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The COVID-19 pandemic resulted in sweeping shutdowns of surgical operations to increase hospital capacity and conserve resources. Our institution, following national and state guidelines, suspended nonessential surgeries from March 16 to May 4, 2020. This study examines the financial impact of this decision on our institution's health system by comparing 2 waves of COVID-19 cases.The total revenue was obtained for surgical cases occurring during the first wave of the pandemic between March 1, 2020 and July 31, 2020 and the second wave between October 1, 2020 and February 29, 2021 for all surgical departments. During the same time intervals, in the prepandemic year 2019, total revenue was also obtained for comparison. Net revenue and work relative value units per month were compared to each respective month for all surgical divisions within the department of surgery.Comparing the 5-month first wave period in 2020 to prepandemic 2019 for all surgical departments, there was a net revenue loss of $99,674,376, which reflected 42% of the health system's revenue loss during this period. The department of surgery contributed to a net revenue loss of $58,368,951, which was 24.9% of the health system's revenue loss. Within the department of surgery, there was a significant difference between the net revenue loss per month per division of the first and second wave: first wave median -$636,952 [interquartile range: -1,432,627; 26,111] and second wave median -$274,626 [-781,124; 396,570] (P = .04). A similar difference was detected when comparing percent change in work relative value units between the 2 waves (wave 1: median -13.2% [interquartile range: -41.3%, -1.8%], wave 2: median -7.8% [interquartile range: -13.0%, 1.8%], P = .003).Stopping elective surgeries significantly decreased revenue for a health system. Losses for the health system totaled $234,839,990 during the first wave, with lost surgical revenue comprising 42% of that amount. With elective surgeries continuing during the second wave of COVID-19 cases, the health system losses were substantially lower. The contribution surgery has to a hospital's cash flow is essential in maintaining financial solvency. It is important for hospital systems to develop innovative and alternative solutions to increase capacity, offer comprehensive care to medical and surgical patients, and prevent shutdowns of surgical activity through a pandemic to maintain financial security.

The American College of Surgeons National Surgical Quality Improvement Program was established to help participating hospitals track and report surgical complications with the goal of improving surgical care. We sought to determine whether this has led to improvements in surgical outcomes for pancreatic malignancies.Patients with pancreatic malignancies who underwent surgical resection were identified from the American College of Surgeons National Surgical Quality Improvement Program database (2006-2019). Thirty-day postoperative major morbidity and mortality were analyzed by year. Major morbidity included organ and deep surgical site infection, venous thromboembolism, cardiac event, pneumonia, acute renal failure, sepsis, and respiratory failure.Of the 28,888 patients identified, 51% were male, the median age was 68, 74.3% underwent a pancreaticoduodenectomy, and 25.7% underwent a distal pancreatectomy. Among patients who underwent a pancreaticoduodenectomy, there was a significant increase in major morbidity (annual percent change 0.77, P = .012) driven by increases in organ space surgical site infection (annual percent change 3.52, P.001) and venous thromboembolism (annual percent change 4.72, P = .005). However, there was a decrease in postoperative mortality (annual percent change -4.58, P = .001). For distal pancreatectomy patients, there was no change in rates of overall major morbidity (annual percent change -1.35, P = .08) or mortality (annual percent change -3.21, P = .25).Although major morbidity and mortality have not significantly changed for distal pancreatectomy patients, mortality has steadily decreased for patients undergoing pancreaticoduodenectomy, despite an increase in major morbidity. Whether this trend reflects a change in patient selection, an increase in detection of postoperative morbidities and/or an improvement in mitigation of these morbidities warrants further study.

