Prediction of Isolated Local Recurrence After Resection of Pancreatic Ductal Adenocarcinoma: A Nationwide Study.

BACKGROUND: Distinguishing postoperative fibrosis from isolated local recurrence (ILR) after resection of pancreatic ductal adenocarcinoma (PDAC) is challenging. A prognostic model that helps to identify patients at risk of ILR can assist clinicians when evaluating patients' postoperative imaging. This nationwide study aimed to develop a clinically applicable prognostic model for ILR after PDAC resection. PATIENTS AND METHODS: An observational cohort study was performed, including all patients who underwent PDAC resection in the Netherlands (2014-2019; NCT04605237). On the basis of recurrence location (ILR, systemic, or both), multivariable cause-specific Cox-proportional hazard analysis was conducted to identify predictors for ILR and presented as hazard ratios (HRs) with 95% confidence intervals (CIs). A predictive model was developed using Akaike's Information Criterion, and bootstrapped discrimination and calibration indices were assessed. RESULTS: Among 1194/1693 patients (71%) with recurrence, 252 patients (21%) developed ILR. Independent predictors for ILR were resectability status (borderline versus resectable, HR 1.42; 95% CI 1.03-1.96; P = 0.03, and locally advanced versus resectable, HR 1.11; 95% CI 0.68-1.82; P = 0.66), tumor location (head versus body/tail, HR 1.50; 95% CI 1.00-2.25; P = 0.05), vascular resection (HR 1.86; 95% CI 1.41-2.45; P < 0.001), perineural invasion (HR 1.47; 95% CI 1.01-2.13; P = 0.02), number of positive lymph nodes (HR 1.04; 95% CI 1.01-1.08; P = 0.02), and resection margin status (R1 < 1 mm versus R0 ≥ 1 mm, HR 1.64; 95% CI 1.25-2.14; P < 0.001). Moderate performance (concordance index 0.66) with adequate calibration (slope 0.99) was achieved. CONCLUSIONS: This nationwide study identified factors predictive of ILR after PDAC resection. Our prognostic model, available through www.pancreascalculator.com , can be utilized to identify patients with a higher a priori risk of developing ILR, providing important information in patient evaluation and prognostication.

Does preoperative multidisciplinary team assessment of high-risk patients improve the safety and outcomes of patients undergoing surgery?

BACKGROUND: International guidelines recommend preoperative multidisciplinary team (MDT) assessment for high-risk surgical patients. Preoperative MDT meetings can help to improve surgical care, but there is little evidence on whether they improve patient outcomes. METHODS: This paper aims to share our experience of MDT meetings for high-risk surgical patients to underline their added value to the current standard of care. An observational study of a retrospective cohort of preoperative high-risk MDT meetings of a tertiary referral hospital between January 2015 and December 2020. For 249 patients the outcomes preoperative data, MDT decisions, and patient outcomes were collected from electronic health records. MAIN RESULTS: A total of 249 patients were discussed at high-risk MDT meetings. Most of the patients (97%) were assessed as having an American Society of Anesthesiology score ≥ 3, and 219 (88%) had a European Society of Cardiology and European Society of Anaesthesiology risk score of intermediate or high. After MDT assessment, 154 (62%) were directly approved for surgery, and 39 (16%) were considered ineligible for surgery. The remaining 56 (23%) patients underwent additional assessments before reconsideration at a high-risk MDT meeting. The main reason for patients being discussed at the high-risk MDT meeting was to assess the risk-benefit ratio of surgery. Ultimately, 184 (74%) patients underwent surgery. Of the operated patients, 122 (66%) did not have a major complication in the postoperative period, and 149 patients (81%) were alive after one year. CONCLUSIONS: This cohort study shows the vulnerability and complexity of high-risk patients but also shows that the use of an MDT assessment contributes too improved peri- and postoperative treatment strategies in high-risk patients. Most patients underwent surgery after careful risk assessment and, if deemed necessary, preoperative and perioperative treatment optimization to reduce their risk.

