Treatment and long term safety outcomes of Peptide Receptor Radionuclide Therapy for metastatic neuroendocrine tumours: an Asian experience.

Peptide-receptor radionuclide therapy (PRRT) is a targeted molecular therapy used to treat neuroendocrine tumours (NET). It has been shown to be effective and well-tolerated in patients with metastatic neuroendocrine tumours in several centres in United States (US), Europe and Australia. Tolerability and efficacy data emerging from Asian centres remain few. Epidemiological evidence suggests that there are differences in neuroendocrine neoplasms between the population groups. We aim to describe the treatment and safety outcomes of PRRT in the Asian population. Methods One hundred and seven (107) patients with metastatic neuroendocrine tumour who had undergone PRRT treatment from January 2012 to March 2019 were included in this retrospective study. The response rates using RECIST1.1 and qualitative analysis were examined. The overall and progression free survival curves were also evaluated. Results The median progression free survival was 49 months. Response assessment after completion of treatment showed that 33(37.9%) of 87 patients had partial or complete response. Subgroup analysis comparing high- and low-grade NET showed that there was a significant difference in the time to progression curves. Comparison of the number of cycles and progression free and overall survival also showed a significant difference. Ten patients (9%) had grade 3 or more haematological toxicities. Four patients (4%) had grade 3/4 hepatobiliary toxicities, although the presence of extensive liver metastases was a confounding factor. None of the patients had grade 3/4 acute kidney injury. Conclusion Our results show that PRRT is safe and effective in the treatment of metastatic neuroendocrine tumour in the Asian population. There was a significant difference in the progression free survival curves between low-grade and high-grade NET, and in the progression free and overall survival comparing the number of cycles received.

Clip-and-line traction method for difficult ERCP cannulation due to choledochocoele.

Video 1Clip-and-line traction method for difficult ERCP cannulation due to choledochocoele.

Outcomes of an international multicenter registry on EUS-guided gallbladder drainage in patients at high risk for cholecystectomy.

Background and study aims The aim of the current study was to review the outcomes of a large-scale international registry on endoscopic ultrasound-guided gallbladder drainage (EGBD) that encompasses different stent systems in patients who are at high-risk for cholecystectomy. Patients and methods This was a retrospective international multicenter registry on EGBD created by 13 institutions around the world. Consecutive patients who received EGBD for several indications were included. Outcomes include technical and clinical success, unplanned procedural events (UPE), adverse events (AEs), mortality, recurrent cholecystitis and learning curve of the procedure. Results Between June 2011 and November 2017, 379 patients were recruited to the study. Technical and clinical success were achieved in 95.3 % and 90.8 % of the patients, respectively. The 30-day AE rate was 15.3 % and 30-day mortality was 9.2 %. UPEs were significantly more common in patients with EGBD performed for conversion of cholecystostomy and symptomatic gallstones ( P  < 0.001); and by endoscopists with experience of fewer than 25 procedures ( P  = 0.033). Both presence of clinical failure ( P  = 0.014; RR 8.69 95 %CI [1.56 - 48.47]) and endoscopist experience with fewer than 25 procedures ( P  = 0.002; RR 4.68 95 %CI [1.79 - 12.26]) were significant predictors of 30-day AEs. Presence of 30-day AEs was a significant predictor of mortality ( P  < 0.001; RR 103 95 %CI [11.24 - 944.04]). Conclusion EGBD was associated with high success rates in this large-scale study. EGBD performed for indications other than acute cholecystitis was associated with higher UPEs. The number of cases required to gain competency with the technique by experienced interventional endosonographers was 25 procedures.

Successful preoperative diagnosis of heterotopic pancreas in the duodenum.

INTRODUCTION: Heterotopic pancreas (HP) is a relatively rare entity occurring in approximately 5% of the general population. It most commonly presents as an asymptomatic mass incidentally picked up on unrelated scans. HP most commonly occurs intra-abdominally, but has been known to occur in extra-abdominal sites such as the lung and brain. It is widely considered to bear little to no malignant potential. Difficulty and ambiguity in the diagnosis of HP commonly results in interventional dilemma and delay. PRESENTATION OF CASE: We present a case of uncomplicated HP that was ultimately treated conservatively. DISCUSSION: A literature review is made of the typical workup in a patient with suspected HP, and the characteristic radiological and endoscopic findings commonly used for diagnosis of this rare condition. A succinct summary of management guidelines for HP is reviewed. CONCLUSION: HP is most commonly an incidental finding. Ambiguity surrounding its diagnosis commonly gives rise to interventional dilemma and delay. The gold standard for diagnosis remains that of EUS and FNA with histological confirmation. This report has been written in concordance with the SCARE criteria Agha et al. [1].