Background Although tumor size and mitotic rate are established prognostic factors for worse survival in patients undergoing surgical resection for gastric gastrointestinal stromal tumors, the impact of microscopic margins, or R1 resection, is not completely established. Methods Patients who received no neoadjuvant therapy and underwent surgical resection for stage I to III gastric gastrointestinal stromal tumors were identified from the 2010 to 2013 National Cancer Database and divided into 2 cohorts, R0 and R1 resections. Cox proportional hazards ratio and Kaplan Meier survival estimates were utilized to analyze 5-y overall survival. Results Of 2,084 patients, those with R1 resection (57, 2.7%) were more likely to have tumors >10 cm (28.1% vs 11.9%, odds ratio 3.51, P = .017) and stage III disease (26.3% vs 11.2%, odds ratio 2.26, P = .047). Although margin status was associated with higher risk tumors, it was not associated with receipt of adjuvant therapy. After multivariate Cox regression, R1 and R0 patients did not have a difference in 5-y overall survival (82.5% vs 88.6%, hazards ratio 1.26, P = .49). When stratified by stage of disease, there remained no difference in survival across all stages when comparing R1 and R0 patients. Conclusion Positive microscopic margins are uncommon but do not appear to impact survival outcomes in patients with resected localized gastric gastrointestinal stromal tumors.

Background The COVID-19 outbreak has spread worldwide and has resulted in hospital restrictions. The perceived impact of these practices on patients undergoing essential surgeries is less understood. Methods Adult (≥18 years) patients who underwent medically-necessary surgical procedures spanning multiple surgical specialties from March 23, 2020 to April 24, 2020 during the COVID-19 pandemic were identified as eligible for a phone survey. Survey responses were analyzed using a mixed-methods approach involving descriptive statistics and thematic analysis of coded and annotated survey results. Results Of the 212 patients who underwent medically-necessary surgical procedures during the COVID-19 pandemic, the majority of these patients were male (61.3%), White (83.5%), married or with a domestic partner (68.9%), and underwent oncologic procedures (69.3%). Of the 46 (21.7%) patients who completed the survey, the majority of these patients indicated that COVID-19 pandemic restrictions had no impact on their inpatient hospital stay and were satisfied with their decision to proceed with surgery. Severity of patient condition (44.4%), the risk/benefit discussion with the surgeon (24.4%), and COVID-19 education and testing (19.5%) were the most important factors in proceeding with surgery during the pandemic; 34.4% of patients felt their inpatient postoperative course was negatively impacted by the lack of visitors. Conclusion Medically-necessary, time-sensitive surgical procedures, as determined by the surgeon, can be performed during a pandemic with good patient satisfaction provided there is an appropriate discussion between the surgeon and patient about the risks and benefits., The COVID-19 outbreak has resulted in hospital restrictions that have decreased operative censuses and altered the surgical experience, but the perceived impact of these practices on patients undergoing medically-necessary surgeries is less understood. The importance of this study was to portray patients’ perceptions of their perioperative experience given the pandemic restrictions by administering a phone survey to those patients undergoing medically-necessary surgical procedures during the pandemic

Background Weight change offers the simplest indication of a patient’s recovery after an operation. There have been no studies that have thoroughly investigated postoperative weight dynamics after pancreatectomy. The aim of this study was to define postoperative weight change after a pancreatectomy and determine factors associated with optimal and poor weight trajectories. Methods From 2004 to 2019, 1,090 proximal (65%) and distal (35%) pancreatectomies were performed in patients with adequate data in the medical records. Patient weights were acquired preoperatively and at postoperative months 1, 3, and 12. Optimal (top quartile, weight restoration) and poor (bottom quartile, persistent weight loss) postoperative weight cohorts were identified at 1 year postoperatively. Results The median percentage weight change 1 year postpancreatectomy was –6.6% (interquartile range: –1.4% to –12.5%), –7.8% for proximal pancreatectomy, and –4.2% for distal pancreatectomy. For most patients (interquartile range cohort), the median percentage weight change at 1, 3, and 12 months was –6.2%, –7.2%, and –6.6%. The independent factors associated with weight restoration were age 10%, distal pancreatectomy, not undergoing vascular resection, and no readmission within 30 days. Conversely, persistent weight loss was associated with American Society of Anesthesiologists classes III to IV, obesity, malignancy, proximal pancreatectomy, blood loss ≥350mL, and experiencing readmission within 30 days. Focusing on pancreatic ductal adenocarcinoma (n = 372) patients, the factors associated with persistent weight loss were obesity, proximal pancreatectomy, and experiencing recurrence within 1 year; however, weight cohorts were not associated with overall survival for pancreatic ductal adenocarcinoma patients. Conclusion These data define weight kinetics after pancreatectomy. Ultimately, postoperative weight trajectories appear to be largely predetermined but may be mitigated by limiting readmissions and complications. Clinicians should use these data to identify patients who continue to lose weight between the first and third month postoperatively with a high suspicion for the requirement of nutritional monitoring or other interventions.

