Automated CT Analysis of Body Composition as a Frailty Biomarker in Abdominal Surgery.

Importance: Prior studies demonstrated consistent associations of low skeletal muscle mass assessed on surgical planning scans with postoperative morbidity and mortality. The increasing availability of imaging artificial intelligence enables development of more comprehensive imaging biomarkers to objectively phenotype frailty in surgical patients. Objective: To evaluate the associations of body composition scores derived from multiple skeletal muscle and adipose tissue measurements from automated segmentation of computed tomography (CT) with the Hospital Frailty Risk Score (HFRS) and adverse outcomes after abdominal surgery. Design, Setting, and Participants: This retrospective cohort study used CT imaging and electronic health record data from a random sample of adults who underwent abdominal surgery at 20 medical centers within Kaiser Permanente Northern California from January 1, 2010, to December 31, 2020. Data were analyzed from April 1, 2022, to December 1, 2023. Exposure: Body composition derived from automated analysis of multislice abdominal CT scans. Main Outcomes and Measures: The primary outcome of the study was all-cause 30-day postdischarge readmission or postoperative mortality. The secondary outcome was 30-day postoperative morbidity among patients undergoing abdominal surgery who were sampled for reporting to the National Surgical Quality Improvement Program. Results: The study included 48 444 adults; mean [SD] age at surgery was 61 (17) years, and 51% were female. Using principal component analysis, 3 body composition scores were derived: body size, muscle quantity and quality, and distribution of adiposity. Higher muscle quantity and quality scores were inversely correlated (r = -0.42; 95% CI, -0.43 to -0.41) with the HFRS and associated with a reduced risk of 30-day readmission or mortality (quartile 4 vs quartile 1: relative risk, 0.61; 95% CI, 0.56-0.67) and 30-day postoperative morbidity (quartile 4 vs quartile 1: relative risk, 0.59; 95% CI, 0.52-0.67), independent of sex, age, comorbidities, body mass index, procedure characteristics, and the HFRS. In contrast to the muscle score, scores for body size and greater subcutaneous and intermuscular vs visceral adiposity had inconsistent associations with postsurgical outcomes and were attenuated and only associated with 30-day postoperative morbidity after adjustment for the HFRS. Conclusions and Relevance: In this study, higher muscle quantity and quality scores were correlated with frailty and associated with 30-day readmission and postoperative mortality and morbidity, whereas body size and adipose tissue distribution scores were not correlated with patient frailty and had inconsistent associations with surgical outcomes. The findings suggest that assessment of muscle quantity and quality on CT can provide an objective measure of patient frailty that would not otherwise be clinically apparent and that may complement existing risk stratification tools to identify patients at high risk of mortality, morbidity, and readmission.

Survival of Elderly Patients Undergoing Pancreatoduodenectomy in an Integrated Health System.

INTRODUCTION: The purpose of this study is to examine pancreatoduodenectomy (PD) perioperative outcomes and consider how age may be related to overall survival in an integrated health system. MATERIALS AND METHODS: A retrospective review was performed of 309 patients who underwent PD between December 2008 and December 2019. Patients were divided into two groups: aged 75 y or less and more than 75 y, defined as senior surgical patients. Univariate and multivariable analyses of predictive clinicopathologic factors associated with overall survival at 5 y were performed. RESULTS: In both groups, the majority underwent PD for malignant disease. The proportion of senior surgical patients alive at 5 y was 33.3% compared to 53.6% of younger patients (P = 0.003). There were also statistically significant differences between the two groups with respect to body mass index, cancer antigen 19-9, Eastern Cooperative Oncology Group performance status, and Charlson comorbidity index. On multivariable analysis, disease type, cancer antigen 19-9, hemoglobin A1c, length of surgery, length of stay, Charlson comorbidity index, and Eastern Cooperative Oncology Group performance status were found to be statistically significant factors for overall survival. Age was not significantly related to overall survival on multivariable logistic regression and when the analysis was limited to pancreatic cancer patients. CONCLUSIONS: Although the difference in overall survival between patients aged less than and more than 75 years was significant, age was not an independent risk factor for overall survival on multivariable analysis. Rather than a patient's chronological age, his/her physiologic age including medical comorbidities and functional status may be more correlated to overall survival.

