Profiling of Adipose and Skeletal Muscle in Human Pancreatic Cancer Cachexia Reveals Distinct Gene Profiles with Convergent Pathways.

The vast majority of patients with pancreatic ductal adenocarcinoma (PDAC) suffer cachexia. Although cachexia results from concurrent loss of adipose and muscle tissue, most studies focus on muscle alone. Emerging data demonstrate the prognostic value of fat loss in cachexia. Here we sought to identify the muscle and adipose gene profiles and pathways regulated in cachexia. Matched rectus abdominis muscle and subcutaneous adipose tissue were obtained at surgery from patients with benign conditions (n = 11) and patients with PDAC (n = 24). Self-reported weight loss and body composition measurements defined cachexia status. Gene profiling was done using ion proton sequencing. Results were queried against external datasets for validation. 961 DE genes were identified from muscle and 2000 from adipose tissue, demonstrating greater response of adipose than muscle. In addition to known cachexia genes such as FOXO1, novel genes from muscle, including PPP1R8 and AEN correlated with cancer weight loss. All the adipose correlated genes including SCGN and EDR17 are novel for PDAC cachexia. Pathway analysis demonstrated shared pathways but largely non-overlapping genes in both tissues. Age related muscle loss predominantly had a distinct gene profiles compared to cachexia. This analysis of matched, externally validate gene expression points to novel targets in cachexia.

Incisional Hernia After Orthotopic Liver Transplantation: A Systematic Review and Meta-analysis.

BACKGROUND: Incisional hernia (IH) is a well-known complication of orthotopic liver transplantation. Despite wide recognition of the impact of this problem, the incidence remains imprecisely known. METHODS: The MEDLINE, EMBASE, Cochrane Central Register of Clinical Trials and Cochrane Database of Systematic Reviews databases were searched from their inception to November 2017 for abstracts documenting IH after orthotropic liver transplantation (OLT). The primary endpoint of this study was incidence of IH, secondary endpoints were time to hernia and recurrence. Three reviewers independently graded abstracts for inclusion in this review. Heterogeneity in combining data was assumed prior to pooling. Random-effects meta-analyses were performed to estimate percentages and 95% CIs. RESULTS: After a review of 77 abstracts, 18 studies were graded as relevant. The methodological quality of studies was assessed with a minimum Oxford Centre for Evidence-Based Medicine level of 2B. These represent a cohort of 981 patients with IH after OLT reported in the literature. A meta-analysis of studies meeting inclusion criteria shows mean incidence of 15.1% (CI 12.1%-18.2%). Aggregate recurrence rate reported in the literature is 12.4% (CI 4.3%-20.5%). Overall reported time to IH after OLT was 42.9 months. CONCLUSIONS: Although reported incidences of IH after OLT vary widely across studies, an overall incidence of 15.1% is reported. This is a relatively late complication after transplantation. Recurrence of hernia after initial repair is 12.4% within this patient population.

Identification of Potential Serum Protein Biomarkers and Pathways for Pancreatic Cancer Cachexia Using an Aptamer-Based Discovery Platform.

Patients with pancreatic ductal adenocarcinoma (PDAC) suffer debilitating and deadly weight loss, known as cachexia. Development of therapies requires biomarkers to diagnose, and monitor cachexia; however, no such markers are in use. Via Somascan, we measured ~1300 plasma proteins in 30 patients with PDAC vs. 11 controls. We found 60 proteins specific to local PDAC, 46 to metastatic, and 67 to presence of >5% cancer weight loss (FC ≥ |1.5|, p ≤ 0.05). Six were common for cancer stage (Up: GDF15, TIMP1, IL1RL1; Down: CCL22, APP, CLEC1B). Four were common for local/cachexia (C1R, PRKCG, ELANE, SOST: all oppositely regulated) and four for metastatic/cachexia (SERPINA6, PDGFRA, PRSS2, PRSS1: all consistently changed), suggesting that stage and cachexia status might be molecularly separable. We found 71 proteins that correlated with cachexia severity via weight loss grade, weight loss, skeletal muscle index and radiodensity (r ≥ |0.50|, p ≤ 0.05), including some known cachexia mediators/markers (LEP, MSTN, ALB) as well as novel proteins (e.g., LYVE1, C7, F2). Pathway, correlation, and upstream regulator analyses identified known (e.g., IL6, proteosome, mitochondrial dysfunction) and novel (e.g., Wnt signaling, NK cells) mechanisms. Overall, this study affords a basis for validation and provides insights into the processes underpinning cancer cachexia.

