Effect of intraoperative secretin on operative outcomes in pancreatic resection: A randomized controlled trial.

BACKGROUND: Objectives: We performed a randomized, double-blind, placebo-controlled trial to determine if using Secretin intra-operatively to identify leaks and subsequently target operative intervention would decrease the frequency of clinically significant post-operative pancreatic fistula formation. METHODS: Patients undergoing pancreaticoduodenectomy or distal pancreatectomy were randomized to receive intra-operative Secretin or placebo intra-operatively following the completed pancreaticojejunostomy or closure of the cut remnant stump. If a potential leak was identified, targeted therapy with directed suture placement was performed. RESULTS: 170 patients were randomized; 83 receiving placebo and 87 receiving Secretin. The rate of clinically significant fistula formation was 3% (3/87) in the Secretin group and 6% (5/83) in the placebo group (p = 0.489). The rate of biochemical leak was 29% (25/87) in the Secretin group and 19% (16/83) in the placebo group (p = 0.157). There were no Grade C post-operative fistula in either group. Of the 9% of patients in the Secretin group who had a targeted intra-operative intervention, none developed a clinically significant fistula. Adverse events were similar between groups. CONCLUSIONS: Compared to placebo, intra-operative Secretin administration was not associated with an overall reduction in clinically significant pancreatic fistula formation. However, patients with an intra-operative leak identified by Secretin may benefit from intervention (clinicaltrials.gov: NCT02160808).

Preoperative ERCP has no impact on islet yield following total pancreatectomy and islet autotransplantation (TPIAT): Results from the Prospective Observational Study of TPIAT (POST) cohort.

BACKGROUND AND AIMS: Many patients undergoing total pancreatectomy with islet autotransplant (TPIAT) for severe, refractory chronic pancreatitis or recurrent acute pancreatitis have a history of endoscopic retrograde cholangiopancreatography (ERCP). Using data from the multicenter POST (Prospective Observational Study of TPIAT) cohort, we aimed to determine clinical characteristics associated with ERCP and the effect of ERCP on islet yield. METHODS: Using data from 230 participants (11 centers), demographics, pancreatitis history, and imaging features were tested for association with ERCP procedures. Logistic and linear regression were used to assess association of islet yield measures with having any pre-operative ERCPs and with the number of ERCPs, adjusting for confounders. RESULTS: 175 (76%) underwent ERCPs [median number of ERCPs (IQR) 2 (1-4). ERCP was more common in those with obstructed pancreatic duct (p = 0.0009), pancreas divisum (p = 0.0009), prior pancreatic surgery (p = 0.005), and longer disease duration (p = 0.004). A greater number of ERCPs was associated with disease duration (p < 0.0001), obstructed pancreatic duct (p = 0.006), and prior pancreatic surgery (p = 0.006) and increased risk for positive islet culture (p < 0.0001). Mean total IEQ/kg with vs. without prior ERCP were 4145 (95% CI 3621-4669) vs. 3476 (95% CI 2521-4431) respectively (p = 0.23). Adjusting for confounders, islet yield was not significantly associated with prior ERCP, number of ERCPs, biliary or pancreatic sphincterotomy or stent placement. CONCLUSIONS: ERCP did not appear to adversely impact islet yield. When indicated, ERCP need not be withheld to optimize islet yield but the risk-benefit ratio of ERCP should be considered given its potential harms, including risk for excessive delay in TPIAT.

Islet autotransplantation improves glycemic control in patients undergoing elective distal pancreatectomy for benign inflammatory disease.

Islet autotransplantation (IAT) is increasingly being performed to mitigate against the diabetic complications of pancreatic resection in patients with benign inflammatory pancreatic disorders; however, the glycemic benefit of IAT in patients undergoing partial pancreatic resection is not known. We aimed to determine whether IAT improved glycemic outcomes in patients undergoing distal pancreatectomy for benign inflammatory disease. We performed a multicenter, retrospective case-control study of patients who underwent distal pancreatic resection with IAT at two U S tertiary care centers. The primary outcome was the mean change in pre- vs post-operative HgA1c following transplant as well as the development of new post-operative diabetes. Nine patients requiring distal pancreatectomy for benign disease underwent IAT and were compared to 13 historical controls without IAT. Baseline characteristics were similar between groups. With a median follow-up of 22 months, those who received an IAT had a smaller increase in their pre- vs post-operative HgA1c (0.42 vs 2.83, P = .004), and one case patient (14.3%) vs three control patients (23.1%) developed new post-operative diabetes (P = .581). We conclude that patients undergoing distal pancreatic resection for benign inflammatory disease should be considered for IAT, as long-term glycemic outcomes appear to be improved in those undergoing transplant.

