Identifying predictors for comorbidities related mortality versus pancreatic cancer related mortality in patients with intraductal papillary mucinous neoplasm.

BACKGROUNDS: Few data are available for surveillance decisions focusing on factors related to mortality, as the primary outcome, in intraductal papillary mucinous neoplasm (IPMN) patients. AIMS: We aimed to identify imaging features and patient backgrounds associated with mortality risks by comparing pancreatic cancer (PC) and comorbidities. METHODS: We retrospectively conducted a multicenter long-term follow-up of 1864 IPMN patients. Competing risk analysis was performed for PC- and comorbidity-related mortality. RESULTS: During the median follow-up period of 5.5 years, 14.0% (261/1864) of patients died. Main pancreatic duct ≥5 mm and mural nodules were significantly related to all-cause and PC-related mortality, whereas cyst ≥30 mm did not relate. In 1730 patients without high-risk imaging features, 48 and 180 patients died of PC and comorbidity. In the derivation cohort, a prediction model for comorbidity-related mortality was created, comprising age, cancer history, diabetes mellitus complications, chronic heart failure, stroke, paralysis, peripheral artery disease, liver cirrhosis, and collagen disease in multivariate analysis. If a patient had a 5 score, 5- and 10-year comorbidity-related mortality is estimated at 18.9% and 50.2%, respectively, more than 7 times higher than PC-related mortality. The model score was also significantly associated with comorbidity-related mortality in a validation cohort. CONCLUSIONS: This study demonstrates main pancreatic duct dilation and mural nodules indicate risk of PC-related mortality, identifying patients who need periodic examination. A comorbidity-related mortality prediction model based on the patient's age and comorbidities can stratify patients who do not require regular tests, especially beyond 5 years, among IPMN patients without high-risk features. CLINICAL TRIAL REGISTRATION: T2022-0046.

Laparoscopic distal pancreatectomy for hemosuccus pancreaticus due to an intraductal papillary mucinous neoplasm.

Hemosuccus pancreaticus (HP) is a condition that is defined as gastrointestinal hemorrhage which occurs through the pancreatic duct. We present the rare case of a 75-year-old woman who developed HP caused by intraductal papillary mucinous neoplasm (IPMN). She had been followed for sarcoidosis, splenic artery aneurysm and pancreatic cyst. The patient presented to the emergency room of our hospital with epigastric pain and bloody discharge. Computed tomography revealed hemorrhage from a splenic artery aneurysm in a cystic lesion of the pancreas. On angiography, extravasation from the splenic artery was observed. Thus, we performed coil embolization. After interventional radiography (IVR), magnetic resonance imaging and endoscopic retrograde pancreatography showed a branch duct IPMN. Based on these findings, elective laparoscopic distal pancreatectomy was performed. The histopathological diagnosis was IPMN with HP caused by rupture of a splenic artery aneurysm. For such complicated cases, minimally invasive surgery is applicable after successful hemostasis by IVR.

[Pseudomyxoma Peritonei Caused by Intraductal Papillary Mucinous Neoplasm-A Three Case Series].

Pseudomyxoma peritonei(PMP)is a rare condition caused by intraductal papillary mucinous neoplasm(IPMN). At our institution, 3 cases, along with literature review, of PMP caused by IPMN were treated with cytoreductive surgery. In case 1, a 70-year-old man was pathologically diagnosed with low-grade PMP with intraductal papillary mucinous carcinoma. Recurrence was discovered 68 months after surgery, and the patient died after 78 months. In case 2, a 69-year-old man was pathologically diagnosed with high-grade PMP with signet-ring cell carcinoma caused by intraductal papillary mucinous carcinoma. The patient died 8 months post-surgery. In case 3, a 77-year-old woman was pathologically diagnosed with low- grade(partially high-grade)PMP with intraductal papillary mucinous adenoma. There was a recurrence 14 months post- surgery. The patient is still alive because of systemic chemotherapy 32 months after surgery.

Long-standing diabetes mellitus increases concomitant pancreatic cancer risk in patients with intraductal papillary mucinous neoplasms.

