Pancreatoscopy-Guided Endotherapies for Pancreatic Diseases.

Per-oral pancreatoscopy (POP) is a pancreas-preserving modality that allows for targeted pancreatic duct interventions, particularly in cases where standard techniques fail. POP specifically has an emerging role in the diagnosis, risk stratification, and disease extent determination of main duct intraductal papillary mucinous neoplasms (IPMNs). It has also been successfully used for laser ablation of IPMNs in poor surgical candidates, lithotripsy for complex stone disease, and laser stricturoplasty. As experience with POP increases beyond select referral center practices, further studies validating POP efficacy with long-term follow-up will help clarify when POP-guided intervention is most beneficial in relation to surgical intervention.

Adjuvant chemotherapy for adenocarcinoma arising from intraductal papillary mucinous neoplasia: multicentre ADENO-IPMN study.

BACKGROUND: The clinical impact of adjuvant chemotherapy after resection for adenocarcinoma arising from intraductal papillary mucinous neoplasia is unclear. The aim of this study was to identify factors related to receipt of adjuvant chemotherapy and its impact on recurrence and survival. METHODS: This was a multicentre retrospective study of patients undergoing pancreatic resection for adenocarcinoma arising from intraductal papillary mucinous neoplasia between January 2010 and December 2020 at 18 centres. Recurrence and survival outcomes for patients who did and did not receive adjuvant chemotherapy were compared using propensity score matching. RESULTS: Of 459 patients who underwent pancreatic resection, 275 (59.9%) received adjuvant chemotherapy (gemcitabine 51.3%, gemcitabine-capecitabine 21.8%, FOLFIRINOX 8.0%, other 18.9%). Median follow-up was 78 months. The overall recurrence rate was 45.5% and the median time to recurrence was 33 months. In univariable analysis in the matched cohort, adjuvant chemotherapy was not associated with reduced overall (P = 0.713), locoregional (P = 0.283) or systemic (P = 0.592) recurrence, disease-free survival (P = 0.284) or overall survival (P = 0.455). Adjuvant chemotherapy was not associated with reduced site-specific recurrence. In multivariable analysis, there was no association between adjuvant chemotherapy and overall recurrence (HR 0.89, 95% c.i. 0.57 to 1.40), disease-free survival (HR 0.86, 0.59 to 1.30) or overall survival (HR 0.77, 0.50 to 1.20). Adjuvant chemotherapy was not associated with reduced recurrence in any high-risk subgroup (for example, lymph node-positive, higher AJCC stage, poor differentiation). No particular chemotherapy regimen resulted in superior outcomes. CONCLUSION: Chemotherapy following resection of adenocarcinoma arising from intraductal papillary mucinous neoplasia does not appear to influence recurrence rates, recurrence patterns or survival.

Diagnosis and management of intraductal papillary mucinous neoplasms of the pancreas. An Useful Update with a Noteworthy Tip.

Not requested.

Clinical outcome of conservatively managed pancreatic intraductal papillary mucinous neoplasms with mural nodules and main duct dilation.

BACKGROUND: Surgical resection of intraductal papillary mucinous neoplasm (IPMN) is strongly recommended for patients exhibiting high-risk stigmata (HRS). However, determining surgical indications for elderly patients with comorbidities is challenging, as clinical outcomes are not well characterized. This multicenter observational study elucidated the clinical outcomes of patients with IPMN exhibiting HRS who did not undergo surgery. METHODS: This study enrolled 101 IPMN patients exhibiting HRS with follow-up observations at 11 hospitals in Japan (2011-2016). The median observation period was 37 months (maximum: 86 months). Primary outcomes were estimated 5-year overall survival (OS) and disease-specific survival (DSS). Survival was also stratified based on HRS features. RESULTS: Of 101 patients, 32 (31.7%) had the main pancreatic duct (MPD) measuring ≥ 10 mm and 80 (79.2%) had mural nodules measuring ≥ 5 mm. The estimated 5-year OS and DSS were 74% and 91%, respectively. In the stratified analysis, the co-presence of MPD ≥ 10 mm and mural nodules ≥ 5 mm or mural nodule ≥ 10 mm were related to worse 5-year DSS (MPD ≥ 10 mm and mural nodules ≥ 5 mm vs other characteristics: 60% vs 95%, log-rank test: p = 0.049; mural nodules ≥ 10 mm vs < 10 mm: 77% vs 95%, log-rank test: p = 0.003). CONCLUSIONS: The estimated 5-year DSS of conservatively managed IPMN patients with mural nodules and main duct dilation was 91%. Only IPMN patients with plural HRS or large nodule formation might have an increased mortality risk. This is an important insight that can help facilitate appropriate clinical decision-making, especially in the elderly or high-surgical risk IPMN patients.