Effects of Medical Cannabis on Use of Opioids and Hospital Visits by Patients With Painful Chronic Pancreatitis.

Pain is the most common and most debilitating aspect of chronic pancreatitis and is difficult to treat.1-3 Clinical management of painful chronic pancreatitis includes abstinence from alcohol and tobacco products, analgesic medications (including opioids), antidepressant medications, and pancreatic enzyme replacement.4-8 Medical cannabis has been proposed as a therapy for chronic pain and has shown some efficacy in neuropathic and cancer pain. In this study, we investigated the efficacy of medical cannabis on pain control for chronic pancreatitis.

A multicenter study of total pancreatectomy with islet autotransplantation (TPIAT): POST (Prospective Observational Study of TPIAT).

BACKGROUND/OBJECTIVES: Total pancreatectomy with islet autotransplantation (TPIAT) is considered for managing chronic pancreatitis in selected patients when medical and endoscopic interventions have not provided adequate relief from debilitating pain. Although more centers are performing TPIAT, we lack large, multi-center studies to guide decisions about selecting candidates for and timing of TPIAT. METHODS: Multiple centers across the United States (9 to date) performing TPIAT are prospectively enrolling patients undergoing TPIAT for chronic pancreatitis into the Prospective Observational Study of TPIAT (POST), a NIDDK funded study with a goal of accruing 450 TPIAT recipients. Baseline data include participant phenotype, pancreatitis history, and medical/psychological comorbidities from medical records, participant interview, and participant self-report (Medical Outcomes Survey Short Form-12, EQ-5D, andPROMIS inventories for pain interference, depression, and anxiety). Outcome measures are collected to at least 1 year after TPIAT, including the same participant questionnaires, visual analog pain scale, pain interference scores, opioid requirements, insulin requirements, islet graft function, and hemoglobin A1c. Health resource utilization data are collected for a cost-effectiveness analysis. Biorepository specimens including urine, serum/plasma, genetic material (saliva and blood), and pancreas tissue are collected for future study. CONCLUSIONS: This ongoing multicenter research study will enroll and follow TPIAT recipients, aiming to evaluate patient selection and timing for TPIAT to optimize pain relief, quality of life, and diabetes outcomes, and to measure the procedure's cost-effectiveness. A biorepository is also established for future ancillary studies.

Long-Term Glycemic Control in Adult Patients Undergoing Remote vs. Local Total Pancreatectomy With Islet Autotransplantation.

OBJECTIVES: Total pancreatectomy with islet autotransplantation (TPIAT) is increasingly performed with remote islet cell processing and preparation, i.e., with islet cell isolation performed remotely from the primary surgical site at an appropriately equipped islet isolation facility. We aimed to determine whether TPIAT using remote islet isolation results in comparable long-term glycemic outcomes compared with TPIAT performed with standard local isolation. METHODS: We performed a retrospective cohort study of adult patients who underwent TPIAT at three tertiary care centers from 2010 to 2013. Two centers performed remote isolation and one performed local isolation. Explanted pancreata in the remote cohort were transported ∼130 miles to and from islet isolation facilities. The primary outcome was insulin independence 1 year following transplant. RESULTS: Baseline characteristics were similar between groups except the remote cohort had higher preoperative hemoglobin A1c (HbA1c; 5.43 vs. 5.25, P=0.02) and there were more females in the local cohort (58% vs. 76%, P=0.049). At 1 year, 27% of remote and 32% of local patients were insulin independent (P=0.48). Remote patients experienced a greater drop in fasting c-peptide (-1.66 vs. -0.64, P=0.006) and a greater rise in HbA1c (1.65 vs. 0.99, P=0.014) at 1-year follow-up. A preoperative c-peptide >2.7 (odds ratio (OR) 4.4, 95% confidence interval (CI) 1.6-14.3) and >3,000 islet equivalents/kg (OR 11.0, 95% CI 3.2-37.3) were associated with one-year insulin independence in the local group. CONCLUSIONS: At 1 year after TPIAT, patients undergoing remote surgery have equivalent rates of long-term insulin independence compared with patients undergoing TPIAT locally, but metabolic control is superior with local isolation.

