Patients with deleterious germline mutations: A heterogeneous population for pancreatic cancer screening?

BACKGROUND AND OBJECTIVES: Modest data exist on the benefits of screening and surveillance for pancreatic cancer (PC) in high-risk individuals. Intraductal papillary mucinous neoplasms (IPMN) are known precursors to PC. We hypothesized that patients with high-risk deleterious germline mutations have a higher prevalence of IPMN. METHODS: All patients undergoing prospective screening at a single institution from 2013 to 2019 were reviewed. RESULTS: Of 1166 patients screened, 358 (31%) possessed germline mutations and/or family history of PC (mutations n = 201/358, 56%, family history n = 226/358, 63%) (median follow-up 2.7 years). IPMN was found in 127 patients (35.5%). The prevalence of IPMN in mutation carriers (18%) was higher than in the general population (p < 0.01). Germline mutation was an independent predictor of IPMN (odds ratio [OR] = 3.2; p < 0.01), while family history was not (p = 0.22). IPMN prevalence was distributed unevenly between mutation types (67%-Peutz-Jeghers; 43%-HNPCC, 24%-BRCA2; 17%-ATM; 9%-BRCA1; 0%-CDKN2A and PALB2). CONCLUSION: In this series, 18% of mutation carriers harbored IPMN, higher than the general population. Germline mutation, but not a family history of PC, was independently associated with IPMN. This prevalence varied across mutation subtypes, suggesting not all mutation carriers develop precancerous lesions. Genetic testing for patients with a positive family history may improve screening modalities for this high-risk population.

Biliary Stricture After Necrotizing Pancreatitis: An Underappreciated Challenge.

OBJECTIVE: Biliary stricture in necrotizing pancreatitis (NP) has not been systematically categorized; therefore, we sought to define the incidence and natural history of biliary stricture caused by NP. SUMMARY OF BACKGROUND DATA: Benign biliary stricture occurs secondary to bile duct injury, anastomotic narrowing, or chronic inflammation and fibrosis. The profound locoregional inflammatory response of NP creates challenging biliary strictures. METHODS: NP patients treated between 2005 and 2019 were reviewed. Biliary stricture was identified on cholangiography as narrowing of the extrahepatic biliary tree to <75% of the diameter of the unaffected duct. Biliary stricture risk factors and outcomes were evaluated. RESULTS: Among 743 NP patients, 64 died, 13 were lost to follow-up; therefore, a total of 666 patients were included in the final cohort. Biliary stricture developed in 108 (16%) patients. Mean follow up was 3.5 ±â€Š3.3 years. Median time from NP onset to biliary stricture diagnosis was 4.2 months (interquartile range, 1.8 to 10.9). Presentation was commonly clinical or biochemical jaundice, n = 30 (28%) each. Risk factors for stricture development were splanchnic vein thrombosis and pancreatic head parenchymal necrosis. Median time to stricture resolution was 6.0 months after onset (2.8 to 9.8). A mean of 3.3 ±â€Š2.3 procedures were performed. Surgical intervention was required in 22 (20%) patients. Endoscopic treatment failed in 17% (17/99) of patients and was not associated with stricture length. Operative treatment of biliary stricture was more likely in patients with infected necrosis or NP disease duration ≥6 months. CONCLUSION: Biliary stricture occurs frequently after NP and is associated with splanchnic vein thrombosis and pancreatic head necrosis. Surgical correction was performed in 20%.

Colon Involvement in Necrotizing Pancreatitis: Incidence, Risk Factors, and Outcomes.

OBJECTIVE: To investigate the incidence, risk factors, and outcomes of colon involvement in patients with necrotizing pancreatitis. SUMMARY/BACKGROUND DATA: Necrotizing pancreatitis is characterized by a profound inflammatory response with local and systemic implications. Mesocolic involvement can compromise colonic blood supply leading to ischemic complications; however, few data exist regarding this problem. We hypothesized that the development of colon involvement in necrotizing pancreatitis (NP) negatively affects morbidity and mortality. METHODS: Six hundred forty-seven NP patients treated between 2005 and 2017 were retrospectively reviewed to identify patients with colon complications, including ischemia, perforation, fistula, stricture/obstruction, and fulminant Clostridium difficile colitis. Clinical characteristics were analyzed to identify risk factors and effect of colon involvement on morbidity and mortality. RESULTS: Colon involvement was seen in 11% (69/647) of NP patients. Ischemia was the most common pathology (n = 29) followed by perforation (n = 18), fistula (n = 12), inflammatory stricture (n = 7), and fulminant C difficile colitis (n = 3). Statistically significant risk factors for developing colon pathology include tobacco use (odds ratio (OR), 2.0; 95% confidence interval (CI), 1.2-3.4, P = 0.009), coronary artery disease (OR, 1.9; 95% CI, 1.1-3.7; P = 0.04), and respiratory failure (OR, 4.7; 95% CI, 1.1-26.3; P = 0.049). When compared with patients without colon involvement, NP patients with colon involvement had significantly increased overall morbidity (86% vs 96%, P = 0.03) and mortality (8% vs 19%, P = 0.002). CONCLUSION: Colon involvement in necrotizing pancreatitis is common; clinical deterioration should prompt its evaluation. Risk factors include tobacco use, coronary artery disease, and respiratory failure. Colon involvement in necrotizing pancreatitis is associated with substantial morbidity and mortality.