Background Periampullary malignancies are often unresectable tumors that frequently cause biliary or duodenal obstruction. Advances in endoscopic and percutaneous options have lessened the need for operative palliation. Nevertheless, many patients are still found to be unresectable at the time of exploration, making palliative bypass a consideration. Several prior studies have examined the morbidity of operative palliation, but many were conducted over lengthy time periods, and few have examined the impact of these procedures on future therapy. This study is a contemporary analysis of the short- and long-term outcomes of palliative bypass procedures for unresectable periampullary malignancies at a single high-volume institution. Methods We identified a contemporary cohort of patients in whom a pancreatoduodenectomy was planned for periampullary malignancy but instead underwent an aborted procedure. Patients were divided into 5 procedure groups: laparoscopy only, laparotomy with or without cholecystectomy, gastrointestinal bypass, biliary bypass, and double bypass (gastrointestinal and biliary). Data regarding the patient cohort, procedures, morbidity/mortality, and the interval to initiation of systemic therapy were collected prospectively and reviewed retrospectively. Results Between July 2011 and November 2018, 128 out of 615 (17%) patients had an aborted pancreatoduodenectomy; 113 out of 128 patients had pancreatic adenocarcinoma, and 86 (67.1%) had duodenal or biliary obstruction at the time of operation. Patients who underwent laparoscopy only (n = 34) had no operative complications and a 90-day mortality of 6%; 88% of these patients went on to receive systemic therapy (median 21 days postprocedure). Double bypass was associated with a far lesser complication rate than in prior studies; 17% of patients had some complication(s), but only 9% had a severe complication. The 90-day all-cause mortality was 13%, and only 71% of these patients went on to receive systemic therapy (median 47 days postprocedure). Notably, 27 out of 34 (79%) of patients who underwent laparoscopy alone needed additional procedures for local obstruction, whereas only 5 out of 42 (12%) double bypass patients needed additional interventions. Median survival for the entire cohort was 10.3 months. Conclusion Palliative procedures in this cohort had a far lesser complication rate than that of historical series. Palliative procedures, however, delayed systemic therapy, and a fair number of patients never received additional treatments. Palliative procedures markedly decreased the need for future interventions. Intraoperative decisions regarding palliative procedures must incorporate the functional status and motivations of the patient; these procedures are increasingly safe but may still affect survival.

Background Hepatic resection of colorectal liver metastases is associated with long-term survival. This study analyzes actual 10-year survivors after resection of colorectal liver metastases, reports the observed rate of cure, and identifies factors that preclude cure. Methods A single-institution, prospectively maintained database was queried for all initial resections for colorectal liver metastases for the years 1992–2004. Observed cure was defined as actual 10-year survival with either no recurrence or resected recurrence with at least 3 years of disease-free follow-up. Clinical risk score was dichotomized into low (0–2) and high (3–5). Semiparametric proportional hazards mixture cure model was utilized to estimate probability of cure. Results We included 1,211 patients with a median follow-up for survivors of 11 years. Median disease-specific survival was 4.9 years (95% CI: 4.4–5.3). 295 patients (24.4%) were actual 10-year survivors. The observed cure rate was 20.6% (n = 250). Among 250 cured patients, 192 (76.8%) had no recurrence and 58 (23.2%) had a resected recurrence with at least 3 years of disease-free follow-up. Extrahepatic disease (n = 88), carcinoembryonic antigen >200 ng/mL (n = 119), positive margin (n = 109), and >10 tumors (n = 31) had observed cure rates less than 10%. In cure model analysis, patients with both extrahepatic disease and high clinical risk score (n = 31) had an estimated probability of cure of 3.5%. Conclusion Actual 10-year survival after resection of colorectal liver metastases is 24% with an observed 20% cure rate. Patients with both high clinical risk score and extrahepatic disease have an estimated probability of cure less than 5%. When such factors are identified, strong consideration may be given to preoperative strategies, such as neoadjuvant chemotherapy, to help select patients for surgical therapy.