[Clinical characteristics and prognosis of intraductal papillary mucinous neoplasm of the biliary tract].

Objective: To study the clinical features, diagnosis, surgery treatment and prognosis of intraductal papillary mucinous neoplasm of the biliary tract (IPMN-B). Methods: The data of 16 patients with IPMN-B admitted to The First Hospital of Jilin University and Xi'an Third Hospital from January 2014 to January 2018 were retrospectively analyzed. Kaplan-Meier method was used to conduct the survival analysis. These patients included 10 males and 6 females, the median age was 57 years. Results: Clinical manifestations were mainly jaundice (11 cases), upper abdominal pain (12 cases) and hyperpyretic chills (4 cases), combined with bile duct stones (14 cases) and hepatic lobe atrophy (2 cases). The average size of the tumor was (2.6±0.7) cm. All of 16 cases were diagnosed as IPMN-B, including 5 cases of invasive carcinoma (4 cases were perineural invasion) without vascular invasion and 6 cases of non-invasion carcinoma. The pathological type included 8 cases of pancreaticobiliary duct type, 5 cases of gastric type, 2 cases of intestinal type and 1 case of eosinophils type. Laboratory tests showed abnormal liver function (12 cases), increased direct bilirubin (9 cases), increased carbohydrate antigen199 (CA199, 8 cases) and carcinoembryonic antigen (CEA, 4 cases). The enhanced CT detection showed 9 cases of intrabile duct mass and 14 cases of bile duct dilatation. Surgical resection is the main treatment method, including 2 cases of partial resection of liver, 12 cases of bile duct mass resection combined with choledochojejunostomy and 2 cases of pancreatoduodenectomy, all of whom achieved R0 resection. Fifteen patients were followed up and 4 died during the period. The median postoperative progression free survival was 31 months (95% CI: 33-47 months), and the recurrence rate at 1 year, 2-years and 3-years were 6.7%, 40.0% and 73.3%, respectively. The median overall survival was 35 months (95% CI: 23-47 months), and the 1 year, 2-years, and 3-years cumulative survival rates were 100%, 80.0%, and 53.3%, respectively. Conclusions: IPMN-B is a rare tumor of biliary tract system, which is difficult to be diagnosed early. The main treatment is surgical resection, which can achieve a good prognosis.

[Clinical profile and results of acute pancreatitis in the Intensive and Intermediate Care Unit of a general hospital]. / Perfil clínico y resultados de la pancreatitis aguda en la Unidad de Cuidados Intensivos e Intermedios de un hospital genera.

Acute pancreatitis (AP) is an acute inflammatory process of the pancreas that, according to the 2012 Atlanta classification, can be mild, moderate or severe. OBJECTIVE: Describe the epidemiological, clinical, therapeutic and outcomes of patients with AP admitted to the intensive care and intermediate care unit of a general hospital and compare them with those described in the national and international literature. MATERIALS AND METHODS: Observational study of patients with AP treated over a period of 3 years. RESULTS: 59 cases were included; the female sex prevailed (54.2%), the average age was 59.3 years, the most frequent etiology was biliary (84.7%). Average entry severity scores were APACHE II of 12.4 points, SOFA of 4.9 points and Marshall modified of 2.8 points; The most frequent organ failure was respiratory (47.5%). The average stay in care was 13.9 days and in the hospital it was 23.3 days. No patients with mild or moderate AP died during their hospital stay, 6 patients with severe AP died during their hospital stay (20% of cases of severe AP). CONCLUSION: The cases of our hospital had a clinical and therapeutic profile similar to that described in the world and Latin American literature. A hospital staying was greater than that described in recent works, but our mortality was lower.

An elevated CA 19-9 is associated with invasive cancer and worse survival in IPMN.

