Natural history and cost analysis of surgical bypass versus endoscopic stenting for the palliative management of malignant gastric outlet obstruction.

BACKGROUND: Malignant gastric outlet obstruction (GOO) is managed with palliative surgical bypass or endoscopic stenting. Limited data exist on differences in cost and outcomes. METHODS: Patients with malignant GOO undergoing palliative gastrojejunostomy (GJ) or endoscopic stent (ES) were identified between 2012 and 2015 using the MarketScan® Database. Median costs (payments) for the index procedure and 90-day readmissions and re-intervention were calculated. Frequency of treatment failure-defined as repeat surgery, stenting, or gastrostomy tube-was measured. RESULTS: A total of 327 patients were included: 193 underwent GJ and 134 underwent ES. Compared to GJ, stenting resulted in lower total median payments for the index hospitalization and procedure-related 90-day readmissions ($18,500 ES vs. $37,200 GJ, p = 0.032). For patients treated with ES, 25 (19%) required a re-intervention for treatment-failure, compared to 18 (9%) patients who underwent GJ (p = 0.010). On multivariable analysis, stenting remained significantly associated with need for secondary re-intervention compared to GJ (HR for ES 2.0 [1.1-3.8], p 0.028). CONCLUSION: In patients with malignant GOO, endoscopic stenting results in significant 90-day cost saving, however was associated with twice the rate of secondary intervention. The decision for surgical bypass versus endoscopic stenting should consider patient prognosis, anticipated cost, and likelihood of needing re-intervention.

Defining the Role of Lymphadenectomy for Pancreatic Neuroendocrine Tumors: An Eight-Institution Study of 695 Patients from the US Neuroendocrine Tumor Study Group.

BACKGROUND: Preoperative factors that reliably predict lymph node (LN) metastases in pancreatic neuroendocrine tumors (PanNETs) are unclear. The number of LNs needed to accurately stage PanNETs has not been defined. METHODS: Patients who underwent curative-intent resection of non-functional PanNETs at eight institutions from 2000 to 2016 were analyzed. Preoperative factors associated with LN metastases were identified. A procedure-specific target for LN retrieval to accurately stage patients was determined. RESULTS: Of 695 patients who underwent resection, 33% of tumors were proximal (head/uncinate) and 67% were distal (neck/body/tail). Twenty-six percent of patients (n = 158) had LN-positive disease, which was associated with a worse 5-year recurrence-free survival (RFS; 60% vs. 86%; p < 0.001). The increasing number of positive LNs was not associated with worse RFS. Preoperative factors associated with positive LNs included tumor size ≥ 2 cm (odds ratio [OR] 6.6; p < 0.001), proximal location (OR 2.5; p < 0.001), moderate versus well-differentiation (OR 2.1; p = 0.006), and Ki-67 ≥ 3% (OR 3.1; p < 0.001). LN metastases were also present in tumors without these risk factors: < 2 cm (9%), distal location (19%), well-differentiated (23%), and Ki-67 < 3% (16%). Median LN retrieval was 13 for pancreatoduodenectomy (PD), but only 9 for distal pancreatectomy (DP). Given that PD routinely includes a complete regional lymphadenectomy, a minimum number of LNs to accurately stage patients was not identified. However, for DP, removal of less than seven LNs failed to discriminate 5-year RFS between LN-positive and LN-negative patients (less than seven LNs: 72% vs. 83%, p = 0.198; seven or more LNs: 67% vs. 86%; p = 0.002). CONCLUSIONS: Tumor size ≥ 2 cm, proximal location, moderate differentiation, and Ki-67 ≥ 3% are preoperative factors that predict LN positivity in resected non-functional PanNETs. Given the 9-23% incidence of LN metastases in patients without such risk factors, routine regional lymphadenectomy should be considered. PD inherently includes sufficient LN retrieval, while DP should aim to remove seven or more LNs for accurate staging.

Analysis of 90-day cost for open versus minimally invasive distal pancreatectomy.