Healthcare cost expenditure for robotic versus laparoscopic liver resection: a bottom-up economic evaluation.

BACKGROUND: Minimally invasive liver surgery (MILS) is increasingly performed via the robot-assisted approach but may be associated with increased costs. This study is a post-hoc comparison of healthcare cost expenditure for robotic liver resection (RLR) and laparoscopic liver resection (LLR) in a high-volume center. METHODS: In-hospital and 30-day postoperative healthcare costs were calculated per patient in a retrospective series (October 2015-December 2022). RESULTS: Overall, 298 patients were included (143 RLR and 155 LLR). Benefits of RLR were lower conversion rate (2.8% vs 12.3%, p = 0.002), shorter operating time (167 min vs 198 min, p = 0.044), and less blood loss (50 mL vs 200 mL, p < 0.001). Total per-procedure costs of RLR (€10260) and LLR (€9931) were not significantly different (mean difference €329 [95% bootstrapped confidence interval (BCI) €-1179-€2120]). Lower costs with RLR due to shorter surgical and operating room time were offset by higher disposable instrumentation costs resulting in comparable intraoperative costs (€5559 vs €5247, mean difference €312 [95% BCI €-25-€648]). Postoperative costs were similar for RLR (€4701) and LLR (€4684), mean difference €17 [95% BCI €-1357-€1727]. When also considering purchase and maintenance costs, RLR resulted in higher total per-procedure costs. DISCUSSION: In a high-volume center, RLR can have similar per-procedure cost expenditure as LLR when disregarding capital investment.

Impact of shifting from laparoscopic to robotic surgery during 600 minimally invasive pancreatic and liver resections.

BACKGROUND: Many centers worldwide are shifting from laparoscopic to robotic minimally invasive hepato-pancreato-biliary resections (MIS-HPB) but large single center series assessing this process are lacking. We hypothesized that the introduction of robot-assisted surgery was safe and feasible in a high-volume center. METHODS: Single center, post-hoc assessment of prospectively collected data including all consecutive MIS-HPB resections (January 2010-February 2022). As of December 2018, all MIS pancreatoduodenectomy and liver resections were robot-assisted. All surgeons had participated in dedicated training programs for laparoscopic and robotic MIS-HPB. Primary outcomes were in-hospital/30-day mortality and Clavien-Dindo ≥ 3 complications. RESULTS: Among 1875 pancreatic and liver resections, 600 (32%) were MIS-HPB resections. The overall rate of conversion was 4.3%, Clavien-Dindo ≥ 3 complications 25.7%, and in-hospital/30-day mortality 1.8% (n = 11). When comparing the period before and after the introduction of robotic MIS-HPB (Dec 2018), the overall use of MIS-HPB increased from 25.3 to 43.8% (P < 0.001) and blood loss decreased from 250 ml [IQR 100-500] to 150 ml [IQR 50-300] (P < 0.001). The 291 MIS pancreatic resections included 163 MIS pancreatoduodenectomies (52 laparoscopic, 111 robotic) with 4.3% conversion rate. The implementation of robotic pancreatoduodenectomy was associated with reduced operation time (450 vs 361 min; P < 0.001), reduced blood loss (350 vs 200 ml; P < 0.001), and a decreased rate of delayed gastric emptying (28.8% vs 9.9%; P = 0.009). The 309 MIS liver resections included 198 laparoscopic and 111 robotic procedures with a 3.6% conversion rate. The implementation of robotic liver resection was associated with less overall complications (24.7% vs 10.8%; P = 0.003) and shorter hospital stay (4 vs 3 days; P < 0.001). CONCLUSION: The introduction of robotic surgery was associated with greater implementation of MIS-HPB in up to nearly half of all pancreatic and liver resections. Although mortality and major morbidity were not affected, robotic surgery was associated with improvements in some selected outcomes. Ultimately, randomized studies and high-quality registries should determine its added value.

Perspectives of patients with colorectal cancer liver metastases on e-consultation in transmural care: a qualitative study : Is privacy really an issue?

