Oncologic outcomes in elderly patients who underwent hysterectomy for endometrial cancer: a multi-institutional survey in Kinki District, Japan.

BACKGROUND: The goal of this study is to assess the oncologic outcomes of elderly patients who underwent hysterectomy for endometrial cancer across three variables: hysterectomy approach, lymph node resection, and adjuvant therapy. METHODS: Hospital records of patients aged ≥ 70 years who underwent hysterectomy for endometrial cancer were obtained from 19 institutions. Patients were categorized into three risk groups: low, intermediate, and high. In each group, disease-free survival and overall survival were compared according to hysterectomy approach, lymph node resection, and adjuvant therapy using Kaplan-Meier method. Cox regression analysis with a 95% confidence interval was performed to estimate relative risk (RR) of death. RESULTS: A total of 1246 patients were included. In the low-risk group, the adjusted RR for death for minimally invasive surgery (MIS) versus laparotomy and lymph node resection versus no lymph node resection were 0.64 (0.24-1.72) and 0.52 (0.24-1.12), respectively. In the intermediate-risk group, the adjusted RR for death for MIS versus laparotomy, lymph node resection versus no lymph node resection, and adjuvant therapy versus no adjuvant therapy were 0.80 (0.36-1.77), 0.60 (0.37-0.98), and 0.89 (0.55-1.46), respectively. In the high-risk group, the adjusted RRs for death for lymph node resection versus no lymph node resection and adjuvant therapy versus no adjuvant therapy were 0.56 (0.37-0.86) and 0.60 (0.38-0.96), respectively. CONCLUSIONS: MIS is not inferior to laparotomy in uterine-confined diseases. Lymph node resection improved the outcome for all disease stages and histological types. In contrast, adjuvant therapy improved the outcomes only in high-risk patients.

APC and PIK3CA Mutational Cooperativity Predicts Pathologic Response and Survival in Patients Undergoing Resection for Colorectal Liver Metastases.

OBJECTIVE: The aim of the study was to determine the prognostic impact of co-existence of APC and PIK3CA mutations in patients undergoing preoperative chemotherapy and resection for colorectal liver metastases (CLM). BACKGROUND: Co-occurring genetic events have been shown to drive carcinogenesis in multiple malignancies. METHODS: We identified 396 patients with primary colorectal cancer and known somatic mutation status by next-generation sequencing who underwent hepatectomy for CLM (2005-2015). Survival after hepatectomy in patients with double mutation of APC and PIK3CA and others was analyzed. Predictors of pathologic response and survival were determined. The prognostic value of double mutation was evaluated with a separate cohort of 157 patients with CLM undergoing chemotherapy alone. RESULTS: Forty-five patients had double mutation of APC and PIK3CA; 351 did not. Recurrence-free survival (RFS) and overall survival (OS) after hepatectomy were worse in patients with double mutation (3-year RFS, 3.1% vs 20% [P < 0.001]; 3-year OS, 44% vs 84% [P < 0.001]). Independent predictors of major pathologic response were bevacizumab use (odds ratio [OR] 2.22; P = 0.001), tumor size <3 cm (OR 1.97; P = 0.004), wild-type RAS (OR 2.00; P = 0.003), and absence of double mutation (OR 2.91; P = 0.002). Independent predictors of worse OS were primary advanced T category (hazard ratio [HR] 2.12; P = 0.021), RAS mutation (HR 1.74; P = 0.015), and double mutation (HR 3.09; P < 0.001). In the different medical cohort, patients with double mutation had worse 3-year OS of 18%, compared with 35% without double mutation (P = 0.023). CONCLUSIONS: Double mutation of APC and PIK3CA predicts inferior response to preoperative chemotherapy and poor survival in patients with CLM.

Clinical features of patients with hepatic portal venous gas.

