Disease-free Survival and Local Recurrence for Laparoscopic Resection Compared With Open Resection of Stage II to III Rectal Cancer: Follow-up Results of the ACOSOG Z6051 Randomized Controlled Trial.

OBJECTIVE: To determine the disease-free survival (DFS) and recurrence after the treatment of patients with rectal cancer with open (OPEN) or laparoscopic (LAP) resection. BACKGROUND: This randomized clinical trial (ACOSOG [Alliance] Z6051), performed between 2008 and 2013, compared LAP and OPEN resection of stage II/III rectal cancer, within 12 cm of the anal verge (T1-3, N0-2, M0) in patients who received neoadjuvant chemoradiotherapy. The rectum and mesorectum were resected using open instruments for rectal dissection (included hybrid hand-assisted laparoscopic) or with laparoscopic instruments under pneumoperitoneum. The 2-year DFS and recurrence were secondary endpoints of Z6051. METHODS: The DFS and recurrence were not powered, and are being assessed for superiority. Recurrence was determined at 3, 6, 9, 12, and every 6 months thereafter, using carcinoembryonic antigen, physical examination, computed tomography, and colonoscopy. In all, 486 patients were randomized to LAP (243) or OPEN (243), with 462 eligible for analysis (LAP = 240 and OPEN = 222). Median follow-up is 47.9 months. RESULTS: The 2-year DFS was LAP 79.5% (95% confidence interval [CI] 74.4-84.9) and OPEN 83.2% (95% CI 78.3-88.3). Local and regional recurrence was 4.6% LAP and 4.5% OPEN. Distant recurrence was 14.6% LAP and 16.7% OPEN.Disease-free survival was impacted by unsuccessful resection (hazard ratio [HR] 1.87, 95% CI 1.21-2.91): composite of incomplete specimen (HR 1.65, 95% CI 0.85-3.18); positive circumferential resection margins (HR 2.31, 95% CI 1.40-3.79); positive distal margin (HR 2.53, 95% CI 1.30-3.77). CONCLUSION: Laparoscopic assisted resection of rectal cancer was not found to be significantly different to OPEN resection of rectal cancer based on the outcomes of DFS and recurrence.

An Optimal Orthotopic Mouse Model for Human Colorectal Cancer Primary Tumor Growth and Spontaneous Metastasis.

BACKGROUND: Colorectal cancer is a leading cause of cancer-related death. Small animal models allow for the study of different metastatic patterns, but an optimal model for metastatic colorectal cancer has not been established. OBJECTIVE: The purpose of this study was to determine which orthotopic model most accurately emulates the patterns of primary tumor growth and spontaneous liver and lung metastases seen in patients with colorectal cancer. DESIGN: Using luciferase-tagged HT-29 cells coinoculated with lymph node stromal analog HK cells, 3 tumor cell delivery models were compared: intrarectal injection, intracecal injection, and acid enema followed by cancer cell instillation. Tumor growth was monitored weekly by bioluminescent imaging, and mice were sacrificed based on primary tumor size or signs of systemic decline. Liver and lungs were evaluated for metastases via bioluminescent imaging and histology. SETTINGS: The study was conducted at a single university center. MAIN OUTCOME MEASURES: Primary tumor and metastasis bioluminescent imaging were measured. RESULTS: Intrarectal injection had the lowest mortality at 4.0% (1/25) compared with the intracecal group at 17.4% (4/23) and the acid enema followed by cancer cell instillation group at 15.0% (3/20).The primary tumors in intrarectal mice had the highest average bioluminescence (3.78 × 10 ± 4.94 × 10 photons) compared with the mice in the intracecal (9.52 × 10 ± 1.92 × 10 photons; p = 0.012) and acid enema followed by cancer cell instillation groups (6.23 × 10 ± 1.23 × 10 photons; p = 0.0016). A total of 100% of intrarectal and intracecal mice but only 35% of mice in the acid enema followed by cancer cell instillation group had positive bioluminescent imaging before necropsy. Sixty percent of intrarectal mice had liver metastases, and 56% had lung metastases. In the intracecal group, 39% of mice had liver metastases, and 35% had lung metastases. Only 2 acid enema followed by cancer cell instillation mice developed metastases. LIMITATIONS: Tumor injections were performed by multiple investigators. Distant metastases were confirmed, but local lymph node status was not evaluated. CONCLUSIONS: Intrarectal injection is the safest, most reproducible, and successful orthotopic mouse model for human colorectal cancer primary tumor growth and spontaneous metastasis.