Friend or foe? Feeding tube placement at the time of pancreatoduodenectomy: propensity score case-matched analysis.

BACKGROUND: The role of concomitant gastrostomy or jejunostomy feeding tube (FT) placement during pancreatoduodenectomy (PD) and its impact on patient outcomes remain controversial. METHODS: NSQIP database was surveyed for patients undergoing PD between 2014 and 2017. FT placement was identified using CPT codes. Propensity scores were used to match the two groups (1:1) on baseline characteristics and intraoperative variables including pancreas specific ones (duct size, gland texture, underlying disease, wound class, use of wound protector, drain placement, type of pancreatic reconstruction and vascular reconstruction). Outcomes were compared. Finally, a subset analyses for patients with delayed gastric emptying (DGE) or postoperative pancreatic fistula (POPF) were performed. RESULTS: Out of 15,224 PD, 1,104 (7.5%) had FT. POPF and DGE rates were 17% and 18%, respectively, for the entire cohort. Feeding jejunostomy was the most placed FT (88.2%). Patients with FT placement were more likely to be older (mean, 65.8 vs. 64.6 y), smokers (22.6% vs. 17.8%) who had preoperative weight loss (22.5% vs. 15.3%), ASA class ≥ 3 (80.8% vs. 77.5%), preoperative transfusion (1.5% vs. 0.84%), chemotherapy (22.8% vs. 17.5%), and radiation (14.5% vs. 6.8%, p < 0.05). The matched cohort included 880 patients in each group with completely balanced preoperative and intraoperative characteristics. In the matched cohort, patients with FT placement had higher overall morbidity (52.2% vs. 44.3%, p = 0.001), major morbidity (28.4% vs. 22.5%, p = 0.004), organ/space infection (14.4% vs. 10.9%, p = 0.026), re-operation (8.6% vs. 5.1%, p = 0.003), DGE (26.8% vs. 16.4%, p < 0.001), and longer mean hospital length of stay (12.9 vs. 11.2 days, p = 0.001) than those without FT. There was no difference in mortality (1.7% vs. 2.2%, p = 0.488) or readmission rate (20.2% vs. 17.2%, p = 0.099). In patients with DGE and POPF, FT placement was not associated with morbidity, mortality, length of stay, or readmission rate (p > 0.05). CONCLUSION: Patients with FT placement during PD tend to have higher postoperative morbidity and delayed recovery.

Outcomes in Endoscopic and Operative Transgastric Pancreatic Debridement.

OBJECTIVES: Select patients with anatomically favorable walled off pancreatic necrosis may be treated by endoscopic (Endo-TGD) or operative (OR-TGD) transgastric debridement (TGD). We compared our experience with these 2 approaches. SUMMARY BACKGROUND DATA: Select necrotizing pancreatitis (NP) patients are suitable for TGD which may be accomplished endoscopically or surgically. Limited experience exists contrasting these techniques exists. METHODS: Patients undergoing Endo-TGD and OR-TGD at a single, high-volume pancreatic center between 2008 and 2019 were identified from a prospective database. Patient characteristics, procedural details, and outcomes of these 2 groups were compared. RESULTS: Among 498 NP patients undergoing necrosis intervention, 160 (32%) had TGD: 59 Endo-TGD and 101 OR-TGD. The groups were statistically similar in age, comorbidity, pancreatitis etiology, necrosis anatomy, pancreatitis severity, and timing of TGD from pancreatitis insult. OR-TGD required 1.1 ±â€Š0.5 and Endo-TGD 3.0 ±â€Š2.0 debridements/patient. Fewer hospital readmissions and repeat necrosis interventions, and shorter total inpatient length of stay were observed in OR-TGD patients. New-onset organ failure [Endo-TGD (13%); OR-TGD (13%); P = 1.0] was similar between groups. Hospital length of stay after TGD was significantly longer in patients undergoing Endo-TGD (13.8 ±â€Š20.8 days) compared to OR-TGD (9.4 ±â€Š6.1 days; P = 0.047). Mortality was 7% in Endo-TGD and 1% in OR-TGD (P = 0.04). CONCLUSIONS: Operative and endoscopic transgastric debridement achieve necrosis resolution with different temporal and procedural profiles. Clear multidisciplinary communication is essential to determine appropriate approach to individual necrotizing pancreatitis patients.