BACKGROUND: Hepatic portal venous gas (HPVG) is a rare clinical condition that is caused by a variety of underlying diseases. However, the factors that would permit accurate identification of bowel ischemia, requiring surgery, in patients with HPVG have not been fully investigated. METHODS: Thirty patients that had been diagnosed with HPVG using computed tomography between 2010 and 2019 were allocated to two groups on the basis of clinical and intraoperative findings: those with (Group 1; n = 12 [40%]) and without (Group 2; n = 18 [60%]) bowel ischemia. Eleven patients underwent emergency surgery, and bowel ischemia was identified in eight of these (73%). Four patients in Group 1 were diagnosed with bowel ischemia, but treated palliatively because of their general condition. We compared the characteristics and outcomes of Groups 1 and 2 and identified possible prognostic factors for bowel ischemia. RESULTS: At admission, patients in Group 1 more commonly showed the peritoneal irritation sign, had lower base excess, higher lactate, and higher C-reactive protein, and more frequently had comorbid intestinal pneumatosis. Of the eight bowel ischemia surgery patients, four (50%) died, mainly because of anastomotic leak following bowel resection and primary anastomosis (3/4, 75%). All except one patient in Group 2, who presented with aspiration pneumonia, responded better to treatment. CONCLUSIONS: Earlier identification and grading of bowel ischemia according to the findings at admission should benefit patients with HPVG by reducing the incidence of unnecessary surgery and increasing the use of safer procedures, such as prophylactic stoma placement.

Deleterious Effect of RAS and Evolutionary High-risk TP53 Double Mutation in Colorectal Liver Metastases.

OBJECTIVE: To assess the impact of somatic gene mutations on survival among patients undergoing resection of colorectal liver metastases (CLM). BACKGROUND: Patients undergoing CLM resection have heterogeneous outcomes, and accurate risk stratification is necessary to optimize patient selection for surgery. METHODS: Next-generation sequencing of 50 cancer-related genes was performed from primary tumors and/or liver metastases in 401 patients undergoing CLM resection. Missense TP53 mutations were classified by the evolutionary action score (EAp53)-a novel approach that dichotomizes mutations as low or high risk. RESULTS: The most frequent somatic gene mutations were TP53 (65.6%), followed by KRAS (48.1%) and APC (47.4%). Double mutation in RAS/TP53, identified in 31.4% of patients, was correlated with primary tumor location in the right colon (P = 0.006). On multivariable analysis, RAS/TP53 double mutation was an independent predictor of shorter overall survival (hazard ratio 2.62, 95% confidence interval 1.41-4.87, P = 0.002). In patients with co-mutated RAS, EAp53 high-risk mutations were associated with shorter 5-year overall survival of 12.2%, compared with 55.7% for TP53 wild type (P < 0.001). The negative prognostic effects of RAS and TP53 mutations were limited to tumors harboring mutations in both genes. CONCLUSIONS: Concomitant RAS and TP53 mutations are associated with decreased survival after CLM resection. A high EAp53 predicts a subset of patients with worse prognosis. These preliminary analyses suggest that surgical resection of liver metastases should be carefully considered in this subset of patients.

RAS Mutation Clinical Risk Score to Predict Survival After Resection of Colorectal Liver Metastases.

OBJECTIVE: To determine the impact of RAS mutation status on the traditional clinical score (t-CS) to predict survival after resection of colorectal liver metastases (CLM). BACKGROUND: The t-CS relies on the following factors: primary tumor nodal status, disease-free interval, number and size of CLM, and carcinoembryonic antigen level. We hypothesized that the addition of RAS mutation status could create a modified clinical score (m-CS) that would outperform the t-CS. METHODS: Patients who underwent resection of CLM from 2005 through 2013 and had RAS mutation status and t-CS factors available were included. Multivariate analysis was used to identify prognostic factors to include in the m-CS. Log-rank survival analyses were used to compare the t-CS and the m-CS. The m-CS was validated in an international multicenter cohort of 608 patients. RESULTS: A total of 564 patients were eligible for analysis. RAS mutation was detected in 205 (36.3%) of patients. On multivariate analysis, RAS mutation was associated with poor overall survival, as were positive primary tumor lymph node status and diameter of the largest liver metastasis >50 mm. Each factor was assigned 1 point to produce a m-CS. The m-CS accurately stratified patients by overall and recurrence-free survival in both the initial patient series and validation cohort, whereas the t-CS did not. CONCLUSIONS: Modifying the t-CS by replacing disease-free interval, number of metastases, and CEA level with RAS mutation status produced an m-CS that outperformed the t-CS. The m-CS is therefore a simple validated tool that predicts survival after resection of CLM.

Establishment of Molecular Design Strategy To Obtain Activatable Fluorescent Probes for Carboxypeptidases.