Cost-effectiveness and clinical efficacy of biliary stents in patients undergoing neoadjuvant therapy for pancreatic adenocarcinoma in a randomized controlled trial.

BACKGROUND AND AIMS: The optimal type of stent for the palliation of malignant biliary obstruction in patients with pancreatic adenocarcinoma undergoing neoadjuvant chemoradiotherapy with curative intent is unknown. We performed a prospective trial comparing 3 types of biliary stents-fully covered self-expandable metal (fcSEMS), uncovered self-expandable metal (uSEMS), and plastic-to determine which best optimized cost-effectiveness and important clinical outcomes. METHODS: In this prospective randomized trial, consecutive patients with malignant biliary obstruction from newly diagnosed pancreatic adenocarcinoma who were to start neoadjuvant chemoradiotherapy were randomized to receive fcSEMSs, uSEMSs, or plastic stents during the index ERCP. The primary outcomes were time to stent occlusion, attempted surgical resection, or death after the initiation of neoadjuvant therapy, and the secondary outcomes were total patient costs associated with the stent, including the index ERCP cost, downstream hospitalization cost due to stent occlusion, and the cost associated with procedural adverse event. RESULTS: Fifty-four patients were randomized and reached the primary end point: 16 in the fcSEMS group, 17 in the uSEMS group, and 21 in the plastic stent group. No baseline demographic or tumor characteristic differences were noted among the groups. The fcSEMSs had a longer time to stent occlusion compared with uSEMSs and plastic stents (220 vs 74 and 76 days, P < .01), although the groups had equivalent rates of stent occlusion, attempted surgical resection, and death. Although SEMS placement cost more during the index ERCP (uSEMS = $24,874 and fcSEMS = $22,729 vs plastic = $18,701; P < .01), they resulted in higher procedural AE costs per patient (uSEMS = $5522 and fcSEMS = $12,701 vs plastic = $0; P < .01). Conversely, plastic stents resulted in an $11,458 hospitalization cost per patient due to stent occlusion compared with $2301 for uSEMSs and $0 for fcSEMSs (P < .01). CONCLUSIONS: In a prospective trial comparing fcSEMSs, uSEMSs, and plastic stents for malignant biliary obstruction in patients undergoing neoadjuvant therapy with curative intent for pancreatic adenocarcinoma, no stent type was superior in optimizing cost-effectiveness, although fcSEMSs resulted in fewer days of neoadjuvant treatment delay and a longer time to stent occlusion. (Clincial trial registration number: NCT01038713.).

Molecular profiling of appendiceal epithelial tumors using massively parallel sequencing to identify somatic mutations.

BACKGROUND: Some epithelial neoplasms of the appendix, including low-grade appendiceal mucinous neoplasm and adenocarcinoma, can result in pseudomyxoma peritonei (PMP). Little is known about the mutational spectra of these tumor types and whether mutations may be of clinical significance with respect to therapeutic selection. In this study, we identified somatic mutations using the Ion Torrent AmpliSeq Cancer Hotspot Panel v2. METHODS: Specimens consisted of 3 nonneoplastic retention cysts/mucocele, 15 low-grade mucinous neoplasms (LAMNs), 8 low-grade/well-differentiated mucinous adenocarcinomas with pseudomyxoma peritonei, and 12 adenocarcinomas with/without goblet cell/signet ring cell features. Barcoded libraries were prepared from up to 10 ng of extracted DNA and multiplexed on single 318 chips for sequencing. Data analysis was performed using Golden Helix SVS. Variants that remained after the analysis pipeline were individually interrogated using the Integrative Genomics Viewer. RESULTS: A single Janus kinase 3 (JAK3) mutation was detected in the mucocele group. Eight mutations were identified in the V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) and GNAS complex locus (GNAS) genes among LAMN samples. Additional gene mutations were identified in the AKT1 (v-akt murine thymoma viral oncogene homolog 1), APC (adenomatous polyposis coli), JAK3, MET (met proto-oncogene), phosphatidylinositol-4,5-bisphosphate 3-kinase (PIK3CA), RB1 (retinoblastoma 1), STK11 (serine/threonine kinase 11), and tumor protein p53 (TP53) genes. Among the PMPs, 6 mutations were detected in the KRAS gene and also in the GNAS, TP53, and RB1 genes. Appendiceal cancers showed mutations in the APC, ATM (ataxia telangiectasia mutated), KRAS, IDH1 [isocitrate dehydrogenase 1 (NADP+)], NRAS [neuroblastoma RAS viral (v-ras) oncogene homolog], PIK3CA, SMAD4 (SMAD family member 4), and TP53 genes. CONCLUSIONS: Our results suggest molecular heterogeneity among epithelial tumors of the appendix. Next generation sequencing efforts have identified mutational spectra in several subtypes of these tumors that may suggest a phenotypic heterogeneity showing mutations that are relevant for targeted therapies.