Introduction Cystic pancreatic endocrine neoplasms (CPENs) are uncommon tumors with uncertain disease biology and ill-defined diagnostic features. Methods A prospectively maintained pancreatic cyst registry was queried, and 31 cases of CPEN that were resected between 1995 and 2010 were identified. Patient and lesion characteristics were detailed and compared with resected non-PEN cystic lesions. Recurrence and survival outcome were compared with 31 noncystic PENs matched for functional status, differentiation, size, World Health Organization classification, grade, and presence of metastases. Results During the study period, CPENs accounted for 7% of resected pancreatic cysts (31/469) and 12% of resected PENs (31/255). CPENs were primarily sporadic (94%), solitary (87%), nonfunctioning (100%), and incidentally discovered (68%). The median diameter was 2.1 cm (range, 0.9–6.2 cm), and preoperative imaging identified septations in 29%, a solid component in 26%, and cyst wall enhancement or a characteristic hypervascular rim in 45% of cases. Preoperative imaging and/or cytology suggested the diagnosis of CPEN in 61%. Compared with resected nonendocrine cystic lesions, CPEN were less frequently symptomatic, less likely to contain septations, and smaller. Compared with matched noncystic PENs, CPENs had comparable demographic, radiologic, and pathologic features and statistically similar long-term outcome (5-year disease-free survival: CPEN: 100% vs PEN: 86%, P = .947). Conclusion In this study, CPENs were primarily asymptomatic small lesions that could be characterized in the majority of cases by cyst wall enhancement on preoperative imaging and/or cytologic assessment. No significant difference in recurrence or survival outcome was identified between cystic and noncystic PENs.

Background Posthepatectomy liver failure is a feared complication after hepatic resection and a major cause of perioperative mortality. There is currently no standardized definition of posthepatectomy liver failure that allows valid comparison of results from different studies and institutions. The aim of the current article was to propose a definition and grading of severity of posthepatectomy liver failure. Methods A literature search on posthepatectomy liver failure after hepatic resection was conducted. Based on the normal course of biochemical liver function tests after hepatic resection, a simple and easily applicable definition of posthepatectomy liver failure was developed by the International Study Group of Liver Surgery. Furthermore, a grading of severity is proposed based on the impact on patients' clinical management. Results No uniform definition of posthepatectomy liver failure has been established in the literature addressing hepatic surgery. Considering the normal postoperative course of serum bilirubin concentration and International Normalized Ratio, we propose defining posthepatectomy liver failure as the impaired ability of the liver to maintain its synthetic, excretory, and detoxifying functions, which are characterized by an increased international normalized ratio and concomitant hyperbilirubinemia (according to the normal limits of the local laboratory) on or after postoperative day 5. The severity of posthepatectomy liver failure should be graded based on its impact on clinical management. Grade A posthepatectomy liver failure requires no change of the patient's clinical management. The clinical management of patients with grade B posthepatectomy liver failure deviates from the regular course but does not require invasive therapy. The need for invasive treatment defines grade C posthepatectomy liver failure. Conclusion The current definition of posthepatectomy liver failure is simple and easily applicable in clinical routine. This definition can be used in future studies to allow objective and accurate comparisons of operative interventions in the field of hepatic surgery.