Carboxypeptidases (CPs) are a family of hydrolases that cleave one or more amino acids from the C-terminal of peptides or proteins. However, methodology to monitor the activities of CPs is poorly developed. Here, we present the first versatile design strategy to obtain activatable fluorescent probes for CPs by utilizing intramolecular spirocyclization of rhodamine to translate the "aliphatic carboxamide to aliphatic carboxylate" structural conversion catalyzed by CPs into dynamic fluorescence activation. Based on this novel strategy, we developed probes for carboxypeptidases A and B. One of these probes was able to detect pancreatic juice leakage in mice ex vivo, suggesting that its suitability for intraoperative diagnosis of pancreatic fistula. This design strategy should be broadly applicable to CPs, as well as other previously untargetable enzymes, enabling development of fluorescent probes to study various pathological and biological processes.

Embryonic Origin of Primary Colon Cancer Predicts Pathologic Response and Survival in Patients Undergoing Resection for Colon Cancer Liver Metastases.

BACKGROUND: The aim of this study was to determine the prognostic value of embryonic origin in patients undergoing resection after chemotherapy for colon cancer liver metastases (CCLM). METHODS: We identified 725 patients with primary colon cancer and known RAS mutation status who underwent hepatic resection after preoperative chemotherapy for CCLM (1990 to 2015). Survival after resection of CCLM from midgut origin (n = 238) and hindgut origin (n = 487) was analyzed. Predictors of pathologic response and survival were determined. Prognostic value of embryonic origin was validated with a separate cohort of 252 patients with primary colon cancer who underwent resection of CCLM without preoperative chemotherapy. RESULTS: Recurrence-free survival (RFS) and overall survival (OS) after hepatic resection were worse in patients with midgut origin tumors (RFS rate at 3 years: 15% vs 27%, P < 0.001; OS rate at 3 years: 46% vs 68%, P < 0.001). Independent factors associated with minor pathologic response were midgut embryonic origin [odds ratio (OR) 1.55, P = 0.010], absence of bevacizumab (OR 1.42, P = 0.034), and mutant RAS (OR 1.41, P = 0.043). Independent factors associated with worse OS were midgut embryonic origin [hazard ratio (HR) 2.04, P < 0.001], carcinoembryonic antigen value ≥5 ng/mL at hepatic resection (HR 1.46, P = 0.0021), synchronous CCLM (HR 1.45, P = 0.012), and mutant RAS (HR 1.43, P = 0.0040). In the validation cohort, patients with CCLM of midgut origin had a worse 3-year OS rate (55% vs 78%, P = 0.003). CONCLUSIONS: Compared with CCLM from hindgut origin, CCLM from midgut origin are associated with worse pathologic response to chemotherapy and worse survival after resection. This effect appears to be independent of RAS mutation status.

Ablation of colorectal liver metastasis: Interaction of ablation margins and RAS mutation profiling on local tumour progression-free survival.

OBJECTIVES: To investigate effects of ablation margins on local tumour progression-free survival (LTPFS) according to RAS status in patients with colorectal liver metastases (CLM). METHODS: This two-institution retrospective study from 2005-2016 included 136 patients (91 male, median age 60 years) with 218 ablated CLM. LTPFS was performed using the Kaplan-Meier method and evaluated with the log-rank test. Uni/multivariate analyses were performed using Cox-regression models. RESULTS: Three-year LTPFS rates for CLM with minimal ablation margin ≤10 mm were significantly worse than those with >10 mm in both mutant-RAS (29% vs. 48%, p=0.038) and wild-type RAS (70% vs. 94%, p=0.039) subgroups. Three-year LTPFS rates of mutant-RAS were significantly worse than wild-type RAS in both CLM subgroups with minimal ablation margin ≤10 mm (29% vs. 70%, p<0.001) and >10 mm (48% vs. 94%, p=0.006). Predictors of worse LTPFS were ablation margins ≤10 mm (HR: 2.17, 95% CI 1.2-4.1, p=0.007), CLM size ≥2 cm (1.80, 1.1-2.8, p=0.017) and mutant-RAS (2.85, 1.7-4.6, p<0.001). CONCLUSIONS: Minimal ablation margin and RAS status interact as independent predictors of LTPFS following CLM ablation. While minimal ablation margins >10 mm should be always the procedural goal, this becomes especially critical for mutant-RAS CLM. KEY POINTS: • RAS and ablation margins are predictors of local tumour progression-free survival. • Ablation margin >10 mm, always desirable, is crucial for mutant RAS metastases. • Interventional radiologists should be aware of RAS status to optimize LTPFS.