The Combination of Low Skeletal Muscle Mass and High Tumor Interleukin-6 Associates with Decreased Survival in Clear Cell Renal Cell Carcinoma.

Clear cell renal carcinoma (ccRCC) is frequently associated with cachexia which is itself associated with decreased survival and quality of life. We examined relationships among body phenotype, tumor gene expression, and survival. Demographic, clinical, computed tomography (CT) scans and tumor RNASeq for 217 ccRCC patients were acquired from the Cancer Imaging Archive and The Cancer Genome Atlas (TCGA). Skeletal muscle and fat masses measured from CT scans and tumor cytokine gene expression were compared with survival by univariate and multivariate analysis. Patients in the lowest skeletal muscle mass (SKM) quartile had significantly shorter overall survival versus the top three SKM quartiles. Patients who fell into the lowest quartiles for visceral adipose mass (VAT) and subcutaneous adipose mass (SCAT) also demonstrated significantly shorter overall survival. Multiple tumor cytokines correlated with mortality, most strongly interleukin-6 (IL-6); high IL-6 expression was associated with significantly decreased survival. The combination of low SKM/high IL-6 was associated with significantly lower overall survival compared to high SKM/low IL-6 expression (26.1 months vs. not reached; p < 0.001) and an increased risk of mortality (HR = 5.95; 95% CI = 2.86-12.38). In conclusion, tumor cytokine expression, body composition, and survival are closely related, with low SKM/high IL-6 expression portending worse prognosis in ccRCC.

Specialized care improves outcomes for patients with cirrhosis who require general surgical operations.

BACKGROUND: General surgical operations on patients with cirrhosis have historically been associated with high morbidity and mortality rates. This study examines a contemporary series of patients with cirrhosis undergoing general surgical procedures. METHODS: A retrospective evaluation of 358 cirrhotic patients undergoing general surgical operations at a single institution between 2004-2015 was performed. Thirty- and 90-day mortality along with complications and subsequent transplantation rates were examined. RESULTS: 358 cirrhotic patients were identified. The majority were Child-Turcotte-Pugh class (CTP) A (55.9%) followed by class B (32.4%) and class C (11.7%). Mean MELD score differed significantly between the groups (8.7 vs. 12.1 vs. 20.1; p<0.001). The most common operations were herniorrhaphy (29.9%), cholecystectomy (19.3%), and liver resection (14.5%). The majority of cases were performed semi-electively (68.4%), however, within the CTP C patients most cases were performed emergently (73.8%). Thirty and 90-day mortality for all patients were 5% and 6%, respectively. Mortality rates increased from CTP A to CTP C (30 day: 3.0% vs. 5.2% vs. 14.3%; p = 0.01; 90 day: 4.5% vs. 6.9% vs. 16.7%; p = 0.016). Additionally, 30-day mortality (12.8% vs. 2.3%; p<0.001), 90 day mortality (16.0% vs. 3.4%; p<0.001) were higher for emergent compared to elective cases. A total of 13 (3.6%) patients underwent transplantation ≤ 90 days from surgery. No elective cases resulted in an urgent transplantation. CONCLUSION: Performing general surgical operations on cirrhotic patients carries a significant morbidity and mortality. This contemporary series from a specialized liver center demonstrates improved outcomes compared to historical series. These data strongly support early referral of cirrhotic patients needing general surgical operation to centers with liver expertise to minimize morbidity and mortality.

Financial Burden of Liver Transplant vs Resection for Hepatocellular Carcinoma.

BACKGROUND: Liver transplant and liver resection are surgical treatments for hepatocellular carcinoma (HCC) performed with curative intent. While liver transplant provides longer survival when compared to resection, the financial burden on patients and payors is significantly greater. With the increase in health care costs and the emergence of high deductible insurance policies that increase out of pocket deductibles for patients, assessment of value-based treatment is warranted. METHODS: We compiled total billable events from diagnosis of HCC through resection (N = 20) or transplant (N = 24) to death or last reported encounter from January 2011 to December 2012. RESULTS: Patients with HCC receiving resection had a model of end stage liver disease of 10.2 ± 1.2, survival 652 days (3-1, 167 days), and billable encounters of $316,873 ($2904/day). HCC patients receiving a liver transplant had a greater liver injury (model of end stage liver disease of 19.2 ± 3.7), longer survival (1579 days), and higher billable encounters, $740,714 ($2889/day). The surgical procedure represented the largest cost category (28% and 26% resection vs transplant, respectively). The cost effectiveness of treatment was directly proportional to length of survival. In resection, patients who survived >30 days (85%) cost per day dropped to $432. Transplant patients who survived >2 years (75%) saw the cost per day drop to $462. CONCLUSION: The relative financial burdens of liver resection vs liver transplant for treating HCC are comparable in patients who survive beyond a certain threshold. Transplant patients survived longer, and survival beyond 2 years makes this approach cost effective. In a health care climate aiming to contain costs and evaluate value-based treatment paradigms, expected survival and financial burden should be included in the treatment decision analysis.