BACKGROUND: Comprehensive cancer networks have been established to deliver high-quality care for patients with cancer. Logistic challenges are faced, when patients need to be referred for specialized treatments. Despite strengthened privacy legislations, digital platforms are increasingly used to consult specialists from dedicated liver centers or refer patients with colorectal cancer liver metastases (CRLM) for local treatment strategies. This qualitative study aimed to explore the perspectives of patients with CRLM regarding e-consultation of transmural specialists. METHODS: A focus group study was conducted. Patients referred from regional hospitals to an academic liver center for treatment of CRLM were asked to participate. Focus group discussions were audio-recorded and transcribed verbatim. A thematic content analysis of data was conducted, comprising open, axial, and selective coding of the transcripts. The consolidated criteria for reporting qualitative research (COREQ) were used. RESULTS: Two focus groups were held, involving 11 patients and 8 relatives. Three major themes were identified with regard to e-consultation in transmural care: 'data management', 'expertise', and 'information and coordination'. Confidence in the expertise of physicians appeared most important during the course of treatment, as patients experienced uncertainty after diagnosis of cancer. Despite the privacy risks, use of digital communication platforms to contact experts in the field were strongly endorsed to improve eligibility for potentially curative treatment. Moreover, e-consultation of specialists may reduce waiting times, due to effective coordination of care. CONCLUSION: Initiatives to improve medical data transfer between care providers were encouraged to achieve effective coordination of oncological care. The potential hazard of privacy violation associated with digital data exchange is accepted by patients and their relatives, provided that use of digital data improves patient's own health care, research or education.

Adjuvant chemotherapy for resected duodenal adenocarcinoma: a case-matched analysis in nation wide cohort.

BACKGROUND: Duodenal adenocarcinoma (DA) is a rare tumor for which survival data on adjuvant chemotherapy in patients after surgical treatment are unclear. This case-matched study in a nationwide cohort aims to investigate the benefit of adjuvant chemotherapy for patients with resectable DA on overall survival. METHODS: All patients diagnosed with DA and intestinal type periampullary adenocarcinoma (PVA) in the Netherlands between 2000 and 2015 were included (n = 1316). Patients with disease stages II and III who underwent resection and adjuvant chemotherapy were matched (1:2), based on identified covariates associated with OS, with patients who underwent surgery alone. Overall survival was compared using Kaplan-Meier estimates. RESULTS: The median OS was 49.9 months in patients who underwent curative resection (n = 649). Univariate and multivariate analysis showed a significant influence of age, lymph node involvement, and T- stage on survival. The group of patients receiving adjuvant treatment consisted of 43 patients and the non-adjuvant group of 83 case-matched patients. The median OS of the complete matched cohort (n = 126) was 26.9 months. No statistically significant survival benefit was found for the adjuvant group as compared to the group treated with surgery alone (median OS = 34.4 months and 23.0 months, p = 0.20). CONCLUSION: This population-based, case-matched analysis demonstrates no statistically significant survival benefit for adjuvant chemotherapy after curative resection in stages II and III patients. Future studies with specified treatment regimens as well as thorough stratification for prognostic factors will be required in order to more definitively determine the role of adjuvant therapy.

Stereotactic ablative radiotherapy or best supportive care in patients with localized pancreatic cancer not receiving chemotherapy and surgery (PANCOSAR): a nationwide multicenter randomized controlled trial according to a TwiCs design.