Pancreatic Adenosquamous Carcinoma: Experience Within an Integrated Health Care System.

Introduction Adenosquamous carcinoma (ASC) of the pancreas is a rare form of pancreatic cancer with a worse prognosis than pancreatic ductal adenocarcinoma. The authors report on a retrospective study of 13 patients diagnosed with ASC in an integrated health care system. Methods A retrospective review was performed of all patients with pancreatic cancer identified between February 2010 and December 2018. Twenty-three patients were diagnosed with pancreatic ASC. Patient demographics, tumor characteristics, treatment modalities, and median survival were evaluated. Results Median overall survival was 8 months (standard devision [SD] = 18.6). Eight out of 13 patients who received surgery upfront had a positive surgical margin (62%). Eleven patients received adjuvant therapy. Median survival for patients who received multimodal treatment was 57 months (SD = 5.7) compared with 2.5 months for patients who received only surgery. Median survival for patients with negative pathologic margins was 17 months (SD = 23.6). One patient was receiving neoadjuvant chemotherapy (6 months into treatment without any evidence of metastatic disease). Discussion The high proportion of positive surgical margins and large tumor size upon presentation suggest that primary tumor downstaging should be considered. The positive results from recent prospective trials on neoadjuvant chemoradiation for pancreatic ductal adenocarcinoma could be a promising foundation of information for the treatment of ASC. Conclusion ASC of the pancreas is an extremely aggressive malignancy with poor prognosis. Further work is needed to determine the optimal multimodal treatment regimen.

Pancreaticogastrostomy as a fistula mitigating strategy for a high-risk pancreatic anastomosis following pancreaticoduodenectomy.

BACKGROUND: Clinically relevant postoperative pancreatic fistula (CR-POPF) following pancreaticoduodenectomy (PD) has been associated with soft gland texture and/or small pancreatic duct. We hypothesized that selective use of pancreaticogastrostomy (PG) over pancreaticojejunostomy (PJ) in those scenarios would decrease the rate of CR-POPF. METHODS: Review of prospective database of all PD's performed at a single institution between 2009 and 2019 was performed. The pancreatic remnant was deemed "high risk" if soft gland and/or small duct were present. RESULTS: PJ was performed in 199 (147 "low-risk" and 52 "high-risk") cases, and 110 patients (all "high-risk") had a PG. Overall CR-POPF rate was 11.9% with no difference between the groups. Risk-stratified analysis within PJ group showed CR-POPF rate of 5.4% versus 36% in "low-risk" versus "high risk" scenarios, respectively; the use of PG significantly decreased CR-POPF rate (9.1%, p < 0.0001). Gastrointestinal bleeding was more likely to occur following PG than PJ. Soft gland texture and gastrointestinal bleeding were the strongest predictors of CR-POPF in PJ and PG groups, respectively. CONCLUSION: Selective use of PG after PD in "high-risk" scenarios mitigates the risk of CR-POPF. Increased rate of gastrointestinal bleeding calls for further refinement of the technique and heightened postoperative vigilance.

A Multicenter Virtual Multidisciplinary Sarcoma Case Conference Improves Outcome for a Rare Soft Tissue Sarcoma (Dermatofibrosarcoma Protuberans).

INTRODUCTION: The purpose of this study is to analyze the impact of a virtual multidisciplinary sarcoma case conference (VMSCC) on the outcomes of dermatofibrosarcoma protuberans (DFSP). METHODS: We compared margin status after surgery and disease-free survival (DFS) on two cohorts of patients with DFSP, one diagnosed from 2010 to 2015 and one from 2016 to 2020 (before and after virtual multidisciplinary sarcoma case conference (VMSCC) within Kaiser Permanente Northern California (KPNC), using Kaplan-Meier curves and Cox proportional hazard regression models. RESULTS: There was no significant difference between the two cohorts on demographics, tumor location, type of surgery, receipt of radiation, receipt of imatinib, or size of tumor. However, the percent of patients with positive margin after final surgery and the percent of local recurrence were significantly different: 6.5% and 6.3% for the 2010-2015 cohort, and .8% and 0% for the 2016-2020 cohort, respectively. CONCLUSION: Our data suggest that the outcomes of DFSP improved significantly after the implementation of VMSCC.