Morbidity Following Coloanal Anastomosis: A Comparison of Colonic J-Pouch vs Straight Anastomosis.

BACKGROUND: Low rectal tumors are often treated with sphincter-preserving resection followed by coloanal anastomosis. OBJECTIVE: The purpose of this study was to compare the short-term complications following straight coloanal anastomosis vs colonic J-pouch anal anastomosis. DESIGN: Patients were identified who underwent proctectomy for rectal neoplasia followed by coloanal anastomosis in the 2008 to 2013 American College of Surgeons National Surgical Quality Improvement Program database. Demographic characteristics and 30-day postoperative complications were compared between groups. SETTINGS: A national sample was extracted from the American College of Surgeons National Surgical Quality Improvement Project database. PATIENTS: Inpatients following proctectomy and coloanal anastomosis for rectal cancer were selected. MAIN OUTCOME MEASURES: Demographic characteristics and 30-day postoperative complications were compared between the 2 groups. RESULTS: One thousand three hundred seventy patients were included, 624 in the straight anastomosis group and 746 in the colonic J-pouch group. Preoperative characteristics were similar between groups, with the exception of preoperative radiation therapy (straight anastomosis 35% vs colonic J-pouch 48%, p = 0.0004). Univariate analysis demonstrated that deep surgical site infection (3.7% vs 1.4%, p = 0.01), septic shock (2.25% vs 0.8%, p = 0.04), and return to the operating room (8.8% vs 5.0%, p = 0.0006) were more frequent in the straight anastomosis group vs the colonic J-pouch group. Major complications were also higher (23% vs 14%, p = 0.0001) and length of stay was longer in the straight anastomosis group vs the colonic J-pouch group (8.9 days vs 8.1 days, p = 0.02). After adjusting for covariates, major complications were less following colonic J-pouch vs straight anastomosis (OR, 0.57; CI, 0.38-0.84; p = 0.005). Subgroup analysis of patients who received preoperative radiation therapy demonstrated no difference in major complications between groups. LIMITATIONS: This study had those limitations inherent to a retrospective study using an inpatient database. CONCLUSION: Postoperative complications were less following colonic J-pouch anastomosis vs straight anastomosis. Patients who received preoperative radiation had similar rates of complications, regardless of the reconstructive technique used following low anterior resection. See Video Abstract at http://links.lww.com/DCR/A468.

Clopidogrel bisulfate (Plavix) does not increase bleeding complications in patients undergoing rubber band ligation for symptomatic hemorrhoids.

BACKGROUND: The incidence of postprocedural bleeding in patients undergoing rubber band ligation (RBL) for symptomatic internal hemorrhoids while taking clopidogrel bisulfate is unknown. To determine the postprocedural bleeding risk of RBL for patients taking clopidogrel compared with age- and sex-matched controls. MATERIALS AND METHODS: This is a retrospective case-controlled cohort study analyzing data from 2005 to 2013 conducted at a single tertiary care academic center. The study included a total of 80 rubber bands placed on 41 patients taking clopidogrel bisulfate and 72 bands placed on 41 control patients not taking clopidogrel matched for age and sex. The 30-d rates of significant and insignificant bleeding events after RBL were recorded. A bleeding event was considered significant if the patient required admission to the hospital, transfusion of blood products, or additional procedures to stop the bleeding. Insignificant bleeding was defined as passage of blood or clots per rectum with spontaneous cessation and no need for additional intervention. RESULTS: There was no significant difference in the number of bleeding events per band placed in the clopidogrel group when compared with the control group (3.75% versus 2.78%, P = 0.7387). The rate of significant (2.5% versus 1.39%, P = 0.6244) and insignificant bleeding events (1.25% versus 1.39%, P = 0.9399) was also similar between the two groups. Two significant bleeding events occurred in the clopidogrel group requiring intervention: cauterization in one patient and colonoscopy and transfusion in the other. CONCLUSIONS: The risk of a bleeding complication after RBL for hemorrhoids does not appear to be increased in patients taking clopidogrel. Our results support the practice of continuing clopidogrel bisulfate in the periprocedural period as the associated risk of thrombosis is greater than the risk of bleeding.

A Novel Wound Retractor Combining Continuous Irrigation and Barrier Protection Reduces Incisional Contamination in Colorectal Surgery.