BACKGROUND: Significant comorbidities, advanced age, and a poor performance status prevent surgery and systemic treatment for many patients with localized (non-metastatic) pancreatic ductal adenocarcinoma (PDAC). These patients are currently treated with 'best supportive care'. Therefore, it is desirable to find a treatment option which could improve both disease control and quality of life in these patients. A brief course of high-dose high-precision radiotherapy i.e. stereotactic ablative body radiotherapy (SABR) may be feasible. METHODS: A nationwide multicenter trial performed within a previously established large prospective cohort (the Dutch Pancreatic cancer project; PACAP) according to the 'Trial within cohorts' (TwiCs) design. Patients enrolled in the PACAP cohort routinely provide informed consent to answer quality of life questionnaires and to be randomized according to the TwiCs design when eligible for a study. Patients with localized PDAC who are unfit for chemotherapy and surgery or those who refrain from these treatments are eligible. Patients will be randomized between SABR (5 fractions of 8 Gy) with 'best supportive care' and 'best supportive care' only. The primary endpoint is overall survival from randomization. Secondary endpoints include preservation of quality of life (EORTC-QLQ-C30 and -PAN26), NRS pain score response and WHO performance scores at baseline, and, 3, 6 and 12 months. Acute and late toxicity will be scored using CTCAE criteria version 5.0: assessed at baseline, day of last fraction, at 3 and 6 weeks, and 3, 6 and 12 months following SABR. DISCUSSION: The PANCOSAR trial studies the added value of SBRT as compared to 'best supportive care' in patients with localized PDAC who are medically unfit to receive chemotherapy and surgery, or refrain from these treatments. This study will assess whether SABR, in comparison to best supportive care, can relieve or delay tumor-related symptoms, enhance quality of life, and extend survival in these patients. TRIAL REGISTRATION: Clinical trials, NCT05265663 , Registered March 3 2022, Retrospectively registered.

Comparing practice and outcome of laparoscopic liver resection between high-volume expert centres and nationwide low-to-medium volume centres.

BACKGROUND: Based on excellent outcomes from high-volume centres, laparoscopic liver resection is increasingly being adopted into nationwide practice which typically includes low-medium volume centres. It is unknown how the use and outcome of laparoscopic liver resection compare between high-volume centres and low-medium volume centres. This study aimed to compare use and outcome of laparoscopic liver resection in three leading European high-volume centres and nationwide practice in the Netherlands. METHOD: An international, retrospective multicentre cohort study including data from three European high-volume centres (Oslo, Southampton and Milan) and all 20 centres in the Netherlands performing laparoscopic liver resection (low-medium volume practice) from January 2011 to December 2016. A high-volume centre is defined as a centre performing >50 laparoscopic liver resections per year. Patients were retrospectively stratified into low, moderate- and high-risk Southampton difficulty score groups. RESULTS: A total of 2425 patients were included (1540 high-volume; 885 low-medium volume). The median annual proportion of laparoscopic liver resection was 42.9 per cent in high-volume centres and 7.2 per cent in low-medium volume centres. Patients in the high-volume centres had a lower conversion rate (7.4 versus 13.1 per cent; P < 0.001) with less intraoperative incidents (9.3 versus 14.6 per cent; P = 0.002) as compared to low-medium volume centres. Whereas postoperative morbidity and mortality rates were similar in the two groups, a lower reintervention rate (5.1 versus 7.2 per cent; P = 0.034) and a shorter postoperative hospital stay (3 versus 5 days; P < 0.001) were observed in the high-volume centres as compared to the low-medium volume centres. In each Southampton difficulty score group, the conversion rate was lower and hospital stay shorter in high-volume centres. The rate of intraoperative incidents did not differ in the low-risk group, whilst in the moderate-risk and high-risk groups this rate was lower in high-volume centres (absolute difference 6.7 and 14.2 per cent; all P < 0.004). CONCLUSION: High-volume expert centres had a sixfold higher use of laparoscopic liver resection, less conversions, and shorter hospital stay, as compared to a nationwide low-medium volume practice. Stratification into Southampton difficulty score risk groups identified some differences but largely outcomes appeared better for high-volume centres in each risk group.

Conservative treatment versus elective repair of umbilical hernia in patients with liver cirrhosis and ascites: results of a randomized controlled trial (CRUCIAL trial).