Predicting early discharge and readmission following pancreaticoduodenectomy [S079].

INTRODUCTION: Implementing enhanced recovery after surgery (ERAS) protocols for major abdominal surgery has been shown to decrease length of stay (LOS) and postoperative complications, including mortality and readmission. Little is known to guide which patients undergoing pancreaticoduodenectomy (PD) should be eligible for ERAS protocols. METHODS AND PROCEDURES: A retrospective chart review of all PD performed from 2010 to 2018 within an integrated healthcare system was conducted. A predictive score that ranges from 0 to 4 was developed, with one point assigned to each of the following: obesity (BMI > 30), operating time > 400 min, estimated blood loss (EBL) > 400 mL, low- or high-risk pancreatic remnant (based on the presence of soft gland or small duct). Chi-squared tests and ANOVA were used to assess the relationship between this score and LOS, discharge before postoperative day 7, readmission, mortality, delayed gastric emptying (DGE), and pancreatic leak/fistula. RESULTS: 291 patients were identified. Mean length of stay was 8.5 days in those patients who scored 0 compared to 16.2 days for those who scored 4 (p = 0.001). 30% of patients who scored 0 were discharged before postoperative day 7 compared to 0% of those who scored 4 (p = 0.019). Readmission rates for patients who scored 0 and 4 were 12% and 33%, respectively (p = 0.017). Similarly, postoperative pancreatic fistula occurred in 2% versus 25% in these groups (p = 0.007). CONCLUSION: A simple scoring system using BMI, operating time, EBL, and pancreatic remnant quality can help risk-stratify postoperative PD patients. Those with lower scores could potentially be managed via an ERAS protocol. Patients with higher scores required longer hospitalizations, and adjunctive therapy such as medication and surgical technique to decrease risk of delayed gastric emptying and pancreatic fistula could be considered.

Comparison of Electronic Frailty Metrics for Prediction of Adverse Outcomes of Abdominal Surgery.

Importance: Electronic frailty metrics have been developed for automated frailty assessment and include the Hospital Frailty Risk Score (HFRS), the Electronic Frailty Index (eFI), the 5-Factor Modified Frailty Index (mFI-5), and the Risk Analysis Index (RAI). Despite substantial differences in their construction, these 4 electronic frailty metrics have not been rigorously compared within a surgical population. Objective: To characterize the associations between 4 electronic frailty metrics and to measure their predictive value for adverse surgical outcomes. Design, Setting, and Participants: This retrospective cohort study used electronic health record data from patients who underwent abdominal surgery from January 1, 2010, to December 31, 2020, at 20 medical centers within Kaiser Permanente Northern California (KPNC). Participants included adults older than 50 years who underwent abdominal surgical procedures at KPNC from 2010 to 2020 that were sampled for reporting to the National Surgical Quality Improvement Program. Main Outcomes and Measures: Pearson correlation coefficients between electronic frailty metrics and area under the receiver operating characteristic curve (AUROC) of univariate models and multivariate preoperative risk models for 30-day mortality, readmission, and morbidity, which was defined as a composite of mortality and major postoperative complications. Results: Within the cohort of 37 186 patients, mean (SD) age, 67.9 (female, 19 127 [51.4%]), correlations between pairs of metrics ranged from 0.19 (95% CI, 0.18- 0.20) for mFI-5 and RAI 0.69 (95% CI, 0.68-0.70). Only 1085 of 37 186 (2.9%) were classified as frail based on all 4 metrics. In univariate models for morbidity, HFRS demonstrated higher predictive discrimination (AUROC, 0.71; 95% CI, 0.70-0.72) than eFI (AUROC, 0.64; 95% CI, 0.63-0.65), mFI-5 (AUROC, 0.58; 95% CI, 0.57-0.59), and RAI (AUROC, 0.57; 95% CI, 0.57-0.58). The predictive discrimination of multivariate models with age, sex, comorbidity burden, and procedure characteristics for all 3 adverse surgical outcomes improved by including HFRS into the models. Conclusions and Relevance: In this cohort study, the 4 electronic frailty metrics demonstrated heterogeneous correlation and classified distinct groups of surgical patients as frail. However, HFRS demonstrated the highest predictive value for adverse surgical outcomes.