BACKGROUND: Minimally invasive distal pancreatectomy (MIDP) is associated with improved peri-operative outcomes compared to the open approach, though cost-effectiveness of MIDP remains unclear. METHODS: Patients with pancreatic tumors undergoing open (ODP), robotic (RDP), or laparoscopic distal pancreatectomy (LDP) between 2012-2014 were identified through the Truven Health MarketScan® Database. Median costs (payments) for the index operation and 90-day readmissions were calculated. Multivariable regression was used to predict associations with log 90-day payments. RESULTS: 693 patients underwent ODP, 146 underwent LDP, and 53 RDP. Compared to ODP, LDP and RDP resulted in shorter median length of stay (6 d. ODP vs. 5 d. RDP vs. 4 d. LDP, p<0.01) and lower median payments ($38,350 ODP vs. $34,870 RDP vs. $32,148 LDP, p<0.01) during the index hospitalization. Total median 90-day payments remained significantly lower for both minimally invasive approaches ($40,549 ODP vs. $35,160 RDP vs. $32,797 LDP, p<0.01). On multivariable analysis, LDP and RDP resulted in 90-day cost savings of 21% and 25% relative to ODP, equating to an amount of $8,500-$10,000. CONCLUSION: MIDP is associated with >$8,500 in lower cost compared to the open approach. Quality improvement initiatives in DP should ensure that lack of training and technical skill are not barriers to MIDP.

Is hepatectomy safe following Yttrium-90 therapy? A multi-institutional international experience.

BACKGROUND: Single institution reports demonstrate variable safety profiles when liver-directed therapy with Yttrium-90 (Y-90) is followed by hepatectomy. We hypothesized that in well-selected patients, hepatectomy after Y90 is feasible and safe. METHODS: Nine institutions contributed data for patients undergoing Y90 followed by hepatectomy (2008-2017). Clinicopathologic and perioperative data were analyzed, with 90-day morbidity and mortality as primary endpoints. RESULTS: Forty-seven patients were included. Median age was 59 (20-75) and 62% were male. Malignancies treated included hepatocellular cancer (n = 14; 30%), colorectal cancer (n = 11; 23%), cholangiocarcinoma (n = 8; 17%), neuroendocrine (n = 8; 17%) and other tumors (n = 6). The distribution of Y-90 treatment was: right (n = 30; 64%), bilobar (n = 14; 30%), and left (n = 3; 6%). Median future liver remnant (FLR) following Y90 was 44% (30-78). Resections were primarily right (n = 16; 34%) and extended right (n = 14; 30%) hepatectomies. The median time to resection from Y90 was 196 days (13-947). The 90-day complication rate was 43% and mortality was 2%. Risk factors for Clavien-Dindo Grade>3 complications included: number of Y-90-treated lobes (OR 4.5; 95% CI1.14-17.7; p = 0.03), extent of surgery (p = 0.04) and operative time (p = 0.009). CONCLUSIONS: These data demonstrate that hepatectomy following Y-90 is safe in well-selected populations. This multi-disciplinary treatment paradigm should be more widely studied, and potentially adopted, for patients with inadequate FLR.

The Impact of Hospital Neoadjuvant Therapy Utilization on Survival Outcomes for Pancreatic Cancer.

BACKGROUND: Many surgeons advocate the use of neoadjuvant treatment for resectable pancreatic cancer, however little is known about variation in the utilization of neoadjuvant therapy (NAT) at the hospital level. METHODS: The National Cancer Data Base was used to identify patients undergoing resection for pancreatic cancer between 2006 and 2014 at high-volume centers. Hospitals were grouped by NAT utilization using standard deviations (SD) from the mean as follows: high neoadjuvant utilizers (> 2 SDs above the mean, > 40% of patients receiving NAT); medium-high (1-2 SDs, 27-40%), medium (0-1 SD, 14-26%); or low (- 1.1 to 0 SDs, < 14%). Overall survival (OS) was compared across NAT utilization groups. RESULTS: Among 107 high-volume centers, 20,119 patients underwent resection. The proportion of patients receiving NAT varied widely among hospitals, ranging from 0 to 74%, with only five centers using NAT in > 40% of patients. These five hospitals had the longest median OS at 28.9 months, compared with 21.1 months for low neoadjuvant utilizers (p < 0.001). On multivariable analysis, high and medium-high NAT utilization predicted improved OS, with a hazard ratio (HR) of 0.68 (95% confidence interval [CI] 0.56-0.83, p < 0.001) and 0.80 (95% CI 0.68-0.95, p = 0.010), respectively, compared with low utilizers. After excluding patients who underwent NAT, there remained an association of improved OS with high NAT utilization (HR 0.74, 95% CI 0.60-0.93, p = 0.009). CONCLUSION: High-volume hospitals that more commonly utilize NAT demonstrated longer survival for all patients treated at those centers. In addition to altering patient selection for surgery, high neoadjuvant utilization may be a marker of institutional factors that contribute to improved outcomes.

