Venous resection for pancreatic cancer, a safe and feasible option? A systematic review and meta-analysis.

BACKGROUND: In pancreatic ductal adenocarcinoma patients with suspected venous infiltration, a R0 resection is most of the time not possible without venous resection (VR). To investigate this special kind of patients, this meta-analysis was conducted to compare mortality, morbidity and long-term survival of pancreatic resections with (VR+) and without venous resection (VR-). METHODS: A systematic search was performed in Embase, Pubmed and Web of Science. Studies which compared over twenty patients with VR + to VR-for PDAC with ≥1 year follow up were included. Articles including arterial resections were excluded. Statistical analysis was performed with the random effect Mantel-Haenszel test and inversed variance method. Individual patient data was compared with the log-rank test. RESULTS: Following a review of 6403 papers by title and abstract and 166 by full text, a meta-analysis was conducted of 32 studies describing 2216 VR+ and 5380 VR-. There was significantly more post-pancreatectomy hemorrhage (6.5% vs. 5.6%), R1 resections (36.7% vs. 28.6%), N1 resections (70.3% vs. 66.8%) and tumors were significantly larger (34.6 mm vs. 32.8 mm) in patients with VR+. Of all VR + patients, 64.6% had true pathological venous infiltration. The 90-day mortality, individual patient data for overall survival and pooled multivariate hazard ratio for overall survival were similar. CONCLUSION: VR is a safe and feasible option in patients with pancreatic cancer and suspicion of venous involvement, since VR during pancreatic surgery has comparable overall survival and complication rates.

Scoring Systems May be Effective in Predicting Mortality Associated with Palliative Emergency Gastrointestinal Surgery: A Retrospective Observational Study.

BACKGROUND: Palliative emergency gastrointestinal surgery is associated with significant morbidity and mortality and weighing up the benefits and harms during the decision-making may be challenging. There are very few studies on surgery in palliative patient population. The aim of this retrospective study was to evaluate morbidity and mortality after palliative emergency gastrointestinal surgery and the usability of scoring systems in predicting the outcome. METHODS: Consecutive adult patients undergoing palliative emergency surgery at a tertiary hospital during the period 2015 to 2016 were included. Pre- and post-operative functional status, morbidity and mortality of patients were assessed. The predictive value of the American Society of Anesthesiologists (ASA) classification, the American College of Surgeons National Surgical Quality Improvement Program Surgical Risk Calculator (ACS NSQIP SRC) and Palliative index (PI) in estimating morbidity and mortality were determined. RESULTS: A total of 93 patients (age 69 [28-92] years, 51% female) were included. Typical indications for surgery were bowel obstruction (52%) and securing food intake (30%). Pre-operatively two patients (2.2%) were totally dependent in daily activities, while post-operatively the respective share was 34% at discharge from hospital. The incidence of post-operative complications was 37% and 14% died during the hospital stay. One-, three-month and one-year mortality rates were 41%, 63% and 87%, respectively. While ASA score, PI score and ACS NSQIP did not predict post-operative morbidity, both ASA score and ACS NSQIP SRC predicted post-operative mortality. CONCLUSIONS: Palliative emergency laparotomy is associated with significant post-operative mortality and morbidity. Scorings, such as ASA score and ACS NSQIP SRC predict mortality in this patient population.

International consensus guidelines for surgery and the timing of intervention in chronic pancreatitis.