Background Despite the potentially severe impact of bile leakage on patients’ perioperative and long-term outcome, a commonly used definition of this complication after hepatobiliary and pancreatic operations has not yet been established. The aim of the present article is to propose a uniform definition and severity grading of bile leakage after hepatobiliary and pancreatic operative therapy. Methods An international study group of hepatobiliary and pancreatic surgeons was convened. A consensus definition of bile leakage after hepatobiliary and pancreatic operative therapy was developed based on the postoperative course of bilirubin concentrations in patients’ serum and drain fluid. Results After evaluation of the postoperative course of bilirubin levels in the drain fluid of patients who underwent hepatobiliary and pancreatic operations, bile leakage was defined as bilirubin concentration in the drain fluid at least 3 times the serum bilirubin concentration on or after postoperative day 3 or as the need for radiologic or operative intervention resulting from biliary collections or bile peritonitis. Using this criterion severity of bile leakage was classified according to its impact on patients’ clinical management. Grade A bile leakage causes no change in patients’ clinical management. A Grade B bile leakage requires active therapeutic intervention but is manageable without relaparotomy, whereas in Grade C, bile leakage relaparotomy is required. Conclusion We propose a simple definition and severity grading of bile leakage after hepatobiliary and pancreatic operative therapy. The application of the present proposal will enable a standardized comparison of the results of different clinical trials and may facilitate an objective evaluation of diagnostic and therapeutic modalities in the field of hepatobiliary and pancreatic operative therapy.

Obstruction at the hepatic duct confluence is generally due to hilar cholangiocarcinoma (HCCA). However, in up to 15% of patients, hilar obstruction could be due to alternative diagnoses other than HCCA. The aim of this study was to determine preoperative criteria that could differentiate HCCA from the alternative diagnoses.All patients with hilar obstruction presumed to represent HCCA were included (1997-2001). The extent of disease was assessed preoperatively with computed tomography, magnetic resonance cholangiopancreatography, and Duplex ultrasonography, and these findings were correlated to the final histopathology.A total of 171 patients were included in the study, with HCCA being the most common diagnosis (141 patients [82.4%], group I). Alternative diagnoses other than HCCA were encountered in 30 patients (17.5%, group II) and included benign stricture (9 patients [5.2%]) and other malignancy (21 patients [12%]). There was a higher incidence of involvement of the second-order bile ducts in group I (26% vs 3% in group II, P.01). Vascular involvement and lobar atrophy were more common in group I (58% and 41%) when compared with group II (16% and 6%, P.005 and P.002). The combination of these 2 findings (vascular invasion+lobar atrophy) was reliable for discriminating patients with HCCA from the alternative diagnoses. (38% in group I and 3.3% in group II, P.001).Involvement of second-order bile ducts, vascular invasion, and lobar atrophy are more likely in patients with HCCA. The combination of vascular invasion and lobar atrophy significantly increases the diagnostic likelihood of HCCA. The absence of these findings should raise awareness of the possibility of an alternative diagnosis.

Background Patients with hepatocellular carcinoma (HCC) are frequently found to be inoperable at surgical exploration. Laparoscopy may reduce the rate of unnecessary laparotomy in these patients. However, there are no criteria for selective use of laparoscopy. Methods Sixty patients with potentially operable HCC underwent laparoscopy prior to planned partial hepatectomy. Intraoperative findings and postoperative course were analyzed, and factors for the selective use of laparoscopy were identified. Results Fourteen of 19 inoperable patients (74%) were identified by means of laparoscopy, which increased the resectability rate from 68% to 89%. Compared with patients undergoing exploratory laparotomy only, patients determined to be inoperable on laparoscopy had significantly less intraoperative blood loss, a shorter operating room time, and a briefer hospital stay. In a multivariate analysis, clinically apparent liver cirrhosis and radiologic evidence of major vascular invasion or bilobar tumors predicted the likelihood of finding inoperable disease at laparoscopy. The initial use of laparoscopy avoided unnecessary laparotomy in almost 30% of patients with—but only 5% of patients without—these features. Conclusions If high-risk patients with HCC are selectively targeted, the yield of laparoscopy is increased and unnecessary laparotomy may be avoided. In patients without cirrhosis, major vascular invasion, or bilobar tumors, the yield of laparoscopy is low and is therefore not generally recommended.