Preoperative platelet-to-lymphocyte ratio improves the performance of the international consensus guidelines in predicting malignant pancreatic cystic neoplasms.

INTRODUCTION: To determine if neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were predictive of malignancy in pancreatic cystic neoplasms (PCN) and if these improved the performance of the international consensus guidelines (ICG) in the initial triage of these patients. METHODS: 318 patients with surgically-treated suspected PCN were retrospectively reviewed. Malignant neoplasms were defined as neoplasms harbouring invasive carcinoma. The optimal cut-off for NLR and PLR were determined by plotting the receiver operating characteristics (ROC) curves of NLR/PLR in predicting malignant PCN and utilizing the Youden index. RESULTS: The optimal NLR and PLR cut-offs were determined to be 3.33 and 205, respectively. Univariate analyses demonstrated that symptomatic PCNs, age, obstructive jaundice, presence of solid component, dilatation of main pancreatic duct ≥10 mm, high NLR and high PLR were predictive of a malignant PCN. Multivariate analyses demonstrated that obstructive jaundice, presence of solid component, MPD ≥10 mm and high PLR but not NLR were independent predictors of a malignant PCN. A high PLR significantly predicted invasive carcinoma in patients classified within the ICG(HR) group. Comparison between the ROC curves of the ICG versus ICG plus high PLR in predicting malignant PCN demonstrated a significant improvement in the accuracy of the ICG when PLR was included [AUC 0.784 (95% CI: 0.740-0.829) vs AUC 0.822 (95% CI: 0.772-0.872) (p = 0.0032)]. CONCLUSIONS: High PLR is an independent predictor of malignancy in PCN. The addition of PLR as a criterion to the ICG improved the accuracy of these guidelines in detecting invasive neoplasms.

Are preoperative blood neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios useful in predicting malignancy in surgically-treated mucin-producing pancreatic cystic neoplasms?

INTRODUCTION: The aim of this study was to determine if neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were predictive of malignancy in mucin-producing pancreatic cystic neoplasms (MpPCN). METHODS: One hundred and twenty patients with MpPCN were retrospectively reviewed. Malignant neoplasms were defined as neoplasms harbouring invasive carcinoma or high grade dysplasia. A high NLR and PLR were defined as ≥2.551 and ≥208.1, respectively. RESULTS: High NLR was significantly associated with symptomatic tumors, larger tumors, solid component, main-duct IPMN, and Sendai high risk category. High PLR was significantly associated with jaundice and Sendai high risk category. On univariate analyses, symptomatic tumors, jaundice, solid component, dilated pancreatic duct, and both a high NLR and PLR were significant predictors of malignant and invasive MpPCN. On multivariate analyses, solid component and dilated pancreatic duct were independent predictors of malignant and invasive MpPCN. PLR was an independent predictor for invasive MpPCN. When MpPCN were stratified by the Fukuoka and Sendai Guidelines, both a high NLR and PLR were significantly associated with malignant neoplasms within the high risk categories. CONCLUSIONS: PLR is an independent predictor of invasive carcinoma. The addition of PLR as a criterion to the FCG and SCG significantly improved the predictive value of these guidelines in detecting invasive neoplasms.

Evaluation of the Fukuoka Consensus Guidelines for intraductal papillary mucinous neoplasms of the pancreas: Results from a systematic review of 1,382 surgically resected patients.

BACKGROUND: International consensus guidelines to guide management of intraductal papillary mucinous neoplasms (IPMN) were revised in Fukuoka and published in 2012. However, despite widespread acceptance of the Fukuoka Consensus Guidelines (FCG), the utility of these guidelines have not been well-validated. This systematic review was performed to evaluate the clinical utility of the FCG. DESIGN: A computerized search of the PubMed and Scopus databases was performed to identify all studies evaluating the utility of the FCG in surgically resected IPMN. IPMN were stratified according to the FCG as high risk (HR), worrisome risk (WR), and low risk (LR). HR and WR IPMN were termed FCG+ve and LR IPMN were termed FCG-ve. RESULTS: Seven studies analyzing 1,382 patients were included. There were 402 malignant neoplasms (29%), including 242 invasive IPMNs. There were 1,000 IPMN classified as FCG+ve. The FCG+ve group had a positive predictive value (PPV) ranging from 27 to 62% and the FCG-ve group had negative predictive value ranging from 82 to 100%. Pooled analysis demonstrated that there was 362 of 1,000 (36%) malignant FCG+ve IPMN and 342 of 382 (90%) benign FCG-ve IPMN. PPV of the HR group and the WR groups alone were 104 of 158 (66%) and 75 of 261 (29%), respectively. Forty of 382 (11%), including 22 (6%) invasive FCG-ve IPMN, were malignant. Twenty-six malignant including 18 invasive FCG-ve IPMN were reported from a single study. When the results from this study were excluded, there were only 14 of 241 malignant neoplasms (6%), including 4 of 241 (2%) invasive FCG-ve IPMN in the remaining 6 studies. CONCLUSION: The FCG+ve criteria had a similarly low PPV compared with the 2006 consensus criteria. Stratification of IPMN into HR and WR groups resulted in a higher PPV in the HR group. Some malignant and even invasive IPMN may be missed by the FCG criteria.