Adaptation and Implementation of a Transitional Care Protocol for Patients Undergoing Complex Abdominal Surgery.

BACKGROUND: Transitional care protocols are effective at reducing readmission for medical patients, yet no evidence-based protocols exist for surgical patients. A transitional care protocol was adapted to meet the needs of patients discharged to home after major abdominal surgery. APPROACH: The Coordinated-Transitional Care (C-TraC) protocol, initially designed for medical patients, was used as the initial framework for the development of a surgery-specific protocol (sC-TraC). Adaptation was accomplished using a modification of the Replicating Effective Programs (REP) model, which has four phases: (1) preconditions, (2) preimplementation, (3) implementation, and (4) maintenance and evolution. A random sample of five patients each month was selected to complete a phone survey regarding patient satisfaction. Preimplementation planning allowed for integration with current systems, avoided duplication of processes, and defined goals for the protocol. The adapted protocol specifically addressed surgical issues such as nutrition, fever, ostomy output, dehydration, drain character/output, and wound appearance. After protocol launch, the rapid iterative adaptation process led to changes in phone call timing, inclusion and exclusion criteria, and discharge instructions. OUTCOMES: Survey responders reported 100% overall satisfaction with the transitional care program. KEY INSIGHTS: The adaptable nature of sC-TraC may allow for low-resource hospitals, such as rural or inner-city medical centers, to use the methodology provided in this study for implementation of local phone-based transitional care protocols. In addition, as the C-TraC program has begun to disseminate nationally across US Department of Veterans Affairs (VA) hospitals and rural health settings, sC-TraC may be implemented using the existing transitional care infrastructure in place at these hospitals.

30-day Readmission After Pancreatic Resection: A Systematic Review of the Literature and Meta-analysis.

OBJECTIVE: The aim of this study was to identify and compare common reasons and risk factors for 30-day readmission after pancreatic resection. BACKGROUND: Hospital readmission after pancreatic resection is common and costly. Many studies have evaluated this problem and numerous discrepancies exist regarding the primary reasons and risk factors for readmission. METHODS: Multiple electronic databases were searched from 2002 to 2016, and 15 relevant articles identified. Overall readmission rate was calculated from individual study estimates using a random-effects model. Study data were combined and overall estimates of odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each risk factor. Multivariable data were qualitatively synthesized. RESULTS: The overall 30-day readmission rate was 19.1% (95% CI 17.4-20.7) across all studies. Infectious complications and gastrointestinal disorders, such as failure to thrive and delayed gastric emptying, together accounted for 58.9% of all readmissions. Demographic factors did not predict readmission. Heart disease (OR 1.37, 95% CI 1.12-1.67), hypertension (OR 1.44, 95% CI 1.09-1.91), and intraoperative blood transfusion (OR 1.45, 95% CI 1.15-1.83) were weak predictors of readmission, while any postoperative complications (OR 2.22, 95% CI 1.55-3.18) or severe complications (OR 2.84, 95% CI 1.65-4.89) were stronger predictors. CONCLUSIONS: Readmission after pancreatic resection is common and can largely be attributed to infectious complications and inability to maintain adequate hydration and nutrition. Focus on outpatient resources and follow-up to address these issues will prove valuable in reducing readmissions.

The inductive role of Wnt-ß-Catenin signaling in the formation of oral apparatus.

Proper patterning and growth of oral structures including teeth, tongue, and palate rely on epithelial-mesenchymal interactions involving coordinated regulation of signal transduction. Understanding molecular mechanisms underpinning oral-facial development will provide novel insights into the etiology of common congenital defects such as cleft palate. In this study, we report that ablating Wnt signaling in the oral epithelium blocks the formation of palatal rugae, which are a set of specialized ectodermal appendages serving as Shh signaling centers during development and niches for sensory cells and possibly neural crest related stem cells in adults. Lack of rugae is also associated with retarded anteroposterior extension of the hard palate and precocious mid-line fusion. These data implicate an obligatory role for canonical Wnt signaling in rugae development. Based on this complex phenotype, we propose that the sequential addition of rugae and its morphogen Shh, is intrinsically coupled to the elongation of the hard palate, and is critical for modulating the growth orientation of palatal shelves. In addition, we observe a unique cleft palate phenotype at the anterior end of the secondary palate, which is likely caused by the severely underdeveloped primary palate in these mutants. Last but not least, we also discover that both Wnt and Shh signalings are essential for tongue development. We provide genetic evidence that disruption of either signaling pathway results in severe microglossia. Altogether, we demonstrate a dynamic role for Wnt-ß-Catenin signaling in the development of the oral apparatus.