A novel biosynthetic scaffold mesh reinforcement affords the lowest hernia recurrence in the highest-risk patients.

INTRODUCTION: Patients with higher postoperative infection risk undergoing ventral hernia repair (VHR) have limited options for mesh use. Biosynthetic mesh is intended to utilize the durability of synthetic mesh combined with the biocompatibility of biologic mesh. We sought to assess the outcomes of a novel biosynthetic scaffold mesh for VHR in higher risk patients over a 12-month postoperative period. METHODS: Two cohorts of 50 consecutive patients who underwent VHR with TELA Bio OviTex biosynthetic or synthetic mesh were retrospectively compared. Endpoints included surgical site occurrence (SSO), readmission rate, and hernia recurrence following VHR at 12 months postoperatively. RESULTS: OviTex mesh placement was associated with higher risk Ventral Hernia Working Group (VHWG) distribution and more contaminated CDC wound class distribution compared to synthetic mesh placement (VHWG grade 3: 68% vs. 6%, p < 0.001; CDC class > I: 70% vs. 6%, p < 0.001). Additionally, concomitant procedures were performed more often with OviTex mesh placement than synthetic mesh placement (70% vs 10%, p < 0.001). The OviTex mesh performed comparably to synthetic mesh in terms of incidences of SSO (36% vs 22%, p = 0.19), readmission rates (24% vs 14%, p = 0.31), and hernia recurrence (6% vs 12%, p = 0.74). On further evaluation, patients who developed SSO with OviTex mesh (n = 18) had a 17% hernia recurrence whereas those with synthetic mesh (n = 11) had an associated 55% hernia recurrence (p = 0.048). CONCLUSIONS: The OviTex biosynthetic mesh was used in higher risk patients and performed similarly to synthetic mesh in regards to rate of SSO, readmissions, and hernia recurrence. Furthermore, patients who developed SSO with Ovitex mesh were significantly less likely to have hernia recurrence than those with synthetic mesh. Overall, the data suggest that biosynthetic mesh is a more desirable option for definitive hernia repair in higher risk patients.

Is resident assistance equivalent to fellows during hepatectomy?

OBJECTIVE: Hepatectomy is a complex operative procedure frequently performed at academic institutions with trainee participation. The aim of this study was to determine the effect of assistant's training level on outcomes following hepatectomy. METHODS: A retrospective review of a prospective, single-institution ACS-NSQIP database was performed for patients that underwent hepatectomy (2013-2016). Patients were divided by trainee assistant level: hepatopancreatobiliary (HPB) fellow versus general surgery resident (PGY 4-5). Demographic, perioperative, and 30-day outcome variables were compared using Chi-Square/Fisher's exact, Mann-Whitney U test, and multivariable regression. Cases involving a senior-level general surgery resident or HPB fellow as first assistant were included (n = 352). Those with a second attending, junior-level resident, or no documented assistant were excluded (n = 39). RESULTS: Patients undergoing hepatectomy with an HPB fellow as primary assistant had more frequent preoperative biliary stenting, longer operative time, and more concomitant procedures including biliary reconstruction, resulting in a higher rate of post-hepatectomy liver failure (PHLF) (15% vs. 8%, P = 0.044). However, trainee level did not impact PHLF on multivariable analysis (OR 0.60, 95% CI [0.29-1.25], P = 0.173). Fellows assisted with proportionally more major hepatectomies (45% vs. 31%; P = 0.010) and resections for hepatobiliary cancers (31% vs. 19%, P = 0.014). On stratified analysis of major and minor hepatectomies, outcomes were similar between trainee groups. CONCLUSION: Fellows performed higher complexity cases with longer operative time. Despite these differences, outcomes were similar regardless of assistant training level. Resident and HPB fellow participation in operations requiring liver resection provide comparable quality of care.

Use of primary surgical drains in synchronous resection for colorectal liver metastases: a NSQIP analysis of current practice paradigm.

