Biliary intervention rates during neoadjuvant therapy for adenocarcinoma of the pancreatic head.

BACKGROUND: Neoadjuvant therapy prior to resection of adenocarcinoma of the pancreatic head increases time to surgery and thus the possibility of biliary complications. We hypothesized that biliary complications during neoadjuvant therapy negatively impact clinical outcomes. METHODS: We completed a retrospective study of a cohort of borderline resectable patients consistently treated with neoadjuvant therapy from May 2014 through March 2019. Biliary complications were defined as new-onset biliary obstruction, existing stent failure, cholecystitis, and cholangitis. RESULTS: Of 59 patients that met inclusion criteria, 34 (57.6%) went on to resection. Biliary complications affected 16 patients (27%); 8 (50%) of these patients went on to surgical resection. Of those 43 patients who did not have a biliary intervention, 26 went on to surgical resection (60.4%). There was no significant effect of a biliary complication on total number of chemotherapy cycles (p = 0.12), proceeding to surgical resection (p = 0.56) or on median survival (p = 0.23). Among patients who did proceed to surgery, there was a notable difference in median survival for patients who required a biliary intervention (17.9 vs 31.0 months) that did not reach significance (p = 0.35). CONCLUSION: The need for further biliary interventions during neoadjuvant therapy for pancreatic adenocarcinoma is common, but does not appear to have a significant effect on number of cycles of neoadjuvant therapy or proceeding to surgical resection. Larger studies are necessary to determine if these events compromise overall survival.

A systematic review of the role of periadventitial dissection of the superior mesenteric artery in affecting margin status after pancreatoduodenectomy for pancreatic adenocarcinoma.

BACKGROUND: Resectable pancreatic ductal adenocarcinoma continues to carry a poor prognosis. Of the controllable clinical variables known to affect outcome, margin status is paramount. Though the importance of a R0 resection is generally accepted, not all margins are easily managed. The superior mesenteric artery [SMA] in particular is the most challenging to clear. The aim of this study was to systematically review the literature with specific focus on the role of a SMA periadventitial dissection during PD and it's effect on margin status in pancreatic adenocarcinoma. STUDY DESIGN: The MEDLINE, EMBASE and Cochrane databases were searched for abstracts that addressed the effect of margin status on survival and recurrence following pancreaticoduodenectomy [PD]. Quantitative analysis was performed. RESULTS: The overall incidence of a R1 resection ranged from 16% to 79%. The margin that was most often positive following PD was the SMA margin, which was positive in 15-45% of resected specimens. Most studies suggested that a positive margin was associated with decreased survival. No consistent definition of R0 resection was observed. CONCLUSIONS: Margin positivity in resectable pancreatic adenocarcinoma is associated with poor survival. Inability to clear the SMA margin is the most common cause of incomplete resection. More complete and consistently reported data are needed to evaluate the potential effect of periadventitial SMA dissection on margin status, local recurrence, or survival.

Clinical Factors as a Component of the Personalized Treatment Approach to Advanced Pancreatic Cancer: a Systematic Literature Review.

INTRODUCTION: Pancreatic cancer is often diagnosed at late stages, where disease is either locally advanced unresectable or metastatic. Despite advances, long-term survival is relatively non-existent. DISCUSSION: This review article discusses clinical factors commonly encountered in practice that should be incorporated into the decision-making process to optimize patient outcomes, including performance status, nutrition and cachexia, pain, psychological distress, medical comorbidities, advanced age, and treatment selection. CONCLUSION: Identification and optimization of these clinical factors could make a meaningful impact on the patient's quality of life.

Analysis of the Cost Effectiveness of Laparoscopic Pancreatoduodenectomy.

OBJECTIVE: We sought to determine if laparoscopic pancreatoduodenectomy (LPD) is a cost-effective alternative to open pancreatoduodenectomy (OPD). METHODS: Hospital cost data, discharge disposition, readmission rates, and readmission costs from periampullary cancer patient cohorts of LPD and OPD were compared. The surgical cohorts over a 40-month period were clinically similar, consisting of 52 and 50 patients in the LPD and OPD groups, respectively. RESULTS: The total operating room costs were higher in the LPD group as compared to the OPD group (median US$12,290 vs US$11,299; P = 0.05) due to increased costs for laparoscopic equipment and regional nerve blocks (P ≤ 0.0001). Although hospital length of stay was shorter in the LPD group (median 7 vs 8 days; P = 0.025), the average hospital cost was not significantly decreased compared to the OPD group (median $28,496 vs $28,623). Surgery-related readmission rates and associated costs did not differ between groups. Compared to OPD patients, significantly more LPD patients were discharged directly home rather than to other healthcare facilities (88% vs 72%; P = 0.047). CONCLUSION: For the index hospitalization, the cost of LPD is equivalent to OPD. Total episode-of-care costs may favor LPD via reduced post-hospital needs for skilled nursing and rehabilitation.