Impact of Prior Hepatectomy History on Local Tumor Progression after Percutaneous Ablation of Colorectal Liver Metastases.

PURPOSE: To test the hypothesis that, given the current resection eligibility criteria for colorectal liver metastasis (CLM), prior hepatectomy would be associated with improved local tumor control and survival after percutaneous ablation of CLMs. MATERIALS AND METHODS: This single-institution retrospective study included 82 consecutive patients with 97 CLMs treated with ablation (radiofrequency ablation, microwave ablation, or cryoablation) from January 2005 to December 2014. Local tumor progression-free survival (LTPFS), recurrence-free survival (RFS) at any organ, and overall survival (OS) were calculated using the Kaplan-Meier method from the time of ablation and compared between patients with (n = 49) and without (n = 33) prior hepatectomy. Cox regression models were used to identify LTPFS predictors. RESULTS: Median overall follow-up period was 28 months (range, 4.5-132 months). Three-year actuarial LTPFS (patient level: 73% vs 34%, P < .001) was significantly higher in patients with than without prior hepatectomy, respectively. Similarly, 3-year RFS (23% vs 9.1%, P = .026) and OS (78% vs 48%, P = .003) were improved in patients with prior hepatectomy. At multivariate analysis, predictors of worse LTPFS were: no prior hepatectomy (hazard ratio [HR] 2.35, 95% confidence interval [CI] 1.02-5.45; P = .045), minimal ablation margin < 5 mm (HR 2.4, 95% CI 1.18-4.87; P = .016), and RAS-mutant tumor (HR 2.65, 95% CI 1.18-5.94; P = .019). CONCLUSIONS: Prior hepatectomy for CLMs is associated with improved local tumor control after percutaneous ablation of post-resection-developed CLMs.

Liver Resection for Hepatocellular Carcinoma in Patients with Renal Dysfunction.

BACKGROUND: The aim of this study was to evaluate the feasibility of liver resection in hepatocellular carcinoma (HCC) patients with preoperative renal dysfunction (RD). METHODS: Data from 735 patients undergoing primary liver resection for HCC between 2002 and 2014 were analyzed. Short- and long-term outcomes were compared between the RD group, defined by a preoperative estimated glomerular filtration rate of <45 mL/min/1.73 m2, and the non-RD group. RESULTS: Sixty-two patients had RD. The incidence of postoperative pleural effusion (24 vs. 11%; P = 0.007) and major complications (Clavien-Dindo III-V; 31 vs. 15%; P = 0.003) were significantly higher in RD patients. In RD patients with Child-Pugh A, 90-day mortality rate (1.9%) and median survival time (6.11 years) were comparable to that of non-RD patients. In contrast, RD patients with Child-Pugh B had a very high 90-day mortality rate (22.2%), and a significant shorter median survival time compared to non-RD patients (1.19 vs. 4.84 years; P = 0.001). CONCLUSIONS: Liver resection for Child-Pugh A patients with RD is safe and has comparable oncological outcomes compared to non-RD patients. However, selection of liver resection candidates from Child-Pugh B patients with RD should be stricter.

Endometrioid carcinoma arising from diaphragmatic endometriosis treated with laparoscopy: A case report.

Malignant transformation of diaphragmatic endometriosis is rare. We present a case of endometrioid carcinoma arising from diaphragmatic endometriosis treated with laparoscopy. A 59-year-old primigravida woman who had undergone abdominal hysterectomy for adenomyosis at the age of 47 years was referred to our hospital for investigation of a tumor on the surface of the liver. An integrated positron emission tomography-computed tomography scan revealed a 3-cm nodule on the surface of the liver with abnormal fluorine-18-deoxyglucose accumulation. Partial resection of the diaphragm and liver was performed. Histopathological examination revealed an endometrioid carcinoma arising from diaphragmatic endometriosis. We additionally performed laparoscopic bilateral salpingo-oophorectomy and partial omentectomy. The resected tissues revealed no malignancy. Adjuvant chemotherapy with paclitaxel and carboplatin was administered. In cases of diaphragmatic tumors, endometriosis and its associated malignancies should be considered. Laparoscopic surgery is effective in patients with such conditions.

Comparative effectiveness of first-line radiofrequency ablation versus surgical resection and transplantation for patients with early hepatocellular carcinoma.