Pancreatic Neuroendocrine Tumor: Rationale for Centralization in an Integrated Health Care System.

OBJECTIVES: Given the complex surgical management and infrequency of pancreatic neuroendocrine tumor, we hypothesized that treatment at a center of excellence improves survival. METHODS: Retrospective review identified 354 patients with pancreatic neuroendocrine tumor treated between 2010 and 2018. Four hepatopancreatobiliary centers of excellence were created from 21 hospitals throughout Northern California. Univariate and multivariate analyses were performed. The χ2 test of clinicopathologic factors determined which were predictive for overall survival (OS). RESULTS: Localized disease was seen in 51% of patients, and metastatic disease was seen in 32% of patients with mean OS of 93 and 37 months, respectively (P < 0.001). On multivariate survival analysis, stage, tumor location, and surgical resection were significant for OS (P < 0.001). All stage OS for patients treated at designated centers was 80 and 60 months for noncenters (P < 0.001). Surgery was more common across stages at the centers of excellence versus noncenters at 70% and 40%, respectively (P < 0.001). CONCLUSIONS: Pancreatic neuroendocrine tumors are indolent but have malignant potential at any size with management often requiring complex surgeries. We showed survival was improved for patients treated at a center of excellence, where surgery was more frequently utilized.

Centralization of pancreatic cancer treatment within an integrated healthcare system improves overall survival.

BACKGROUND: Higher-volume centers for pancreatic cancer surgeries have been shown to have improved outcomes such as length of stay. We examined how centralization of pancreatic cancer care within a regional integrated healthcare system improves overall survival. METHODS: We conducted a retrospective study of 1621 patients treated for pancreatic cancer from February 2010 to December 2018. Care was consolidated into 4 Centers of Excellence (COE) in surgery, medical oncology, and other specialties. Descriptive statistics, bivariate analysis, Chi-square tests, and Kaplan-Meier analysis were performed. RESULTS: Neoadjuvant chemotherapy use rose from 10% to 31% (p < .001). The median overall survival (OS) improved by 3 months after centralization (p < .001), but this did not reach significance on multivariate analysis. CONCLUSIONS: Our results suggest that in a large integrated healthcare system, centralization improves overall survival and neoadjuvant therapy utilization for pancreatic cancer patients.

Feasibility and Value of Establishing a Community-Based Virtual Multidisciplinary Sarcoma Case Conference.

PURPOSE: Management of soft tissue and bone sarcoma presents many challenges, both diagnostically and therapeutically, and requires multidisciplinary collaboration; however, such collaboration is often challenging to establish, especially in the community setting. We share our experiences of a virtual multidisciplinary sarcoma case conference (VMSCC). METHODS: We conducted retrospective review of the VMSCC data-initially via Webex, now Microsoft Teams-and the surveys of referring physicians to understand the feasibility and value of the VMSCC. RESULTS: The VMSCC was established in March 2013 in Kaiser Permanente Northern California with consistent participation of the Departments of Musculoskeletal Oncology (orthopedic oncology), Musculoskeletal Radiology, Pathology, Medical Oncology, Radiation Oncology, Nuclear Medicine, Surgical Oncology, and Genetics. Pediatric Oncology participated ad hoc when pediatric sarcoma cases were presented. Referrals were from multiple specialties and regions, including the Kaiser Permanente Mid-Atlantic and Hawaii regions. From March 2013 to December 2019, 1,585 cases were reviewed encompassing 36 histologic types. More than 300 cases were reviewed per year from 2017 to 2019. Survey results of referring physicians demonstrate that the VMSCC enhanced the confidence of treating physicians, and its recommendations frequently led to treatment changes. CONCLUSION: Establishing a valuable community-based VMSCC is feasible. VMSCC recommendations frequently led to treatment changes and improved the confidence of treating physicians.

Association of Low Muscle Mass and Low Muscle Radiodensity With Morbidity and Mortality for Colon Cancer Surgery.