BACKGROUND: Surgical site infection (SSI) remains a persistent and morbid problem in colorectal surgery. Key to its pathogenesis is the degree of intraoperative bacterial contamination at the surgical site. The purpose of this study was to evaluate a novel wound retractor at reducing bacterial contamination. METHODS: A prospective multicenter pilot study utilizing a novel wound retractor combining continuous irrigation and barrier protection was conducted in patients undergoing elective colorectal resections. Culture swabs were collected from the incision edge prior to device placement and from the exposed and protected incision edge prior to device removal. The primary and secondary endpoints were the rate of enteric and overall bacterial contamination on the exposed incision edge as compared to the protected incision edge, respectively. The safety endpoint was the absence of serious device-related adverse events. RESULTS: A total of 86 patients were eligible for analysis. The novel wound retractor was associated with a 66% reduction in overall bacterial contamination at the protected incision edge compared to the exposed incision edge (11.9 vs. 34.5%, P < 0.001), and 71% reduction in enteric bacterial contamination (9.5% vs. 33.3%, P < 0.001). The incisional SSI rate was 2.3% in the primary analysis and 1.2% in those that completed the protocol. There were no adverse events attributed to device use. CONCLUSIONS: A novel wound retractor combining continuous irrigation and barrier protection was associated with a significant reduction in bacterial contamination. Improved methods to counteract wound contamination represent a promising strategy for SSI prevention (NCT 02413879).

The critical roles of tumor-initiating cells and the lymph node stromal microenvironment in human colorectal cancer extranodal metastasis using a unique humanized orthotopic mouse model.

Colorectal cancer (CRC) is the second-most common cause of cancer-related mortality. The most important prognostic factors are lymph node (LN) involvement and extranodal metastasis. Our objective is to investigate the interactions between CD133(+)CXCR4(+) (CXC receptor 4) colorectal cancer tumor-initiating cells (Co-TICs) and the LN stromal microenvironment in human CRC extranodal metastasis. We established a unique humanized orthotopic xenograft model. Luciferase-tagged CRC cell lines and human cancer cells were injected intrarectally into nonobese diabetic/SCID mice. Mesenteric LN stromal cells, stromal cell line HK, or CXCL12 knockdown HK (HK-KD-A3) cells were coinoculated with CRC cells. Tumor growth and metastasis were monitored by bioluminescent imaging and immunohistochemistry. We found that this model mimics the human CRC metastatic pattern with CRC cell lines or patient specimens. Adding LN stromal cells promotes CRC tumor growth and extranodal metastasis (P < 0.001). Knocking down CXCL12 impaired HK cell support of CRC tumor formation and extranodal metastasis. When HK cells were added, sorted CD133(+)CXCR4(+) Co-TICs showed increased tumor formation and extranodal metastasis capacities compared to unseparated and non-Co-TIC populations. In conclusion, both Co-TIC and LN stromal factors play crucial roles in CRC metastasis through the CXCL12/CXCR4 axis. Blocking Co-TIC/LN-stromal interactions may lead to effective therapy to prevent extranodal metastasis.

Current State of Colorectal Surgery Training: A Survey of Program Directors, Current and Recently Matched Colorectal Residents, and Recent Colorectal Graduates.

BACKGROUND: Colorectal residency has become one of the more competitive postgraduate training opportunities; however, little information is available to guide potential applicants in gauging their competitiveness. OBJECTIVE: The aim of this study was to identify the current trends colorectal residency training and to identify what factors are considered most important in ranking a candidate highly. We hypothesized that there was a difference in what program directors, current and recently matched colorectal residents, and recent graduates consider most important in making a candidate competitive for a colorectal residency position. DESIGN: Three 10-question anonymous surveys were sent to 59 program directors, 87 current and recently matched colorectal residents, and 119 recent graduates in March 2015. SETTINGS: The study was conducted as an anonymous internet survey. MAIN OUTCOME MEASURES: Current trends in applying for a colorectal residency, competitiveness of recent colorectal residents, factors considered most important in ranking a candidate highly, and what future colorectal surgeons can expect after finishing their training were measured. RESULTS: The study had an overall response rate of 43%, with 28 (47%) of 59 program directors, 46 (53%) of 87 current and recently matched colorectal residents, and 39 (33%) of 119 recent graduates responding. The majority of program directors felt that a candidate's performance during the interview process was the most important factor in making a candidate competitive, followed by contact from a colleague, letters of recommendation, American Board of Surgery In-Training Exam scores, and number of publications/presentations. The majority of current and recently matched colorectal residents felt that a recommendation/telephone call from a colleague was the most important factor, whereas the majority of recent graduates favored letters of recommendation as the most important factor in ranking a candidate highly. LIMITATIONS: Limitations to the study include its small sample size, selection bias, responder bias, and misclassification bias. CONCLUSIONS: There are differences in what program directors and current/recent residents consider most important in making an applicant competitive for colorectal residency.