BACKGROUND: Significant controversy exists as to which treatment modality is most effective for small, solitary hepatocellular carcinomas (HCCs): radiofrequency ablation (RFA), surgical resection (RXN), or transplantation (TXP). Size cutoff values ranging from 20 to 50 mm have been proposed to achieve complete ablation. The current study compares outcomes between RFA, RXN, and TXP as first-line therapy for patients with HCC tumors measuring as large as 50 mm. METHODS: The Surveillance, Epidemiology, and End Results database was queried for patients with HCC tumors measuring up to 50 mm who were treated with RFA, RXN, or TXP between 2004 and 2013. Overall survival (OS) and disease-specific survival (DSS) were examined in patients with tumors measuring ≤20 mm, 21 to 30 mm, or 31 to 50 mm. The impact of an increase in tumor size of only 5 mm beyond 30 mm was evaluated by also examining outcomes in patients with tumors measuring 31 to 35 mm. RESULTS: Of 1894 cases, patients with HCC tumors measuring ≤20 mm and 21 to 30 mm demonstrated no difference in OS or DSS regardless of whether RFA and RXN was used. RFA was associated with a worse OS and DSS than TXP, whereas there was no difference in OS observed between RXN and TXP. In patients with tumors measuring 31 to 50 mm, OS and DSS were worse with RFA compared with RXN or TXP. Most important, the inferior DSS and OS noted with RFA were observed with only a 5-mm increase in tumors measuring >30 mm. CONCLUSIONS: Although RFA frequently is used as first-line treatment of HCC tumors measuring as large as 50 mm, it is associated with worse results than RXN or TXP for tumors measuring >30 mm. To the best of the authors' knowledge, the results of the current study are the first to demonstrate that although RFA is an appropriate option for patients with HCC tumors measuring ≤30 mm, its use for tumors even slightly larger than 30 mm is associated with inferior outcomes. Cancer 2017;123:1817-1827. © 2017 American Cancer Society.

Local therapy reduces the risk of liver failure and improves survival in patients with intrahepatic cholangiocarcinoma: A comprehensive analysis of 362 consecutive patients.

BACKGROUND: Treatment methods for intrahepatic cholangiocarcinoma (ICC) have improved, but their impact on outcome remains unclear. We evaluated the outcomes of patients definitively treated with resection, radiation, and chemotherapy for ICC, stratified by era. METHODS: Clinico-pathologic characteristics, cause of death, disease-specific survival (DSS), and intrahepatic progression-free survival (IPFS) were compared among patients who underwent resection, radiation, or chemotherapy as definitive treatment strategies for ICC (without distant organ metastasis) between 1997 and 2015. Variables were also analyzed by era (1997-2006 [early] or 2007-2015 [late]) within each group. RESULTS: Among 362 patients in our cohort, 122 underwent resection (early, 38; late, 84), 85 underwent radiation (early, 17; late, 68), and 148 underwent systemic chemotherapy alone (early, 51; late, 97) as definitive treatment strategies, and 7 patients received best supportive care. In the resection group, the 3-year DSS rate was 58% for the early era and 67% for the late era (P = .036), and the 1-year IPFS was 50% for the early era and 75% for the late era (P = .048). In the radiation group, the 3-year DSS was 12% for the early era and 37% for the late era (P = .048), and the 1-year IPFS was 48% for the early era and 64% for the late era (P = .030). In the chemotherapy group, DSS and IPFS did not differ by era. Patients treated with chemotherapy developed liver failure at the time of death significantly more frequently than patients treated with resection (P < .001) or radiation (P < .001). Multivariable analysis identified local therapy (resection or radiation) as a sole predictor of death without liver failure. CONCLUSION: Survival outcomes have improved for local therapy-based definitive treatment strategies for ICC, which may be attributable to maintaining control of intrahepatic disease, thereby reducing the occurrence of death due to liver failure. Cancer 2017;123:1354-1362. © 2016 American Cancer Society.

Hepatic atrophy following preoperative chemotherapy predicts hepatic insufficiency after resection of colorectal liver metastases.