BACKGROUND/OBJECTIVES: Chronic pancreatitis (CP) is a complex inflammatory disease with pain as the predominant symptom. Pain relief can be achieved using invasive interventions such as endoscopy and surgery. This paper is part of the international consensus guidelines on CP and presents the consensus guideline for surgery and timing of intervention in CP. METHODS: An international working group with 15 experts on CP surgery from the major pancreas societies (IAP, APA, JPS, and EPC) evaluated 20 statements generated from evidence on 5 questions deemed to be the most clinically relevant in CP. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to evaluate the level of evidence available for each statement. To determine the level of agreement, the working group voted on the 20 statements for strength of agreement, using a nine-point Likert scale in order to calculate Cronbach's alpha reliability coefficient. RESULTS: Strong consensus was obtained for the following statements: Surgery in CP is indicated as treatment of intractable pain and local complications of adjacent organs, and in case of suspicion of malignant (cystic) lesion; Early surgery is favored over surgery in a more advanced stage of disease to achieve optimal long-term pain relief; In patients with an enlarged pancreatic head, a combined drainage and resection procedure, such as the Frey, Beger, and Berne procedure, may be the treatment of choice; Pancreaticoduodenectomy is the most suitable surgical option for patients with groove pancreatitis; The risk of pancreatic carcinoma in patients with CP is too low (2% in 10 year) to recommend active screening or prophylactic surgery; Patients with hereditary CP have such a high risk of pancreatic cancer that prophylactic resection can be considered (lifetime risk of 40-55%). Weak agreement for procedure choice in patients with dilated duct and normal size pancreatic head: both the extended lateral pancreaticojejunostomy and Frey procedure seems to provide equivalent pain control in patients. CONCLUSIONS: This international expert consensus guideline provides evidenced-based statements concerning key aspects in surgery and timing of intervention in CP. It is meant to guide clinical practitioners and surgeons in the treatment of patients with CP.

Pancreatic resections are not only safest but also most cost-effective when performed in a high-volume centre: A Finnish register study.

BACKGROUND: It is not known whether the treatment costs of pancreatic surgery can be reduced by centralisation. The aim of this study was to analyse the impact of hospital volume on the short-term prognosis and costs in a nationwide study. METHODS: The National registry was searched for patients undergoing pancreatoduodenectomy (PD) in Finland between 2012 and 2014. Patient data was recorded up to ninety days postoperatively and Charlson comorbidity index (CCI) calculated. Complications were classified according to Clavien-Dindo. A CCI was calculated for each patient. The hospitals were categorized by yearly resection rate: high (≥20, HVC), medium (6-19, MVC) and low (≤5, LVC). Costs were calculated according to the 2012 billing list. RESULTS: The study population comprised 466 patients. Demographics were similar in the HVC, MVC and LVC groups. Mortality was lower in the HVCs than in MVCs and LVCs at 30 days (0.8% vs. 8.8-12.9%; p < 0.01) and at 90 days (1.9% vs. 10.5-16.1%; p < 0.01). Hospital volume and CCI were significant factors for mortality in multivariate analysis. Median costs among all patients were lower in the HVC group than in the MVC/LVC groups (p = 0.019), among Clavien-Dindo class III (0.020), among patients over 75 years (p < 0.001) and among patients who survived over five days (p = 0.015). CONCLUSIONS: Thirty- and 90-day mortality is 10 times lower when the patient is operated on in an HVC. The study shows that the median overall costs of surgical treatment are 82-88% of the median costs in lower volume centres.

Management of postoperative complications may favour the centralization of distal pancreatectomies. Nationwide data on pancreatic distal resections in Finland 2012-2014.

BACKGROUND: Centralization of pancreatic surgery has proceeded in the last few years in many countries. However, information on the effect of hospital volume specifically on distal pancreatic resections (DP) is lacking. AIM: To investigate the effect of hospital volume on postoperative complications in DP patients in Finland. METHODS: All DP performed in Finland during the period 2012-2014 were analyzed, information having been retrieved from the appropriate national registers. Hospital volumes, postoperative pancreatic fistulae (POPF) and overall complications were graded. High volume centre (HVC) was defined as performing > 10 DPs, median volume centre (MVC) 4-9 DPs and low volume centre (LVC) fewer than 4 DP annually. RESULTS: A total of 194 DPs were performed at 18 different hospitals. Of these 42% (81) were performed in HVCs (2 hospitals), 43% (84) in MVCs (6 hospitals) and the remaining 15% (29) in LVCs (10 hospitals). Patient demographics did not differ between the hospital volume groups. The overall rate of clinically relevant POPF, Clavien-Dindo grade 3-5 complications, and 90-day mortality showed no significant differences between the different hospital volumes. Grade C POPF was found more often in LVCs, being 1.2% in HVCs, 0% in MCVs and 6.9% in LVCs, p = 0.030. More reoperations were performed in LVCs (10.3%) than in HVCs (1.2%) or MVCs (1.2%); p = 0.025. CONCLUSIONS: Even though the rate of postoperative complications after DP is not affected by hospital volume, reoperations were performed ten times more often in the low-volume centres. Optimal management of postoperative complications may favour centralization not only of PD, but also of DP.