Role for targeted resection in the multidisciplinary treatment of metastatic gastrointestinal stromal tumor.

The management of advanced gastrointestinal stromal tumors (GISTs) has evolved in the modern era due to the discovery of c-kit mutations and the development of tyrosine kinase inhibitors (TKIs). Until the advent of TKIs such as imatinib, the median survival reported for patients with advanced GIST was 19 months. Although surgery is the treatment of choice for resectable primary GIST, its role in cases of recurrence and metastasis remains to be unclear. This review outlines the potential beneficial role of repeat surgical resection in the multidisciplinary treatment of advanced GIST in the era of TKIs.

Postoperative renal impairment is associated with increased length of stay for incisional hernia repair after liver transplantation.

BACKGROUND: Incisional hernia repair is the most common procedure after orthotopic liver transplantation. Although enhanced recovery protocols are increasingly employed, the post-orthotopic liver transplantation patient may not benefit from all aspects of these models. The aim of the present study is to assess which perioperative interventions and patient factors affect hospital length of stay in a cohort of post-orthotopic liver transplantation patients undergoing incisional hernia repair. METHODS: We conducted a retrospective review of a series of adult patients undergoing incisional hernia repair after orthotopic liver transplantation. The primary endpoint was length of stay. Results were stratified by demographic, intraoperative, and postoperative variables. RESULTS: Eleven percent (172/1523) of patients who received orthotopic liver transplantation during the study period underwent subsequent incisional hernia repair. Median length of stay was 5 days (range 2-50). The strongest predictor of length of stay was postoperative renal function. Despite liberal intraoperative administration of volume (median 642 mL/h) and brisk intraoperative urine output (median 72 mL/h), postoperative acute kidney injury occurred in 48% of patients. Those that developed acute kidney injury received less intraoperative volume (6 vs 8.5 mL/kg/h; P = .031) and the severity of postoperative renal injury was inversely related to the amount intraoperative volume given. CONCLUSIONS: In patients undergoing incisional hernia repair after orthotopic liver transplantation, postoperative renal function is frequently impaired. Although many aspects of current ERAS protocols may be applied to post-transplant patients, restrictive intraoperative fluid administration strategies should be employed with caution given a high propensity for the development of post-operative acute kidney injury in this complex population.

Outcomes of pancreatoduodenectomy in the cirrhotic patient: risk stratification and meta-analysis.

BACKGROUND: Cirrhosis increases the risk of perioperative mortality in gastrointestinal surgery. Though cirrhosis is sometimes considered a contraindication to pancreatoduodenectomy (PD), few data are available in this patient population. The aim of the present study is to identify predictors of outcome in cirrhotic patients undergoing PD. METHODS: Patients undergoing PD with biopsy-proved cirrhosis were evaluated. Primary endpoints were morbidity and mortality. Child score, MELD score, and radiographic evidence of portal hypertension (pHTN) were assessed for accuracy in preoperative risk stratification. A systematic review of the literature with meta-analysis was also performed to query morbidity and mortality of patients with cirrhosis reported to undergo PD. RESULTS: Between 2005 and 2015, 36 cirrhotic patients underwent PD; three year follow-up was complete. Median Child score was 6 (range 5-10); median MELD score was 9 (range 7-18). Perioperative (90-day) mortality was 6/36. Median survival was 37 months (range 0.2-116). MELD ≥ 10 was associated with increased mortality (4/13 vs. 2/13, p = 0.004). Irrespective of Child or MELD score, those with pHTN had poor outcomes including significantly greater intraoperative blood loss, increased incidence of major complication, and length of stay. Postoperative mortality was significantly higher with pHTN (3/16 vs. 1/13, p = 0.012). CONCLUSION: Pancreatoduodenectomy may be considered in carefully selected cirrhotic patients. MELD ≥ 10 predicts increased risk of postoperative mortality. Specific attention should be afforded to patients with preoperative radiographic evidence of portal hypertension as this group experiences poor outcomes irrespective of MELD or Child score.