Quality of Life Following Total Pancreatectomy With Islet Autotransplantation: A Patient Experience Survey.

OBJECTIVES: Total pancreatectomy with islet autotransplantation (TPIAT) is performed to improve the quality of life (QOL) of patients with chronic pancreatitis. Few reports have documented QOL following TPIAT, with none using the pancreatitis-specific Pancreatitis Quality of Life Instrument (PANQOLI). We surveyed patients at our center who underwent TPIAT to document postoperative QOL. MATERIALS AND METHODS: We collected survey data from 18 adult patients who underwent TPIAT at our medical center from 2012 to 2020. Patients were asked questions assessing QOL following TPIAT and completed the Short-Form Health Survey and PANQOLI instruments. RESULTS: Forty-three patients who underwent TPIAT were mailed surveys, and 18 were returned. The mean age was 45 years, and 67% of respondents were female. Almost half (44%) had hereditary pancreatitis. Sixty-seven percent believed that their overall QOL had improved after surgery. The mean postoperative Short-Form Health Survey physical score was 38.9 and mean mental score was 44. The mean PANQOLI score was 66 (physical function 20, role function 16, emotional function 14, self-worth 15). Following surgery, 33% were using opiate medications and 67% were using antihyperglycemic medications. CONCLUSIONS: TPIAT resulted in improved self-reported QOL in most patients, although postoperative physical and mental QOL are less compared to the average healthy United States adult.

Surveillance With Serial Imaging and CA 19-9 Tumor Marker Testing After Resection of Pancreatic Cancer: A Single-Center Retrospective Study.

OBJECTIVES: Most patients receiving curative-intent surgery for pancreatic cancer will experience cancer recurrence. However, evidence that postoperative surveillance testing improves survival or quality of life is lacking. We evaluated the use and characteristics of surveillance with serial imaging and CA 19-9 tumor marker testing at an NCI-designated comprehensive cancer center. METHODS: We conducted a retrospective cohort study of patients who entered surveillance after curative-intent resection of pancreatic adenocarcinoma. We abstracted information from the electronic medical record about oncology office visits, surveillance testing (cross-sectional imaging and CA 19-9 tumor marker testing), and pancreatic cancer recurrence, with follow-up through 2 years after pancreatectomy. We conducted analyses to describe the use of surveillance testing and to characterize the sensitivity and specificity of CA 19-9 tumor marker testing for the identification of cancer recurrence. RESULTS: We identified 90 patients entering surveillance after pancreatectomy. CA 19-9 was the most frequently used surveillance test, followed by CT imaging. Forty-seven patients (52.2%) experienced recurrence within two years of pancreatectomy. Recurrence risk was 58.8% versus 31.8% in patients with elevated versus normal CA 19-9 at diagnosis ( P =0.03). Elevated CA 19-9 at any point during surveillance was significantly associated with 2-year recurrence risk ( P <0.001). Elevated CA 19-9 had a sensitivity of 83% (95% CI 0.72-0.95) and specificity of 87% (0.76-0.98) for identification of recurrence within 2 years of pancreatectomy. CONCLUSIONS: CA 19-9 demonstrates clinical validity for identifying recurrence of pancreatic cancer during surveillance. Surveillance approaches with reduced reliance on imaging should be prospectively evaluated.

Pancreatic cyst prevalence and the risk of mucin-producing adenocarcinoma in US adults.