BACKGROUND: When monitoring patients with an intraductal papillary mucinous neoplasm (IPMN), it is important to consider both IPMN-derived carcinoma and concomitant ductal adenocarcinoma (PDAC). The latter is thought to have a poorer prognosis. We retrospectively analyzed the risk factors for concomitant PDAC in IPMN. METHODS: In total, 547 patients with pancreatic cysts, including IPMNs inappropriate for surgery on initial diagnosis, encountered from April 2005 to June 2019, were reviewed. We performed surveillance by imaging examination once or twice a year. RESULTS: Five IPMNs with high-grade dysplasia and one IPMN associated with invasive carcinoma were encountered. In comparison, 14 concomitant PDACs were encountered. The prognosis was very poor for concomitant PDACs. All 14 PDAC patients had IPMNs. In patients with IPMNs, long-standing diabetes mellitus was the only significant risk factor for concomitant PDAC in both univariate and multivariate analyses (P < 0.001 and P < 0.01, respectively). Furthermore, patients with IPMNs and diabetes mellitus had a high frequency of concomitant PDACs (9.5%, 9/95) in a median 48-month surveillance period. CONCLUSIONS: When monitoring IPMNs, the development of not only IPMN-derived carcinomas but also concomitant PDACs should be considered. During this period, it may be prudent to concentrate on patients with other risk factors for PDAC, such as long-standing diabetes mellitus.

Pancreatic Adenocarcinoma Associated to Intraductal Papillary Mucinous Neoplasia: Histopathological Particularities and Clinical Implications.

Background: Pancreatic ductal adenocarcinoma (PDAC) is the most common pancreatic tumor, known for an aggressive evolution. Intraductal papillary mucinous neoplasm (IPMN) is a rare pancreatic tumor, considered a premalignant lesion with the possibility of carcinogenesis towards PDAC. The clinical, surgical and histopathological particularities of the association between PDAC and IPMN are yet unknown, further research being needed. Methods: We have conducted a retrospective descriptive study, on a nine-year period (2012-2020), with the aim of comparing the characteristics of patients that underwent curative surgical interventions for solitary PDAC and PDAC associated to IPMN. Results: Fifteen patients with PDAC associated with IPMN (Group 1) and 386 patients with solitary PDAC (Group 2) were included in our study. Group 1 had a younger average age (61.8 years) compared to Group 2 (63.89 years). Total pancreatectomy was more frequently performed for Group 1 than Group 2 (33.33% vs 12.43%). Group 1 had a higher percentage of cases with positive perineural, perilymphatic and perivascular invasion. Group 1 registered a worse overall survival, as well as a worse short-time survival compared to Group 2. Conclusions: PDAC associated to IPMN registers distinct epidemiological, clinical and histopathological characteristics compared to solitary PDAC.

Technical Aspects of a Posterior Pancreatic Head Enucleation - An Organ-Sparing Alternative to Pancreatico-Duodenectomy for Benign and Low-Grade Malignant Pancreatic Tumors.

From a technical point of view, enucleation can be challenging for a few locations with hard access, such as the posterior pancreatic head, particularly for deeply-located lesions, in close relationship with the main pancreatic duct (MPD). The risk of MPD injuries with secondary pancreatic fistula is high in these specific situations. Hereby we describe a technique of posterior pancreatic head enucleation in a 48-year-old male patient diagnosed with a deeply-located branch duct type intraductal papillary mucinous neoplasm (BD-IPMN). A posterior pancreatic head enucleation of the BD-IPMN was performed along with segmental resection of the MPD and end-to-end anastomosis, with protection by a plastic stent passing both through the MPD anastomosis and major duodenal papilla. No protective pancreatico-jejunostomy was necessary. A grade B pancreatic fistula complicated the postoperative course, and a grade A delayed gastric emptying, both conservatively managed. Enucleation of deeply-located tumors at the dorsal pancreatic head is challenging but feasible and safe. Segmental resection of the MPD with end-to-end anastomosis protected by a transpapillary plastic stent for injuries during enucleation can be safely performed. Thus, the operative time during enucleation is reduced, and the potential morbidity of a pancreaticojejunostomy is eliminated.

Number of Worrisome Features and Risk of Malignancy in Intraductal Papillary Mucinous Neoplasm.