Three cachexia phenotypes and the impact of fat-only loss on survival in FOLFIRINOX therapy for pancreatic cancer.

BACKGROUND: By the traditional definition of unintended weight loss, cachexia develops in ~80% of patients with pancreatic ductal adenocarcinoma (PDAC). Here, we measure the longitudinal body composition changes in patients with advanced PDAC undergoing 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin therapy. METHODS: We performed a retrospective review of 53 patients with advanced PDAC on 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin as first line therapy at Indiana University Hospital from July 2010 to August 2015. Demographic, clinical, and survival data were collected. Body composition measurement by computed tomography (CT), trend, univariate, and multivariate analysis were performed. RESULTS: Among all patients, three cachexia phenotypes were identified. The majority of patients, 64%, had Muscle and Fat Wasting (MFW), while 17% had Fat-Only Wasting (FW) and 19% had No Wasting (NW). NW had significantly improved overall median survival (OMS) of 22.6 months vs. 13.0 months for FW and 12.2 months for MFW (P = 0.02). FW (HR = 5.2; 95% confidence interval = 1.5-17.3) and MFW (HR = 1.8; 95% confidence interval = 1.1-2.9) were associated with an increased risk of mortality compared with NW. OMS and risk of mortality did not differ between FW and MFW. Progression of disease, sarcopenic obesity at diagnosis, and primary tail tumours were also associated with decreased OMS. On multivariate analysis, cachexia phenotype and chemotherapy response were independently associated with survival. Notably, CT-based body composition analysis detected tissue loss of >5% in 81% of patients, while the traditional definition of >5% body weight loss identified 56.6%. CONCLUSIONS: Distinct cachexia phenotypes were observed in this homogeneous population of patients with equivalent stage, diagnosis, and first-line treatment. This suggests cellular, molecular, or genetic heterogeneity of host or tumour. Survival among patients with FW was as poor as for MFW, indicating adipose tissue plays a crucial role in cachexia and PDAC mortality. Adipose tissue should be studied for its mechanistic contributions to cachexia.

Biliary Bypass with Laparoscopic Choledochoduodenostomy.

Laparoscopic choledochoduodenostomy (LCDD) is employed to treat many benign biliary diseases when endoscopic or percutaneous techniques are not feasible. We describe our technique for LCDD, which utilizes common bile duct transection and an end-to-side biliary-enteric anastomosis. This procedure includes the following elements: isolation and transection of the common bile duct, mobilization of the duodenum (Kocher maneuver), inspection of the common bile duct, and end-to-side biliary-enteric anastomosis. Key details and pitfalls are discussed. Over a 5-year period, LCDD was performed on 18 patients. Indications included intractable abdominal pain (10) and choledocholithiasis (8). The majority of patients, 83%, tolerated the operation well with no complications. There was one postoperative intra-abdominal abscess and two anastomotic strictures, one in the immediate postoperative period and the other 9 months after the operation. The median length of stay was 4 days (IQR 3.0-5.3), and there was minimal blood loss. Based on our experience, LCDD with transection and end-to-side biliary-enteric anastomosis is a safe and effective biliary bypass technique.

Integrating therapies for surgical adult soft tissue sarcoma patients.

Sarcomas are an uncommon group of over 50 different individual histological malignancies arising from mesenchymal (non-epithelial or connective) tissues. Overall, they constitute 1% of human malignancies with an annual incidence rate of fewer than 5 patients per million. Sarcoma may arise from any mesenchymal cell lineages including fat, muscle, or other connective tissues. Due to the rarity of these groups of malignancies, many subtypes were, and still today, are managed as a single entity. This review focused on soft tissue sarcomas with an emphasis on how to integrate therapies for patients with this rare disorder. The role for surgical resection in cure and palliation as well as the relative benefits of adjuvant therapies such as chemotherapy and radiation therapy are discussed.

Approach to wild-type gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GISTs) arise from the intestinal pacemaker cells of Cajal. Wild-type gastrointestinal stromal tumors (WT-GIST) are a unique and uncommon subtype of GISTs that lack activating mutations in the tyrosine kinase c-KIT or platelet derived growth factor receptor alpha (PDGFRA) receptors. The lack of these growth-stimulating mutations renders tyrosine kinase receptor inhibitors, such as imatinib mesylate, relatively ineffective against these tumors. WT-GIST arises most commonly due to underlying alternate proliferative signals associated with germ-line, genetic mutations. WT-GIST frequently arises in patients with BRAF mutations, Carney's Triad or neurofibromatosis type-1 (NF-1). All patients with WT-GIST require a careful examination for germ-line mutations and very close observation for recurrent tumors. Surgery remains a mainstay therapy for these patients. This review aims to discuss the most recent data available on the diagnosis and treatment of WT-GIST.