OBJECTIVES: The presence of a pancreatic cyst often prompts concern, although the rate of malignant transformation to mucin-producing adenocarcinoma is not known. We aimed to determine the prevalence rate of mucin-producing adenocarcinoma in US adults with pancreatic cysts. METHODS: This retrospective, population-based cross-sectional study calculated the annual number of mucin-producing adenocarcinomas using the Surveillance Epidemiology and End Results (SEER 18) database and the 2010 US census. The overall prevalence rate of cysts in the population was found using data from large cross-sectional imaging studies of incidental cyst prevalence. Prevalence rates were then calculated by dividing the annual number of mucin-producing adenocarcinomas by the cyst prevalence rate. RESULTS: Between 2005 and 2009, 1,137 mucin-producing adenocarcinomas were estimated to be found annually in a US adult population of 137,154,960. The total number of pancreas cysts, given a cyst prevalence rate of 2.5%, was 3,428,874. Therefore, the prevalence rate of mucin-producing adenocarcinoma arising in patients with pancreatic cysts was 33.2 per 100,000 (95% confidence interval (CI): 21.9-44.5). The prevalence rate was 32.8 per 100,000 (95% CI: 21.6-44.0) in women and 33.5 per 100,000 (95% CI: 22.2-44.8) in men. As expected, the rate of malignant transformation increased linearly with advancing age (highest 38.6 per 100,000 in 80- to 84-year-old men). CONCLUSIONS: Malignant transformation of pancreatic cysts into mucin-producing adenocarcinoma in US adults is a very rare event. Current clinical guidelines and resource allocation for pancreatic cyst disease should be reconsidered given these findings.

CT characterization of retractor related liver injuries after pancreaticoduodenectomy: Retrospective analysis of a single institution experience.

PURPOSE: Retractor related liver injuries (RRLI) are reported after upper gastrointestinal tract surgeries; most commonly laparoscopic cholecystectomy and gastric surgeries. The aim of this study was to characterize the incidence, identification, type, severity, clinical features and risk factors for RRLI after open and robotic pancreaticoduodenectomy. METHODS: A 6-year retrospective study of 230 patients was performed. Clinical data was extracted from the electronic medical record. Post-operative imaging was reviewed and graded using the American Association for the Surgery of Trauma (AAST) liver injury scale. RESULTS: 109 patients met eligibility criteria. RRLI occurred in 23/109 (21.1%), with a higher incidence in the robotic/combinedapproach (4/9) compared with open (19/100). Most common injury was an intraparenchymal hematoma (56.5%), grade II (78.3%), located in segments II/III (77%). 39.1% of injuries were not reported on the CT interpretation. There was a statistically significant elevation of postoperative AST/ALT in the RRLI group [median AST 219.5 vs. 72.0 (p < 0.001), ALT 203.0 vs. 69.0 (p < 0.001)]. Trends toward lower preoperative platelet counts and longer operations were observed in the RRLI group. No significant difference in hospital length of stay or post-operative pain scores were noted. CONCLUSION: RRLI occurred frequently after pancreaticoduodenectomy, however most injuries were low grade and the only clinical significance was a transient increase in transaminases. A trend toward higher injury rates was observed in robotic cases. In this population, RRLI was often unrecognized on postoperative imaging.

Pancreaticoduodenectomy for the treatment of groove pancreatitis.

BACKGROUND AND AIM: Groove pancreatitis is a segmental form of chronic pancreatitis that can be treated with pancreaticoduodenectomy (PD), although outcome studies for this approach are lacking. We performed an assessment of pain symptoms, need for opioids, and weight gain following PD for symptomatic groove pancreatitis. METHODS: The study was a retrospective case series describing all patients with groove pancreatitis who underwent PD at our medical center. The primary outcome was the change in pain level and opioid use following PD. RESULTS: Five patients underwent PD for treatment of groove pancreatitis. Patients' perception of pain, using a 10-point visual analog scale, improved after surgery from 5.0 to 0.2. Opioid analgesics, as measured by oral morphine equivalents, dropped from 77.6 to 0 mg daily, with all five patients being completely free of opioids post-operatively. Weight loss ceased in all five patients, with an overall mean weight gain of 15.4 pounds post-operatively. CONCLUSIONS: PD reduces pain and opioid analgesic use in groove pancreatitis. This intervention should be considered for patients with this condition.

Effectiveness of Intraoperative Versus Dedicated Islet Cell Laboratory Isolation for Total Pancreatectomy With Islet Autotransplant.

