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Background: Sarcopenic obesity and muscle attenuation have been associated with survival in patients with borderline resectable and advanced pancreatic ductal adenocarcinoma (PDA); however, these relationships are unknown for patients with resectable PDA. This study examined the associations between skeletal muscle and adipose tissue as measured on baseline computed tomography (CT) and the overall survival (OS) of participants with resectable PDA in a secondary analysis of the Southwest Oncology Group S1505 clinical trial (identifier: NCT02562716)., Methods: The S1505 phase II clinical trial enrolled patients with resectable PDA who were randomized to receive modified FOLFIRINOX or gemcitabine and nab-paclitaxel as perioperative chemotherapy, followed by surgical resection. Baseline axial CT images at the L3 level were analyzed with externally validated software, and measurements were recorded for skeletal muscle area and skeletal muscle density, visceral adipose tissue area (VATA) and density, and subcutaneous adipose tissue area and density. The relationships between CT metrics and OS were analyzed using Cox regression models, with adjustment for baseline participant characteristics., Results: Of 98 eligible participants with available baseline abdominal CT, 8 were excluded because of imaging quality (eg, orthopedic hardware), resulting in 90 evaluable cases: 51 men (57.0%; mean age, 63.2 years [SD, 8.5]; mean body mass index [BMI], 29.3 kg/m 2 [SD, 6.4]), 80 White (89.0%), 6 Black (7.0%), and 4 unknown race (4.0%). Sarcopenia was present in 32 participants (35.9%), and sarcopenic obesity was present in 10 participants (11.2%). Univariable analyses for the 6 variables of interest indicated that the standardized mean difference (hazard ratio [HR], 0.75; 95% CI, 0.57-0.98; P = .04) was statistically significantly associated with OS. In models adjusted for sex, race, age, BMI, performance score, contrast use, sarcopenia, and sarcopenic obesity, VATA was statistically significantly associated with OS (HR, 1.58; 95% CI, 1.00-2.51; P = .05). No difference was observed in OS between participants according to sarcopenic obesity or sarcopenia categories. The median OS estimates were 25.1 months for participants without sarcopenic obesity, 18.6 months for participants with sarcopenic obesity, 23.6 months for participants without sarcopenia, and 27.9 months for participants with sarcopenia., Conclusion: This was the first study to systematically evaluate body composition parameters in a prospective multicenter trial of patients with resectable PDA who received perioperative chemotherapy. Visceral adipose tissue was associated with survival; however, there was no association between OS and sarcopenia or sarcopenic obesity. Further studies should evaluate these findings in more detail., (Copyright © 2023. Published by Elsevier Inc.)

Background: Open cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is associated with high morbidity, which limits the degree to which patients may benefit from this therapy. This study aimed to determine the feasibility of laparoscopic CRS/HIPEC., Methods: This was a single institution prospective clinical trial and comparative study using historical controls. Patients with histologically confirmed peritoneal surface malignancy (PSM) of appendiceal, colorectal, ovarian, or primary peritoneal origin, peritoneal carcinomatosis index (PCI) [Formula: see text] 10 were eligible., Results: Clinical trial: 18 patients (median age 57 years, 39% female) with appendiceal (15) or colorectal (3) primary PSM underwent laparoscopic CRS/HIPEC. Median and range outcomes were: operative time 219 min (134-378), EBL 10 mL (0-100), time to return to bowel function 3 days (1-7), duration IV narcotic use 3 days (1-8), length of stay 6 days (3-11). All patients had a complete cytoreduction (CC-score 0). Three (17%) experienced minor morbidity, with no major morbidity or mortality. Median DFS and OS were not reached with median follow-up of 48 months. Comparative analysis: Laparoscopic approach associated with reduced time to return of bowel function (3 versus 4 days, p = 0.001), length of stay (8 versus 5 days, p < 0.001), and morbidity (16% versus 42%, p = 0.008). Independent predictors of DFS included prior chemotherapy (HR 5.07, 95% CI 1.85, 13.89; p = 0.002), and CC-score > 0 (HR 3.31, 95% CI 1.19, 9.41; p = 0.025), but not surgical approach. CC-score > 0 was the only independent predictor of OS (HR 10.12, 95% CI 2.16, 47.30, p = 0.003)., Conclusions and Relevance: Laparoscopic CRS/HIPEC should be considered for patients with PSM with low-volume disease, including those with adenocarcinoma histology., Trial Registration: Clinicaltrials.gov; NCT02463877., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal metastases traditionally includes omentectomy, even in the absence of visible omental metastases. We sought to determine the rate of occult histologic omental metastasis (OHOM), evaluate morbidity with omentectomy, and examine the rate of omental recurrence among patients undergoing CRS-HIPEC., Methods: All CRS-HIPEC procedures from August 2007 to August 2020 were included in this single-center, retrospective, cohort study. Procedures were divided into those that included greater omentectomy (OM) and those that did not (NOM). The incidence of OHOM was evaluated specifically among the OM group with a grossly normal omentum. Multivariate regression analyses were performed to evaluate return of bowel function, ileus, and morbidity in the OM and NOM groups., Results: Among 683 CRS-HIPEC procedures, 578 (84.6%) included omentectomy and 105 (15.4%) did not. The OM group had higher operative time, blood loss, peritoneal cancer index, number of visceral resections, and length of stay. In the OM group, 72 (12.5%) patients had a grossly normal omentum, and 23 (31.9%) of these had OHOM. Risk-adjusted return of bowel function, ileus, and 60-day complications were no different in the OM and NOM groups. Among 43 patients with residual omentum, 24 (55.8%) recurred, including 9 (20.9%) with omental recurrence., Conclusions: Histologically occult metastasis was present in one-third of patients undergoing omentectomy during CRS-HIPEC. Omentectomy did not increase the rate of overall morbidity, and one-fifth of patients with residual omentum later developed omental recurrence. Thus, omentectomy is warranted in the absence of gross metastases during CRS-HIPEC., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Peritoneal dissemination of low-grade appendiceal mucinous neoplasms (LAMNs), sometimes referred to as pseudomyxoma peritonei, can result in significant morbidity and mortality. Little is known about the natural history of localized (non-disseminated) LAMNs., Objective: The goal of this study was to evaluate the risk of peritoneal recurrence in patients with localized LAMNs., Methods: We performed a multi-institutional retrospective review of patients with pathologically confirmed localized LAMNs. Baseline characteristics, pathology, and follow-up data were collected. The primary endpoint was the rate of peritoneal recurrence., Results: We identified 217 patients with localized LAMNs. Median age was 59 years (11-95) and 131 (60%) patients were female. Surgical management included appendectomy for 124 (57.1%) patients, appendectomy with partial cecectomy for 26 (12.0%) patients, and colectomy for 67 (30.9%) patients. Pathology revealed perforation in 46 patients (37.7% of 122 patients with perforation status mentioned in the report), extra-appendiceal acellular mucin (EAM) in 49 (22.6%) patients, and extra-appendiceal neoplastic cells (EAC) in 13 (6.0%) patients. Median follow-up was 51.1 months (0-271). Seven (3.2%) patients developed a peritoneal recurrence, with a median time to recurrence of 14.4 months (2.5-47.0). Seven (15.2%) patients with histologic evidence of perforation had recurrence, versus no patients (0%) without perforation (p < 0.001); five (10.2%) patients with EAM versus two (1.2%) patients without EAM (p = 0.007), and one (7.7%) patient with EAC versus six (2.9%) patients without EAC (p = 0.355) had recurrence., Conclusions: This multi-institutional study represents the largest reported series of patients with localized LAMNs. In the absence of perforation or extra-appendiceal mucin or cells, recurrence was extremely rare; however, patients with any of these pathologic findings require careful follow-up.