Risk of malignancy in resected pancreatic mucinous cystic neoplasms.

BACKGROUND: Pancreatic mucinous cystic neoplasms (MCNs) are rare mucin-producing cystic tumours defined by the presence of ovarian-type stroma. MCNs have a malignant potential and thus surgery is frequently performed. The aim of this cohort study was to define better the criteria for surgical resection in patients with MCN. METHODS: This multicentre retrospective study included all resected MCNs between 2003 and 2015 in participating centres. Lesions without ovarian-type stroma were excluded. Patient characteristics, preoperative findings, histopathology findings and follow-up data were recorded. RESULTS: The study included 211 patients; their median age was 53 (range 18-82) years, and 202 (95·7 per cent) were women. Median preoperative tumour size was 55 (range 12-230) mm. Thirty-four of the 211 (16·1 per cent) were malignant, and high-grade dysplasia (HGD) was found in a further 13 (6·2 per cent). One-third of MCNs in men were associated with invasive cancer, compared with 15·3 per cent in women. Five cases of malignant transformation occurred in MCNs smaller than 4 cm. All cases of malignancy or HGD were associated with symptoms or features of concern on preoperative cross-sectional imaging. In multivariable analysis, raised carbohydrate antigen 19-9 (odds ratio (OR) 10·54, 95 per cent c.i. 2·85 to 218·23; P < 0·001), tumour size (OR 4·23, 3·02 to 11·03; P = 0·001), mural nodules (OR 3·55, 1·31 to 20·55; P = 0·002) and weight loss (OR 3·40, 2·34 to 12·34; P = 0·034) were independent factors predictive of malignant transformation. CONCLUSIONS: Small indeterminate MCNs with no symptoms or features of concern may safely be observed as they have a low risk of malignant transformation.

Effect of centralization on long-term survival after resection of pancreatic ductal adenocarcinoma.

BACKGROUND: Centralization of pancreatic surgery has resulted in improved short-term outcomes in a number of healthcare systems. The aim of this study was to see whether hospital volume influenced long-term prognosis, use of adjuvant therapy or histopathological evaluation of patients undergoing surgical resection for pancreatic ductal adenocarcinoma (PDAC). METHODS: Patients undergoing surgical resection of PDAC in Finland between 2002 and 2008 were identified from national registers. Demographic, histopathological, operative and oncological data were recorded, and the histopathological slides of patients who survived for more than 4 years were reviewed. Operative volume was defined according to the annual rate of pancreatoduodenectomy as: high-volume centres (HVCs; 20 or more resections per year), medium-volume centres (MVCs; 6-19 resection annually) and low-volume centres (LVCs; 5 or fewer resections annually). RESULTS: Some 467 patients who had undergone resectional surgery for PDAC at 22 centres were included. Patient demographics and resection types did not differ between centres. Thirty- and 90-day mortality rates were significantly lower in HVCs compared with LVCs: 0 versus 5·5 per cent (P = 0·001) and 2·5 versus 11·0 per cent (P = 0·003) respectively. Tumours in HVCs were generally at a more advanced stage than those in LVCs (stage IIB: 65·7 versus 40·6 per cent respectively; P < 0·001), but with no greater use of adjuvant therapy. Significantly more patients survived for 2 years (43·3 versus 29·7 per cent; P = 0·034) and 3 years (25·4 versus 14·1 per cent; P = 0·045) after surgery in HVCs than in LVCs. More information was missing in the histopathological reports from LVCs and MVCs than in those from HVCs (P ≤ 0·002). CONCLUSION: Both short- and long-term survival was significantly better for patients operated on in HVCs. Histopathological analysis appears to be more comprehensive in HVCs.