BACKGROUND: There are no studies examining the use of subhepatic drains after simultaneous resection of synchronous colorectal liver metastases (sCRLM). This study aimed to (1) describe the current practices regarding primary drain placement, (2) evaluate drain efficacy in mitigating postoperative complications, and (3) determine impact of drain maintenance duration on patient outcomes. METHODS: The ACS-NSQIP targeted data from 2014 to 2017 were analyzed. Propensity score of surgical drain versus no drain cohorts was performed. Main study outcomes were mortality, major morbidity, organ/space surgical site infection (SSI), secondary drain/aspiration procedure, and any septic events. Additional univariate/multivariate logistic analyses were performed to identify associations with drain placement and duration. Major hepatectomy was defined as formal right hepatectomy and any trisectionectomy. RESULTS: 584 combined liver and colorectal resection (CRR) cases were identified. Open partial hepatectomy with colectomy was the most common procedure (70%, n = 407). Nearly 40% of patients received surgical drains (n = 226). Major hepatectomy, lower serum albumin, and no intraoperative portal vein occlusion (Pringle maneuver) were significantly associated with drain placement (p < 0.05). In the matched cohort (n = 190 in each arm), patients with surgical drains experienced higher rates of major morbidity (30% vs 12%), organ/space SSI (16% vs 6%), postoperative drain/aspiration procedures (9% vs 3%), and sepsis/septic shock (12% vs 4%) (all p < 0.05). Patients with severely prolonged drain removal, defined as after postoperative day 13 (POD13), had higher risk of postoperative morbidity compared to those with earlier drain removal (p < 0.01). 30-day mortality rate was not significantly different between the two groups. CONCLUSION: Primary surgical drains were placed in a substantial percentage of patients undergoing combined resection for sCRLM. This case-matched analysis suggested that surgical drains are associated with an increase in postoperative morbidity. Postoperative drain maintenance past 13 days is associated with worse outcomes compared to earlier removal.

Disconnected pancreatic duct syndrome predicts failure of percutaneous therapy in necrotizing pancreatitis.

BACKGROUND/OBJECTIVES: Minimally invasive approaches, such as percutaneous drainage (PD), are increasingly utilized as initial treatment in necrotizing pancreatitis (NP) requiring intervention. Predictors of success of PD as definitive treatment are lacking. Our aim was to assess the application, predictors of success, and natural history of PD in NP. We hypothesized that necrosis morphology patterns and disconnected pancreatic duct syndrome (DPDS) may predict the ability of PD to provide definitive therapy. METHODS: 714 NP patients were treated from 2005 to 2018. Patients achieving disease resolution with PD alone (PD) were compared to those requiring an escalation in intervention (Step). Outcomes were compared between groups using independent samples t-test, Fisher's exact test, and Pearson's correlation, as appropriate. P < 0.05 was accepted as statistically significant. RESULTS: 115 patients were initially managed with PD (42 PD, 73 Step). No difference in necrosis morphology was seen between the two groups. The PD group underwent significantly more repeat percutaneous interventions (PD, 3.2; Step, 2.0; P = 0.0006) including additional drain placement and drain upsize/reposition procedures. Patients with DPDS were more likely to require an escalation in intervention (odds ratio, 3.4; 95% confidence interval, 1.5-7.6; P = 0.003). The mean number of months to NP resolution was similar (PD, 5.7; Step, 5.8; P = 0.9). Mortality was similar (PD, 7%; Step 14%, P = 0.3). CONCLUSIONS: Necrosis morphology in and of itself does not reliably predict successful definitive treatment by percutaneous drainage. However, patients with disconnected pancreatic duct syndrome were less likely to have definitive resolution with PD alone.

Improved Outpatient Communication Decreases Unplanned Readmission in Necrotizing Pancreatitis.

BACKGROUND: Unplanned readmission rates in necrotizing pancreatitis (NP) are among the highest of any medical disease (72%). Recent work has identified several potentially preventable causes of unplanned readmission in NP. We hypothesized that intensive outpatient communication would identify developing problems and decrease unplanned hospital readmission. MATERIALS AND METHODS: A review of NP patients treated at a single institution between 2016 and 2019 compared patients 2 y before (NP-pre, 2016-2018) and 1 y after (NP-post, 2018-2019) the establishment of a dedicated pancreatitis nurse coordinator. Unplanned hospital readmission and emergency room visits were compared between groups. RESULTS: A total of 178 NP patients were treated-112 patients in the NP-pre group and 66 patients in the NP-post group. No differences between groups were observed in age, sex, comorbidities, pancreatitis etiology, NP severity, or mortality. A mean of 5.4 ± 0.2 outpatient communications per patient with the pancreatitis nurse coordinator was documented in the NP-post group. Unplanned readmission rates decreased significantly from 64% (NP-pre) to 45% (NP-post; P = 0.02). The frequency of readmission decreased from 1.6 readmissions per patient (NP-pre) to 0.8 readmissions per patient (NP-post; P = 0.001). Readmissions because of symptomatic necrosis, failure to thrive, nonnecrosis infection, and drain dysfunction decreased (P < 0.05). Overall disease duration was similar (NP-pre, 4.6 ± 0.3 mo; NP-post, 5.0 ± 0.3 mo; P = 0.4); however, the mean number of unplanned inpatient days decreased from 15.4 ± 2.2 d (NP-pre) to 7.8 ± 1.6 d (NP-post; P = 0.02). CONCLUSIONS: Improved outpatient communication identifies treatable problems and significantly decreases unplanned readmission in NP patients.