Background Hospital readmission rates after surgery are increasingly used as a measure of quality of care. Numerous efforts to decrease these rates have been established by care providers and insurance companies. There is sparse information available regarding readmission rates after liver resection for metastatic colorectal cancer (mCRC). Methods Data from hospital readmissions occurring within 30 days after liver resection and/or open ablation for mCRC between 2005 and 2010 were captured from the urgent care center (emergency room) database and were compared with data from the institutional database. Complications during the primary stay and those leading to readmission were analyzed and graded with an established scoring system. The time course of complications and their therapeutic management were analyzed as well. Results Of 746 patients who underwent surgery during this period, 277 (37%) developed medical or surgical complications within 30 days, and 97 (13%) required readmission after discharge. The most common causes for readmission were perihepatic or intra-abdominal collections (40%), wound issues (13%), and gastrointestinal issues (12%). Forty-four patients had complications grade 3 or higher during readmission, thus representing 34% of all major complications (grade 3 or higher). Seventy-four readmitted patients (27% of all patients with complications) had a complication of lesser grade during their primary stay. The median postoperative day of readmission was 15 (range, 6–30) with wide variation among complication types. Conclusion Readmission is common after liver resection and/or ablation for mCRC. One quarter of patients who develop complications postoperatively will have their most significant complication as an outpatient and require rehospitalization.

Background Liver angiomyolipomas (AML) are mesenchymal neoplasms with an uncertain clinical behavior. The spectrum of presentation, imaging and histologic features, and outcomes were analyzed in all patients treated at Memorial Sloan-Kettering Cancer Center. Methods Demographics, disease, pathologic, treatment, and outcome-related variables for consecutive patients were reviewed retrospectively. All imaging studies obtained at presentation were reexamined, categorized, and compared using Fisher and Wilcoxon tests. Results Between 1989 and 2010, 238 patients with AML were seen and 22 (9.3%) had liver involvement (exclusive = 17; combined with kidney = 5). The median age was 53 years; 18 were females, and 15 had symptoms. AML was not suspected at initial presentation in any patient. Fat-containing neoplasms on imaging were larger ( P = .03), with more heterogeneous enhancement compared with fat-poor neoplasms ( P = .001), but none of the imaging/histologic features correlated with outcome. Thirteen patients underwent resection (R0 = 9), 4 were observed, 2 received chemotherapy, 2 embolization, and 1 embolization plus intra-arterial chemotherapy. Two patients treated with R0-resection recurred and 2 treated with chemotherapy progressed, but no patient died of AML-related causes. At a median follow-up of 36 months, 7 patients were free of disease, 13 were alive with disease, 1 died of an unrelated cause, and another was lost to follow-up. Conclusion AMLs are rare neoplasms with an indolent course in most patients. Subtypes based on fat content are recognized, but clinical behavior does not seem to be different. Recurrence after resection is not associated with disease-related mortality. Resection may be unnecessary in selected asymptomatic patients if the diagnosis can be established definitively.

Background Despite improved clinical characterization, autoimmune pancreatitis is often still diagnosed only after a major operative procedure. This study seeks to elucidate the circumstances that contribute to an inaccurate preoperative diagnosis. Methods Two independent reviewers identified retrospectively an institutional cohort of 68 patients with adequate clinical data to support the diagnosis of autoimmune pancreatitis. Further data regarding presentation, diagnostic studies, and clinical course was abstracted from medical records. Comparative analyses were performed between those patients who underwent major operative procedures and those who did not. Results Fifty-three patients underwent operative intervention as their initial treatment. Compared to the 15 patients avoiding operation, these patients were less likely to have diffuse pancreatic enlargement identified on pretreatment imaging (8% vs 80%) or to have pretreatment serum IgG4 level evaluations (11% vs 100%). Among the 21 patients in whom IgG4 levels were first checked postoperatively, only 12 had increases of at least twice the upper limit of normal. Pretreatment fine needle aspirates were interpreted incorrectly as definite or suspicious for adenocarcinoma in 12 patients, of whom 10 underwent operation. Clinically important postoperative disease recurrence was suspected or proven in 13 patients. Conclusion Pitfalls leading to major pancreatic resections in autoimmune pancreatitis include unnecessarily high thresholds for initiating serum IgG4 evaluation, false positive cytologic evaluations for malignancy, and failure to recognize non-classic initial presentations, or recurrence of disease. Better diagnostic strategies are needed, but awareness of these specific findings should help to decrease the number of patients undergoing operation for unrecognized autoimmune pancreatitis.

