data was collected after a five-year follow-up period. RESULTS: The final database included 225 patients with operated PCN. After reviewing the incomplete pathology reports, in 44 cases the original diagnosis was changed, mostly from MCN to IPMN. The most common histopathological diagnoses were IPMN (94/225; 50/225 MD-IPMN, 30/225 MX-IPMN and 14/225 BD-IPMN), SCN (41/225) and MCN (40/225). Overall, 53/225 (23.6%) of the tumours were malignant. Malignancy was detected in MD-IPMN 29/50 (58%), MX-IPMN 10/30 (33.3%), MCN 12/40 (30%), BD-IPMN 2/14 (14.3%) patients. Median 5-year survival for all patients was 77%: 87% in patients without malignancy, 77% with HGD and 27% in patients with a malignant resected PCN. CONCLUSION: One fourth of the PCNs operated on nationwide were malignant, with a five-year survival of 27%, compared to overall survival of 87% in patients with non-malignant disease and 77% in those with HGD. Detecting - and operating on - a PCN before the malignant transfer remains a great challenge.

Biodegradable biliary stents preferable to plastic stent therapy in post-cholecystectomy bile leak and avoid second endoscopy.

BACKGROUND: The treatment of post-cholecystectomy bile leak is endoscopic retrograde cholangiography (ERC) with plastic stent (PS) insertion combined with external drainage. Self-expanding biodegradable biliary stents (BDBS) have only recently become available. AIM: The aim was to compare success rate, adverse events and costs of BDBS with PS in the treatment of post-cholecystectomy cystic duct leak Materials and methods: Patients recruited prospectively for treatment with BDBS during the period 2014-2017 were compared to a control group treated with PS in a non-randomized setting. RESULTS: Altogether 32 patients (median age 68, range 33-88, 59% male) were treated for Strasberg A bile leak over a period of 3.5 years, accounting for 1.8% of all ERCs. Eight patients were treated with BDBS and 24 with PS. Treatment with BDBS was safe; rate of readmissions and 30-day adverse events were 13% in both groups. There was no statistical difference in the clinical success rate. All cases with laparoscopic lavation or re-ERC with stent exchange occurred in the PS group. Total drain output was lower in BDBS patients (330ml vs 83ml, p=.002). All PS patients required another endoscopy for stent removal, whereas all BDBS patients were spared repeated endoscopy. CONCLUSION: Treatment of cystic duct leak with BDBS is highly successful and as safe as traditional treatment with PS. The most obvious benefit of BDBS is that it avoids stent removal. The lower drain output after ERC with a trend for fewer unplanned interventions may indicate more efficient leak resolution with the large bore BDBS.

Prognosis of sporadic resected small (≤2 cm) nonfunctional pancreatic neuroendocrine tumors - a multi-institutional study.

BACKGROUND: Malignant potential of small (≤20 mm) nonfunctional pancreatic neuroendocrine tumors (sNF-PNET) is difficult to predict and management remain controversial. The aim of this study was to assess the prognosis of sporadic nonmetastatic sNF-PNETs. METHODS: Patients were identified from databases of 16 centers. Outcomes and risk factors for recurrence were identified by uni- and multivariate analyses. RESULTS: sNF-PNET was resected in 210 patients, and 66% (n = 138) were asymptomatic. Median age was 60 years, median tumor size was 15 mm, parenchyma-sparing surgery was performed in 42%. Postoperative mortality was 0.5% (n = 1), severe morbidity rate was 14.3% (n = 30), and 14 of 132 patients (10.6%) with harvested lymph nodes had metastatic lymph nodes. Tumor size, presence of biliary or pancreatic duct dilatation, and WHO grade 2-3 were independently associated with recurrence. Patients with tumors sized ≤10 mm were disease free at last follow-up. The 1-, 3- and 5-year disease-free survival rates for patients with tumors sized 11-20 mm on preoperative imaging were 95.1%, 91.0%, and 87.3%, respectively. CONCLUSIONS: In sNF-PNETs, the presence of biliary or pancreatic duct dilatation or WHO grade 2-3 advocate for surgical treatment. In the remaining patients, a wait-and-see policy might be considered.

Nature and management of pancreatic mucinous cystic neoplasm (MCN): A systematic review of the literature.