BACKGROUND & AIMS: For patients with colorectal liver metastases (CLM) undergoing major hepatectomy, extensive preoperative chemotherapy has been associated with increased morbidity and mortality. The impact of extensive chemotherapy on total liver volume (TLV) change is unclear. The aims of the current study were twofold: (1) to determine the change of TLV following preoperative chemotherapy in patients undergoing resection for CLM and (2) to investigate the correlations among TLV change, postoperative hepatic insufficiency (PHI), and death from liver failure. METHODS: Clinicopathological features of patients with CLM who underwent preoperative chemotherapy and curative resection were reviewed (2008-2015). TLV change (degree of atrophy) was defined as the percentage difference of TLV (estimated by manual volumetry)/standardized liver volume (SLV) ratio: ([Pre-chemotherapy TLV]-[Post-chemotherapy TLV])×100÷SLV (%). Receiver operating characteristic (ROC) analysis was performed to decide the accurate cut-off value of degree of atrophy to predict PHI. The Cox proportional hazard model was performed to identify the predictors of severe degree of atrophy and PHI. RESULTS: The study cohort consisted of 459 patients, of which 154 patients (34%) underwent extensive preoperative chemotherapy (≥7 cycles). ROC analysis identified the degree of atrophy ≥10% as an accurate cut-off to predict PHI, which was significantly correlated with ≥7 cycles of preoperative chemotherapy. Four factors independently predicted PHI: standardized future liver remnant ≤30% (odds ratio [OR] 4.03, p=0.019), high aspartate aminotransferase-to-platelet ratio index (OR 5.27, p=0.028), degree of atrophy ≥10% (OR 43.5, p<0.001), and major hepatic resection (OR 5.78, p=0.005). Degree of atrophy ≥10% was associated with increased mortality from liver failure (0% [0/374] vs. 15% [13/85], p<0.001). CONCLUSION: Extensive preoperative chemotherapy induced significant atrophic change of TLV. Degree of atrophy ≥10% is an independent predictor of PHI and death in patients with CLM undergoing preoperative chemotherapy and resection. LAY SUMMARY: Extensive preoperative chemotherapy for patients with colorectal liver metastases (CLM) could induce hepatic atrophy. A higher degree of atrophy is an independent predictor of postoperative hepatic insufficiency and death in patients with CLM undergoing preoperative chemotherapy and resection.

Pancreatic Chymotrypsin Activity Rather Than Amylase Level Better Predicts Postoperative Pancreatic Fistula.

OBJECTIVE: To assess the predictive value of chymotrypsin activity in pancreatic juice on clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreatic resection, since pancreatic peptidases rather than glycolytic enzymes play a pivotal role in causing tissue damage due to pancreatic leakage. BACKGROUND: The risk of CR-POPF has been estimated based on amylase level in abdominal drainage fluid. METHODS: Eighty-one consecutive patients underwent pancreatoduodenectomy, and postoperative pancreatic juice and drainage fluids were collected for 14 days. The chymotrypsin activity and fluid amylase level in these fluids were measured, and their susceptibility to the elapsed postoperative time and circadian rhythm were evaluated. The predictive value for the development of CR-POPF was compared between assessment of pancreatic chymotrypsin activity versus fluid amylase level. RESULTS: No significant differences in the daily pancreatic chymotrypsin activity were observed, whereas the amylase level in pancreatic juice was susceptible to the postoperative interval and circadian rhythm. CR-POPF developed in 19 patients (23%). Assessment of pancreatic chymotrypsin activity on the first postoperative day predicted CR-POPF with a sensitivity/specificity of 84/87% (area under the curve, 0.855; cut-off value, 0.5 arbitrary units), which was better than measurement of fluid amylase level. Independent predictors of CR-POPF were the day-1 pancreatic chymotrypsin activity (≥0.5 arbitrary units, P < 0.001) and the main pancreatic duct index (<0.25, P = 0.039). CONCLUSIONS: Assessment of pancreatic chymotrypsin activity may allow for more rapid and accurate prediction of CR-POPF than use of conventional diagnostic criteria based on fluid amylase level, enabling individualized surgical procedures and postoperative drain management.

Comprehensive Complication Index Predicts Cancer-specific Survival After Resection of Colorectal Metastases Independent of RAS Mutational Status.