BACKGROUND: Current guidelines for IPMN include an elevated serum carbohydrate antigen (CA) 19-9 among the worrisome features. However, the correlation of CA 19-9 with histological malignant features and survival is unclear. Serum CEA is also currently used for preoperative management of IPMN, although its measurement is not evidence-based. Accordingly, we aimed to assess the role of these tumor markers as predictors of malignancy in IPMN. METHODS: IPMN resected between 1998 and 2018 at Massachusetts General Hospital were analyzed. Clinical, pathological and survival data were collected and compared to preoperative levels of CA 19-9 and CEA. Receiver operating characteristic (ROC) and Cox regression analyses were performed considering cut-offs of 37 U/ml (CA 19-9) and 5 µg/l (CEA). RESULTS: Analysis of 594 patients showed that preoperative CA 19-9 levels > 37 U/ml (n = 128) were associated with an increased likelihood of invasive carcinoma when compared to normal levels (45.3% vs. 18.0%, P < 0.001), while there was no difference with respect to high-grade dysplasia (32.9% vs 31.9%, P = 0.88). The proportion of concurrent pancreatic cancer was higher in patients with CA 19-9 > 37 U/ml (17.2% vs 4.9%, P < 0.001). An elevated CA 19-9 was also associated with worse overall and disease-free survival (HR = 1.943, P = 0.007 and HR = 2.484, P < 0.001 respectively). CEA levels did not correlate with malignancy. CONCLUSION: In patients with IPMN, serum CA19-9 > 37 U/ml is associated with invasive IPMN and concurrent pancreatic cancer as well as worse survival, but not with high-grade dysplasia. Serum CEA appears to have minimal utility in the management of these patients.

Review of the diagnosis and management of intraductal papillary mucinous neoplasms.

Intraductal papillary mucinous neoplasms are common lesions with the potential of harbouring/developing a pancreatic cancer. An accurate evaluation of intraductal papillary mucinous neoplasms with high-resolution imaging techniques and endoscopic ultrasound is mandatory in order to identify patients worthy either of surgical treatment or surveillance. In this review, the diagnosis and management of patients with intraductal papillary mucinous neoplasms are discussed with a specific focus on current guidelines. Areas of uncertainty are also discussed, as there are controversies related to the optimal indications for surgery, surveillance protocols and surveillance discontinuation.

Nomograms predicting long-term survival in patients with invasive intraductal papillary mucinous neoplasms of the pancreas: A population-based study.

BACKGROUND: There are few effective tools to predict survival in patients with invasive intraductal papillary mucinous neoplasms of the pancreas. AIM: To develop comprehensive nomograms to individually estimate the survival outcome of patients with invasive intraductal papillary mucinous neoplasms of the pancreas. METHODS: Data of 1219 patients with invasive intraductal papillary mucinous neoplasms after resection were extracted from the Surveillance, Epidemiology, and End Results database, and randomly divided into the training (n = 853) and the validation (n = 366) cohorts. Based on the Cox regression model, nomograms were constructed to predict overall survival and cancer-specific survival for an individual patient. The performance of the nomograms was measured according to discrimination, calibration, and clinical utility. Moreover, we compared the predictive accuracy of the nomograms with that of the traditional staging system. RESULTS: In the training cohort, age, marital status, histological type, T stage, N stage, M stage, and chemotherapy were selected to construct nomograms. Compared with the American Joint Committee on Cancer 7th staging system, the nomograms were generally more discriminative. The nomograms passed the calibration steps by showing high consistency between actual probability and nomogram prediction. Categorial net classification improvements and integrated discrimination improvements suggested that the predictive accuracy of the nomograms exceeded that of the American Joint Committee on Cancer staging system. With respect to decision curve analyses, the nomograms exhibited more preferable net benefit gains than the staging system across a wide range of threshold probabilities. CONCLUSION: The nomograms show improved predictive accuracy, discrimination capability, and clinical utility, which can be used as reliable tools for risk classification and treatment recommendations.

Branch Duct Intraductal Papillary Mucinous Neoplasms: Recommendations for Follow-Up and Surgery.

BACKGROUND AND AIMS: Pancreatic cysts are increasingly diagnosed, mainly during abdominal imaging performed for other reasons. Between pancreatic cystic neoplasm, intraductal papillary mucinous neoplasms are the most common pre-malignant entities. Intraductal papillary mucinous neoplasms involving side branches overall harbor a low risk of malignancy, and in the recent past, a progressively more conservative approach has been consolidated. Purpose of this report is to summarize the evidence supporting the current practice for the management of branch duct intraductal papillary mucinous neoplasm and to offer a useful practical guide from first observation to post-operative follow-up. MATERIALS AND METHODS: Review of the most important scientific literature on intraductal papillary mucinous neoplasms was made. In this review article, we also report the experience of a high volume center in managing Pancreatic cystic neoplasms. RESULTS: The correct management during surveillance still is a matter of debate, since many guidelines have been published suggesting different clinical approaches. Recently, follow-up discontinuation has also been proposed in selected cases. CONCLUSION: Despite significant improvements made by the increase of evidence, selecting surgical candidates because of an increased risk of malignant progression remains an unsolved issue and a hot topic for pancreatologists.

The management of intraductal papillary mucinous neoplasms of the pancreas.