Systematic review and meta-analysis of the spectrum and outcomes of different histologic subtypes of noninvasive and invasive intraductal papillary mucinous neoplasms.

BACKGROUND: Our aim was to review the available evidence to determine the clinical importance of the histologic subtypes of noninvasive and invasive intraductal papillary mucinous neoplasms (IPMNs) on disease characteristics and overall survival. METHODS: We reviewed systematically 14 comparative studies that reported clinicopathologic characteristics and survival of 1,617 patients with IPMN (900 noninvasive and 717 invasive). RESULTS: The pancreatobiliary subtype was associated with the greatest likelihood of tumor invasion (67.9%; odds ratio [OR], 2.87; 95% CI, 1.90-4.35), harboring an associated mural nodule (56.6%; OR, 2.92; 95% CI, 1.21-7.04), demonstrating tumor recurrence (46.3%; OR, 3.28; 95% CI, 1.41-7.66) and transformation to tubular adenocarcinoma (81.8%; OR, 92.96; 95% CI, 20.76-416.28) among all subtypes. The gastric subtype was associated with the least likelihood of tumor invasion (10.2%; OR, 0.18; 95% CI, 0.13-0.26), association with main duct IPMN (19.2%; OR, 0.12; 95% CI, 0.06-0.26), and tumor recurrence (9.4%; OR, 0.47; 95% CI, 0.26-0.83) among all subtypes. The intestinal subtype had the greatest likelihood of progressing to colloid carcinoma among all subtypes. Tubular adenocarcinoma was associated with an increased risk of vascular invasion (32.9%; OR, 4.86; 95% CI, 1.96-12.01), perineural invasion (54.5%; OR, 2.30; 95% CI, 1.22-4.34), nodal metastasis (52.4%; OR, 3.31; 95% CI, 1.79-6.14), and a positive margin status (17.3%; OR, 8.45; 95% CI, 1.52-46.83). Tubular adenocarcinoma (hazard ratio [HR], 1.90; 95% CI, 1.36-2.67) had a poorer 5-year overall survival compared with colloid carcinoma and was similar to the survival observed in pancreatic ductal adenocarcinoma (HR, 2.00; 95% CI, 1.59-2.52). CONCLUSION: The prognosis of IPMN depends on its pathologic subtype. Subtype identification should be considered an essential component in future guidelines for the management of IPMN.

Utility of the sendai consensus guidelines for branch-duct intraductal papillary mucinous neoplasms: a systematic review.

INTRODUCTION: The Sendai Consensus Guidelines (SCG) was formulated in 2006 to guide the management of intraductal papillary mucinous neoplasms (IPMN). The main area of controversy is the criteria for selection of branch duct (BD)-IPMN for resection. Although these guidelines have gained widespread acceptance, there is limited data to date supporting its use. This systematic review is performed to evaluate the utility of the Sendai Consensus Guidelines (SCG) for BD-IPMN. METHODS: Studies evaluating the clinical utility of the SCG in surgically resected neoplasms were identified. The SCG were retrospectively applied to all resected neoplasms in these studies. BD-IPMNs which met the criteria for resection were termed SCG+ve and those for surveillance were termed SCG-ve. RESULTS: Twelve studies were included, of which, 9 were suitable for pooled analysis. There were 690 surgically resected BD-IPMNs, of which, 24% were malignant. Five hundred one BD-IPMNs were classified as SCG+ve and 189 were SCG-ve. The positive predictive value (PPV) of SCG+ve neoplasms ranged from 11 to 52% and the NPV of SCG-ve neoplasms ranged from 90 to 100%. Overall, there were 150/501 (29.9%) of malignant BD-IPMNs in the SCG+ve group and 171/189 (90%) of benign BD-IPMNs in the SCG-ve group. Of the 18 reported malignant (11 invasive) BD-IPMNs in the SCG-ve group, 17 (including all 11 invasive) were from a single study. When the results from this single study were excluded, 170/171 (99%) of SCG-ve BD-IPMNs were benign. CONCLUSION: The results of this review confirm the limitations of the SCG for BD-IPMN. The PPV of the SCG in predicting a malignant BD-IPMN was low and some malignant lesions may be missed based on these guidelines.