Temporal and spatial dissection of Shh signaling in genital tubercle development.

Genital tubercle (GT) initiation and outgrowth involve coordinated morphogenesis of surface ectoderm, cloacal mesoderm and hindgut endoderm. GT development appears to mirror that of the limb. Although Shh is essential for the development of both appendages, its role in GT development is much less clear than in the limb. Here, by removing Shh at different stages during GT development in mice, we demonstrate a continuous requirement for Shh in GT initiation and subsequent androgen-independent GT growth. Moreover, we investigated the Hh responsiveness of different tissue layers by removing or activating its signal transducer Smo with tissue-specific Cre lines, and established GT mesenchyme as the primary target tissue of Shh signaling. Lastly, we showed that Shh is required for the maintenance of the GT signaling center distal urethral epithelium (dUE). By restoring Wnt-Fgf8 signaling in Shh(-/-) cloacal endoderm genetically, we revealed that Shh relays its signal partly through the dUE, but regulates Hoxa13 and Hoxd13 expression independently of dUE signaling. Altogether, we propose that Shh plays a central role in GT development by simultaneously regulating patterning of the cloacal field and supporting an outgrowth signal.

Identifying Risk Factors and Patterns for Early Recurrence of Pancreatic Neuroendocrine Tumors: A Multi-Institutional Study.

BACKGROUND: Identifying patients at risk for early recurrence (ER) following resection for pancreatic neuroendocrine tumors (pNETs) might help to tailor adjuvant therapies and surveillance intensity in the post-operative setting. METHODS: Patients undergoing surgical resection for pNETs between 1998-2018 were identified using a multi-institutional database. Using a minimum p-value approach, optimal cut-off value of recurrence-free survival (RFS) was determined based on the difference in post-recurrence survival (PRS). Risk factors for early recurrence were identified. RESULTS: Among 807 patients who underwent curative-intent resection for pNETs, the optimal length of RFS to define ER was identified at 18 months (lowest p-value of 0.019). Median RFS was 11.0 months (95% 8.5-12.60) among ER patients (n = 49) versus 41.0 months (95% CI: 35.0-45.9) among non-ER patients (n = 77). Median PRS was worse among ER patients compared with non-ER patients (42.6 months vs. 81.5 months, p = 0.04). On multivariable analysis, tumor size (OR: 1.20, 95% CI: 1.05-1.37, p = 0.007) and positive lymph nodes (OR: 4.69, 95% CI: 1.41-15.58, p = 0.01) were independently associated with ER. CONCLUSION: An evidence-based cut-off value for ER after surgery for pNET was defined at 18 months. These data emphasized the importance of close follow-up in the first two years after surgery.

National Trends in Centralization of Surgical Care and Multimodality Therapy for Pancreatic Adenocarcinoma.

BACKGROUND: Studies have demonstrated that multimodality therapy and surgery at high volume centers are associated with a longer survival. However, it is unknown if these data have translated into national changes in care delivery. METHODS: Patients with stages I-III pancreatic adenocarcinomas who underwent resections between 2004 and 2010 were identified from the National Cancer Data Base. The primary outcome was a 3-year overall survival. Temporal trends in survival outcomes and treatment variables were measured. A mediation analysis using the Lin method was used to discern the relative contribution of changes in treatment variables towards improvements in survival over time. RESULTS: A total of 22,196 patients were identified. Between 2004 and 2010, a 90-day peri-operative mortality remained unchanged (8.5 % to 8.4 %, p = 0.488), 3-year overall survival improved from 26 to 30% (p < 0.001), use of adjuvant/neoadjuvant chemotherapy increased (51 % to 61 %, p < 0.001), and more cases shifted to high volume centers (46 % at institutions performing > 10 cases/year in 2004 vs. 65 % in 2010, p < 0.001). On multivariable analysis, 32 % of the improvement in survival over time was attributable to receipt of chemotherapy, while 12 % was due to the shift of patients towards high volume centers (p < 0.001). CONCLUSIONS: Over the period from 2004 to 2010, a 3-year survival increased for patients undergoing resection for pancreatic cancer. This survival improvement can be partially attributed to the increasing utilization of chemotherapy and centralization of surgical care at high volume centers. A continued emphasis on these factors will likely result in further prolongation of a survival following resection.