Pancreaticojejunostomy Stricture After Pancreatoduodenectomy: Outcomes After Operative Revision.

INTRODUCTION: The natural history of radiographic strictures of the pancreaticojejunostomy (PJ) after pancreatoduodenectomy (PD) is difficult to characterize. The purpose of this study was to identify the indications for operative revision of PJ strictures after PD for benign and malignant disease and to evaluate its safety and clinical efficacy. METHODS: A retrospective review of all patients undergoing operative revision of PJ strictures following PD at a single academic institution over an 8-year period (2006-2014) was performed. RESULTS: Twenty-seven patients underwent revision of a symptomatic radiographically detectable PJ stricture. The median time from PD to PJ stricture diagnosis was 46 months. The median increase in the main pancreatic duct diameter between the time of PD and PJ revision was 2 mm. The overall morbidity after PJ revision was 26 %. No postoperative mortality occurred. Twenty-one (78 %) patients experienced resolution of symptoms without recurrent acute pancreatitis after PJ revision during a median follow-up of 30 months. Durable symptom resolution was reported among 60 % of patients with chronic pancreatitis. CONCLUSIONS: Surgical revision of pancreaticojejunostomy strictures is technically safe and clinically effective for selected patients who experience recurrent acute pancreatitis after pancreatoduodenectomy for either benign or malignant disease.

Significance of Portal Vein Invasion and Extent of Invasion in Patients Undergoing Pancreatoduodenectomy for Pancreatic Adenocarcinoma.

INTRODUCTION: Several studies have confirmed the safety of pancreatoduodenectomy with portal/mesenteric vein resection and reconstruction in select patients. The effect of vein invasion and extent of invasion on survival is less clear. The purpose of this study was to examine the association between tumor invasion of the portal/mesenteric vein and long-term survival. METHODS: A retrospective review of a prospectively maintained database of patients who underwent pancreatoduodenectomy for pancreatic adenocarcinoma at a single academic medical center (2000-2014) was performed. Survival was compared using the Kaplan-Meier method and log-rank test. P < 0.05 was considered statistically significant. RESULTS: After non-pancreatic periampullary adenocarcinomas and patients with non-segmental (lateral wall only) resection of portal/mesenteric vein were excluded, there were 567 eligible patients. Of these, segmental vein resection was performed in 90 (16 %) with end-to-end primary anastomosis (67) or interposition graft reconstruction (23). Patients with vein resection more likely received neoadjuvant systemic therapy (59 vs. 4 %, p < 0.0001). Histopathology of patients undergoing vein resection revealed a distribution of T stage toward larger tumors and higher rates of perineural invasion. Portal/mesenteric vein resection, however, was not associated with differences in hospital stay, postoperative complications, or operative mortality. Patients with or without vein resection had comparable overall survival rates at 1-, 3-, and 5-years. On final surgical histopathology, only 52 of 90 (58 %) vein resections had adenocarcinoma involvement of the venous wall. Of these, depth of invasion was at the level of the adventitia (9), media/intima (34), and full thickness/intraluminal (9). Venous wall invasion (52) did not significantly influence overall survival (14 vs. 21 months, p = 0.08) but was associated with significantly shorter median disease-free survival (11.3 vs. 15.8 months, p = 0.03), predominantly due to local recurrence. The extent of invasion (adventitia, media/intima, full thickness/intraluminal) did not impact overall survival or disease-free survival (14.4 vs. 15.5 vs. 7.4 months, p = 0.08 and 11.2 vs. 12.2 vs. 5 months, 0.59, respectively). Portal/mesenteric vein resection, histopathologic invasion, or the extent of invasion were not independent predictors of overall survival in Cox regression analysis. CONCLUSION: Although Portal/mesenteric vein resection is associated with increased 90-day mortality, venous resection is not prognostic of overall survival. Although a subgroup analysis showed that a direct tumor invasion into the vein wall on final histopathology was associated with a higher rate of local recurrence but with no difference in overall survival (even when stratified according to extent of venous wall invasion), larger studies with an increased power will be needed to confirm these findings.

Intraductal papillary mucinous neoplasm of the pancreas, one manifestation of a more systemic disease?