The prognostic relevance of variations in expression of specific tumor genes in colorectal cancer liver metastases (CRCLMs) in patients treated with resection and modern chemotherapy is not known.Patients submitted to liver resection for CRCLM between January 2000 and October 2007 were studied. A clinical risk score (CRS; range, 0-5) was calculated for each patient. RNA was extracted from histologically confirmed tumor isolates, and using real-time polymerase chain reaction (PCR) studies, we assessed the quantitative expression of 12 genes with potential importance in chemotherapy resistance and tumor progression, including thymidylate synthase (TS; 5-fluorouracil), excision repair cross complementing gene-1, and xeroderma pigmentosum groups A through G (oxaliplatin), topoisomerase-I (irinotecan), c-met, and hepatocyte growth factor. Primary outcomes were recurrence-free survival (RFS) and disease-specific survival (DSS) after hepatic resection.One-hundred fifty-five patients with good quality tumor mRNA were identified. Median follow-up was 32 months for survivors, and the median CRS was 2. Eighty-seven patients (56%) received preoperative chemotherapy, and 124 (80%) received postoperative chemotherapy. Median RFS for all patients was 13 months, and 3-year DSS was 69%. Median RFS and 3-year DSS for patients with an increased CRS (3-5) was lower (7 vs 18 months [P.0001] and 50% vs. 80% [P.0001], respectively). Of the 12 genes studied, only increased TS expression was associated with a lower RFS (hazard ratio, 1.16; 95% confidence interval, 1.0-1.3; P = .03) and DSS (hazard ratio, 1.25; 95% confidence interval, 1.0-1.5; P = .03). Median RFS and 3-year DSS for patients with increased TS expression was decreased (9 vs. 15 months [P = .03] and 48% vs. 82% [P = .001], respectively). TS expression had prognostic value that was independent of CRS on multivariate analysis.In patients with hepatic CRCLM treated with resection and modern chemotherapy, increased expression of TS improves outcome stratification and appears to be a useful biomarker.

Background. The short-chain fatty acid butyrate inhibits growth of colorectal carcinoma cells in vitro. Mevalonate, a short-chain fatty acid structurally and metabolically related to butyrate, is important in signal transduction and is essential for cell growth. We investigated butyrate's effects on seeding and growth of colorectal tumor cells metastatic to the liver in vivo and hypothesized that butyrate's antiproliferative effects are associated with inhibition of mevalonate-mediated cell growth. Methods. Hepatic metastases were induced by injecting 1×105 MC-26 (N-methyl-N-nitrosourea-induced murine colorectal carcinoma) cells into the spleen of BALB/c mice. Mice were treated with a continuous intravenous infusion of butyrate (2 gm/kg/day) for 7 days starting 24 hours before tumor cells were injected. Study variables included liver weight and number of hepatic surface metastases. Proliferation studies on MC-26 cells were performed in vitro to examine the effects of butyrate alone or combined with mevalonate or mevastatin (an inhibitor of mevalonate synthesis). Results. Butyrate reduced seeding and growth of colorectal tumor cells in vivo. Mevalonate diminished butyrate's antiproliferative action in vitro, whereas mevastatin potentiated this effect. Conclusions. These studies (1) show that butyrate inhibits seeding and growth of hepatic colorectal metastases in vivo, (2) associate butyrate's antiproliferative effects with inhibition of mevalonate-mediated cell growth, and (3) indicate that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors may have synergistic antiproliferative effects when combined with butyrate.