Background: Circulating tumor DNA (ctDNA) is a promising technology for treatment selection, prognostication, and surveillance after definitive therapy. Its use in the perioperative setting for patients with metastatic disease has not been well studied. We characterize perioperative plasma ctDNA and its association with progression-free survival (PFS) in patients undergoing surgery for peritoneal metastases., Patients and Methods: We recruited 71 patients undergoing surgery for peritoneal metastases and evaluated their plasma with a targeted 73-gene ctDNA next-generation sequencing test before and after surgery. The association between perioperative ctDNA, as well as other patient factors, and PFS was evaluated by Cox regression., Results: ctDNA was detectable in 28 patients (39.4%) preoperatively and in 37 patients (52.1%) postoperatively. Patients with high ctDNA [maximum somatic variant allele fraction (MSVAF) > 0.25%] had worse PFS than those with low MSVAF (< 0.25%) in both the pre- and postoperative settings (median 4.8 vs. 19.3 months, p < 0.001, and 9.2 vs.15.0 months, p = 0.049, respectively; log-rank test). On multivariate analysis, high-grade histology [hazard ratio (HR) 3.42, p = 0.001], incomplete resection (HR 2.35, p = 0.010), and high preoperative MSVAF (HR 3.04, p = 0.001) were associated with worse PFS. Patients with new postoperative alterations in the context of preoperative alteration(s) also had a significantly shorter PFS compared with other groups (HR 4.28, p < 0.001)., Conclusions: High levels of perioperative ctDNA and new postoperative ctDNA alterations in the context of preoperative alterations predict worse outcomes in patients undergoing resection for peritoneal metastases. This may highlight a role for longitudinal ctDNA surveillance in this population.

Background: No guidelines exist for surveillance following cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) for appendiceal and colorectal cancer. The primary objective was to define the optimal surveillance frequency after CRS/HIPEC., Methods: The U.S. HIPEC Collaborative database (2000-2017) was reviewed for patients who underwent a CCR0/1 CRS/HIPEC for appendiceal or colorectal cancer. Radiologic surveillance frequency was divided into two categories: low-frequency surveillance (LFS) at q6-12mos or high-frequency surveillance (HFS) at q2-4mos. Primary outcome was overall survival (OS)., Results: Among 975 patients, the median age was 55 year, 41% were male: 31% had non-invasive appendiceal (n = 301), 45% invasive appendiceal (n = 435), and 24% colorectal cancer (CRC; n = 239). With a median follow-up time of 25 mos, the median time to recurrence was 12 mos. Despite less surveillance, LFS patients had no decrease in median OS (non-invasive appendiceal: 106 vs. 65 mos, p < 0.01; invasive appendiceal: 120 vs. 73 mos, p = 0.02; colorectal cancer [CRC]: 35 vs. 30 mos, p = 0.8). LFS patients had lower median PCI scores compared with HFS (non-invasive appendiceal: 10 vs. 19; invasive appendiceal: 10 vs. 14; CRC: 8 vs. 11; all p < 0.01). However, on multivariable analysis, accounting for PCI score, LFS was still not associated with decreased OS for any histologic type (non-invasive appendiceal: hazard ratio [HR]: 0.28, p = 0.1; invasive appendiceal: HR: 0.73, p = 0.42; CRC: HR: 1.14, p = 0.59). When estimating annual incident cases of CRS/HIPEC at 375 for non-invasive appendiceal, 375 invasive appendiceal and 4410 colorectal, LFS compared with HFS for the initial two post-operative years would potentially save $13-19 M/year to the U.S. healthcare system., Conclusions: Low-frequency surveillance after CRS/HIPEC for appendiceal or colorectal cancer is not associated with decreased survival, and when considering decreased costs, may optimize resource utilization.