Background: Total pancreatectomy with islet autotransplantation (TPIAT) requires a complex islet isolation process of the explanted pancreas. Islet isolation has historically required a specialized laboratory to perform islet isolation. We report our experience with a novel technique of intraoperative islet isolation that does not require a specialized islet laboratory, thereby making the isolation process simpler, more accessible, and less costly. Methods: We performed a retrospective, comparative effectiveness analysis of 50 adult patients who underwent TPIAT from 2012 to 2020 (TPIAT with remote isolation [n = 20] versus intraoperative isolation of islet cells [n = 30]). The primary outcome was islet equivalents per body weight (IEQ/kg) for patients in each group. Results: Mean IEQ/kg's (4294 remote group versus 3015 intraoperative group, P = 0.06) and 1-y postoperative C-peptide levels (1.51 ng/mL remote group versus 0.91 ng/mL intraoperative group, P = 0.10) were not different between groups. Mean 1-y HbA1c levels (7.7% in the remote group versus 7.1% intraoperative group, P = 0.67) and 1-y insulin requirements (P = 0.31) were not statistically different. Lower average cost of hospitalization was seen in the intraoperative group, although this was not statistically significant ($104 398 remote versus $78 986 intraoperative, P = 0.81). Conclusions: Intraoperative islet isolation has similar effectiveness in regard to glycemic outcomes compared with the use of a dedicated islet cell isolation laboratory at a lower cost.

The expression of c-Met pathway components in unclassified pleomorphic sarcoma/malignant fibrous histiocytoma (UPS/MFH): a tissue microarray study.

AIMS: Subclassification of undifferentiated pleomorphic sarcoma/malignant fibrous histiocytoma (UPS/MFH) into distinct biological cohorts based on the expression patterns of molecular markers can identify patient subsets with especially unfavourable clinical outcomes. Identification of molecular prognosticators amenable for drug targeting can facilitate rational development of UPS/MFH tailored therapies. The aim was to evaluate expression of c-Met pathway components in a large cohort of UPS/MFH samples. METHODS AND RESULTS: An immunohistochemical analysis for hepatocyte growth factor (HGF), c-Met, phospho-c-Met (pc-Met), phospho-mitogen-activated protein kinase kinase (MAPKK) also known as mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase (p-MEK) and phospho-protein kinase B (p-AKT) was performed on a clinically annotated tissue microarray of 158 UPS/MFH samples. Univariable and multivariable analyses were conducted to evaluate the correlation of molecular variables with UPS/MFH disease specific survival. All evaluated markers were expressed in UPS/MFH to varying levels. Most importantly, strong HGF, pc-Met, p-MEK and p-AKT expression correlated significantly with dismal patient outcome on univariable statistical analysis. Expression of p-MEK and p-AKT remained statistically significant independent prognosticators on multivariable analysis. CONCLUSIONS: c-Met pathway components and especially p-MEK and p-AKT are potential prognostic biomarkers for UPS/MFH; their inclusion in future molecular-based staging systems should be evaluated. Furthermore, novel approaches targeting HGF, c-Met, MEK/extracellular-regulated kinase (ERK) and/or AKT should be considered for a subset of UPS/MFH patients.

Clinical significance of acellular mucin in rectal adenocarcinoma patients with a pathologic complete response to preoperative chemoradiation.

OBJECTIVE: The objective of this study was to determine the prevalence and prognostic significance of acellular mucin within resected specimens of rectal cancer patients with a pCR following preoperative chemoradiation. SUMMARY BACKGROUND DATA: The presence of acellular mucin pools in the resected specimens of patients with a complete response to preoperative chemoradiation is frequently reported as a marker of treatment effect. The clinical significance of the presence of acellular mucin with respect to local recurrence and survival outcomes is unknown. METHODS: Data from a rectal cancer database was used to analyze 562 patients with nonmetastatic rectal adenocarcinoma treated between 1989 and 2004. The presence or absence of acellular mucin within the specimen was identified by the surgical pathology reports and confirmed by re-examination of H&E sections of surgical specimens. RESULTS: Among the 562 patients, 100 patients (18%) had pCR. Acellular mucin was present in 27 (27%) of the 100 patients with pCR. The median follow-up interval was 87 months (range, 1-198 months). Local and distant failures occurred in 0 and 2 patients with acellular mucin, and in 1 and 6 patients without acellular mucin, respectively. The actuarial 7-year overall survival rates were 85% for patients with acellular mucin and 92% for patients without acellular mucin (P = 0.954). The actuarial 7-year disease-free survival rates were 81% and 87% (P = 0.764) and the 7-year freedom from relapse rates were 93% and 91% (P = 0.881) in patients with and without acellular mucin, respectively. CONCLUSIONS: Acellular mucin is present within 27% of resected specimens in rectal cancer patients with a pCR after preoperative chemoradiation. However, the presence of acellular mucin has no prognostic significance.