BACKGROUND: The current management of pancreatic mucinous cystic neoplasms (MCN) is defined by the consensus European, International Association of Pancreatology and American College of Gastroenterology guidelines. However, the criterion for surgical resection remains uncertain and differs between these guidelines. Therefore through this systematic review of the existing literature we aimed to better define the natural history and prognosis of these lesions, in order to clarify recommendations for future management. METHODS: A systematic literature search was performed (PubMed, EMBASE, Cochrane Library) for studies published in the English language between 1970 and 2015. RESULTS: MCNs occur almost exclusively in women (female:male 20:1) and are mainly located in the pancreatic body or tail (93-95%). They are usually found incidentally at the age of 40-60 years. Cross-sectional imaging and endoscopic ultrasound are the most frequently used diagnostic tools, but often it is impossible to differentiate MCNs from branch duct intraductal papillary mucinous neoplasms (BD-IPMN) or oligocystic serous adenomas pre-operatively. In resected MCNs, 0-34% are malignant, but in those less than 4 cm only 0.03% were associated with invasive adenocarcinoma. No surgically resected benign MCNs were associated with a synchronous lesion or recurrence; therefore further follow-up is not required after resection. Five-year survival after surgical resection of a malignant MCN is approximately 60%. CONCLUSIONS: Compared to other pancreatic tumors, MCNs have a low aggressive behavior, with exceptionally low rates of malignant transformation when less than 4 cm in size, are asymptomatic and lack worrisome features on pre-operative imaging. This differs significantly from the natural history of small BD-IPMNs, supporting the need to differentiate mucinous cyst subtypes pre-operatively, where possible. The findings support the recommendations from the recent European Consensus Guidelines, for the more conservative management of MCNs.

Safety and Efficacy of Acute Endoscopic Retrograde Cholangiopancreatography in the Elderly.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is a frequent procedure in elderly patients. AIMS: We aimed to determine the safety and efficacy of acute ERCP in older patients. METHODS: A prospectively managed, hospital-based registry containing all ERCP procedures and complications at a tertiary referral center was used to form the study population, which consisted of consecutive elderly (≥65 years) patients undergoing acute ERCP during the 5-year study period. Indications, details, outcome, and complications of the procedure were analyzed in relation to patient age, gender, and co-morbidities. RESULTS: A total of 480 elderly patients (median age 78; range 65-97; 48 % men) underwent 531 ERCPs during the study period. The most common indications were bile duct stones (56.1 %) and biliary obstruction caused by malignancy (33.7 %). Successful stone extraction was achieved in 72.8 %, and with an additional, planned ERCP in 96.6 % of the patients. Post-ERCP complications developed in 3.4 % of the patients. These included pancreatitis in 1.7 %, hemorrhage in 0.6 %, and duodenal perforation in 0.2 % of the patients. One of these (0.2 %) was considered severe as this patient required invasive treatments and prolonged hospital stay. The risk of complications was associated with chronic obstructive pulmonary disease and difficult cannulation. Procedure-related mortality was zero, but overall 30-day mortality was 10 %, being 24 % in the patients with malignancy. CONCLUSIONS: ERCP can be safely and efficaciously performed on elderly patients. The high mortality should be taken into consideration when selecting therapeutic options.

Is Roux-Y binding pancreaticojejunal anastomosis feasible for patients undergoing left pancreatectomy? Results from a prospective randomized trial.

BACKGROUND: After pancreaticoduodenectomy, the Finnish binding pancreaticojejunal anastomosis (FBPJ) seems to reduce the risk for pancreatic fistula (POPF). Our aim was to investigate whether FBPJ is feasible and prevents the risk for POPF even after left pancreatectomy (LP). PATIENTS AND METHODS: 47 consecutive patients underwent LP. 27 patients were recruited on the basis of CT and, of these, 16 patients were randomized on the basis of findings during surgery (transection line must be left of portal vein, as 2-3 cm pancreatic mobilization is required for FBPJ) to receive either Roux-Y FBPJ or hand-sewn closure of the pancreatic remnant. RESULTS: Only 34% (16/47) of the patients met the randomization criteria. Clinically significant POPF rate was higher in FBPJ group (60%) compared to thand-sewn closure group (13%; P<0.05). POPF rate in FBPJ group was higher even when compared to all patients with hand-sewn closure (60% versus 37%; P<0.05). Overall, FBPJ was technically feasible for only 28% of patients. CONCLUSION: FBPJ cannot be recommended for the routine closure of the pancreatic remnant after LP, as it was not technically achievable in 72% of the cases. Moreover, the technique does not seem to reduce the risk for POPF compared to the hand-sewn closure.