Solitary fibrous tumor.

Solitary fibrous tumor (SFT) is a rare tumor of mesenchymal origin that account for less than 2% of all soft tissue masses. Initially identified in the pleura, SFT has been identified in multiple anatomic locations and can arise anywhere in the body. The varying histologic features along with non-specific means of identification have led SFT to be associated with several different names. Over the last several decades, sustained advances through research and technology have led to more reliable methods for differentiating this distinct soft tissue tumor. Advances specifically in immunohistochemistry and molecular diagnostics have identified CD34 as the most consistent marker in SFT, however even this lacks specificity to conclusively narrow down the broad differential for exact identification. More recently the discovery of the NAB2-STAT6 fusion gene has led to more precise diagnosis of SFT. Like many other soft tissue tumors, surgical management is the mainstay of treatment for SFT with emphasis on obtaining tumor-negative margins. Radiation therapy and chemotherapy regimens have not demonstrated global effectiveness, and thus no standardized treatments have been identified. Given the rarity of SFT and current supportive evidence for therapies, management should be focused on tumor extirpation. Nonetheless, individualized therapy, determined within a multidisciplinary setting should be considered.

Sarcopenia is a Significant Predictor of Mortality After Abdominal Aortic Aneurysm Repair.

AIMS: Repair of abdominal aortic aneurysms (AAA) decreases the incidence of rupture and death. In cancer patients, sarcopenia has been associated with increased surgical complications and mortality. The impact of sarcopenia on survival after AAA repair has yet to be described. METHODS AND RESULTS: Patient demographic, laboratory, body composition measurements and survival data were obtained from patients undergoing AAA repair at the Indiana University medical campus over a 5-year period. Univariate and multivariate analyses were performed to identify factors associated with overall survival. Overall, 58.2% presented with sarcopenia. Sarcopenic patients were older (71.8±8.3 versus 66.8±8.1 years; p<0.001), had lower body mass index (BMI) (26.3±5.2 versus 31.5±5.9 kg/m2; p<0.001), higher rates of myosteatosis (84.4% versus 52.%; p<0.001), greater AAA diameter (60.6±14.0 versus 57.8±11.7 mm; p=0.016), higher Charlson Comorbidity Index (CCI) (32.3% versus 25.1% ≥6; p=0.034), and increased rates of rupture (8.2% versus 3.8%; p=0.047). Sarcopenic and nonsarcopenic patients had no difference in 30-day morbidity (8.5% versus 8.5%; p=0.991) or mortality (3.7% versus 0.9%; p=0.07). Univariate analysis demonstrated age, sarcopenia, myosteatosis, CCI, and BMI to be associated with long-term survival. There was no correlation between BMI and sarcopenia. Both sarcopenia and myosteatosis resulted in decreased one-, three-, and five-year survivals compared to their counterparts. On multivariate analysis sarcopenia is independently associated with survival, conferring a 1.6-fold increase in death (p=0.04). The combination of sarcopenia plus myosteatosis doubled the risk of death compared to sarcopenia alone. CONCLUSIONS: This is the first study to demonstrate that over half of all patients undergoing AAA repair are sarcopenic, a condition associated with increased mortality. Sarcopenia with myosteatosis is associated with double the mortality of sarcopenia alone. CT scan, but not BMI, accurately identifies sarcopenia and myosteatosis. Defining the mechanisms through which sarcopenia contributes to late death after AAA repair is critical to developing novel interventions that may improve survival in this high risk population.

The model for end-stage liver disease predicts outcomes in patients undergoing cholecystectomy.