Background: Patients with peritoneal metastases from appendiceal cancer are at high risk of malignant bowel obstruction (MBO), which is associated with significant morbidity and mortality. There are no definitive treatment guidelines regarding operative intervention for MBO. We sought to evaluate the efficacy and safety of operative intervention in this population., Methods: We identified patients with peritoneal metastases from appendiceal cancer who underwent surgery for MBO at our institution between 2011 and 2018. Baseline characteristics, postoperative complications, and follow-up data were collected. The primary endpoint was obstruction-free survival (OFS). Other endpoints were postoperative recovery of bowel function, 60-day Clavien-Dindo (CD) morbidity, and overall survival (OS)., Results: Twenty-six patients underwent operative treatment for MBO, of whom 14 had high-grade (HG) histology and 12 had low-grade (LG) histology. Seven (25.9%) patients had severe (CD grade 3 or higher) 60-day complications, including one (3.8%) postoperative death. All remaining patients had return of bowel function and resumed oral intake during hospitalization. Six (23.1%) patients had repeat admissions for MBO after surgery. Median OFS was 17.0 months (95% confidence interval [CI] 2.3-31.8), and median OS was 18.5 months (95% CI 3.6-33.3) following surgery., Conclusion: In this carefully selected group of patients with peritoneal metastases from appendiceal cancer, surgery for MBO provided durable palliation with acceptable morbidity.

Background: The risk factors and incidence of venous thromboembolism (VTE) are not well defined in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). We sought to characterize the incidence, risk factors, and pharmacothromboprophylaxis strategies for VTE after CRS/HIPEC., Patients and Methods: We performed a retrospective study of CRS/HIPEC procedures at our institution from 8/2007 to 11/2017, examining the 60-day VTE incidence. Baseline, potential risk factor, and prevention strategy data were collected. Univariate and multivariate regression analysis was used to determine risk factors associated with 60-day VTEs., Results: We identified 25 60-day VTEs among 447 CRS/HIPEC procedures (5.6%). VTEs were discovered on median postoperative day 20 (range 2-59); pulmonary emboli (68%) were the most common type of VTE. The 60-day VTE rate was 10.2% before versus 4.9% after initiation of a policy to discharge patients on pharmacothromboprophylaxis (p = 0.10). Patients with 60-day VTEs had longer average length of stay (14 vs. 11 days, p = 0.01) and higher 60-day mortality rate (4% vs. 0.2%, p = 0.02) than those without VTEs. Caprini score (odds ratio [OR] 1.53, 95% confidence interval [CI] 1.10-2.15, p = 0.01), preoperative serum albumin level (OR 0.40, 95% CI 0.16-1.00, p = 0.05), and 60-day non-VTE serious morbidity (OR 3.45, 95% CI 1.25-9.51, p = 0.02) were risk factors associated with 60-day VTEs on multivariate analysis., Conclusions: VTEs are relatively common after CRS/HIPEC and are associated with high Caprini scores, low serum albumin levels, and additional inpatient comorbidities. They result in longer length of stay and higher mortality rate. Compliance with current guidelines for extended postoperative thromboprophylaxis was likely associated with reduced VTE rate.

Introduction: The clinical relevance of primary tumor sidedness is not fully understood in colon cancer patients with peritoneal metastasis treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC)., Methods: This was a retrospective cohort study of a multi-institutional database of patients with peritoneal surface malignancy at 12 participating high-volume academic centers from the US HIPEC Collaborative., Results: Overall, 336 patients with colon primary tumors who underwent curative-intent CRS with or without HIPEC were identified; 179 (53.3%) patients had right-sided primary tumors and 157 (46.7%) had left-sided primary tumors. Patients with right-sided tumors were more likely to be older, male, have higher Peritoneal Cancer Index (PCI), and have a perforated primary tumor, but were less likely to have extraperitoneal disease. Patients with complete cytoreduction (CC-0/1) had a median disease-free survival (DFS) of 11.5 months (95% confidence interval [CI] 7.6-15.3) versus 13.1 months (95% CI 9.5-16.8) [p = 0.158] and median overall survival (OS) of 30 months (95% CI 23.5-36.6) versus 45.4 months (95% CI 35.9-54.8) [p = 0.028] for right- and left-sided tumors; respectively. Multivariate analysis revealed that right-sided primary tumor was an independent predictor of worse DFS (hazard ratio [HR] 1.75, 95% CI 1.19-2.56; p =0.004) and OS (HR 1.72, 95% CI 1.09-2.73; p = 0.020)., Conclusion: Right-sided primary tumor was an independent predictor of worse DFS and OS. Relevant clinicopathologic criteria, such as tumor sidedness and PCI, should be considered in patient selection for CRS with or without HIPEC, and guide stratification for clinical trials.