Evaluation of the Sendai and 2012 International Consensus Guidelines based on cross-sectional imaging findings performed for the initial triage of mucinous cystic lesions of the pancreas: a single institution experience with 114 surgically treated patients.

BACKGROUND: The Sendai Consensus Guidelines (SCG) were formulated in 2006 to guide the management of mucinous cystic lesions of the pancreas (CLPs) and were updated in 2012 (International Consensus Guidelines, ICG 2012). This study aims to evaluate the clinical utility of the ICG 2012 with the SCG based on initial cross-sectional imaging findings. METHODS: One hundred fourteen patients with mucinous CLPs were reviewed and classified according to the ICG 2012 as high risk (HR(ICG2012)), worrisome (W(ICG2012)), and low risk (LR(ICG2012)), and according to the SCG as high risk (HR(SCG)) and low risk (LR(SCG)). RESULTS: On univariate analysis, the presence of symptoms, obstructive jaundice, elevated serum carcinoembryonic antigen (CEA)/carbohydrate antigen (CA)19-9, solid component, main pancreatic duct ≥ 10 mm, and main pancreatic duct ≥ 5 mm was associated with high grade dysplasia/invasive carcinoma in all mucinous CLPs. Increasing number of HR(SCG) or HR(ICG2012) features was associated with a significantly increased likelihood of malignancy. The positive predictive value of HR(SCG) and HR(ICG2012) for high grade dysplasia/invasive carcinoma was 46% and 62.5% respectively. The negative predictive value of both LR(SCG) and LR(ICG2012) was 100%. CONCLUSION: Both the guidelines were useful in the initial cross-sectional imaging evaluation of mucinous CLPs. The ICG 2012 guidelines were superior to the SCG guidelines.

Are the Sendai and Fukuoka consensus guidelines for cystic mucinous neoplasms of the pancreas useful in the initial triage of all suspected pancreatic cystic neoplasms? A single-institution experience with 317 surgically-treated patients.

BACKGROUND: The Sendai Consensus Guidelines (SCG) were formulated in 2006 and updated in Fukuoka in 2012 (FCG) to guide management of cystic mucinous neoplasms of the pancreas. This study aims to evaluate the clinical utility of the SCG and FCG in the initial triage of all suspected pancreatic cystic neoplasms. STUDY DESIGN: Overall, 317 surgically-treated patients with a suspected pancreatic cystic neoplasm were classified according to the SCG as high risk (HR(SCG)) and low risk (LR(SCG)), and according to the FCG as high risk (HR(FCG)), worrisome (W(FCG)), and low risk (LR(FCG)). Cystic lesions of the pancreas (CLP) were classified as potentially malignant/malignant or benign according to the final pathology. RESULTS: The presence of symptoms, proximal lesions with obstructive jaundice, elevated serum carcinoembryonic antigen/carbohydrate antigen 19-9 (CEA/CA 19-9), size ≥3 cm, presence of solid component, main pancreatic duct dilatation, thickened enhancing walls, and change in ductal caliber with distal atrophy were predictive of a potentially malignant/malignant CLP on univariate analyses. The positive predictive value (PPV) and negative predictive value (NPV) of HR(SCG) and HR(ICG2012) for a potentially malignant/malignant lesion was 67 and 88 %, and 88 and 92.5 %, respectively. There were no malignant lesions in both LR groups but some potentially malignant lesions such as cystic pancreatic neuroendocrine neoplasms with uncertain behavior were classified as LR. CONCLUSION: The updated FCG was superior to the SCG for the initial triage of all suspected pancreatic cystic neoplasms. CLP in the LR(FCG) group can be safely managed conservatively, and those in the HR(FCG) group should undergo resection.

Clinics in diagnostic imaging. 145.

A 63-year-old man presented with painless jaundice, loss of appetite and significant weight loss. Cross-sectional imaging showed a diffusely enlarged pancreas, with no significant fat stranding and a hypodense rim on computed tomography, which appeared hypointense on T2-weighted magnetic resonance imaging. There was a narrowed pancreatic duct and features of common bile duct narrowing in the region of the pancreatic head. However, there was no obvious mass seen in the pancreatic head region. These features were classical of autoimmune pancreatitis with diffuse involvement of the gland. Laboratory investigation showed abnormal liver function and the classical sign of raised immunoglobulin G class 4 antibodies. The patient showed dramatic response to high-dose steroids, with resolution of both the laboratory and imaging abnormalities within one month. We discuss the classical imaging features of Type 1 autoimmune pancreatitis, an uncommon condition that needs to be differentiated from pancreatic malignancy.