PURPOSE: To establish optimal management of patients with an umbilical hernia complicated by liver cirrhosis and ascites. METHODS: Patients with an umbilical hernia and liver cirrhosis and ascites were randomly assigned to receive either elective repair or conservative treatment. The primary endpoint was overall morbidity related to the umbilical hernia or its treatment after 24 months of follow-up. Secondary endpoints included the severity of these hernia-related complications, quality of life, and cumulative hernia recurrence rate. RESULTS: Thirty-four patients were included in the study. Sixteen patients were randomly assigned to elective repair and 18 to conservative treatment. After 24 months, 8 patients (50%) assigned to elective repair compared to 14 patients (77.8%) assigned to conservative treatment had a complication related to the umbilical hernia or its repair. A recurrent hernia was reported in 16.7% of patients who underwent repair. For the secondary endpoint, quality of life through the physical (PCS) and mental component score (MCS) showed no significant differences between groups at 12 months of follow-up (mean difference PCS 11.95, 95% CI - 0.87 to 24.77; MCS 10.04, 95% CI - 2.78 to 22.86). CONCLUSION: This trial could not show a relevant difference in overall morbidity after 24 months of follow-up in favor of elective umbilical hernia repair, because of the limited number of patients included. However, elective repair of umbilical hernia in patients with liver cirrhosis and ascites appears feasible, nudging its implementation into daily practice further, particularly for patients experiencing complaints. TRIAL REGISTRATION: Clinicaltrials.gov , NCT01421550, on 23 August 2011.

Exocrine pancreatic insufficiency after esophagectomy: a systematic review of literature.

Complaints of maldigestion, malabsorption, and unintended weight loss after esophagectomy are often attributed to an impaired exocrine pancreatic function. This review systematically summarizes all literature reporting on the presence of exocrine pancreatic insufficiency (EPI) after esophagectomy and the effect of treatment with pancreatic enzymes on gastrointestinal complaints, body weight, and quality of life. Databases of PubMed, Embase, and Wiley/Cochrane Library were searched systematically until July 2020. Studies reporting on EPI and pancreatic enzyme replacement therapy after esophagectomy were included. The Newcastle-Ottawa scale was used to assess study quality. Four studies, including 158 patients, were selected. The maximum score for study quality was six (range 4-6). Exocrine pancreatic function was investigated in three studies, measured by fecal elastase-1 and 72-hour fecal fat excretion. Fecal elastase-1 levels <200 µg/g were reported in 16% of patients at 4 months, 18% at 6 months, and 31% at 18-24 months postoperatively. A decreased fecal fat absorption was noticed in 57% 1 month postoperatively. Treatment with pancreatic enzymes was reported in two studies. In patients with fecal elastase-1 levels <200 µg/g, 90% of patients reported improvement in symptoms and 70% reported improvement in weight. In patients with complaints of steatorrhea, 87% noticed settlement of symptoms. Based on current literature, complaints of maldigestion, malabsorption, and unintended weight loss after esophagectomy are common and can be related to an impaired exocrine pancreatic function. High-quality studies evaluating the presence of EPI and the effect of treatment with pancreatic enzymes after esophagectomy are needed to verify this conclusion.

The role of abdominal drainage in pancreatic resection - A multicenter validation study for early drain removal.

BACKGROUND: Abdominal drainage and the timing of drain removal in patients undergoing pancreatic resection are under debate. Early drain removal after pancreatic resection has been reported to be safe with a low risk for clinical relevant postoperative pancreatic fistula (CR-POPF) when drain amylase on POD1 is < 5000U/L. The aim of this study was to validate this algorithm in a large national cohort. METHODS: Patients registered in the Dutch Pancreatic Cancer Audit (2014-2016) who underwent pancreatoduodenectomy, distal pancreatectomy or enucleation were analysed. Data on post-operative drain amylase levels, drain removal, postoperative pancreatic fistulae were collected. Univariate and multivariate analysis using a logistic regression model were performed. The primary outcome measure was grade B/C pancreatic fistula (CR-POPF). RESULTS: Among 1402 included patients, 433 patients with a drain fluid amylase level of <5000U/L on POD1, 7% developed a CR-POPF. For patients with an amylase level >5000U/L the CR-POPF rate was 28%. When using a cut-off point of 2000U/L or 1000U/L during POD1-3, the CR-POPF rates were 6% and 5% respectively. For patients with an amylase level of >2000U/L and >1000UL during POD 1-3 the CR-POPF rates were 26% and 22% respectively (n = 223). Drain removal on POD4 or thereafter was associated with more complications (p = 0.004). Drain amylase level was shown to be the most statistically significant predicting factor for CR-POPF (Wald = 49.7; p < 0.001). CONCLUSION: Our data support early drain removal after pancreatic resection. However, a cut-off of 5000U/L drain amylase on POD1 was associated with a relatively high CR-POPF rate of 7%. A cut-off point of 1000U/L during POD1-3 resulted in 5% CR-POPF and might be a safer alternative.