Nighttime Appendectomy is Safe and has Similar Outcomes as Daytime Appendectomy: A Study of 1198 Appendectomies.

INTRODUCTION: Although it is controversial whether appendectomy can be safely delayed, it is often unnecessary to postpone operation as a shorter delay may increase patient comfort, enables quicker recovery, and decreases costs. In this study, we sought to study whether the time of day influences the outcomes among patients operated on for acute appendicitis. MATERIALS AND METHODS: Consecutive patients undergoing appendectomy at Tampere University Hospital between 1 September 2014 and 30 April 2017 for acute appendicitis were included. Primary outcome measures were postoperative morbidity, mortality, length of hospital stay, and amount of intraoperative bleeding. Appendectomies were divided into daytime and nighttime operations. RESULTS: A total of 1198 patients underwent appendectomy, of which 65% were operated during daytime and 35% during nighttime. Patient and disease-related characteristics were similar in both groups. The overall morbidity and mortality rates were 4.8% and 0.2%, respectively. No time categories were associated with risk of complications or complication severity. Neither was there difference in operation time and clinically significant difference in intraoperative bleeding. Patients undergoing surgery during night hours had a shorter hospital stay. In multivariate analysis, only complicated appendicitis was associated with worse outcomes. DISCUSSION: We have shown that nighttime appendectomy is associated with similar outcomes than daytime appendectomy. Subsequently, appendectomy should be planned for the next available slot, minimizing delay whenever possible.

Centralization of Pancreatic Surgery Improves Results: Review.

BACKGROUND AND AIMS: The effect of operation volume on the outcomes of pancreatic surgery has been a subject of research since the 1990s. In several countries around the world, this has led to the centralization of pancreatic surgery. However, controversy persists as to the benefits of centralization and what the optimal operation volume for pancreatic surgery actually is. This review summarizes the data on the effect of centralization on mortality, complications, hospital facilities used, and costs regarding pancreatic surgery. MATERIALS AND METHODS: A systematic librarian-assisted search was performed in PubMed covering the years from August 1999 to August 2019. All studies comparing results of open pancreatic resections from high- and low-volume centers were included. In total 44, published articles were analyzed. RESULTS: Studies used a variety of different criteria for high-volume and low-volume centers, which hampers the evaluating of the effect of operation volume. However, mortality in high-volume centers is consistently reported to be lower than in low-volume centers. In addition, failure to rescue critically ill patients is more common in low-volume centers. Cost-effectiveness has also been evaluated in the literature. Length of hospital stay in particular has been reported to be shorter in high-volume centers than in low-volume centers. CONCLUSION: The effect of centralization on the outcomes of pancreatic surgery has been under active research and the beneficial effect of it is associated especially with better short-term prognosis after surgery.

In the Era of the Leeds Protocol: A Systematic Review and A Meta-Analysis on the Effect of Resection Margins on Survival Among Pancreatic Ductal Adenocarcinoma Patients.

BACKGROUND AND AIMS: A positive resection margin is considered to be a factor associated with poor prognosis after pancreatic ductal adenocarcinoma resection. However, analysis of the resection margin is dependent on the pathological slicing technique. The aim of this systematic review and meta-analysis was to study the impact of resection margin on the survival of pancreatic ductal adenocarcinoma patients whose specimens were analyzed using the axial slicing technique. MATERIAL AND METHODS: A systematic search in the PubMed, Cochrane, and Embase datasets covering the time period from November 2006 to January 2019 was performed. Only studies with axial slicing technique (Leeds Pathology Protocol or Royal College of Pathology Protocol) were included in the final database. Meta-analysis between the marginal distance and survival was performed with the Inverse Variance Method in RevMan. RESULTS: The systematic search resulted in nine studies meeting the inclusion criteria. The median survival for a resection margin 0 mm ranged from 12.3 to 23.4 months, for resection margin <0.5 mm 16 months, for resection margin <1 mm ranged from 11 to 27.5 months, for resection margin <1.5 mm ranged from 16.9 to 21.2 months, and for resection margin >2 mm ranged from 53.9 to 63.1 months. Five studies were eligible for meta-analysis. The pooled multivariable hazard ratio favored resection margin ⩾1 mm (hazard ratio: 1.32 and 95% confidence interval: 1.03-1.68, p = 0.03). CONCLUSION: Resection margins ⩾1 mm seem to lead to better survival in pancreatic ductal adenocarcinoma patients than resection margin <1 mm. However, there is not enough data to evaluate the effect of oncologic therapy or to analyze the impact of other resection margin distances on survival.