Background: Primary tumor location has been shown to be prognostic of overall survival (OS) in patients with both locally advanced and metastatic colorectal cancer. The impact of sidedness on prognosis has not been evaluated in the setting of peritoneal-only metastases treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC)., Methods: A retrospective review of prospectively maintained databases of patients with peritoneal surface malignancy undergoing CRS/HIPEC from three high-volume centers was performed., Results: A total of 115 patients with metastatic colon cancer to the peritoneum who underwent CRS/HIPEC with mitomycin C were identified. Fifty-one patients (45%) had left-sided primary tumors, and 64 (55%) had right-sided primary tumors. Patients with right-sided tumors were more likely to be older (median age 56 vs. 49 years, p = 0.007) and to have signet ring cell histology (17% vs. 4%, p = 0.026). Patients with right-sided tumors had median disease-free survival (DFS) and OS of 14 months (95% confidence interval [CI] 10.5-17.5) and 36 months (95% CI 27.4-44.6), respectively, versus 16 months (95% CI 11.0-21.0) and 69 months (95% CI 24.3-113.7) for those patients with left-sided tumors. On multivariate analysis, primary tumor side was an independent predictor of both DFS and OS., Conclusions: In this study, there was a dramatic, clinically significant difference in OS between patients with right- and left-sided tumors, and primary tumor side was an independent predictor of DFS and OS. Primary tumor side should be considered in patient selection for CRS with or without HIPEC.

Background: Next-generation sequencing (NGS) is a useful tool for detecting genomic alterations in circulating tumor DNA (ctDNA). To date, most ctDNA tests have been performed on patients with widely metastatic disease. Patients with peritoneal carcinomatosis (metastases) present unique prognostic and therapeutic challenges. We therefore explored preoperative ctDNA in patients with peritoneal metastases undergoing surgery., Methods: Patients referred for surgical resection of peritoneal metastases underwent preoperative blood-derived ctDNA analysis (clinical-grade NGS [68-73 genes]). ctDNA was quantified as the percentage of altered circulating cell-free DNA (% cfDNA)., Results: Eighty patients had ctDNA testing: 46 (57.5%) women; median age 55.5 years. The following diagnoses were included: 59 patients (73.8%), appendix cancer; 11 (13.8%), colorectal; five (6.3%), peritoneal mesothelioma; two (2.5%), small bowel; one (1.3%) each of cholangiocarcinoma, ovarian, and testicular cancer. Thirty-one patients (38.8%) had detectable preoperative ctDNA alterations, most frequently in the following genes: TP53 (25.8% of all alterations detected) and KRAS (11.3%). Among 15 patients with tissue DNA NGS, 33.3% also had ctDNA alterations (overall concordance = 96.7%). Patients with high ctDNA quantities (≥ 0.25% cfDNA, n = 25) had a shorter progression-free survival (PFS) than those with lower ctDNA quantities (n = 55; 7.8 vs. 15.0 months; hazard ratio 3.23, 95% confidence interval 1.43-7.28, p = 0.005 univariate, p = 0.044 multivariate)., Conclusions: A significant proportion of patients with peritoneal metastases referred for surgical intervention have detectable ctDNA alterations preoperatively. Patients with high levels of ctDNA have a worse prognosis independent of histologic grade.

Background: Mucinous appendiceal tumors (MAT) are rare neoplasms that can metastasize to the peritoneum and often are treated with cytoreductive surgery (CRS) and HIPEC. Pathologic classification and outcomes vary, but standardized histologic definitions are emerging. We sought to evaluate outcomes in this disease after CRS/HIPEC using standardized pathologic criteria., Method: Outcomes of MAT with peritoneal metastases (PM) after CRS/HIPEC from 2007 to 2015 were reviewed at our institution. Standardized histologic categories per WHO and consensus definitions were used: low-grade appendiceal mucinous neoplasm (LAMN), low-grade adenocarcinoma (LGAC), or high-grade adenocarcinoma (HGAC) primary tumors; and acellular mucin (AM), low-grade mucinous carcinoma peritonei (LGMCP), or high-grade mucinous carcinoma peritonei (HGMCP) peritoneal metastases. Cox proportional hazards model was used identify predictors of progression-free survival (PFS) by univariate and multivariate analyses., Results: A total of 183 patients undergoing 197 CRS/HIPECs were included. Among 75 patients with primary histology review, there were 33 (44.0%) LAMNs, 28 (37.3%) LGACs, and 14 (18.7%) HGACs. Peritoneal histology was benign in 6 (3.0%), AM in 33 (16.8%), LGMCP in 114 (57.9%), and HGMCP in 44 (22.3%). PFS was not reached for AM, 34.3 months for LGMCP, and 16.8 months for HGMCP (p < 0.001). Peritoneal histology predicted PFS on multivariate analysis (hazard ratio 9.82 and 24.60 for LGMCP and HGMCP, respectively, vs. AM, p < 0.001). Among the LGMCP group, CEA and completeness of cytoreduction (CC score) predicted PFS on multivariate analysis., Conclusions: Standardized peritoneal histology in patients with PM from MAT predicts PFS and patients with low-grade histology can be further discriminated by CEA and CC score.