Key biological processes driving metastatic spread of pancreatic cancer as identified by multi-omics studies.

Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive malignancy, characterized by a high metastatic burden, already at the time of diagnosis. The metastatic potential of PDAC is one of the main reasons for the poor outcome next to lack of significant improvement in effective treatments in the last decade. Key mutated driver genes, such as activating KRAS mutations, are concordantly expressed in primary and metastatic tumors. However, the biology behind the metastatic potential of PDAC is not fully understood. Recently, large-scale omic approaches have revealed new mechanisms by which PDAC cells gain their metastatic potency. In particular, genomic studies have shown that multiple heterogeneous subclones reside in the primary tumor with different metastatic potential. The development of metastases may be correlated to a more mesenchymal transcriptomic subtype. However, for cancer cells to survive in a distant organ, metastatic sites need to be modulated into pre-metastatic niches. Proteomic studies identified the influence of exosomes on the Kuppfer cells in the liver, which could function to prepare this tissue for metastatic colonization. Phosphoproteomics adds an extra layer to the established omic techniques by unravelling key functional signaling. Future studies integrating results from these large-scale omic approaches will hopefully improve PDAC prognosis through identification of new therapeutic targets and patient selection tools. In this article, we will review the current knowledge on the biology of PDAC metastasis unravelled by large scale multi-omic approaches.

Irreversible Electroporation in Hepatopancreaticobiliary Tumours.

Hepatopancreaticobiliary tumours are often diagnosed at an advanced disease stage, in which encasement or invasion of local biliary or vascular structures has already occurred. Irreversible electroporation (IRE) is an image-guided tumour ablation technique that induces cell death by exposing the tumour to high-voltage electrical pulses. The cellular membrane is disrupted, while sparing the extracellular matrix of critical tubular structures. The preservation of tissue integrity makes IRE an attractive treatment option for tumours in the vicinity of vital structures such as splanchnic blood vessels and major bile ducts. This article reviews current data and discusses future trends of IRE for hepatopancreaticobiliary tumours.

Ablation of colorectal liver metastases by irreversible electroporation: results of the COLDFIRE-I ablate-and-resect study.

OBJECTIVES: Irreversible electroporation (IRE) is a new ablation technique that relies on high-voltage electrical pulses. This clinical study evaluates the pathological response of colorectal liver metastases (CRLM) treated with IRE and the clinical safety and feasibility. METHODS: Ten patients with resectable CRLM were included. During laparotomy, the metastases were treated with IRE and resected 60 min later. Safety and feasibility were assessed based on adverse events, laboratory values, technical success and intra-operative ultrasound findings. Tissue response was assessed using triphenyl tetrazolium chloride (TTC) vitality staining and (immuno)histochemical stainings (HE, complement-3d and caspase-3). RESULTS: Ten lesions with a mean diameter of 2.4 cm were successfully electroporated and resected, on average, 84 min later (range 51-153 min). One minor transient cardiac arrhythmia occurred during IRE. Ultrasound showed a sharply demarcated hypoechoic ablation zone around the tumour. TTC showed avitality of all lesions, covering the complete tumour in 8/10 lesions. Although immunohistochemistry proved heterogeneous and difficult to interpret within the tumours, it confirmed irreversible cell damage in the tumour-free margin of all specimens. CONCLUSIONS: This ablate-and-resect study demonstrated avitality caused by IRE of CRLM in humans. Further characterisation of tissue- and tumour-specific electrical properties is warranted to improve ablation protocols for maximised tissue ablation. KEY POINTS: • Irreversible electroporation induces cell death in colorectal liver metastases within 1 h. • The ablation zone shows a sharp demarcation between avital and vital tissue. • Apoptosis is involved in cell death of colorectal liver metastases after IRE. • Effects of IRE can be monitored real-time using intraoperative ultrasound. • Local electrical heterogeneities of tumour tissue may require tumour-specific ablation protocols.