Pancreatic Adenocarcinoma Causing Necrotizing Pancreatitis: Not as Rare as You Think?

BACKGROUND: Necrotizing pancreatitis (NP) presents a unique clinical challenge because of its complex and lengthy disease course. Pancreatic necrosis occurs in 10%-20% of acute pancreatitis cases and may result from any etiology. Scattered reports describe pancreatic tumors causing NP; however, the relationship between these disease processes is not clear. We have treated patients whose NP was caused by pancreatic ductal adenocarcinoma (PDAC) and therefore sought to clarify the clinical outcomes of these patients. METHODS: Patients treated between 2005 and 2018 for NP caused by PDAC were identified. The relationship between NP and PDAC was examined, and the clinical courses of both disease processes were evaluated. RESULTS: Among 647 patients treated for NP, seven patients (1.1%) had PDAC and NP. The mean age at NP diagnosis was 60.6 y (range, 49-66). Two patients had postprocedural pancreatitis after cancer diagnosis, and the remaining five patients had NP caused by PDAC. Median duration between diagnoses of NP and PDAC was 5.6 mo (range, 3.5-21.8). For PDAC treatment, four patients received chemotherapy alone, one received palliative radiation therapy, and one died without oncologic management. One patient underwent operative resection of PDAC. Median survival was 12.7 mo (range, 0.4-49.9). CONCLUSIONS: PDAC may be a more common cause of NP than previously considered and should be considered in patients with NP of appropriate age in whom etiology is otherwise unclear. Prompt diagnosis facilitates optimal treatment in this challenging clinical situation.

Disconnected Pancreatic Duct Syndrome: Spectrum of Operative Management.

BACKGROUND: Disconnected pancreatic duct syndrome (DPDS) is common after necrotizing pancreatitis (NP). Surgical management may be by internal drainage or left (distal) pancreatectomy. Therapeutic decision-making must consider sinistral portal hypertension, parenchymal volume of disconnected pancreas, and timing relative to definitive management of pancreatic necrosis. The aim of this study is to evaluate outcomes after operative management for DPDS. METHODS: All patients with NP undergoing an operation for DPDS were included in the study (2005-2017). Perioperative outcomes and long-term durability were evaluated. RESULTS: Among 647 patients with NP, 299 (46%) had DPDS. Operative management was required in 202/299 (68%) patients with DPDS. Median follow-up was 30 mo (2-165). Definitive operative therapy included internal drainage (n = 111) or resection (n = 91). Time from NP diagnosis to operation was 126 d (20 d to 81 mo). Overall morbidity was 46%. Postoperative length of stay was 7 d (2-97). Readmission was required in 39 patients (19%). Mortality was 2%. Repeat pancreatic intervention was required in 23 patients (11%) at a median of 15 mo (1-98). Repeat pancreatectomy was performed in nine patients and the remaining 14 patients were managed with endoscopic therapy. CONCLUSIONS: DPDS is a common and challenging consequence of NP. Appropriate operation is durable in nearly 90% of patients.

Visceral artery pseudoaneurysm in necrotizing pancreatitis: incidence and outcomes.

Background: Visceral artery pseudoaneurysms (VA-PSA) occur in necrotizing pancreatitis; however, little is known about their natural history. This study sought to evaluate the incidence and outcomes of VA-PSA in a large cohort of patients with necrotizing pancreatitis. Methods: Data for patients with necrotizing pancreatitis who were treated between 2005 and 2017 at Indiana University Health University Hospital and who developed a VA-PSA were reviewed to assess incidence, presentation, treatment and outcomes. Results: Twenty-eight of 647 patients with necrotizing pancreatitis (4.3%) developed a VA-PSA between 2005 and 2017. The artery most commonly involved was the splenic artery (36%), followed by the gastroduodenal artery (24%). The most common presenting symptom was bloody drain output (32%), followed by incidental computed tomographic findings (21%). The median time from onset of necrotizing pancreatitis to diagnosis of a VA-PSA was 63.5 days (range 1-957 d). Twenty-five of the 28 patients who developed VA-PSA (89%) were successfully treated with percutaneous angioembolization. Three patients (11%) required surgery: 1 patient rebled following embolization and required operative management, and 2 underwent upfront operative management. The mortality rate attributable to hemorrhage from a VA-PSA in the setting of necrotizing pancreatitis was 14% (4 of 28 patients). Conclusion: In this study, VA-PSA occurred in 4.3% of patients with necrotizing pancreatitis. Percutaneous angioembolization effectively treated most cases; however, mortality from VA-PSA was high (14%). A high degree of clinical suspicion remains critical for early diagnosis of this potentially fatal problem.