Importance: Given the risks of postoperative morbidity and its consequent economic burden and impairment to patients undergoing colon resection, evaluating risk factors associated with complications will allow risk stratification and the targeting of supportive interventions. Evaluation of muscle characteristics is an emerging area for improving preoperative risk stratification. Objective: To examine the associations of muscle characteristics with postoperative complications, length of hospital stay (LOS), readmission, and mortality in patients with colon cancer. Design, Setting, and Participants: This population-based retrospective cohort study was conducted among 1630 patients who received a diagnosis of stage I to III colon cancer from January 2006 to December 2011 at Kaiser Permanente Northern California, an integrated health care system. Preliminary data analysis started in 2017. Because major complication data were collected between 2018 and 2019, the final analysis using the current cohort was conducted between 2019 and 2020. Exposures: Low skeletal muscle index (SMI) and/or low skeletal muscle radiodensity (SMD) levels were assessed using preoperative computerized tomography images. Main Outcomes and Measures: Length of stay, any complication (≥1 predefined complications) or major complications (Clavien-Dindo classification score ≥3), 30-day mortality and readmission up to 30 days postdischarge, and overall mortality. Results: The mean (SD) age at diagnosis was 64.0 (11.3) years and 906 (55.6%) were women. Patients with low SMI or low SMD were more likely to remain hospitalized 7 days or longer after surgery (odds ratio [OR], 1.33; 95% CI, 1.05-1.68; OR, 1.39; 95% CI, 1.05-1.84, respectively) and had higher risks of overall mortality (hazard ratio, 1.40; 95% CI, 1.13-1.74; hazard ratio, 1.44; 95% CI, 1.12-1.85, respectively). Additionally, patients with low SMI were more likely to have 1 or more postsurgical complications (OR, 1.31; 95% CI, 1.04-1.65) and had higher risk of 30-day mortality (OR, 4.85; 95% CI, 1.23-19.15). Low SMD was associated with higher odds of having major complications (OR, 2.41; 95% CI, 1.44-4.04). Conclusions and Relevance: Low SMI and low SMD were associated with longer LOS, higher risk of postsurgical complications, and short-term and long-term mortality. Research should evaluate whether targeting potentially modifiable factors preoperatively, such as preserving muscle mass, could reverse the observed negative associations with postoperative outcomes.

Feasibility and Value of Establishing a Community-Based Virtual Multidisciplinary Sarcoma Case Conference.

PURPOSE: Management of soft tissue and bone sarcoma presents many challenges, both diagnostically and therapeutically, and requires multidisciplinary collaboration; however, such collaboration is often challenging to establish, especially in the community setting. We share our experiences of a virtual multidisciplinary sarcoma case conference (VMSCC). METHODS: We conducted retrospective review of the VMSCC data-initially via Webex, now Microsoft Teams-and the surveys of referring physicians to understand the feasibility and value of the VMSCC. RESULTS: The VMSCC was established in March 2013 in Kaiser Permanente Northern California with consistent participation of the Departments of Musculoskeletal Oncology (orthopedic oncology), Musculoskeletal Radiology, Pathology, Medical Oncology, Radiation Oncology, Nuclear Medicine, Surgical Oncology, and Genetics. Pediatric Oncology participated ad hoc when pediatric sarcoma cases were presented. Referrals were from multiple specialties and regions, including the Kaiser Permanente Mid-Atlantic and Hawaii regions. From March 2013 to December 2019, 1,585 cases were reviewed encompassing 36 histologic types. More than 300 cases were reviewed per year from 2017 to 2019. Survey results of referring physicians demonstrate that the VMSCC enhanced the confidence of treating physicians, and its recommendations frequently led to treatment changes. CONCLUSION: Establishing a valuable community-based VMSCC is feasible. VMSCC recommendations frequently led to treatment changes and improved the confidence of treating physicians.

Experience with a Nonopioid Protocol in Ambulatory Breast Surgery: Opioids are Rarely Necessary and Use is Surgeon-Dependent.