Serum level of Ca 19-9 increases ability of IgG4 test to distinguish patients with autoimmune pancreatitis from those with pancreatic carcinoma.

BACKGROUND: Autoimmune pancreatitis (AIP) is often difficult to distinguish from pancreatic carcinoma or other pancreatobiliary diseases. High serum levels of carbohydrate antigen 19-9 (Ca 19-9) are indicative of malignancies, whereas high levels of immunoglobulin (Ig)G4 (>1.4 g/l) are characteristic of AIP. We investigated whether serum levels of these proteins can differentiate between these diseases. METHODS: We measured levels of Ca 19-9 and IgG4 in serum samples from 33 patients with AIP, 53 with pancreatic carcinoma, and 145 with other pancreatobiliary disorders. We determined cut-off levels for each assay. Logistic regression analysis was used to evaluate combined data on Ca 19-9, IgG4, and bilirubin levels. RESULTS: Low levels of Ca 19-9 were independently associated with AIP, compared with pancreatic adenocarcinoma [odds ratio (OR) 0.28; 95% confidence interval (CI) 0.13-0.59; p = 0.0001]. Using an upper level of 74 U/ml, the assay for Ca 19-9 identified patients with AIP with 73% sensitivity and 74% specificity. Using a lower level of 2.6 g/l, the assay for IgG4 identified these patients with 70% sensitivity and 100% specificity. Combining data, levels of Ca 19-9 < 74 U/ml and IgG4 > 1.0 g/l identified patients with AIP with 94% sensitivity and 100 % specificity. CONCLUSIONS: Patients with AIP have lower levels of Ca 19-9 than those patients with pancreatic carcinoma. Measurement of either the Ca 19-9 or the IgG4 level alone are not accurate enough for diagnosis. However, the combination of Ca 19-9 < 74 U/ml and IgG4 > 1.0 g/l distinguishes patients with AIP from those patients with pancreatic carcinoma with 94% sensitivity and 100% specificity.

The good, the bad and the ugly: a tale of miR-101, miR-21 and miR-155 in pancreatic intraductal papillary mucinous neoplasms.

BACKGROUND: This multicenter study evaluated three candidate microRNAs (miRNAs) (miR-21, miR-155 and miR-101) as potential biomarkers in intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. PATIENTS AND METHODS: miRNA expression was quantified by quantitative RT-PCR in 86 laser-microdissected specimens, including 65 invasive IPMNs, 16 non-invasive IPMNs and 5 normal pancreatic ductal tissues. Univariate and multivariate analyses compared miRNAs and clinical parameters with overall (OS) and disease-free survival (DFS). RESULTS: miR-21 and miR-155 were up-regulated in invasive IPMNs compared with non-invasive IPMNs, as well as in non-invasive IPMNs compared with normal tissues. Conversely, miR-101 levels were significantly higher in non-invasive IPMNs and normal tissues compared with invasive IPMNs. High levels of miR-21 were associated with worse OS [hazard ratio (HR) = 2.47, 95% confidence interval (CI) = 1.37-5.65, P = 0.0047]. Patients with high-miR-21 expression also had a shorter median DFS (10.9 versus 29.9 months, P = 0.01). Multivariate analysis confirmed miR-21 as independently prognostic for mortality and disease progression (death risk: HR = 3.3, 95% CI = 1.5-7.0, P = 0.02; progression risk: HR = 2.3, 95% CI = 1.2-4.8, P = 0.02), as well as positive lymph-node status (death risk: HR = 2.6, 95% CI = 1.1-6.3, P = 0.03; progression risk: HR = 2.2, 95% CI = 1.0-4.8, P = 0.04). CONCLUSIONS: miR-21, miR-155 and miR-101 showed significant differences in invasive versus non-invasive IPMNs. miR-21 emerged as an independent prognostic biomarker in invasive IPMNs and should be validated in prospective studies.