BACKGROUND: The 2017 revised International Association of Pancreatology guidelines for management of intraductal papillary mucinous neoplasm (IPMN) describe worrisome features (WF) and high-risk stigmata (HRS), recommending resection in the latter and further work-up and close surveillance for patients with WF. The effect of multiple WF on the likelihood of malignancy has not been evaluated. STUDY DESIGN: Eight hundred ten patients who underwent pancreatic resection for IPMN in 2 tertiary referral centers were identified from prospective institutional databases. Patients were retrospectively categorized into subgroups according to the number of WF or HRS and presence of malignancy, defined as high-grade dysplasia (HGD) or invasive cancer on final pathology. RESULTS: Three hundred seventy-nine (47%) patients had HRS, 370 (46%) had 1 or more WF, and 61 patients (7%) had neither. Malignancy was present in 70% (n = 267) of patients with HRS and in 30% (n = 127) of those with WF. Only 3 of 61 patients without WF/HRS had malignancy, and all only in the form of HGD. The risk of malignancy increased in a stepwise fashion with the number of WF, to 22%, 34%, and 59% with 1, 2, and 3 WF, respectively (p = 0.001), and reached 100% in patients with 4 or more WF. Although the relative risks differed for particular WF, the areas under the curve were not statistically different. CONCLUSION: We confirm that presence of HRS in IPMN is associated with a very high likelihood of malignancy. The presence of a single WF has a malignancy risk of 22%, and additional WF increase this risk significantly. When 3 or more WF are present, the risk is similar to that of HRS.

[Resection Strategies in BD-IPMN - Enucleation or Standard Resection?] / Resektionsstrategien beim BD-IPMN - Enukleation oder onkologische Resektion?

BACKGROUND: The malignant potential and the surgical management of branch duct intraductal papillary mucinous neoplasms (BD-IPMNs) remain controversial. Enucleation (EN), as parenchyma-sparing resections of the pancreas, may be a valuable alternative to standard resections (SR), e.g., Whipple or distal pancreatectomy, for the treatment of BD-IPMN. However, its role is still poorly defined. The objective of this review is to compare indications and postoperative outcomes after pancreatic EN versus SR. METHODS: A review of the literature was carried out. Short- and long-term postoperative outcomes of both surgical approaches were evaluated. RESULTS: EN is associated with shorter operation time and less blood loss than SR. The overall surgical morbidity does not differ between the two approaches. Although EN is less invasive, the development of pancreatic fistula is the most important complication after EN, as several studies have reported a higher rate of pancreatic fistula than after SR. However, the differences between the two procedures are mitigated in high-volume centres. EN more frequently allows the preservation of pancreatic exocrine and endocrine function in comparison to SR and this is the most important advantage of this procedure. CONCLUSIONS: EN appears to be a safe and effective alternative to treat low-risk BD-IPMN, and allows preservation of endocrine and exocrine function. Moreover, postoperative complications and recurrence rates after EN are comparable to the much more extensive surgical procedures. However, pancreatic EN should be performed by experienced surgeons and, as non-oncological procedure, patients should be very accurately selected. This underlines the importance of treatment in high-volume institutions.

Pancreatic ductal adenocarcinomas associated with intraductal papillary mucinous neoplasms (IPMNs) versus pseudo-IPMNs: relative frequency, clinicopathologic characteristics and differential diagnosis.