Introduction: Readmission rates following surgery are subject to scrutiny in efforts to control health care costs. This study was designed to define the 60-day readmission rate following cytoreduction and HIPEC at a high-volume center and to identify factors associated with readmission., Methods: Patients who underwent complete cytoreduction and HIPEC at a single institution from August 2007 through June 2014 were identified from a prospectively maintained database. Multiple preoperative and operative factors were analyzed for their ability to predict 60-day readmission following surgery., Results: A total of 250 patients were identified. Forty patients (17%) experienced readmission within 60 days of surgery. The most common reasons for readmission were ileus/dehydration (12, 31%), deep space infection (8, 21%), and DVT/PE (6, 15%). Initial postoperative length of stay was longer for patients readmitted within 60 days (median 12 vs. 9 days, p = 0.013). Of categorical variables analyzed, including gender, histology, HIPEC agent, intraoperative transfusion, and individual procedures performed during cytoreduction, adjuvant systemic therapy, and postoperative morbidity, only Charlson comorbidity index CCI (odds ratio (OR) = 3.80 [1.68-8.60]) and stoma creation (OR = 6.04 [1.56-12.14]) were associated with 60-day readmission., Conclusions: Few measurable variables are associated with readmission following cytoreduction and HIPEC. Patients with high CCI and those with stomas created at the time of CRS/HIPEC may be at increased risk of readmission within 60 days. Earlier or more frequent follow-up for high-risk patients should be considered as a strategy to reduce readmissions.

Background: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) has an emerging role in the treatment of peritoneal malignancies. The CRS-HIPEC approach has known treatment-related toxicities. This study sought to determine the predictors of major postoperative complications after CRS-HIPEC in a high-volume center., Methods: From a single-institution database, this study investigated complications experienced by patients undergoing CRS-HIPEC. Multiple preoperative and operative factors were analyzed for their ability to predict 60-day Clavien grade 3 and greater (major) complications by logistic regression. A predictive model was created from preoperative factors using multivariate logistic regression. The model was tested by Akaike's information criterion, the Hosmer and Lemeshow Goodness-of-Fit Test, the receiver operating characteristic, and the Youden Index., Results: The study evaluated 247 patients undergoing CRS-HIPEC. The primary tumor site was the appendix in 166 cases (67.2 %), the colorectal area in 51 cases (20.6 %), the peritoneum (mesothelioma) in 22 cases (8.9 %), the ovary in 5 cases (2 %), and the small bowel in 3 cases (1.2 %). The median peritoneal cancer index was 14 (range 0-29), and 235 patients (95.1 %) had a complete (CC-0/1) cytoreduction. Major complications occurred for 41 patients (16.6 %), classified as grade 3 in 33 cases (13.4 %), grade 4 in 5 cases (2 %), and grade 5 (deaths) in 3 cases (1.2 %). The factors predictive of major complications in the multivariate analysis were a Charlson Comorbidity Index (CCI) score higher than 0 [odds ratio (OR), 2.505; p = 0.035], presence of preoperative symptoms (OR 1.951; p = 0.064), and prior resection status [no resection or prior CRS-HIPEC (OR 2.087) vs. prior resection without CRS-HIPEC (OR 3.209); p = 0.046]. These variables were used to create a tool predictive of postoperative complications., Conclusion: Presence of symptoms, CCI, and prior resection status predict major complications and define a low-risk population after CRS-HIPEC.

Background: Completeness of cytoreduction is a significant predictor of long-term outcome after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Imaging has limited sensitivity to identify peritoneal metastases and therefore predict whether complete cytoreduction is possible. We reviewed our experience using laparoscopy to determine candidates for complete cytoreduction and HIPEC., Methods: This single-center, retrospective study examined patients from 2007 to 2014 who underwent laparoscopy to determine complete cytoreduction (CC-0/1)/HIPEC candidacy. Preoperative, intraoperative, and postoperative data were collected., Results: A total of 145 laparoscopies were performed on 141 patients, 72 (51.1 %) of whom were female, with a median age of 53 years (range 20-79). The primary site was appendiceal in 67 (47.5 %) patients, colorectal in 43 (30.5 %), mesothelioma in 17 (12.1 %), unknown in 9 (6.4 %), small bowel in 3 (2.1 %), gastric in 1, and ovarian in 1 (0.7 % each). Overall, 115 (81.6 %) patients had prior abdominal surgery, 111 (76.6 %) had evidence of disease on imaging, and 117 (80.7 %) underwent prior chemotherapy, with a median of 5.9 weeks between the last treatment and laparoscopy (0.9-498.9 weeks). Four (2.8 %) intraoperative complications were observed (one liver laceration, two enterotomies, and one air embolus), and nine (6.2 %) postoperative complications [four (2.8 %) Clavien grade (CG) I, three (2.8 %) CG II, one (0.7 %) CG III (return to operating room) and one (0.7 %) CG IV (transient ischemic attack)]. Forty-eight patients deemed candidates by laparoscopy underwent CRS/HIPEC (positive predictive value 82.8 %)., Conclusion: Diagnostic laparoscopy is a safe, feasible, and accurate staging tool in patients with suspected peritoneal metastases being considered for CRS.