OBJECTIVE: To investigate prognostic impact of postoperative complications for colorectal liver metastases (CLM) in the era of RAS mutation analysis. BACKGROUND: Postoperative complications have been associated with cancer-specific outcomes in multiple malignancies. METHODS: We identified 575 patients with known RAS mutation status who underwent hepatic resection for CLM during 2008 to 2014. Postoperative complications were scored with the comprehensive complication index (CCI), and the neutrophil-to-lymphocyte ratio (NLR) was used as an indicator of systemic inflammation before and after surgery. Survival after resection of CLM was stratified by CCI (high, ≥26.2; low, <26.2). RESULTS: Eighty-eight patients had high and 487 low CCI. Recurrence-free survival (RFS) and cancer-specific survival (CSS) after hepatic resection were worse in patients with high CCI than in patients with low CCI (RFS at 3 yrs 26% vs. 41%, P = 0.003; CSS at 5 yrs 46% vs. 64%, P = 0.003). High CCI (odds ratio 3.99, P <0.001) was associated with high NLR (>5) 3 months after hepatic resection. Five factors were associated with worse CSS: high CCI [hazard ratio (HR) 1.61, P = 0.022], primary positive node (HR 1.70, P = 0.003), multiple CLM (HR 1.72, P = 0.001), CLM ≥3 cm (HR 1.73, P <0.001), and mutant RAS (HR 2.04, P <0.001). Receiver operating characteristic and area under receiver operating characteristic curves revealed CCI to be a more sensitive, specific, and accurate predictor of RFS and CSS than NLR. CONCLUSIONS: High CCI is a potent predictor of worse RFS and CSS after resection of CLM. The ramifications of postsurgical complications extend beyond direct influence on patient outcomes to impact cancer-related survival.

Individualized Treatment Sequencing Selection Contributes to Optimized Survival in Patients with Rectal Cancer and Synchronous Liver Metastases.

BACKGROUND: The optimal treatment sequence for patients with advanced rectal cancer and synchronous resectable liver metastases is controversial. We examined the outcomes associated with an individualized selection of classic, reversed, or combined approaches. METHODS: Between 1999 and 2014, 268 patients with rectal cancer and synchronous liver-only metastases underwent curative-intent multimodality therapy. Demographics and tumor and treatment details were reviewed. Survival outcomes were examined across treatment sequences and time periods (1999-2003, 2004-2008, and 2009-2014). RESULTS: Overall, 150 (56.0%) patients underwent primary tumor resection first ('classic' approach), 44 (16.4%) patients underwent simultaneous resection of the primary and liver metastases ('combined' approach), and 74 (27.6%) patients underwent liver resection first ('reversed' approach). Patients who underwent the reversed approach had more liver metastases (3 [2-5]) at presentation (vs. 1 [1-2.5] in the combined approach or 1 [1-3] in the classic approach; p < 0.001). Over time (from 1999 to 2003, to 2009 to 2014), both patients undergoing curative-intent treatment (62-122 patients) and the relative proportion of patients undergoing the reversed approach (6.4-37.7%) significantly increased. Despite higher disease burden, the 5-year overall survival (OS) was higher for patients treated in 2009-2014 versus those treated in 1999-2003 (76% vs. 45%; p < 0.002). Two hundred and ten patients (78%) were rendered free of disease; however, 58 were not due to disease progression or treatment complications, and their 5-year OS was poor at 6%. CONCLUSIONS: Individualized selection of treatment sequence based on the liver metastases and primary tumor disease burden allowed most patients to complete resection of all gross disease, and is associated with a 5-year OS rate approaching that for stage III rectal cancer in the most recent era.

Efficacy of Preoperative Portal Vein Embolization Among Patients with Hepatocellular Carcinoma, Biliary Tract Cancer, and Colorectal Liver Metastases: A Comparative Study Based on Single-Center Experience of 319 Cases.

BACKGROUND: Efficacy of preoperative portal vein embolization (PVE) has been established; however, differences of outcomes among diseases, including hepatocellular carcinoma (HCC), biliary tract cancer (BTC), and colorectal liver metastases (CLM), are unclear. METHODS: Subjects included patients in a prospectively collected database undergoing PVE (from 1995 to 2013). A future liver remnant (FLR) volume ≥40% is the minimal requirement for patients with an indocyanine green retention rate at 15 min (ICGR15) <10%, and stricter criteria (FLR volume ≥50%) have been applied for patients with 20% > ICGR15 ≥ 10%. Patient characteristics and survivals were compared among those three diseases, and predictors of dropout and better FLR hypertrophy were determined. RESULTS: In 319 consecutive patients undergoing PVE for HCC (n = 70), BTC (n = 172), and CLM (n = 77), the degree of hypertrophy did not significantly differ by cancer types (median 10, 9.6, and 10%, respectively). Eighty percent (256 of 319) of patients completed subsequent hepatectomy after a median waiting interval of 24 days (range 5-90), while dropout after PVE was more common in BTC or CLM (odds ratio 2.75, p = 0.018), mainly because of disease progression. Ninety-day liver-related mortality after hepatectomy was 0% in the entire cohort, and 5-year overall survival of patients with HCC, BTC, and CLM was 56, 50, and 51%, respectively (p = 0.948). No patients who dropped out survived more than 2.5 years after PVE. CONCLUSION: PVE produced equivalent FLR hypertrophy among the three diseases as long as liver function was fulfilling the preset criteria; however, the completion rate of subsequent hepatectomy was highest in HCC. PVE followed by hepatectomy was a safe and feasible strategy for otherwise unresectable disease irrespective of cancer types.