BACKGROUND: The magnitude of risk for patients undergoing cholecystectomy with high model for end-stage liver disease (MELD) scores is poorly understood. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database from 2005 to 2013 was used to study patients undergoing cholecystectomy. Patients were excluded if they had choledocholithiasis or preoperative dialysis. Bivariate data analysis was performed and logistic regression modeling was conducted to calculate risk-adjusted 30-day outcomes. RESULTS: A total of 63,464 patients were included in the study. Unadjusted mortality significantly increased as the MELD score increased in the laparoscopic (MELD = 6-10, 0.2%; 11-15, 1.1%; 16-20, 3.2%; >20, 5.8%) and open groups (MELD = 6-10, 1.5%; 11-15, 3.7%; 16-20, 8.6%; >20, 17.9%) (p-value <0.001 for both). Unadjusted morbidity also increased with MELD score increases in the laparoscopic (MELD = 6-10, 3.8%; 11-15, 9.9%; 16-20, 16.3%; >20, 22.8%) and open groups (MELD = 6-10, 18.7%; 11-15, 28.2%; 16-20, 40.7%; >20, 57.8%) (p-value <0.001 for both). Patients with ascites and high MELD scores had higher rates of mortality (laparoscopic, MELD > 20, 33.3%; open, MELD > 20, 48.5%) and morbidity (laparoscopic, MELD > 20, 66.7%; open, MELD > 20, 75.8%) across all MELD scores. After adjustment, MELD score acted as a progressive and independent predictor of morbidity and mortality. CONCLUSIONS: The MELD score is an objective and easy to calculate scoring system that independently predicts postoperative morbidity and mortality in patients undergoing cholecystectomy. Patients with ascites have substantially worse outcomes across all MELD scores. Open cholecystectomy is associated with significantly more morbidity and mortality than laparoscopic cholecystectomy across all MELD groups.

The impact of members of the Society of University Surgeons on the scholarship of American surgery.

BACKGROUND: A core objective of the Society of University Surgeons (SUS) is research focused: to "advance the art and science of surgery through original investigation." This study sought to determine the current impact of the SUS on academic surgical productivity. METHODS: Individual faculty data for numbers of publications, citations, and National Institute of Health (NIH) funding history were collected for 4,015 surgical faculty at the top 55 NIH-funded departments of surgery using SCOPUS and the NIH Research Portfolio Online Reporting Tools. SUS membership was determined from membership registry data. RESULTS: Overall, 502 surgical faculty (12.5%) were SUS members with 92.7% holding positions of associate or full professor (versus 59% of nonmembers). Median publications (P) and citations (C) among SUS members were P: 112, C: 2,460 versus P: 29, C: 467 for nonmembers (P < .001). Academic productivity was considerably higher by rank for SUS members than for nonmembers: associate professors (P: 61 vs 36, C: 1,199 vs 591, P < .001) and full professors (P: 141 vs 81, C: 3,537 vs 1,856, P < .001). Among full professors, SUS members had much higher rates of NIH funding than did nonmembers (52.6% vs 26%, P < .05) and specifically for R01, P01, and U01 awards (37% vs 17.7%, P < .01). SUS members were 2 times more likely to serve in divisional leadership or chair positions (23.5% vs 10.2%, P < .05). CONCLUSION: SUS society members are a highly productive academic group. These data support the premise that the SUS is meeting its research mission and identify its members as very academically productive contributors to research and scholarship in American surgery and medicine.

Differential Bone Loss in Mouse Models of Colon Cancer Cachexia.

Cachexia is a distinctive feature of colorectal cancer associated with body weight loss and progressive muscle wasting. Several mechanisms responsible for muscle and fat wasting have been identified, however it is not known whether the physiologic and molecular crosstalk between muscle and bone tissue may also contribute to the cachectic phenotype in cancer patients. The purpose of this study was to clarify whether tumor growth associates with bone loss using several experimental models of colorectal cancer cachexia, namely C26, HT-29, and ApcMin/+. The effects of cachexia on bone structure and strength were evaluated with dual energy X-ray absorptiometry (DXA), micro computed tomography (µCT), and three-point bending test. We found that all models showed tumor growth consistent with severe cachexia. While muscle wasting in C26 hosts was accompanied by moderate bone depletion, no loss of bone strength was observed. However, HT-29 tumor bearing mice showed bone abnormalities including significant reductions in whole-body bone mineral density (BMD), bone mineral content (BMC), femoral trabecular bone volume fraction (BV/TV), trabecular number (Tb.N), and trabecular thickness (Tb.Th), but no declines in strength. Similarly, cachexia in the ApcMin/+ mice was associated with significant decreases in BMD, BMC, BV/TV, Tb.N, and Tb.Th as well as decreased strength. Our data suggest that colorectal cancer is associated with muscle wasting and may be accompanied by bone loss dependent upon tumor type, burden, stage and duration of the disease. It is clear that preserving muscle mass promotes survival in cancer cachexia. Future studies will determine whether strategies aimed at preventing bone loss can also improve outcomes and survival in colorectal cancer cachexia.