Management of Colorectal Anastomotic Leak.

The aim of this article is to present strategies for preventing and managing the failure of the surgical restoration of intestinal continuity. Despite improvements in surgical technique and perioperative care, anastomotic leaks still occur, and with them occur increased morbidity, mortality, length of stay, and costs. Due to the devastating consequences for patients with failed anastomoses, there have been a myriad of materials and techniques used by surgeons to create better intestinal anastomoses. We will also discuss the management strategies for anastomotic leak when they do inevitably occur.

Current status: new technologies for the treatment of patients with fecal incontinence.

Fecal incontinence is a frequent and debilitating condition that may result from a multitude of different causes. Treatment is often challenging and needs to be individualized. During the last several years, new technologies have been developed, and others are emerging from clinical trials to commercialization. Although their specific roles in the management of fecal incontinence have not yet been completely defined, surgeons have access to them and patients may request them. The purpose of this project is to put into perspective, for both the patient and the practitioner, the relative positions of new and emerging technologies in order to propose a treatment algorithm.

CD 133+ and CXCR4+ colon cancer cells as a marker for lymph node metastasis.

INTRODUCTION: Colorectal cancer (CRC) stem cells or tumor-initiating cells (Co-TIC) are implicated in both cancer recurrence and extranodal metastasis. CD133 and CXCR4 are specific cell surface markers that are indicators of Co-TIC. The presence of lymph node (LN) metastases is one of the strongest negative prognostic factors for CRC patients. We examined the relationship between the Co-TIC markers CD133 and CXCR4 and LN involvement in CRC. METHODS: CRC cells were isolated via enzymatic digestion. CD133(+), CXCR4(+), and double-positive CRC cells were detected by fluorescence-activated cell sorting analysis. The percentages of CD133(+), CXCR4(+), and double-positive cells were identified and correlated to the number and percentage of positive LN on staging. RESULTS: Twenty-seven samples underwent fluorescence-activated cell sorting analysis. The mean percentage of CD133(+) cells was 3.94% (range 0.15%-19.06%). The mean percentage of CXCR4(+) cells was 6.15% (range 0%-27.11%). The mean percentage of CD133(+)CXCR4(+) cells was 0.45% (range 0%-2.08%). Thirteen patients had LN metastasis: 8 N1 disease and 5 N2 disease. The correlation coefficients between the percentage of Co-TIC marker-positive cells and percentage of positive LN were r = 0.58 (P = 0.0016) for CD133(+) cells, r = 0.36 (P = 0.5868) for CXCR4(+) cells, and r = 0.56 (P = 0.0022) for double-positive cells. DISCUSSION: Our results show CD133(+) and CD133(+)CXCR4(+) cancer cells correlate with the presence of LN metastasis in CRC. Further studies will examine whether these markers can give consistent prognostic information and may help to develop novel diagnostic and therapeutic options.

Social media and the surgeon.

As the Internet has matured, social media has developed and become a part of our everyday life. Whether it is Facebook, YouTube, or LinkedIn, we now communicate with each other and the world in a very different manner. As physicians, and specifically colon and rectal surgeons, it is important that we understand this new technology, learn its limitations, and utilize it to foster growth of our practice, trade, and potentially result in better patient care.

The impact of health care economics on surgical education.

Just like the world economy in 2012, health care is in a state of flux. The current economic environment will impact not only current colorectal surgery residents, but also future generations of surgical trainees. To understand the economic impact of the current health care environment on colorectal surgery residencies, we need to know the basics of graduate medical education (GME) funding for all residents. Since the 1960s with the initiation of Medicare, the federal government through the Center for Medicare and Medicaid Services (CMS) has been the largest source of GME funding. There are two types of costs associated with GME. Direct GME (DME) funding covers costs directly attributed to the training of residents. These costs include residents' stipends, salaries, and benefits; cost of supervising faculty; direct program administration costs; overhead; and malpractice coverage. Indirect GME (IME) costs are payments to hospitals as an additional or add-on payment for the increased cost of care that is generally found in teaching hospitals. In 2010, President Barak Obama signed into law H.R. 3200, the Patient Protection and Affordable Care Act (PPACA). In 2011, the Supreme Court held that the majority of the PPACA is constitutional. Although the true impact of this bill is unknown, it will change the formula for Medicare GME reimbursement as well as shift unused residency positions to primary care.