Background: Long-term survival of patients with appendiceal or colorectal peritoneal carcinomatosis (PC) may be achieved by combining cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). Unfortunately, such favorable outcomes are realized in a minority of patients. Given the morbidity of the CRS/HIPEC and the uncertain role of postresection systemic therapy, it is important that prognostic factors in high-grade PC be clearly defined., Methods: This single center, retrospective, cohort study examined the outcomes of CRS/HIPEC performed on patients with high-grade PC secondary to appendiceal or colorectal adenocarcinoma between 2007 and 2013. Cox regression analysis was utilized to evaluate the association between potential prognostic factors [age, sex, primary site, lymph node (LN) status, peritoneal cancer index (PCI) score, completeness of cytoreduction score (CC score), number of visceral resections, and systemic chemotherapy] and progression-free survival (PFS)., Results: A total of 70 patients with high-grade appendiceal or colorectal PC underwent CRS/HIPEC during the study period; 82.9 % underwent complete (CC-0) cytoreduction with a median PFS of 9.7 months. Positive LNs at the time of CRS/HIPEC were predictors of worse PFS on univariate and multivariate analysis. No association was demonstrated between pre- or post-HIPEC systemic chemotherapy and PFS., Conclusions: High-grade PC secondary to appendiceal or colorectal adenocarcinoma can be managed with CRS/HIPEC. The number of LN metastases at the time of CRS/HIPEC is the strongest predictor of progression and must be considered when determining patient eligibility for this aggressive treatment.

Introduction: Accumulation of mucinous ascites causes significant morbidity for patients with unresectable pseudomyxoma peritonei (PMP). The success of paracentesis for mucin evacuation is limited due to the presence of adhesions, disease burden, and the viscous nature of mucinous ascites. We sought to review our experience with laparoscopic evacuation of mucinous ascites for palliation of PMP., Methods: Records were reviewed for patients who underwent laparoscopy for carcinomatosis secondary to appendix or colon cancer from July 2007 to January 2014. Of 123 patients, 10 were identified who underwent 17 laparoscopic procedures for palliative evacuation of mucinous ascites., Results: All patients had primary appendiceal cancers and all presented with symptomatic ascites causing abdominal distension and bloating. Pneumoperitoneum was established with a Veress needle or 5-mm optical viewing trocar in the majority of cases (n = 11). In the remaining six cases, an open technique was used and a 10-mm Hasson trocar was placed. There were no trocar-related complications. The median volume of mucin evacuated was 2.0 liters (range 1.7-8.0). All procedures were done as same-day surgeries; no patients required hospitalization. All patients reported symptomatic improvement following the procedure. One patient experienced a grade 1 complication of persistent drainage from one incision, which was managed in the outpatient setting. The median follow-up for all pts was 9.1 months. The median time to recurrent symptoms requiring repeat intervention was 5.3 months., Conclusions: Laparoscopic evacuation of mucinous ascites for select patients with PMP is feasible and results in significant, durable symptom control with minimal morbidity.

Background: Currently, patients with locally advanced esophageal cancer receive neoadjuvant chemoradiotherapy but only about half of these patients benefit from this treatment. GNAS T393C has been shown to predict the postoperative course in solid tumors and may therefore be useful for treatment stratification. The aim of the present study was to determine if the single-nucleotide polymorphism GNAS T393C can be used for treatment stratification in esophageal cancer patients., Methods: A total of 596 patients underwent surgical resection for esophageal carcinoma from 1996 to 2008; 279 patients received chemoradiotherapy prior to surgery (RTX-SURG group). All patients and a reference group of 820 healthy White individuals were genotyped for GNAS T393C., Results: The 5-year-survival rate for the 317 patients who underwent esophagectomy as initial treatment (SURG group) was 57 % for homozygous C-allele carriers (n = 99) and 43 % for T-allele carriers (n = 218; log- rank test p = 0.025). Multivariate analysis revealed the GNAS T393C genotype (p = 0.034), pT (p < 0.001), pN (p < 0.001) and age (p < 0.001) as prognostic of survival. Homozygous C-allele carriers with a locally advanced tumor stage (cT3/T4, n = 129) in the SURG group had a 5-year survival rate of 37 %, which, remarkably, exceeded the 5-year survival rate of 30 % for the entire RTX-SURG group (n = 279). In the RTX-SURG group, the GNAS T393C genotype did not show any prognostic significance., Conclusions: Patients with a locally advanced esophageal cancer and an homozygous GNAS 393C genotype do not benefit from platinum-based neoadjuvant chemoradiotherapy, indicating that these patients should be treated by alternative treatment strategies.