CONTEXT: Surgeons write 1.8% of all prescriptions and 9.8% of all opioid prescriptions. Even small doses prescribed for short-term use can lead to abuse; thus, surgeons are uniquely able to combat the opioid epidemic by changing prescribing practices. As part of a department wide quality improvement project, we initiated a nonopioid protocol for all patients undergoing ambulatory breast surgery. OBJECTIVE: To determine the feasibility of a nonopioid protocol for patients undergoing ambulatory breast surgery and to determine if patient-related factors contribute to surgeon adherence to a nonopioid protocol in ambulatory breast surgery. DESIGN: Retrospective chart review of a prospectively collected database, with χ2 analysis and a multiple logistic regression model with the surgeon as the random effect. MAIN OUTCOME MEASURE: Protocol adherence. RESULTS: A total of 180 patients, with a median age of 63 years (range = 18-95 years), were included. Of these, 127 (70.6%) did not receive opioids; in this group there were 2 hematomas (1.6%), and 3 patients required an opioid prescription (2.4%). Fifty-three (29.4%) were prescribed opioids against protocol; in this group, there was 1 hematoma (1.9%). The operating surgeon was the only variable independently correlated with protocol adherence (p < 0.0001). Age, race/ethnicity, surgery type, and history of long-term opioid use were not. CONCLUSION: Ambulatory breast surgery patients tolerated a nonopioid pain regimen well. Surgeons' decisions, rather than patient characteristics, primarily drove the choice of pain management in our study. We believe our protocol can be improved with stricter implementation and education, which must be balanced with practitioner independence.

Melanoma of the Foot Is Associated With Advanced Disease and Poorer Survival.

The purpose of the present study was to review the outcomes and assess the prognostic factors associated with foot melanoma. We hypothesized that primary melanoma of the foot would be more likely to present at an advanced stage and be associated with poorer outcomes. Both univariate and multivariate analyses were conducted to examine the relationships between patients' demographic, clinical, and pathologic characteristics and deaths within 5 years. Categorical data were summarized as frequencies and percentages and continuous variables as mean ± standard deviation. The primary outcome measure was overall survival. On univariate analysis, the significant prognostic variables found included Breslow thickness, ulceration, sentinel node positivity, and localized presentation on the toe. Age, sex, and race were not prognostically significant in this model. Multivariate Cox proportional hazards analysis resulted in a model of foot melanoma with ulceration and location on the toe as independent prognostic variables. The 5-year survival rate for melanoma of the toe was 50%. The results of the present study have shown that physicians should have a low threshold to biopsy suspicious lesions of the foot and ankle. Advanced disease and poorer survival were noted with toe melanoma. An ulcerative lesion of the foot was also associated with poorer survival.

Management and recurrence patterns of desmoids tumors: a multi-institutional analysis of 211 patients.

BACKGROUND: Desmoid tumors are rare soft-tissue neoplasms with limited data on their management. We sought to determine the rates of recurrence following surgery for desmoid tumors and identify factors predictive of disease-free survival. METHODS: Between January 1983 and December 2011, 211 patients with desmoid tumors were identified from three major surgical centers. Clinicopathologic and treatment characteristics were analyzed to identify predictors of recurrence. RESULTS: Median age was 36 years; patients were predominantly female (68 %). Desmoid tumors most commonly arose in extremities (32 %), abdominal cavity (23 %) or wall (21 %), and thorax (15 %); median size was 7.5 cm. Most patients had an R0 surgical margin (60 %). The 1- and 5-year recurrence-free survival was 81.3 and 52.8 %, respectively. Factors associated with worse recurrence-free survival were: younger age (for each 5-year increase in age, hazard ratio [HR] = 0.90, 95 % confidence interval [95 % CI] 0.82-0.98) and extra-abdominal tumor location (abdominal wall referent: extra-abdominal site, HR = 3.28, 95 % CI, 1.46-7.36) (both P < 0.05). CONCLUSIONS: Recurrence remains a problem following resection of desmoid tumors with as many as 50 % of patients experiencing a recurrence within 5 years. Factors associated with recurrence included age, tumor location, and margin status. While surgical resection remains central to the management of patients with desmoid tumors, the high rate of recurrence highlights the need for more effective adjuvant therapies.

Sequential intra-arterial therapy and portal vein embolization is feasible and safe in patients with advanced hepatic malignancies.