Angiosarcoma: clinical and molecular insights.

OBJECTIVE: Angiosarcoma (AS) is a rare understudied soft tissue sarcoma exhibiting endothelial cell differentiation. We sought to evaluate AS natural history in the largest patient cohort reported to date and further unravel commonly deregulated molecular events of potential therapeutic utility. METHODS: Medical records of AS patients (n = 222) treated at our institution from 1993 to 2007 were reviewed. Univariable and multivariable analyses were used to identify independent outcome prognosticators. An AS tissue microarray (n = 68 human specimens) was constructed for immunohistochemical analysis of multiple potential drugable kinase-related molecular markers. RESULTS: Forty-three (19.4%) metastatic AS patients and 179 patients (80.6%) with localized disease were included. Median survival of localized versus metastatic AS was 49 (range, 2-188) versus 10 (range, 1-69) months (P < 0.0001). Patients with localized AS who underwent complete surgical resection (n = 136; 76%) demonstrated significantly better outcome compared with those with unresectable tumors (n = 43; 24%; P < 0.0001). Of several factors identified on univariable analysis as significantly adverse for disease-specific survival, tumor size (>5 cm vs. < or = 5 cm, P = 0.01) and epithelioid histologic component (P = 0.008) remained significant on multivariable analysis as independent adverse prognosticators in complete resection patients. Immunohistochemistry identified significant overexpression of vascular endothelial growth factor-A and C as well as p-AKT, p-4EBP1, and eIF4E in human AS. CONCLUSIONS: AS harbors a dismal outcome and even patients with disease amenable to complete surgical resection exhibit a 5-year disease-specific survival of only 53%. There is a crucial need for better therapies. Data presented here support further study of the AKT/mTOR pathway as novel molecular targets for AS therapy.

Outcomes of Neoadjuvant Chemoradiation With and Without Systemic Chemotherapy in Resectable and Borderline Resectable Pancreatic Adenocarcinoma.

Introduction: Neoadjuvant therapy is increasingly being used for localized pancreatic adenocarcinoma. While there is evidence supporting neoadjuvant systemic chemotherapy as well as chemoradiation, more evidence is needed to determine whether systemic chemotherapy with chemoradiation offers benefits over chemoradiation alone. This study compares the outcomes of neoadjuvant chemoradiation therapy with and without systemic chemotherapy in resectable and borderline resectable pancreatic cancers. Methods: This retrospective study evaluated patients with resectable and borderline resectable pancreatic adenocarcinoma who completed neoadjuvant chemoradiation therapy with and without systemic chemotherapy prior to surgical resection. 149 patients met inclusion criteria, with 75 having resectable cancer and 74 having borderline resectable cancer. Outcomes included recurrence free and overall survival rates at 6, 12, and 36 months. Results: In resectable pancreatic carcinoma, 72% of patients treated with chemoradiation alone achieved 1 year recurrence free survival compared to 78% of patients treated with systemic chemotherapy and chemoradiation (p = 0.55). 28% of patients treated with chemoradiation alone had 3 years recurrence free survival compared to 31% of patients who received systemic and chemoradiation therapy (p = 0.75). In both treatment groups, 92% of patients lived past 1 year (p = 0.92), and 44% of patients survived at least 3 years (p = 0.95). In borderline resectable pancreatic carcinoma, 50% of patients treated with chemoradiation alone achieved 1 year recurrence free survival compared to 70% of patients treated with systemic chemotherapy and chemoradiation (p = 0.079). The 3 years recurrence free survival was 26 and 29% for the chemoradiation alone group and the systemic chemotherapy plus chemoradiation group, respectively (p = 0.85). There was no significant difference in 1 year overall survival: 85% of patients treated with chemoradiation alone survived compared to 92% of patients treated with systemic chemotherapy and chemoradiation (p = 0.32). Both groups had 41% 3 years overall survival (p = 0.96). Discussion: In resectable and borderline resectable pancreatic adenocarcinoma, there was no significant difference in overall or recurrence free survival between patients treated with chemoradiation with and without systemic chemotherapy. Our findings suggest that systemic neoadjuvant chemotherapy with chemoradiation and chemoradiation alone are efficacious treatments for localized pancreatic carcinoma. This brings into question whether more effective systemic chemotherapy is necessary to increase survival benefit.