Background: Extensive clinical experience suggests that hyperthermic intraperitoneal chemotherapy (HIPEC) may play an important role in the management of colorectal cancer patients with peritoneal carcinomatosis (CRCPC). However, there remains no established nonsurgical process to rationally select patients for this management, either for inclusion/stratification in clinical trials or as a component of standard of care. The Peritoneal Surface Disease Severity Score (PSDSS) was introduced as a basis to improve patient selection., Methods: The American Society of Peritoneal Surface Malignancies conducted a retrospective review of 1,013 CRCPC patients. The PSDSS was evaluated on 3 specific criteria obtained before surgery (symptoms, extent of peritoneal dissemination, and primary tumor histology). Overall survival was analyzed according to four tiers of disease severity, and a comparison was made between patients who underwent cytoreductive surgery + HIPEC and those who did not., Results: The PSDSS was calculated on 884 patients (87 %). The median survival of 275 patients not undergoing CRS/HIPEC based on their PSDSS-I (n = 8), II (n = 80), III (n = 55), and IV (n = 132)-was 45, 19, 8, and 6 months, respectively. The median survival of 609 patients who underwent CRS/HIPEC based on their PSDSS-I (n = 75), II (n = 317), III (n = 82), and IV (n = 135)-was 86, 43, 29, and 28 months, respectively., Conclusions: These data support that the PSDSS, undertaken before surgery, is capable of defining CRCPC populations who have a statistically defined high or considerably lower likelihood of long-term survival after CRS/HIPEC. The PSDSS can be quite useful in the decision to enter CRCPC patients into, and their stratification within, clinical trials.

Background: Methodological limitations of prior studies have prevented progress in the treatment of patients with borderline resectable pancreatic adenocarcinoma. Shortcomings have included an absence of staging and treatment standards and pre-existing biases with regard to the use of neoadjuvant therapy and the role of vascular resection at pancreatectomy., Methods: In this manuscript, we review limitations of studies of borderline resectable PDAC reported to date, highlight important controversies related to this disease stage, emphasize the research infrastructure necessary for its future study, and present a recently-approved Intergroup pilot study (Alliance A021101) that will provide a foundation upon which subsequent well-designed clinical trials can be performed., Results: We identified twenty-three studies published since 2001 which report outcomes of patients with tumors labeled as borderline resectable and who were treated with neoadjuvant therapy prior to planned pancreatectomy. These studies were heterogeneous in terms of the populations studied, the metrics used to characterize therapeutic response, and the indications used to select patients for surgery. Mechanisms used to standardize these and other issues that are incorporated into Alliance A021101 are reviewed., Conclusions: Rigorous standards of clinical trial design incorporated into trials of other disease stages must be adopted in all future studies of borderline resectable pancreatic cancer. The Intergroup trial should serve as a paradigm for such investigations.

Introduction: Chemokine receptors may regulate the progression and metastasis of invasive malignancies. There are little data, however, regarding their role in premalignant lesions. Our objective was to determine the role of CC chemokine receptor 9 (CCR9) in pancreatic intraepithelial neoplasia (PanIN)., Methods: Human and murine formalin-fixed paraffin-embedded (FFPE) PanIN specimens were assessed for CCR9 expression. The established murine PanIN, invasive pancreatic cancer (5143PDA) and liver metastasis (5143LM) cell lines, and human pancreatic cancer cell line (PANC-1) were obtained to verify CCR9 expression and function., Results: Immunohistochemistry of FFPE specimens demonstrated CCR9 expression in both murine and human PanIN lesions. CCR9 expression in murine and human cell lines was verified by Western blot assay, immunofluorescence, and flow cytometry. CCR9 function was demonstrated by in vitro exposure to CCL25, the selective CCR9 ligand, which resulted in significantly increased cell proliferation in PanIN and pancreatic cancer cell lines., Conclusions: This is the first report of chemokine receptor CCR9 expression in murine and human PanIN tissues. Our results demonstrate enhanced PanIN and pancreatic cancer cell proliferation with activation of CCR9 by its selective ligand CCL25. CCR9 may prove to be a novel therapeutic target for PanIN and its progression to invasive cancer.

Surgical resection is necessary but generally insufficient as curative treatment for pancreatic cancer. Traditionally, postoperative (adjuvant) therapies have been utilized in an attempt to improve outcome, yet these efforts have met with extremely limited success. As preoperative (neoadjuvant) treatment strategies have evolved for the treatment of other malignancies, preoperative therapy for pancreatic cancer has been investigated by several groups over the past decade. At this time, no randomized trials comparing adjuvant and neoadjuvant therapies have been performed, nor have there been any large multicenter trials of neoadjuvant therapy for pancreatic cancer. In this manuscript, the rationale for neoadjuvant strategies are discussed in the context of the available data on both adjuvant and neoadjuvant therapy and clinical trials currently in development.

Background: High levels of vascular endothelial growth factor (VEGF) in ovarian cancer metastases are associated with a worse prognosis in patients treated with chemotherapy. VEGF-directed therapy improves survival for those with metastatic colorectal cancer. Patients with mucinous adenocarcinomas metastatic to the peritoneal surfaces can be treated with cytoreductive surgery, and both tumor grade and cytoreduction status are prognostic. We hypothesized that angiogenic indices may be prognostic in patients undergoing cytoreductive surgery for mucinous adenocarcinoma of the appendix and colon., Methods: Cytoreductive cases from a 5-year period from the University of Cincinnati peritoneal malignancy database were reviewed. CD 34 counts (blood vessels) and VEGF expression was evaluated by means of immunohistochemistry on specimens from patients undergoing cytoreductive surgery and intraperitoneal hyperthermic perfusion (IPHP) for mucinous adenocarcinoma., Results: A total of 26 males and 9 females, with a mean age of 50 years, underwent cytoreductive surgery and IPHP for mucinous adenocarcinoma of appendiceal (n = 32) or colonic (n = 3) origin. With a mean follow-up of 18 months (range 1-63 months), 23 had disease recurrence and 12 were alive without recurrence. The mean survival was 19 months (range 1-63 months). CD34 counts did not correlate with recurrence or survival; however, average VEGF counts correlated with survival (P = 0.017), and, for patients with recurrence, this correlation was stronger (P = 0.002)., Conclusions: These results suggest that markers of tumor angiogenesis may predict survival in patients with peritoneal surface metastases from mucinous adenocarcinoma. These findings provoke the hypothesis that antiangiogenic therapies may be effective in patients with this devastating disease.