Contexte: Les faux anévrismes des artères viscérales (FAAV) surviennent en présence d'une pancréatite nécrosante; on en sait cependant peu sur leur histoire naturelle. L'objectif de l'étude était d'évaluer l'incidence et les issues des FAAV dans une grande cohorte de patients atteints de pancréatite nécrosante. Méthodes: Nous avons examiné les données des patients atteints de pancréatite nécrosante traités entre 2005 et 2017 à l'Hôpital universitaire de l'Université de l'Indiana qui ont fait un FAAV afin d'évaluer l'incidence, les premiers signes, le traitement et les issues de cette affection. Résultats: Vingt-huit (4,3 %) des 647 patients atteints de pancréatite nécrosante inclus (2005­2017) ont fait un FAAV. L'artère la plus souvent touchée était l'artère splénique (36 %), suivie de l'artère gastroduodénale (24 %). Les premiers signes les plus courants étaient la présence de sang dans les liquides évacués par drainage (32 %), puis les résultats d'une tomodensitométrie effectuée pour une autre raison (21 %). Le délai médian entre l'apparition de la pancréatite nécrosante et le diagnostic de FAAV était de 63,5 jours (intervalle : 1 à 957 jours). Vingt-cinq des 28 patients ayant fait un FAAV (89 %) ont été traités avec succès par angioembolisation percutanée. Trois patients (11 %) ont dû être opérés : 2 dès le début, et le troisième parce qu'il a recommencé à saigner après l'embolisation. Le taux de mortalité par hémorragie due à un FAAV chez les personnes atteintes d'une pancréatite nécrosante était de 14 % (4 patients sur 28). Conclusion: Dans cette étude, 4,3 % des patients atteints de pancréatite nécrosante ont connu un FAAV. L'angioembolisation percutanée s'est avérée efficace dans la plupart des cas; cependant, la mortalité associée aux FAAV était élevée (14 %). Il est crucial de faire preuve d'une grande suspicion clinique afin de diagnostiquer tôt cette affection potentiellement mortelle.

Cystic pancreatic neuroendocrine tumors: A more favorable lesion?

BACKGROUND: Pancreatic neuroendocrine tumors (PNETs) are predominantly solid lesions with malignant potential. Cystic PNETs are a small subset in which data are scarce. The aim of this study was to compare clinical and biologic differences between cystic and solid PNETs. METHODS: Patients with PNETs undergoing pancreatectomy between 1988 and 2016 at a high-volume center were reviewed retrospectively. Demographic, clinical, and histopathologic data were collected and analyzed. RESULTS: 347 patients with PNETs were identified; 27% (n = 91) were cystic. Patients with cystic PNETs were generally older (59 vs. 55 years, p = 0.05). Cystic PNETs were more commonly non-functional (95% vs. 82%, p = 0.004), asymptomatic (44% vs. 28%, p = 0.009), and located in the pancreatic body/tail (81% vs. 60%, p < 0.001) than solid PNETs. Although cystic and solid PNETs had similar sizes and pathologic stage at the time of resection, Ki-67 proliferation index (Ki-67 ≤ 9%: 98% vs. 85%; p = 0.007), and histologic grade (grade I: 84% vs. 59%; p = 0.009) had less aggressive features in cystic PNETs. CONCLUSION: In addition to reporting a higher than previously published incidence of cystic PNET (27%), this study found significant differences in multiple clinicopathologic variables between cystic and solid PNETs. Cystic PNET may be a distinct and possibly less aggressive subtype of PNET yet have similar pathologic stage, recurrence, and survival to solid PNETs. Cystic PNETs require further attention to better understand the true natural history.

Sphincter of Oddi Dysfunction After Gastric Bypass: Surgical or Endoscopic Therapy?

BACKGROUND: Management of Sphincter of Oddi Dysfunction (SOD) requires advanced techniques (endoscopic retrograde cholangiopancreatography via gastrostomy [GERCP]) after Roux-en-Y gastric bypass (RYGB) for obesity. Transduodenal sphincteroplasty (TS) is also performed yet carries the risks of surgery. We hypothesized that TS would have increased morbidity and mortality but provide a more durable remission of symptoms. METHODS: All patients between 2005 and 2016 with RYGB for obesity undergoing endoscopic or surgical management for type I or II SOD were included in the study. Patients with type III SOD, or who underwent RYGB for nonobesity indications, were excluded. RESULTS: Thirty-eight patients were identified. GERCP was initially performed in 17 patients, whereas TS was performed in 21. Thirty-day mortality was 0% in our cohort, and 30-d morbidity was similar between GERCP and TS (29% versus 10%; P = 0.207). Resolution of symptoms after initial therapy was seen in 41% of GERCP (7/17) and 67% of TS (14/21) (P = 0.190), respectively, and overall after 35% (8/23) and 64% (16/24) of procedures performed (P = 0.042). Symptom resolution, as defined by the median ratio of days of total remission by total days of observed follow-up, was shorter after initial and all interventions with GERCP compared with TS (0.67 versus 1.00, P = 0.036 and 0.52 versus 1.00, P = 0.028, respectively). CONCLUSIONS: Endoscopic and surgical treatment of SOD had similar morbidity and mortality. However, treatment success and duration of remission was higher in those treated with surgery.