Intraductal papillary mucinous neoplasms (IPMN) of the pancreas are one of the most common preneoplastic entities among pancreatic cystic neoplasms (PCN). Their incidence is increasing due to an extensive use of cross-sectional imaging, but management still remains controversial. Among IPMNs, the main duct (MD-IPMN) and mixed (MT-IPMN) types harbor a high risk of malignant degeneration requiring resection in most of cases. The branch duct type (BD-IPMN), on the other side, can be safely surveilled as surgical resection is limited to selected cases deemed at high risk of malignant progression according to specific clinical and radiological features. An accurate diagnosis and a correct assessment of malignant potential are often hard to achieve, and clinical management still relies on the experience of the gastroenterologist/surgeon that is called to choose between a major pancreatic resection burdened by high morbidity and mortality rates and a life-long surveillance. The purpose of this report is to summarize the available evidence supporting the current practice for the management of IPMN and to offer a useful practical guide from first observation to postoperative follow-up.

Per Oral Pancreatoscopy Identification of Main-duct Intraductal Papillary Mucinous Neoplasms and Concomitant Pancreatic Duct Stones: Not Mutually Exclusive.

OBJECTIVES: Per oral pancreatoscopy (POP) assists in the evaluation and treatment of select benign and neoplastic pancreatic disorders including main-duct intraductal papillary mucinous neoplasm (MD-IPMN). Although pancreatic duct stones are classically thought of as pathognomonic for chronic pancreatitis, its co-occurrence with MD-IPMN as identified via POP may help identify an alternative etiology for presumed idiopathic chronic pancreatitis. METHODS: This was a multicenter retrospective case series of patients found to have pancreatic duct stones with concomitant MD-IPMN by POP. RESULTS: Thirteen patients with presumed idiopathic chronic calcific pancreatitis were found on POP to have both pancreatic duct stones and MD-IPMN. All patients had a dilated pancreatic duct, and most (92.3%) were symptomatic. CONCLUSIONS: Per-oral pancreatoscopy may identify MD-IPMN as an etiology for patients with presumed idiopathic chronic calcific pancreatitis and associated dilated pancreatic duct. Larger prospective studies are needed to validate these findings.

Characteristics and Outcomes of Pancreatic Cancer by Histological Subtypes.

OBJECTIVES: Except pancreatic adenocarcinoma, pancreatic cancer has several uncommon histological subtypes, including invasive intraductal papillary mucinous neoplasm (IPMN), pancreatic neuroendocrine tumor (pNET), adenosquamous carcinoma, invasive mucinous cystic neoplasm (MCN), acinar cell carcinoma (ACC), squamous cell carcinoma (SCC), and invasive solid pseudopapillary tumor (SPT). However, features of theses uncommon subtypes are not systematically analyzed. METHODS: Subjects with different histological subtypes of pancreatic cancers were retrieved from the Surveillance, Epidemiology, and End Results registry. Characteristics and behaviors of uncommon subtypes were compared. RESULTS: Pancreatic adenocarcinoma (85.8%) represented most primary pancreatic cancers, and other subtypes were rare (14.2%). Features of uncommon subtypes included females with SPT and MCN, located at the pancreatic body/tail of pNET, SPT, and MCN; poor differentiation of adenosquamous carcinoma and SCC; and large size of MCN, SPT, ACC, and SCC. In addition, IPMN, pNET, MCN, ACC, and SPT were indolent. For indolent subtypes, patients with locoregional tumor had prominent prognosis compared with patients with distant disease, especially for invasive IPMN (median survival, localized, 30.0 months; regional, 11.0 months; distant, 4.0 months). CONCLUSIONS: The study systematically summarizes characteristics and behaviors of primary pancreatic cancer by histological subtypes, which can facilitate the management of pancreatic cancer.

The diagnosis and management of intraductal papillary mucinous neoplasms of the pancreas: has progress been made?