BACKGROUND: A major hepatic resection for malignancies requires an adequate post-operative liver reserve. Portal vein embolization (PVE) with intra-arterial therapy (IAT) may increase future liver remnant (FLR) hypertrophy. As such, the feasibility, safety and efficacy of IAT+PVE were investigated. METHODS: Between 2000 to 2011, 86 patients with malignancy of the liver were identified from a multi-institutional database. Twenty-nine patients underwent sequential IAT+PVE, 25 had PVE alone and 32 had IAT alone. Clinicopathological data were evaluated. RESULTS: Most patients had hepatocellular carcinoma (HCC) (65.1%) and 31.4% had secondary metastatic disease. A complete or partial response using European Association for the Study of the Liver (EASLD) criteria was seen in 48.3% of patients undergoing IAT+PVE vs. 56.6% among patients undergoing IAT (P = 0.601). The median increase in percentage FLR volume was comparable in IAT+PVE (7.4%) vs. PVE only (7.9%) (P = 0.203). There were no IAT+PVE-associated deaths and only one complication. Among patients treated with IAT+PVE (n = 29), 27 underwent a subsequent hepatic resection. Peri-operative morbidity and mortality was 29.6% and 7.4%, respectively. Among the patients with HCC who underwent curative intent surgery after IAT+PVE, the median survival was 59.0 months. CONCLUSIONS: Sequential IAT and PVE are feasible and safe. Utilization of IAT+PVE before a resection can lead to long-term survival and should be considered in the treatment of patients with advanced hepatic malignancies.

Robot-assisted laparoscopic ultrasonography for hepatic surgery.

INTRODUCTION: This study describes and evaluates a novel, robot-assisted laparoscopic ultrasonographic device for hepatic surgery. Laparoscopic liver surgery is being performed with increasing frequency. One major drawback of this approach is the limited capability of intraoperative ultrasonography (IOUS) using standard laparoscopic devices. Robotic surgery systems offer the opportunity to develop new tools to improve techniques in minimally invasive surgery. This study evaluates a new integrated ultrasonography (US) device with the da Vinci Surgical System for laparoscopic visualization, comparing it with conventional handheld laparoscopic IOUS for performing key tasks in hepatic surgery. METHODS: A prototype laparoscopic IOUS instrument was developed for the da Vinci Surgical System and compared with a conventional laparoscopic US device in simulation tasks: (1) In vivo porcine hepatic visualization and probe manipulation, (2) lesion detection accuracy, and (3) biopsy precision. Usability was queried by poststudy questionnaire. RESULTS: The robotic US proved better than conventional laparoscopic US in liver surface exploration (85% success vs 73%; P = .030) and tool manipulation (79% vs 57%; P = .028), whereas no difference was detected in lesion identification (63 vs 58; P = .41) and needle biopsy tasks (57 vs 48; P = .11). Subjects found the robotic US to facilitate better probe positioning (80%), decrease fatigue (90%), and be more useful overall (90%) on the post-task questionnaire. CONCLUSION: We found this robot-assisted IOUS system to be practical and useful in the performance of important tasks required for hepatic surgery, outperforming free-hand laparoscopic IOUS for certain tasks, and was more subjectively usable to the surgeon. Systems such as this may expand the use of robotic surgery for complex operative procedures requiring IOUS.

Hepatic resection for metastatic gastrointestinal stromal tumors in the tyrosine kinase inhibitor era.

BACKGROUND: Before the advent of tyrosine kinase inhibitors (TKIs), surgical resection was the primary treatment for hepatic gastrointestinal stromal tumor (GIST) metastases. Although TKIs have improved survival in the metastatic setting, outcomes after multimodal therapy comprised of hepatectomy and TKIs for GIST are unknown. The objective of this study was to determine whether combination therapy for hepatic GIST metastases is associated with improved overall survival compared with reported outcomes from surgery or TKI therapy alone. METHODS: Demographics, clinicopathologic tumor characteristics, treatments, and outcomes of patients who underwent hepatic resection at 3 high-volume centers from 1995 to 2010 were reviewed. RESULTS: In total, 39 patients underwent hepatectomy for metastatic GISTs, and 27 patients received postoperative TKI therapy. At a median follow-up of 39.7 months, 23 patients (59%) experienced recurrence at a median of 18 months. The 1-year, 2-year, and 3-year overall survival rates were 96.7%, 76.8%, and 67.9%, respectively. Median survival was not reached at 5 years. The rates of severe complication and mortality were 10.2% (4 patients) and 2.5% (1 patient), respectively. When controlling for confounders, postoperative TKI therapy was associated with improved survival (hazard ratio, 0.04; 95% confidence interval, 0.01-0.50; P = .006), and extrahepatic disease was associated with worse survival (hazard ratio, 9.51; 95% confidence interval, 1.63-55.7; P = .012). CONCLUSIONS: Overall survival after combination therapy exceeded previous reports for the treatment of metastatic GIST with hepatic resection or TKI therapy alone and was significantly enhanced by postoperative TKI therapy. The results from this study support findings that combination therapy for GIST liver metastases comprised of surgical resection and TKI therapy is more effective than surgery or TKI therapy alone.