Anastomotic Leak is Increased With Clostridium difficile Infection After Colectomy: Machine Learning-Augmented Propensity Score Modified Analysis of 46 735 Patients.

BACKGROUND: Clostridium difficile infection (CDI) is now the most common cause of healthcare-associated infections, with increasing prevalence, severity, and mortality of nosocomial and community-acquired CDI which makes up approximately one third of all CDI. There are also increased rates of asymptomatic colonization particularly in high-risk patients. C difficile is a known collagenase-producing bacteria which may contribute to anastomotic leak (AL). METHODS: Machine learning-augmented multivariable regression and propensity score (PS)-modified analysis was performed in this nationally representative case-control study of CDI and anastomotic leak, mortality, and length of stay for colectomy patients using the ACS-NSQIP database. RESULTS: Among 46 735 colectomy patients meeting study criteria, mean age was 61.7 years (SD 14.38), 52.2% were woman, 72.5% were Caucasian, 1.5% developed CDI, 3.1% developed anastomotic leak, and 1.6% died. In machine learning (backward propagation neural network)-augmented multivariable regression, CDI significantly increases anastomotic leak (OR 2.39, 95% CI 1.70-3.36; P < .001), which is similar to the neural network results. Having CDI increased the independent likelihood of anastomotic leak by 3.8% to 6.8% overall, and in dose-dependent fashion with increasing ASA class to 4.3%, 5.7%, 7.6%, and 10.0%, respectively, for ASA class I to IV. In doubly robust augmented inverse probability weighted PS analysis, CDI significantly increases the likelihood of AL by 4.58% (95% CI 2.10-7.06; P < .001). CONCLUSIONS: This is the first known nationally representative study on CDI and AL, mortality, and length of stay among colectomy patients. Using advanced machine learning and PS analysis, we provide evidence that suggests CDI increases AL in a dose-dependent manner with increasing ASA Class.

Variations in perioperative steroid management among surgical subspecialists.

Previously we demonstrated consistency in perioperative steroid dosing among colon and rectal surgeons. To determine whether patterns have changed and if dosing schedules differ across surgical specialties, we evaluated multiple specialties. Questionnaires were mailed to members of the American Society of Colon and Rectal Surgeons (CRS) (n = 1523), American Society of Transplant Surgeons (TS) (n = 988), American Society of General Surgeons (GS) (n = 2750), and American Association of Endocrine Surgeons (ES) (n = 278). Surveys addressed demographic factors and factors in dosing, whether steroids are managed by surgeon alone or in collaboration with colleagues, and the most common taper regimens used. Four hundred fifty surveys were returned. Sixty-four respondents had retired or answered less than 50 per cent; 386 (211CRS, 116GS, 45TS, and 14ES) were available for analysis. The majority managed both perioperative (85.5%) and tapers (77%) themselves; TS and ES were significantly less likely to use other physicians (P < 0.001). The preoperative dose used most frequently was 100 mg hydrocortisone intravenously (76% CRS, 64% GS, 22% TS, and 93% ES). Most CRS (44.5%) and GS (24.1%) taper intravenous steroids over 3 days, whereas TS (33.3%) and ES (50%) return patients to prednisone within 1 to 2 days. Discharge steroid use was inconsistent with CRS (46.4%) tapering prednisone over greater than 21 days, GS (19%) over less than 21 days, and TS (20%) and ES (21.4%) taper over 21 days to preoperative prednisone doses (P < 0.001). In the absence of standard guidelines for perioperative corticosteroid administration, significant variations exist in the regimens used by surgeons in multiple specialties.

Modified Frailty Index Predicts Postoperative Outcomes in Patients Undergoing Radical Pelvic Surgery.