BACKGROUND: Several studies have demonstrated a high prevalence of extrapancreatic malignancies, and an association with autoimmune pancreatitis in patients with intraductal papillary mucinous neoplasm (IPMN). We hypothesized that IPMNs were associated with an increase rate of systemic diseases. METHODS: From 1996 to 2013, a retrospective analysis of a prospectively collected database was performed and supplemented with electronic medical charts review. RESULTS: Two hundred twenty extrapancreatic malignancies were found in 185 patients (22%) compared with expected 5% in the general population. Colorectal, lung, and renal cell carcinoma had significant observed/expected ratios (P < .0001). One hundred ten synchronous autoimmune diseases were found in 96 patients (11%). Systemic lupus erythematosus, rheumatoid arthritis, and inflammatory bowel disease showed statistically significant observed/expected ratios (P < .0001, .01, and <.0001, respectively). There was no impact of immunosuppressive treatment on the IPMN subtype and malignancy rate. CONCLUSIONS: IPMN are associated with surprisingly high rates of autoimmune diseases suggesting that IPMN might be 1 manifestation of a more systemic disease.

Invasive, mixed-type intraductal papillary mucinous neoplasm: superior prognosis compared to invasive main-duct intraductal papillary mucinous neoplasm.

PURPOSE: It is unclear whether the duct involvement subtypes of intraductal papillary mucinous neoplasm (IPMN), ie, main (MD), mixed (MT), and branch (BD), confer any survival advantage when invasive IPMN occurs. We hypothesized that invasive MT-IPMN was associated with a better prognosis than invasive MD-IPMN. METHODS: A retrospective review of a prospectively maintained database was performed of patients who underwent resection for IPMN at a single academic institution from 1992 to 2014. Characterization of IPMN subtype was assessed on final operative pathology. Statistics included univariate analysis, Kaplan-Meier survival curves, and Cox regression for independent predictors of increased survival. RESULTS: Of 390 patients eligible for study, 74 had invasive IPMN (IPMC). Of these, 71 patients had complete data and were included in the analysis (17 MD-IPMC, 39 MT-IPMC, and 15 BD-IPMC). Median follow-up was 20 months (range, 2-174). MT-IPMC was associated with significantly greater overall survival (OS) (47 months) compared with MD-IPMC (12 months) (P = .049), but not with BD-IPMC (44 months) (P = .67). Multivariate Cox regression yielded a family history of pancreatic cancer, absence of jaundice, N0 status, negative margins, absence of lymphovascular invasion, and MT subtype as independent predictors of greater OS (P = .035, .015, .013, .036, .045, .043, respectively). No characteristic of IPMN (including MD diameter, solid component/mural nodule) was predictive of OS. CONCLUSION: MT-IPMC appeared to be associated with a greater OS compared with pure MD-IPMC. This begs the question of a different underlying biology of MT-IPMN and argues against classification of all main duct involved IPMN into a single category.

Local blockade of integrins in the temporomandibular joint region reduces Fos-positive neurons in trigeminal subnucleus caudalis of female rats produced by jaw movement.

This study assessed the influence of integrins on trigeminal brainstem neural activity evoked during jaw movement (JM). Limited range of motion and pain during jaw opening are common complaints of patients with temporomandibular joint (TMJ) disorders. JM (0.5 Hz, 30 min) was presented to ovariectomized (OvX) female rats given estrogen replacement and males under barbiturate anesthesia. Quantification of Fos-like immunoreactivity (Fos-LI) after JM served as an index of evoked neural activity. Rats were injected locally in the TMJ with either an active (GRGDS, 300 microM, 25 microl) or an inactive integrin antagonist (SDGRG) prior to JM. The effect of prior inflammation of the TMJ region was assessed in separate groups of rats by injecting bradykinin (10 microM, 25 microl) with or without integrin drugs prior to JM. Active integrin antagonist significantly reduced JM-evoked Fos-LI in superficial laminae at the trigeminal subnucleus caudalis/upper cervical cord (Vc/C2) junction in OvX compared to male rats independent of bradykinin pretreatment. Fos-LI produced in the dorsal paratrigeminal and trigeminal subnucleus interpolaris/caudalis (Vi/Vc) transition regions was not reduced by active integrin antagonist in males or OvX females. Active integrin antagonist did not affect Fos-LI produced after injection of bradykinin alone into the TMJ. These results suggest that RGD binding integrins contribute to JM-evoked neural activity at the Vc/C2 junction under naive and inflamed conditions in a sex-dependent manner.