The literature is highly conflicted on what percentage of pancreatic ductal adenocarcinomas (PDACs) arise in association with intraductal papillary mucinous neoplasms (IPMNs). Some studies have claimed that even small (Sendai-negative) IPMNs frequently lead to PDAC. Recently, more refined pathologic definitions for mucin-lined cysts were provided in consensus manuscripts, but so far there is no systematic analysis regarding the frequency and clinicopathologic characteristics of IPMN-mimickers, i.e., pseudo-IPMNs. In this study, as the first step in establishing frequency, we performed a systematic review of the pathologic findings in 501 consecutive ordinary PDACs, which disclosed that 10% of PDACs had associated cysts ≥1 cm. While 31 (6.2%) of these were IPMN or mucinous cystic neoplasm (MCN), 19 (3.8%) were other cyst types that mimicked IPMN (pseudo-IPMNs) per recent WHO/consensus criteria. As the second step of the study, we performed a comparative clinicopathologic analysis by also including our entire surgical pathology/consultation databases that was comprised of 60 IPMN-associated PDACs, 30 MCN-associated PDACs and 40 pseudo-IPMN-associated PDACs. We found that 84% of true IPMNs were pre-operatively recognized, whereas IPMN was considered in differential diagnosis of 33% of pseudo-IPMNs. Of the 40 pseudo-IPMNs, there were 15 secondary duct ectasias; 6 large-duct-type PDACs; 5 pseudocysts; 5 cystic tumor necrosis; 4 simple mucinous cysts; 3 groove pancreatitis-associated paraduodenal wall cysts; and 2 congenital cysts. Microscopically, pseudo-IPMNs had at least partial mucinous-lining mimicking IPMN but had smaller cystic (mean = 1.9 cm) and larger PDAC (mean = 3.8 cm) components compared to true IPMNs (cyst = 5.7 cm; PDAC = 2.0 cm). In summary, in this pathologically verified analysis that utilized refined criteria, 10% of PDACs were discovered to have cysts ≥1 cm, about two-thirds of which were IPMN/MCN but about one-third were pseudo-IPMNs. True IPMNs underlying the PDACs are often large and are already diagnosed pre-operatively as having an IPMN component, whereas only a third of the pseudo-IPMNs receive IPMN diagnosis by imaging and their cysts are smaller. At the histopathologic level, pseudo-IPMNs are highly prone to misdiagnosis as IPMN, which presumably accounts for much higher association of IPMNs with PDAC as reported in some studies. The subtle but salient characteristics of pseudo-IPMNs elucidated in this study should be combined with careful radiological/clinical correlation in order to exclude pseudo-IPMNs.

Pancreatic and hepatobiliary manifestations of nonalcoholic fatty pancreatic disease: a referral multi-center experience.

BACKGROUND: Nonalcoholic fatty pancreatic disease (NAFPD) is an increasingly recognized disease with accumulating evidence of associated co-morbidities. However, data linked with other pancreatic and hepatobiliary disorders are still being studied. AIMS: To investigate the association of pancreato-hepato-biliary disorders with NAFPD. METHODS: At two Israeli medical centers, a total of 569 patients were analyzed who underwent endoscopic ultrasound for hepatobiliary indications. They were divided into groups depending on the presence or absence of NAFPD. RESULTS: Seventy-eight patients (13.7%) had NAFPD (NAFPD group) vs. 491 patients (86.3%) without (non-NAFPD group). NAFPD was significantly associated with obesity [odds ratio (OR) 4.98, 95% confidence interval (CI) 3.02-8.24, P < 0.0001], hypertension (OR 2.55, 95% CI 1.57-4.15, P = 0.0002), active smoking (OR 2.02, 95% CI 1.04-3.93, P = 0.03), and hyperlipidemia (OR 2.86, 95% CI 1.58-5.18, P = 0.0005). On multivariate regression analysis: fatty liver (OR 5.49, 95% CI 2.88-10.49, P < 0.0001), main duct intraductal papillary mucinous neoplasm (M-IPMN) (OR 2.69, 95% CI 1.05-6.9, P = 0.04), and gallstones (OR 1.93, 95% CI 1.1-3.38, P = 0.02) were the most endoscopically and ultrasonographically detected diseases that significantly correlated with NAFPD. CONCLUSION: NAFPD was associated with several diseases, most importantly the premalignant M-IPMN. Further investigation for these coexisting diseases should be considered.

Facility Type Affects Treatment Outcomes for Patients With Mucinous Cystic Neoplasms and Intraductal Papillary Mucinous Neoplasms of the Pancreas.

OBJECTIVE: Academic centers report better outcomes for pancreatic ductal adenocarcinoma. We hypothesized that treatment outcomes for mucinous cysts differ according to institution type. METHODS: Using the National Cancer Data Base, we analyzed data on patients with mucinous cystic neoplasms (MCNs) and intraductal papillary mucinous neoplasms (IPMNs). RESULTS: Of 3278 identified patients, 2622 (80%) had IPMNs and 656 (20%) had MCNs. While most academic/research programs (ARCPs, 84.9%) treated more than 10 patients/year, this was true for only 59% of integrated network cancer programs, 37.3% of comprehensive community cancer programs, and 0% of community cancer programs (P < 0.001). Surgery was used more often in ARCPs and for smaller tumors. The ARCPs had higher rates of margin negative resections with retrieval of 15 or more nodes with the lowest 30- and 90-day mortality rates. The median overall survival was better in ARCPs (110.3 months) than comprehensive community cancer programs (75.1 mo), community cancer programs (75.1 mo), or integrated network cancer programs (100.8 mo, P < 0.001). CONCLUSIONS: Treatment of MCNs and IPMNs of the pancreas at academic centers is associated with a higher probability of pancreatectomy, disease identification in a noninvasive stage, and better overall survival. Centralization of care for mucinous pancreatic cysts will lead to improved outcomes.