Incidental Gallbladder Cancer: Residual Cancer Discovered at Oncologic Extended Resection Determines Outcome: A Report from High- and Low-Incidence Countries.

BACKGROUND: Gallbladder cancer detected incidentally after cholecystectomy (IGBC) currently is the most common diagnosis of gallbladder cancer, and oncologic extended resection (OER) is recommended for tumors classified higher than T1b. However, the precise prognostic significance of residual cancer (RC) found at the time of OER has not been well established. This analysis aimed to determine the prognostic impact of RC found in patients with IGBC undergoing OER. METHODS: Outcomes for IGBC at a center for a low-incidence country (USA) and a high-incidence country (Chile) between January 1999 and June 2015 were analyzed. Residual cancer was defined as histologically proven cancer at OER. Predictors of disease-specific survival (DSS) were analyzed. RESULTS: Of 187 patients, 171 (91.4%) achieved complete resection (R0) at OER. The rates of surgical mortality and severe morbidity were respectively 1.1 and 9.6%. Of the 187 patients, 73 (39%) had RC. Perineural invasion and/or lymphovascular invasion and T3 stage were associated with the presence of RC. In both countries, RC was associated with a significantly shorter median survival (23% vs not reached; p < 0.001) and lower 5-year DSS rate (19% vs. 74%; p < 0.001) despite R0 resection. In the multivariable analysis, RC was an independent poor predictor of DSS (hazard ratio [HR], 4.00; 95% confidence interval [CI], 2.13-7.47; p < 0.001), as were lymphovascular and/or perineural invasion (HR, 1.95; 95% CI, 1.19-3.21; p = 0.008). CONCLUSIONS: The presence of RC in patients undergoing OER for IGBC is associated with poor DSS in both high- and low-incidence countries, even when R0 resection is achieved. Residual cancer defines a high-risk cohort for whom adjuvant therapy may be beneficial.

Laparoscopic Partial Splenectomy for Unknown Primary Cancer: A Stepwise Approach.

BACKGROUND: Laparoscopic partial splenectomy (LPS) for focal splenic lesions is technically demanding and carries risk of hemorrhage. Nevertheless, it can be a valuable option, particularly for children and adults in whom attempt at preservation of splenic immunologic function outweighs risk associated with organ preservation. PATIENT: A 58-year-old man was diagnosed with a focal splenic lesion at the upper splenic pole on surveillance imaging following axillary lymph node metastasis for cancer of unknown primary origin (CUP). After an interval of 8 months, repeat FDG-PET showed increase in size and PET-avidity without any evidence of new lesions. Due to isolated site and history of CUP, the patient was considered for a LPS. TECHNIQUE: With the patient in reversed modified French position, the upper pole splenic vessels were controlled and a well-defined area of ischemia encompassing the lesion identified. Under intermittent inflow occlusion and ultrasonography guidance, the parenchymal transection was performed. Total operative time was 180 min, estimated blood loss was 175 cc, the patient was discharged on postoperative day 2, and final pathology confirmed an Epstein-Barr virus associated inflammatory pseudotumor.1 , 2 CONCLUSION: Safe LPS requires systematic pre-operative assessment of hilar vascular anatomy and a stepwise approach to controlling the vessels intra-operatively. Anatomic parenchymal transection and intermitted vascular isolation for lesions close to the demarcation zone minimizes blood loss. Risk/benefit stratification of LPS may be beneficial in select patients only. Whether in patients with CUP LPS may aid in preserving innate and adaptive immunity with potential clinical, including oncologic, benefits will require further investigations.3 - 5.