Construction and characterization of a doxycycline-inducible transgenic system in Msx2 expressing cells.

Homeobox gene Msx2 is widely expressed during both embryogenesis and postnatal development and plays important roles during organogenesis. We developed an Msx2-rtTA BAC transgenic line which can activate TetO-Cre expression in Msx2-expressing cells upon doxycycline (Dox) treatment. Using the Rosa26-LacZ (R26R) reporter line, we show that rtTA is activated in Msx2-expressing organs including the limb, heart, external genitalia, urogenital system, hair follicles and craniofacial regions. Moreover, we show that in body appendages, the transgene can be activated in different domains depending on the timing of Dox treatment. In addition, the transgene can also be effectively activated in adult tissues such as the hair follicle and the urogenital system. Taken together, this Msx2-rtTA;TetO-Cre system is a valuable tool for studying gene function in the development of the aforementioned organs in a temporal and spatially-restricted manner, as well as for tissue lineage tracing of Msx2-expressing cells. When induced postnatally, this system can also be used to study gene function in adult tissues without compromising normal development and patterning.

Natural History and Treatment Trends in Pancreatic Cancer Subtypes.

BACKGROUND: While pancreatic ductal adenocarcinoma is the most common form of pancreatic cancer, many other histologic forms of pancreatic cancer are also recognized. These histologic variants portray unique characteristics in terms of patient demographics, tumor behavior, survival, and responsiveness to treatments. MATERIALS AND METHODS: Patients who underwent surgical resection of the pancreas for non-metastatic, invasive pancreatic cancer between 2004 and 2014 were selected from the National Cancer Data Base and categorized by histologic variant according to WHO classification guidelines. Patient demographics, tumor variables, treatment characteristics, and survival were compared between histologic groups and subgroups. RESULTS: A total of 57,804 patients met inclusion and exclusion criteria and were grouped into eight major histologic categories. Survival analysis by the histologic group showed median overall survival of 20.2 months for ductal adenocarcinoma, 20.5 months for squamous cell carcinoma, 26.8 months for mixed acinar-neuroendocrine carcinomas, 52.6 months for cystic mucinous neoplasms with an associated invasive carcinoma, 67.5 months for acinar cell carcinoma, and 69.3 months for mesenchymal tumors. Median survival was not reached for neuroendocrine tumors and solid-pseudopapillary neoplasms, with 5-year overall survival rates of 84% and 97% respectively. CONCLUSIONS: Rare subtypes of pancreatic cancer present unique clinicopathologic characteristics and display distinct tumor biologies. This study presents data on demographic, prognostic, treatment, and survival outcomes between rare forms of pancreatic neoplasms in order to aid understanding of the natural history and behavior of these neoplasms, with the hope of serving as a reference in clinical decision-making and ability to provide accurate prognostic information to patients.

Gastric carcinoids: Does type of surgery or tumor affect survival?

BACKGROUND: Gastric carcinoids are rare neuroendocrine tumors of the gastrointestinal tract. They are typically managed according to their etiology. However, there is little known about the impact of surgical strategy on the long-term outcomes of these patients. METHODS: All patients who underwent resection of gastric carcinoids at 8 institutions from 2000 to 2016 were analyzed retrospectively. Tumors were stratified according to subtype (I, II, III, IV) and resection type (local resection, LR or formal gastrectomy, FG). Clinicopathological parameters, recurrence-free (RFS) and overall survival (OS) were compared between groups. RESULTS: Of 79 patients identified with gastric carcinoids, 34 had type I lesions associated with atrophic gastritis, 4 had type II lesions associated with a gastrinoma, 37 had type III sporadic lesions, and 4 had type IV poorly-differentiated lesions. The mean age of presentation was 56 years in predominantly Caucasian (77%) and female (63%) patients. Mean tumor size was 2.4 cm and multifocal tumors were found in 24 (30%) of patients with the majority occurring in those with type I tumors. Lymph node positive tumors were seen in 15 (19%) patients and 7 (8%) had M1 disease; both most often in type IV followed by type III tumors. R0 resection was achieved in 56 (71%) patients while 15 (19%) had R1 resections and 6 (8%) R2 resections. Patients with type I and III tumors were equally likely to have a LR (50% and 43% respectively) compared to FG while those with type II and IV all had FG with one exception. Type IV tumors had the poorest RFS and OS while Type II tumors had the most favorable RFS and OS (p < 0.04 and p < 0.0004, respectively). While there was no difference in RFS in those patients undergoing FG versus LR, OS was worse in the FG group (p < 0.017). This trend persisted when type II and type IV groups were excluded (p < 0.045). CONCLUSION: Gastric carcinoid treatment should be tailored to tumor type, as biologic behavior rather than resection technique is the more important factor contributing to long-term outcomes.