Are BRCA1 and BRCA2 gene mutation patients underscreened for pancreatic adenocarcinoma?

BACKGROUND: Breast cancer (BRCA) mutations account for the highest proportion of hereditary causes of pancreatic ductal adenocarcinoma (PDAC). Screening is currently recommended only for patients with one first-degree relative or two family members with PDAC. We hypothesized that screening all BRCA1/2 patients would identify a higher rate of pancreatic abnormalities. METHODS: All BRCA1/2 patients at a single academic center were retrospectively reviewed (2005-2015). Pancreatic abnormalities were defined on cross-sectional imaging as pancreatic neoplasm (cystic/solid) or main-duct dilation. RESULTS: Two hundred and four patients were identified with BRCA mutations. Forty-seven (40%) had abdominal imaging (20 computerized tomography and 27 magnetic resonance imaging). Twenty-one percent had pancreatic abnormalities (PDAC [n = 2] and intraductal papillary mucinous neoplasm [IPMN; n = 8]). The prevalence of pancreatic abnormalities and IPMN was higher in BRCA2 patients than in the general population (21% vs 8% and 17% vs 1%; P = 0.0007 and P < 0.0001, respectively), with no influence of family history. Similarly, BRCA1 patients had an increased prevalence of IPMN (8.3% vs 1%; P < 0.0001). CONCLUSIONS: In this series, 4% and 17% of BRCA2 patients developed PDAC and IPMN, respectively. Eight percent of BRCA1 patients developed IPMN. Under current recommended screening, 60% of BRCA1/2 patients had incompletely pancreatic assessment. With no influence of family history, this study suggests all BRCA1/2 patients should undergo a high-risk screening protocol that will identify a higher rate of precancerous pancreatic neoplasms amenable to curative resection.

Outcomes of pancreatoduodenectomy in the cirrhotic patient: risk stratification and meta-analysis.

BACKGROUND: Cirrhosis increases the risk of perioperative mortality in gastrointestinal surgery. Though cirrhosis is sometimes considered a contraindication to pancreatoduodenectomy (PD), few data are available in this patient population. The aim of the present study is to identify predictors of outcome in cirrhotic patients undergoing PD. METHODS: Patients undergoing PD with biopsy-proved cirrhosis were evaluated. Primary endpoints were morbidity and mortality. Child score, MELD score, and radiographic evidence of portal hypertension (pHTN) were assessed for accuracy in preoperative risk stratification. A systematic review of the literature with meta-analysis was also performed to query morbidity and mortality of patients with cirrhosis reported to undergo PD. RESULTS: Between 2005 and 2015, 36 cirrhotic patients underwent PD; three year follow-up was complete. Median Child score was 6 (range 5-10); median MELD score was 9 (range 7-18). Perioperative (90-day) mortality was 6/36. Median survival was 37 months (range 0.2-116). MELD ≥ 10 was associated with increased mortality (4/13 vs. 2/13, p = 0.004). Irrespective of Child or MELD score, those with pHTN had poor outcomes including significantly greater intraoperative blood loss, increased incidence of major complication, and length of stay. Postoperative mortality was significantly higher with pHTN (3/16 vs. 1/13, p = 0.012). CONCLUSION: Pancreatoduodenectomy may be considered in carefully selected cirrhotic patients. MELD ≥ 10 predicts increased risk of postoperative mortality. Specific attention should be afforded to patients with preoperative radiographic evidence of portal hypertension as this group experiences poor outcomes irrespective of MELD or Child score.

Travel distance affects rates and reasons for inpatient visits after pancreatectomy.