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.

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.

Neuromyelitis optica spectrum disorder with lung adenocarcinoma and intraductal papillary mucinous neoplasm.

Few cases reported the coexistence of tumors and neuromyelitis optica spectrum disorder (NMOSD), which is generally considered idiopathic. Here we describe a 61-year-old woman who developed anti-aquaporin-4 IgG positive myelitis with a pathologically-diagnosed lung adenocarcinoma and a radiologically-diagnosed intraductal papillary mucinous neoplasm. With corticosteroids and immunoglobulin in the acute phase and surgical resection of the lung adenocarcinoma, the patient recovered substantially. This case highlights the need for tumor screening in patients with NMOSD, especially those over 50 years old.

Cabergoline in severe ectopic or occult Cushing's syndrome.

CONTEXT: Cabergoline has been shown to have some effect in the treatment of moderate Cushing's disease, but its effectiveness in Cushing's syndrome of ectopic or occult origin remains to be investigated. CASE SERIES: In this case series, cabergoline was used in combination with steroidogenesis inhibitors in nine patients with severe Cushing's syndrome of ectopic or occult origin. Cabergoline's effectiveness enabled rapid withdrawal of the steroidogenesis inhibitors and long-term control of the hypercortisolism in three of the cases. REVIEW OF THE LITERATURE: In the literature, we found only 11 cases of ectopic or occult Cushing's syndrome treated with dopamine receptor agonists, alone or in combination. Yet of these 11 cases, 10 responded. CONCLUSIONS: Although limited, the existing experience highlights the potential value of cabergoline in the treatment of ectopic or occult Cushing's syndrome.

Pancreaticogastric Fistula Due to Infiltration of a Mixed Type Intrapapillary Mucinous Neoplasia of the Pancreas.

BACKGROUND: A 68-year-old asymptomatic patient was incidentally diagnosed with an intraductal papillary mucinous neoplasia (IPMN) of the pancreas with a pancreaticogastric fistula. He had a history of a right sided nephrectomy due to a renal cell carcinoma 9 years before. The patient underwent an uneventful total pancreatectomy and wedge resection of the stomach. METHODS: The patient's medical history was studied and compared to recent literature via PubMed. RESULTS: Pathohistological evaluation confirmed a mixed type IPMN of an intestinal subtype with pancreaticogastric fistula. CONCLUSION: Pancreaticogastric fistula due to benign IPMN is extremely rare. Surgical resection including wedge resection of the stomach is the treatment of choice.

The Actual Prevalence of Symptoms in Pancreatic Cystic Neoplasms: A Prospective Propensity Matched Cohort Analysis.

BACKGROUND: The prevalence of symptoms in pancreatic cystic neoplasms (PCNs) is mainly based on retrospective surgical series. The aim of this study is to describe the actual prevalence of symptoms in PCNs under surveillance. METHODS: Patients with PCNs under surveillance observed from 2015 to 2017 were submitted to magnetic resonance imaging (MRI) and a specific interview. An identical survey was carried out on a control population matched for age, sex, and comorbidities in which any pancreatic disease was excluded by MRI. RESULTS: Two groups of 184 individuals were compared. Patients with PCNs have a similar prevalence of abdominal pain when compared to controls (35.2 vs. 28.8, p = 0.2). PCNs in the distal pancreas experienced a significantly increased prevalence of abdominal pain (42.3 vs. 28.8%, p = 0.04), whereas size and presumed connection with the ductal system did not affect the prevalence of abdominal pain. PCNs associated with abdominal pain did not differ in terms of clinical and radiological features from asymptomatic ones. CONCLUSION: Patients with PCNs under surveillance have a similar prevalence of abdominal pain when compared to a matched population of controls. Abdominal pain might not correlate with radiological signs of malignancy.