Meta-analysis of glue versus sutured mesh fixation for Lichtenstein inguinal hernia repair.

BACKGROUND: Chronic pain remains a frequent complication after Lichtenstein inguinal hernia repair. As a consequence, mesh fixation using glue instead of sutures has become popular. This meta-analysis aimed to clarify which fixation technique is to be preferred for elective Lichtenstein inguinal hernia repair. METHODS: A meta-analysis was conducted according to the PRISMA guidelines. Articles published between January 1990 and April 2012 were searched for in MEDLINE, Embase and the Cochrane Library. Randomized controlled trials (RCTs) comparing glue and sutured mesh fixation in elective Lichtenstein repair for unilateral inguinal hernia were included. The quality of the RCTs and the potential risk of bias were assessed using the Cochrane risk of bias tool. RESULTS: Of 254 papers found in the initial search, a meta-analysis was conducted of seven RCTs comprising 1185 patients. With the use of glue mesh fixation, the duration of operation was shorter (mean difference -2·57 (95 per cent confidence interval (c.i.) -4·88 to -0·26) min; P = 0·03), patients had lower visual analogue scores for postoperative pain (mean difference -0·75 (-1·18 to -0·33); P = 0·001), early chronic pain occurred less often (risk ratio 0·52, 95 per cent c.i. 0·31 to 0·87; P = 0·01), and time to return to daily activities was shorter (mean difference -1·17 (-2·30 to -0·03) days; P = 0·04). The hernia recurrence rate did not differ significantly. CONCLUSION: Elective Lichtenstein repair for inguinal hernia using glue mesh fixation compared with sutures is faster and less painful, with comparable hernia recurrence rates.

Meta-analysis of laparoscopic versus open cholecystectomy for patients with liver cirrhosis and symptomatic cholecystolithiasis.

BACKGROUND: Open cholecystectomy (OC) is often preferred over laparoscopic cholecystectomy (LC) in patients with liver cirrhosis and portal hypertension, but evidence is lacking to support this practice. This meta-analysis aimed to clarify which surgical technique is preferable for symptomatic cholecystolithiasis in patients with liver cirrhosis. METHODS: A meta-analysis was conducted according to the PRISMA guidelines. Articles published between January 1990 and October 2011 were identified from MEDLINE, Embase and the Cochrane Library. Randomized clinical trials (RCTs) comparing outcomes of OC versus LC for cholecystolithiasis in patients with liver cirrhosis were included. The quality of the RCTs was assessed using the Jadad criteria. RESULTS: Following review of 1422 papers by title and abstract, a meta-analysis was conducted of four RCTs comprising 234 surgical patients. They provided evidence of at least level 2b on the Oxford Level of Evidence Scale, but scored poorly according to the Jadad criteria. Some 97·0 per cent of the patients had Child-Turcotte-Pugh (CTP) grade A or B liver cirrhosis. In all, 96·6 per cent underwent elective surgery. No postoperative deaths were reported. LC was associated with fewer postoperative complications (risk ratio 0·52, 95 per cent confidence interval (c.i.) 0·29 to 0·92; P = 0·03), a shorter hospital stay (mean difference -3·05 (95 per cent c.i. -4·09 to -2·01) days; P < 0·001) and quicker resumption of a normal diet (mean difference -27·48 (-30·96 to -23·99) h; P < 0·001). CONCLUSION: Patients with CTP grade A or B liver cirrhosis who undergo LC for symptomatic cholecystolithiasis have fewer overall postoperative complications, a shorter hospital stay and resume a normal diet more quickly than those who undergo OC.