Influence of carcinoid syndrome on the clinical characteristics and outcomes of patients with gastroenteropancreatic neuroendocrine tumors undergoing operative resection.

BACKGROUND: The incidence, clinical characteristics, and long-term outcomes of patients with gastroenteropancreatic neuroendrocrine tumors and carcinoid syndrome undergoing operative resection have not been well characterized. METHODS: Patients undergoing resection of primary or metastatic gastroenteropancreatic neuroendrocrine tumors between 2000 and 2016 were identified from an 8-institution collaborative database. Clinicopathologic and postoperative characteristics as well as overall survival and disease-free survival were compared among patients with and without carcinoid syndrome. RESULTS: Among 2,182 patients who underwent resection, 139 (6.4%) had preoperative carcinoid syndrome. Patients with carcinoid syndrome were more likely to have midgut primary tumors (44.6% vs 21.4%, P < .001), lymph node metastasis (63.4% vs 44.3%, P < .001), and metastatic disease (62.8% vs 26.7%, P < .001). There was no difference in tumor differentiation, grade, or Ki67 status. Perioperative carcinoid crisis was rare (1.6% vs 0%, P < .01), and the presence of preoperative carcinoid syndrome was not associated with postoperative morbidity (38.8% vs 45.5%, P = .129). Substantial symptom improvement was reported in 59.5% of patients who underwent curative-intent resection, but occurred in only 22.7% who underwent debulking. Despite an association on univariate analysis (P = .04), carcinoid syndrome was not independently associated with disease-free survival after controlling for confounding factors (hazard ratio 0.97, 95% confidence interval 0.64-1.45). Preoperative carcinoid syndrome was not associated with overall survival on univariate or multivariate analysis. CONCLUSION: Among patients undergoing operative resection of gastroenteropancreatic neuroendrocrine tumors, the prevalence of preoperative carcinoid syndrome was low. Although operative intervention with resection or especially debulking in patients with carcinoid syndrome was disappointing and often failed to improve symptoms, after controlling for markers of tumor burden, carcinoid syndrome was not independently associated with worse disease-free survival or overall survival.

Predictive Value of Chromogranin A and a Pre-Operative Risk Score to Predict Recurrence After Resection of Pancreatic Neuroendocrine Tumors.

INTRO: Chromogranin A (CgA) may be prognostic for patients with neuroendocrine tumors; however, the clinical utility of this test is unclear. METHODS: Patients undergoing resection for pancreatic neuroendocrine tumors (pNET) were selected from the eight institutions of the US Neuroendocrine Tumor Study Group database. Cox regression was used to identify pre-operative variables that predicted recurrence-free survival (RFS), and those with p < 0.1 were included in a risk score. The risk score was tested in a unique subset of the overall cohort. RESULTS: In the entire cohort of 287 patients, median follow-up time was 37 months, and 5-year RFS was 73%. Cox regression analysis identified four variables for inclusion in the risk score: CgA > 5x ULN (HR 4.3, p = 0.01), tumor grade 2/3 (HR 3.7, p = 0.01), resection for recurrent disease (HR 6.2, p < 0.01), and tumor size > 4 cm (HR 4.5, p = 0.1). Each variable was assigned 1 point. Risk-score testing in the unique validation cohort of 63 patients revealed a 95% negative predictive value for recurrence in patients with zero points. DISCUSSION: This simple pre-operative risk scoring system resulted in a high degree of specificity for identifying patients at low-risk for tumor recurrence. This test can be utilized pre-operatively to aid informed decision-making.

Improving Patient-Centered Transitional Care after Complex Abdominal Surgery.