BACKGROUND: Centralization of complex surgical care leads to increased travel distances for patients. We sought to determine if increased travel distance to the index hospital altered inpatient Visit rates following pancreatectomy. METHODS: Pancreatectomies from 2013-2016 were reviewed retrospectively from a single high-volume institution. Travel distance for 936 patients was determined, and patients were grouped by 50-mile increments. Visits (Observations or Readmissions) and corresponding reasons were gathered. RESULTS: 222 patients (23.7%) had a Visit to any hospital (AH) within 90 days postoperative; 195 (87.8%) were to the index hospital (IH). The <50 miles group had the highest Visit rate to AH (28.6% vs. 17.8% vs. 24.6%; P = 0.008) and the IH (26.9% vs. 15.2% vs. 20.6%; P = 0.002) compared to 50-100 and > 100 miles. This trend was statistically significant for Observations, but not Readmissions. Gastrointestinal (GI) complaints alone led to 20.7% patients requiring Visits to AH at 90-days, mostly in <50miles group for Visits and Observations at AH and IH. CONCLUSIONS: Patients closest to the IH had the highest Visit and Observation rate following pancreatectomy without affecting Readmission rate, with GI complaints as a driving factor. Inpatient education and outpatient symptom management may reduce repeat hospitalization.

Clinical criteria for integrated molecular pathology in intraductal papillary mucinous neoplasm: less is more.

BACKGROUND: For pancreatic cysts with negative cytology, Integrated Molecular Pathology (IMP) is a malignancy risk score integrating clinical criteria with pancreatic cyst fluid DNA profiling. Aside from main pancreatic duct (MPD) diameter, integrated clinical criteria are not International Consensus Guidelines High-Risk Stigmata. We predicted exclusion of clinical criteria except MPD diameter could simplify the IMP and better distinguish invasive/malignant disease. METHODS: Records of >1100 patients with IPMN were reviewed retrospectively. Sensitivity, specificity, and accuracy of conventional IMP for invasive/malignant disease was compared to DNA profile including only MPD ≥10mm (IMP-10.) Invasive outcomes were invasive-IPMN/adenocarcinoma on surgical pathology, pathologic or radiographic evidence of invasive/metastatic disease during surveillance. Malignant outcomes included high grade dysplastic IPMN (HGD-IPMN). RESULTS: 225 patients who met study criteria underwent 283 IMP evaluations: 98 followed by surgery, 185 followed by ≥ 23 months surveillance. IMP-10 had greater specificity (90.1% vs. 73.7%) and accuracy (89.8% vs. 74.2%) for invasive disease compared to IMP in surgery + surveillance patients, but lower sensitivity (77.8% vs. 88.9%). Trends were similar in surgery patients alone and malignant outcome analyses. CONCLUSION: IMP-10 excludes less-reliable clinical factors resulting in greater accuracy in predicting invasive/malignant disease and fewer patients with benign disease being recommended for surgery.

Laparoscopic distal pancreatectomy for pancreatic cancer is safe and effective.

PURPOSE: To compare the short-term and oncologic outcomes of patients with pancreatic ductal adenocarcinoma (PDAC) undergoing laparoscopic distal pancreatectomy (LDP) and open distal pancreatectomy (ODP). METHODS: Consecutive cases of distal pancreatectomy (DP) (n = 422) were reviewed at a single high-volume institution over a 10-year period (2005-2014). Inclusion criteria consisted of any patient with PDAC by surgical pathology. Ninety-day outcomes were monitored through a prospectively maintained pancreatic resection database. The Social Security Death Index was used for 5-year survival. Two-way statistical analyses were used to compare categories; variance was reported with standard error of the mean; * indicates P value <0.05. RESULTS: Seventy-nine patients underwent DP for PDAC. Thirty-three underwent LDP and 46 ODP. There were no statistical differences in demographics, BMI, and ASA classification. Intraoperative and surgical pathology variables were comparable for LDP versus ODP: operative time (3.9 ± 0.2 vs. 4.2 ± 0.2 h), duct size, gland texture, stump closure, tumor size (3.3 ± 0.3 vs. 4.0 ± 0.4 cm), lymph node harvest (14.5 ± 1.1 vs. 17.5 ± 1.2), tumor stage (see table), and negative surgical margins (77 vs. 87%). Patients who underwent LDP experienced lower blood loss (310 ± 68 vs. 597 ± 95 ml; P = 0.016*) and required fewer transfusions (0 vs. 13; P = 0.0008*). Patients who underwent LDP had fewer positive lymph nodes (0.8 ± 0.2 vs. 1.6 ± 0.3; P = 0.04*) and a lower incidence of type C pancreatic fistula (0 vs. 13%; P = 0.03*). Median follow-up for all patients was 11.4 months. Long-term oncologic outcomes revealed similar outcomes including distant or local recurrence (30 vs. 52%; P = 0.05) and median survival (18 vs. 15 months), as well as 1-year (73 vs. 59%), 3-year (22 vs. 21%), and 5-year (20 vs. 15%) survival for LDP and ODP, respectively. CONCLUSIONS: The results of this series suggest that LDP is a safe surgical approach that is comparable from an oncologic standpoint to ODP for the management of pancreatic adenocarcinoma.