Patients undergoing radical pelvic surgery such as proctectomy or radical cystectomy are at risk of experiencing a variety of complications. Frailty renders patients vulnerable to adverse events. We hypothesize that frailty measured preoperatively using a validated scoring system correlates with increased likelihood of experiencing Clavien-Dindo grade IV complications and 30-day mortality and may be used as a predictive model for patients preoperatively. The NSQIP database was queried for patients who underwent proctectomy or radical cystectomy from 2008 to 2012. Preoperative frailty was calculated using the 11-point modified frailty index (MFI). Patients were scored based on the presence of indicators and categorized into two groups (<3 or ≥3). Major postoperative morbidities and mortality were identified and analyzed in each group. 10,048 proctectomy and cystectomy patients were identified. The MFI was found to be predictive of both 30-day mortality (P < 0.0001) and Clavien-Dindo grade IV complications (P < 0.0001). Receiver operating characteristic analysis demonstrated improved discriminative power of the MFI with the addition of American Society of Anesthesiologists class for both prediction of complications and 30-day mortality. An MFI score of ≥3 is predictive of postoperative morbidity and mortality. Providers should be encouraged to calculate frailty preoperatively to predict adverse outcomes.

Impact of a Novel Surgical Wound Protection Device on Observed versus Expected Surgical Site Infection Rates after Colectomy Using the National Surgical Quality Improvement Program Risk Calculator.

BACKGROUND: Surgical site infection (SSI) remains a persistent and morbid problem in colorectal surgery. A novel surgical device that combines barrier surgical wound protection and continuous surgical wound irrigation was evaluated in a cohort of elective colorectal surgery patients. A retrospective analysis was performed comparing rates of SSI observed in a prospective cohort study with the predicted rate of SSI using the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) Risk Calculator. PATIENTS AND METHODS: A prospective multi-center study of colectomy patients was conducted using a study device for surgical site retraction and protection, as well as irrigation of the incision. Patients were followed for 30 days after the surgical procedure to assess for SSI. After completion of the study, patients' characteristics were inserted into the ACS-NSQIP Risk Calculator to determine the predicted rate of SSI for the given patient population and compared with the observed rate in the study. RESULTS: A total of 108 subjects were enrolled in the study. The observed rate of SSI in the prospective study using the novel device was 3.7% (4/108). The predicted rate of SSI in the same patient population utilizing the ACS-NSQIP Risk Calculator was estimated to be 9.5%. This demonstrated a 61% difference (3.7% vs. 9.5%, p = 0.04) in SSI from the NSQIP predicted rate with the use of the irrigating surgical wound protection and retraction device. CONCLUSIONS: These data suggest the use of a novel surgical wound protection device seems to reduce the rate of SSIs in colorectal surgery.

Patient-derived Orthotopic Xenograft Models for Human Urothelial Cell Carcinoma and Colorectal Cancer Tumor Growth and Spontaneous Metastasis.

Cancer patients have poor prognoses when lymph node (LN) involvement is present in both high-grade urothelial cell carcinoma (HG-UCC) of the bladder and colorectal cancer (CRC). More than 50% of patients with muscle-invasive UCC, despite curative therapy for clinically-localized disease, will develop metastases and die within 5 years, and metastatic CRC is a leading cause of cancer-related deaths in the US. Xenograft models that consistently mimic UCC and CRC metastasis seen in patients are needed. This study aims to generate patient-derived orthotopic xenograft (PDOX) models of UCC and CRC for primary tumor growth and spontaneous metastases under the influence of LN stromal cells mimicking the progression of human metastatic diseases for drug screening. Fresh UCC and CRC tumors were obtained from consented patients undergoing resection for HG-UCC and colorectal adenocarcinoma, respectively. Co-inoculated with LN stromal cell (LNSC) analog HK cells, luciferase-tagged UCC cells were intra-vesically (IB) instilled into female non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice, and CRC cells were intra-rectally (IR) injected into male NOD/SCID mice. Tumor growth and metastasis were monitored weekly using bioluminescence imaging (BLI). Upon sacrifice, primary tumors and mouse organs were harvested, weighed, and formalin-fixed for Hematoxylin and Eosin and immunohistochemistry staining. In our unique PDOX models, xenograft tumors resemble patient pre-implantation tumors. In the presence of HK cells, both models have high tumor implantation rates measured by BLI and tumor weights, 83.3% for UCC and 96.9% for CRC, and high distant organ metastasis rates (33.3% detected liver or lung metastasis for UCC and 53.1% for CRC). In addition, both models have zero mortality from the procedure. We have established unique, reproducible PDOX models for human HG-UCC and CRC, which allow for tumor formation, growth, and metastasis studies. With these models, testing of novel therapeutic drugs can be performed efficiently and in a clinically-mimetic manner.