Sarcopenia negatively impacts short-term outcomes in patients undergoing hepatic resection for colorectal liver metastasis.

BACKGROUND: As indications for liver resection expand, objective measures to assess the risk of peri-operative morbidity are needed. The impact of sarcopenia on patients undergoing liver resection for colorectal liver metastasis (CRLM) was investigated. METHODS: Sarcopenia was assessed in 259 patients undergoing liver resection for CRLM by measuring total psoas area (TPA) on computed tomography (CT). The impact of sarcopenia was assessed after controlling for clinicopathological factors using multivariate modelling. RESULTS: Median patient age was 58 years and most patients (60%) were male. Forty-one (16%) patients had sarcopenia (TPA ≤ 500 mm(2) /m(2) ). Post-operatively, 60 patients had a complication for an overall morbidity of 23%; 26 patients (10%) had a major complication (Clavien grade ≥3). The presence of sarcopenia was strongly associated with an increased risk of major post-operative complications [odds ratio (OR) 3.33; P= 0.008]. Patients with sarcopenia had longer hospital stays (6.6 vs. 5.4 days; P= 0.03) and a higher chance of an extended intensive care unit (ICU) stay (>2 days; P= 0.004). On multivariate analysis, sarcopenia remained independently associated with an increased risk of post-operative complications (OR 3.12; P= 0.02). Sarcopenia was not significantly associated with recurrence-free [hazard ratio (HR) = 1.07] or overall (HR = 1.05) survival (both P > 0.05). CONCLUSIONS: Sarcopenia impacts short-, but not long-term outcomes after resection of CRLM. While patients with sarcopenia are at an increased risk of post-operative morbidity and longer hospital stay, long-term survival is not impacted by the presence of sarcopenia.

Both CD4 and CD8 T cells mediate equally effective in vivo tumor treatment when engineered with a highly avid TCR targeting tyrosinase.

Tyrosinase, an enzyme involved in melanin synthesis, is expressed in nearly all primary and metastatic melanoma lesions and thus is an attractive target for TCR-based gene therapy using adoptive cell transfer. The TCR alpha- and beta-chain genes from a tumor-infiltrating lymphocyte, which recognized the tyrosinase 368-376 peptide in the context of HLA-A2, were cloned into a gamma-retroviral vector. Following transduction of PBL, specific reactivity was confirmed by cytokine production following coculture with tumor targets. Experiments using Ab blockade and CD4/CD8 sorting of the transduced PBLs demonstrated that this antityrosinase TCR was CD4/CD8 independent. The introduction of a second disulfide bond between the TCR constant regions and/or creation of a chimeric protein in which the human constant regions were replaced by murine homologs resulted in enhanced TCR expression as demonstrated by tetramer staining and improved tumor reactivity that was comparable to PBL transduced with either anti-melanoma Ag recognized by T cells-1 or anti-gp100 TCR vectors currently used in clinical trials. The chimeric TCR also allowed us to test antitumor function of in HLA-A2/K(b)-transgenic mice. Transfer of the antityrosinase TCR into mouse splenocytes conferred CD4/CD8-independent, HLA-A2-restricted Ag reactivity against B16/A2K(b) murine melanoma in vitro. Furthermore, adoptive transfer of transduced splenocytes mediated B16/A2K(b) melanoma tumor regression in lymphodepleted mice, and, surprisingly, both CD8 and CD4 T cells were equally effective in mediating tumor regression. These results suggest that this highly active tyrosinase-specific TCR could be of value in adoptive cell transfer for melanoma.