Intraductal papillary mucinous neoplasms (IPMN) of the pancreas are premalignant mucin-producing epithelial tumors that arise from the pancreatic ductal system. These cystic tumors represent 15-30% of cystic lesions of the pancreas [Basturk et al. in Am J Surg Pathol 39(12):1730-1741, 1; Ferrone et al. in Arch Surg (Chicago, Ill: 1960) 144(5):448-454, 2, Kosmahl et al. in Virchows Arch Int J Pathol 445(2):168-178, 3; Spinelli et al. in Ann Surg. 239(5):651-657, 4]. It is believed that IPMN can progress from low-grade dysplasia to high-grade dysplasia to invasive cancer, and this pathway of progression accounts for 20-30% of pancreatic cancer [Adsay et al. in Am J Surg Pathol 28(7):839-848, 5; Tanaka et al. in J Gastroenterol 40(7):669-675, 6; Wu et al. in Sci Transl Med 3(92):92ra66, 7]. Furthermore, it is also widely believed that IPMN represent a field defect of the pancreas in which the entire ductal system is at risk of developing invasive carcinoma, not only in the area of radiographically detectable IPMN, and thus the remaining gland should undergo surveillance after partial pancreatectomy [Salvia et al. in Ann Surg 239(5):678-685, 8; Izawa et al. in Cancer 92(7):1807-1817, 9; Yamaguchi and Tanaka in Jpn J Clin Oncol 41(7):836-840, 10]. Increasingly, surgeons are faced with the dilemma between recommending highly complex resections-that have significant morbidity and mortality-in patients who may have low-risk IPMN (low-grade dysplasia), or alternatively, recommending observation for those who could possibly be harboring a radiographically occult malignancy. Given the complexity of the management decisions for patients with IPMN, the purpose of this paper is to review the current literature and to provide a summary of how accurate we are currently with the identification of high-grade dysplasia or progression to carcinoma in patients who present with IPMN.

Vimentin-positive circulating tumor cells as a biomarker for diagnosis and treatment monitoring in patients with pancreatic cancer.

The identification of circulating tumor cells (CTCs) relies on epithelial tumor cell markers. In the present study, we aimed to determine whether cell-surface vimentin could be a biomarker to isolate CTCs in pancreatic ductal adenocarcinoma (PDAC). Vimentin was identified as highly expressed on the surface of mesenchymal-phenotype pancreatic tumor cells. Vimentin+ CTCs were detected in 76% of patients with PDAC (76/100) using CTCs enriched via a microfluidic assay. A cut-off value of two vimentin+ CTCs distinguished patients with PDAC from healthy individuals. Combined vimentin+ CTCs and Carbohydrate antigen 19-9 provided favorable diagnostic potency, with an area under the curve of 0.968. Vimentin+ CTCs counts correlated with the change in tumor burden for patients undergoing resection. Significantly reduced CTC counts were observed after chemotherapy in subjects that responded to treatment. Preoperatively higher CTCs counts correlated with shortened recurrence-free survival. Taken together, vimentin+ CTCs could be a reliable biomarker in pancreatic cancer. The enrichment of mesenchymal CTCs complements the strategy of capturing epithelial CTCs, allowing a more thorough interrogation of the biology and clinical significance of CTCs in PDAC.

Oncology Navigation Decreases Time to Treatment in Patients with Pancreatic Malignancy.

BACKGROUND: Care of pancreatic cancer patients has become increasingly complex, which has led to delays in the initiation of therapy. Nurse navigators have been added to care teams, in part, to ameliorate this delay. This study investigated the difference in time from first oncology visit to first treatment date in patients with any pancreatic malignancy before and after the addition of an Oncology Navigator. METHODS: A single-institution database of patients with any pancreatic neoplasm evaluated by a provider in radiation, medical, or surgical oncology between 1 October 2015 and 30 September 2017 was analyzed. After 1 October 2016, an Oncology Navigator met patients at their initial visit and coordinated care throughout treatment. The cohort was divided into two groups: patients evaluated prior to the implementation of an Oncology Navigator and patients evaluated after implementation. Patient demographics and time from first visit to first intervention were compared. RESULTS: Overall, 147 patients with a new diagnosis of pancreatic neoplasm were evaluated; 57 patients were seen prior to the start of the Oncology Navigator program and 79 were evaluated after the navigation program was implemented. On univariate analysis, time from first contact by any provider to intervention was 46 days prior to oncology navigation and 26 days after implementation of oncology navigation (p = 0.005). While controlling for other covariates, employment of the Oncology Navigator decreased the time from first contact by any provider to intervention by almost 16 days (p = 0.009). CONCLUSIONS: Implementing an oncology navigation program significantly decreased time to treatment in patients with pancreatic malignancy.

Develop Nomogram to Predict Malignancy of Intraductal Papillary Mucinous Neoplasm.

A nomogram is a useful graphical tool for presenting a risk prediction and prognosis prediction in medical research. Intraductal papillary mucinous neoplasm (IPMN) is the premalignant lesions of the pancreas. Among the IPMN, branch duct (BD) IPMN is hard to determine whether progress to an invasive tumor or not. Surgery on the pancreas part is likely to lower the quality of life of the patient, so avoiding surgery to remove IPMN tissue of the patients with low risk should be carefully decided. In this study, we introduce the process of constructing a nomogram and illustrate it with a prediction model to predict malignancy of IPMN.