Bile flow to the duodenum is reduced in hypothyreosis and enhanced in hyperthyreosis.

Disturbances in sphincter of Oddi (SO) function may prevent normal bile flow and thus enhance probability of common bile duct stone (CBDS) formation. We have previously shown increased prevalence of diagnosed hypothyroidism in CBDS patients, which may be explained by thyroxine-induced inhibition of SO contractility, in addition to previously suggested changes in bile composition and hepatocytic excretion. The aim of this study was to investigate biliary dynamics in relation to altered thyroid gland function in rat, a rodent without a gallbladder. Euthyroid, hypothyroid or hyperthyroid Spraque-Dawley rats were anaesthetized with i.p. urethane, and exsanguinated at 15, 45, or 60 min after intravenous 99mTc HIDA injection. At these timepoints, the bile flow to intestine was determined by measuring the relative intestine vs. liver radioactivity. At 45 min this was 44% lower in hypothyroid rats and at 60 min 73% higher in hyperthyroid rats compared to euthyroid rats, while hepatic radioactivity at 15 min and blood pressure at injection were similar in the groups. We conclude that the bile flow to duodenum is reduced in hypothyreosis and enhanced in hyperthyreosis.

Mechanism of the prorelaxing effect of thyroxine on the sphincter of Oddi.

BACKGROUND: Disturbances in the function of sphincter of Oddi (SO) may prevent normal bile flow and thus enhance the probability of common bile duct stone (CBDS) formation. Previously, we have shown increased prevalence of hypothyroidism in CBDS patients. METHODS: In animal (pig) experiments, thyroxine (T4) and triiodothyronine have a specific inhibitory effect on SO contractility, which raises the possibility that the lack of this prorelaxing effect in hypothyroidism could, at least in part, explain the increased prevalence of CBDS. The aims of the present study were to investigate, whether human SO reacts similarly to T4, and to study the mechanisms of the T4 prorelaxing effect. RESULTS: We found that T4 had similar inhibitory effects on both human and pig SO contractions. The T4 effect was dose-dependent, and maximum was observed in 30 min. The maximal prorelaxing effect was achieved with 0.1 nM T4 concentration, the effect of the physiological T4 concentration (0.01 nM) being about half of the maximal effect. Addition of alpha-adrenoceptor antagonist phentolamine, beta-adrenoceptor antagonist propranolol, nitric oxide (NO)-synthesis inhibitor L-NAME, nerve conductance blocker tetrodotoxin, or cyclooxygenase inhibitor diclofenac did not affect the T4-induced inhibition of contraction. Addition of transcription inhibitor actinomycin D or translation inhibitor cyclophosphamide partially reversed the T4-induced inhibition of contraction. Addition of K+ channel blocker glibenclamide totally reversed the T4-induced inhibition of contraction. In Western blotting, the thyroid hormone receptor (TR) antibody recognized 53 kDa and 58 kDa proteins, corresponding to beta1 and beta2 isoforms of TR, in the human SO tissue. CONCLUSIONS: We conclude that T4 has a direct prorelaxing effect on human SO that expresses TR beta1 and beta2. This effect is mediated through a transcriptional mechanism that requires new mRNA and protein synthesis and subsequently leads to the activation of K+ channels.