Focal nodular hyperplasia (FNH) is a relatively common condition, the diagnosis of which is now regularly made with diagnostic imaging. Cases of multiple FNH (more than four lesions) are rare, however, and the presence of numerous lesions may complicate the workup and diagnosis. We recently treated a young woman with multiple FNH. We report this case to highlight the clinical issues presented by this rare variant of a common benign hepatic disease.

Background: Cytoreductive surgery and intraperitoneal hyperthermic chemoperfusion (IPHC) are an aggressive treatment for patients with peritoneal based malignancies or those with peritoneal dissemination of select histology. Although promising, this therapeutic regimen has been associated with significant morbidity, long hospital stays, and, in some reports, moderate risk for perioperative mortality. Recent experience suggests that these outcomes may be improved., Methods: Thirty-three patients underwent cytoreductive surgery and intraperitoneal hyperthermic perfusion during the period of December 1999 to July 2002. All patients underwent resection by a three-surgeon team, followed by IPHC with an open technique. Peritonectomy was performed with the goal of total gross excision of disease., Results: Thirty-five procedures were performed in 33 patients (20 female) with a mean age of 49 years (range, 26-72). Complete cytoreduction was achieved in 22 cases (63%), and in 6 cases (17%) residual disease was <4 mm. There were nine major perioperative complications (27%) and no perioperative deaths. The median hospital stay was 11 days., Conclusions: These results demonstrate that cytoreductive surgery and IPHC can be performed with morbidity and mortality rates in line with those of other major oncologic operations. Employment of a three-surgeon approach, limited peritonectomy, and an open technique may help to reduce the morbidity from this aggressive treatment. Continued investigation of this promising treatment regimen is warranted.

Autologous islet cell transplantation after near-total or total pancreatic resection can alleviate pain in patients with severe chronic pancreatitis and preserve endocrine function. From February 2000 to February 2003, a total of 22 patients, whose median age was 38 years, underwent pancreatectomy and autologous islet cell transplantation. Postoperative complications, metabolic studies, insulin usage, pain scores, and quality of life were recorded for all of these patients. The average number of islet cells harvested was 245,457 (range 20,850 to 607,466). Operative data revealed a mean estimated blood loss of 635 ml, an average operative time of 9 hours, and a mean length of hospital stay of 15 days. Sixty-eight percent of the patients had either a minor or major complication. Major complications included acute respiratory distress syndrome (n=2), intra-abdominal abscess (n=1), and pulmonary embolism (n=1). There were no deaths in our series. All patients demonstrated C-peptide and insulin production indicating graft function. Forty-one percent are insulin independent, and 27% required minimal amount of insulin or a sliding scale. All patients had preoperative pain and had been taking opioid analgesics; 82% no longer required analgesics postoperatively. Pancreatectomy with autologous islet cell transplantation can alleviate pain for patients with chronic pancreatitis and preserve endocrine function.

Two cases of ampullary carcinoid tumor are reported. These tumors are among the most rare of GI tract carcinoids and appear to have a distinct presentation and biological behavior from carcinoids arising in the duodenum. The existing literature is reviewed with attention to the implications for surgical management of this rare disease.

Background: beta-Catenin functions as an integral part of the E-cadherin/catenin adhesion complex to maintain epithelial cell integrity. beta-Catenin also functions as part of the Wnt signal transduction pathway to transmit growth-promoting signals to the nucleus via its interactions with Tcf/Lef transcription factors. Previous reports have demonstrated altered beta-catenin expression in numerous tumor types; however, reports regarding beta-catenin expression in pancreatic cancer have been conflicting., Methods: beta-Catenin expression was examined in 10 pancreatic cancer cell lines by Western and Northern analysis and by immunofluorescence. Expression was also examined by immunohistochemistry in 57 primary pancreatic cancers and 7 foci of carcinoma-in-situ., Results: Reduced expression of beta-catenin was observed in 4 of 10 pancreatic cancer cell lines. Reduced membranous expression was noted in 32 pancreatic cancers (56%) and correlated with loss of tumor differentiation. Nuclear beta-catenin expression was identified in two tumors (4%). beta-Catenin expression was present in all seven foci of carcinoma-in-situ; however, nuclear expression was predominant in four of the seven cases., Conclusions: Alterations in beta-catenin expression are common in pancreatic cancer; however, signaling and adhesion functions may be perturbed at different times during tumor progression. Therefore, dysregulation of beta-catenin may contribute to the development and progression of this disease through distinct mechanisms.