BACKGROUND: Poor-quality transitions of care from hospital to home contribute to high rates of readmission after complex abdominal surgery. The Coordinated Transitional Care (C-TraC) program improved readmission rates in medical patients, but evidence-based surgical transitional care protocols are lacking. This pilot study evaluated the feasibility and preliminary effectiveness of an adapted surgical C-TraC protocol. STUDY DESIGN: The intervention includes in-person enrollment of patients. Follow-up protocolized phone calls by specially trained surgical C-TraC nurses addressed medication management, clinic appointments, operation-specific concerns, and identification of red-flag symptoms. Enrollment criteria included pancreatectomy, gastrectomy, operative small bowel obstruction or perforation, ostomy, discharge with a drain, in-hospital complication, and clinician discretion. Engaged patients participated in the first phone call, which was within 48 to 72 hours of discharge and continued every 3 to 4 days. Patients completed the program once they and surgical C-TraC nurse agreed that no additional follow-up was needed or the patient was readmitted. RESULTS: Two hundred and twelve patients were enrolled, October 2015 through April 2016, with a mean age of 56 years (range 19 to 89 years); 33% of patients were 65 years or older. Surgery sites included colon (46%), small bowel (16%), pancreas (12%), multivisceral (9%), liver (4.5%), retroperitoneum/soft tissue (4.5%), gastric (4%), biliary (2%), and appendix (1.5%). Refusal rate was 1% and engagement was 95%. At initial call, 47% of patients had at least 1 medication discrepancy (range 0 to 6). Mean number of calls from provider to patient was 3.2 (range 0 to 20, median 3). CONCLUSIONS: A phone-based transitional care protocol for surgical patients is feasible, with <1% refusals and 95% engagement. Medication management is a prominent issue. Future studies are needed to assess the impact of surgical C-TraC on post-discharge healthcare use.

Homeodomain Transcription Factor Msx-2 Regulates Uterine Progenitor Cell Response to Diethylstilbestrol.

The fate of mouse uterine epithelial progenitor cells is determined between postnatal days 5 to 7. Around this critical time window, exposure to an endocrine disruptor, diethylstilbestrol (DES), can profoundly alter uterine cytodifferentiation. We have shown previously that a homeo domain transcription factor MSX-2 plays an important role in DES-responsiveness in the female reproductive tract (FRT). Mutant FRTs exhibited a much more severe phenotype when treated with DES, accompanied by gene expression changes that are dependent on Msx2. To better understand the role that MSX-2 plays in uterine response to DES, we performed global gene expression profiling experiment in mice lacking Msx2 By comparing this result to our previously published microarray data performed on wild-type mice, we extracted common and differentially regulated genes in the two genotypes. In so doing, we identified potential downstream targets of MSX-2, as well as genes whose regulation by DES is modulated through MSX-2. Discovery of these genes will lead to a better understanding of how DES, and possibly other endocrine disruptors, affects reproductive organ development.

High readmission rates after surgery for chronic pancreatitis.

BACKGROUND: Readmission after complex gastrointestinal surgery is a frequent occurrence that burdens the health care system and leads to increased cost. Recent studies have demonstrated 30- and 90-day readmission rates of 15% and 19%, respectively, following pancreaticoduodenectomy. Given the psychosocial issues often associated with chronic pancreatitis, we hypothesized that readmission rates following surgery for chronic pancreatitis would be higher than previously reported for pancreaticoduodenectomy. METHODS: We retrospectively reviewed patients undergoing surgery for chronic pancreatitis at a single institution between 2001 and 2013. Patients in this cohort underwent pancreaticoduodenectomy, Berne, Beger, or Frey procedures. Readmission to a primary or secondary hospital was evaluated at both 30 and 90 days after discharge. Multivariate logistic regression analysis was performed to identify factors associated with readmission. RESULTS: The records of 111 patients were evaluated, of which 69 (62%) underwent duodenal-preserving pancreatic head resection (Berne, Beger, or Frey), while the remaining 42 (38%) underwent pancreaticoduodenectomy. Within the duodenal-preserving pancreatic head resection arm, readmission rates at 30 and 90 days were 30.4% and 43.5%, respectively. Readmission rates following pancreaticoduodenectomy were similar with 33.3% at 30 days and 40.5% at 90 days. The most common reasons for readmission were pain control, infectious complications, and recurrent pancreatitis. On multivariate analysis, wound infection during the initial hospital stay was a predictor of readmission at both 30 and 90 days (P = .02). CONCLUSION: To our knowledge, our data represent the first report demonstrating very high readmission rates after surgery for chronic pancreatitis, more than double the previous rates reported for pancreaticoduodenectomy. This cohort of patients requires extensive discharge planning focused on pain control, nutritional optimization, and close postoperative monitoring.