Intracorporeal and extracorporeal anastomosis for robotic-assisted and laparoscopic right colectomy: short-term outcomes of a multi-center prospective trial.

BACKGROUND: Studies to date show contrasting conclusions when comparing intracorporeal and extracorporeal anastomoses for minimally invasive right colectomy. Large multi-center prospective studies comparing perioperative outcomes between these two techniques are needed. The purpose of this study was to compare intracorporeal and extracorporeal anastomoses outcomes for robotic assisted and laparoscopic right colectomy. METHODS: Multi-center, prospective, observational study of patients with malignant or benign disease scheduled for laparoscopic or robotic-assisted right colectomy. Outcomes included conversion rate, gastrointestinal recovery, and complication rates. RESULTS: There were 280 patients: 156 in the robotic assisted and laparoscopic intracorporeal anastomosis (IA) group and 124 in the robotic assisted and laparoscopic extracorporeal anastomosis (EA) group. The EA group was older (mean age 67 vs. 65 years, p = 0.05) and had fewer white (81% vs. 90%, p = 0.05) and Hispanic (2% vs. 12%, p = 0.003) patients. The EA group had more patients with comorbidities (82% vs. 72%, p = 0.04) while there was no significant difference in individual comorbidities between groups. IA was associated with fewer conversions to open and hand-assisted laparoscopic approaches (p = 0.007), shorter extraction site incision length (4.9 vs. 6.2 cm; p ≤ 0.0001), and longer operative time (156.9 vs. 118.2 min). Postoperatively, patients with IA had shorter time to first flatus, (1.5 vs. 1.8 days; p ≤ 0.0001), time to first bowel movement (1.6 vs. 2.0 days; p = 0.0005), time to resume soft/regular diet (29.0 vs. 37.5 h; p = 0.0014), and shorter length of hospital stay (median, 3 vs. 4 days; p ≤ 0.0001). Postoperative complication rates were comparable between groups. CONCLUSION: In this prospective, multi-center study of minimally invasive right colectomy across 20 institutions, IA was associated with significant improvements in conversion rates, return of bowel function, and shorter hospital stay, as well as significantly longer operative times compared to EA. These data validate current efforts to increase training and adoption of the IA technique for minimally invasive right colectomy.

Perfusion Assessment in Left-Sided/Low Anterior Resection (PILLAR III): A Randomized, Controlled, Parallel, Multicenter Study Assessing Perfusion Outcomes With PINPOINT Near-Infrared Fluorescence Imaging in Low Anterior Resection.

BACKGROUND: Indocyanine green fluoroscopy has been shown to improve anastomotic leak rates in early phase trials. OBJECTIVE: We hypothesized that the use of fluoroscopy to ensure anastomotic perfusion may decrease anastomotic leak after low anterior resection. DESIGN: We performed a 1:1 randomized controlled parallel study. Recruitment of 450 to 1000 patients was planned over 2 years. SETTINGS: This was a multicenter trial. PATIENTS: Included patients were those undergoing resection defined as anastomosis within 10 cm of the anal verge. INTERVENTION: Patients underwent standard evaluation of tissue perfusion versus standard in conjunction with perfusion evaluation using indocyanine green fluoroscopy. MAIN OUTCOME MEASURES: Primary outcome was anastomotic leak, with secondary outcomes of perfusion assessment and the rate of postoperative abscess requiring intervention. RESULTS: This study was concluded early because of decreasing accrual rates. A total of 25 centers recruited 347 patients, of whom 178 were randomly assigned to perfusion and 169 to standard. The groups had comparable tumor-specific and patient-specific demographics. Neoadjuvant chemoradiation was performed in 63.5% of perfusion and 65.7% of standard (p > 0.05). Mean level of anastomosis was 5.2 ± 3.1 cm in perfusion compared with 5.2 ± 3.3 cm in standard (p > 0.05). Sufficient visualization of perfusion was reported in 95.4% of patients in the perfusion group. Postoperative abscess requiring surgical management was reported in 5.7% of perfusion and 4.2% of standard (p = 0.75). Anastomotic leak was reported in 9.0% of perfusion compared with 9.6% of standard (p = 0.37). On multivariate regression analysis, there was no difference in anastomotic leak rates between perfusion and standard (OR = 0.845 (95% CI, 0.375-1.905); p = 0.34). LIMITATIONS: The predetermined sample size to adequately reduce the risk of type II error was not achieved. CONCLUSIONS: Successful visualization of perfusion can be achieved with indocyanine green fluoroscopy. However, no difference in anastomotic leak rates was observed between patients who underwent perfusion assessment versus standard surgical technique. In experienced hands, the addition of routine indocyanine green fluoroscopy to standard practice adds no evident clinical benefit. See Video Abstract at http://links.lww.com/DCR/B560. VALORACIN DE LA IRRIGACIN DE LADO IZQUIERDO/RESECCIN ANTERIOR BAJA PILAR III UN ESTUDIO ALEATORIZADO, CONTROLADO, PARALELO Y MULTICNTRICO QUE EVALA LOS RESULTADOS DE LA IRRIGACIN CON PINPOINT IMGENES DE FLUORESCENCIA CERCANA AL INFRARROJO EN LA RESECCIN ANTERIOR BAJA: ANTECEDENTES:Se ha demostrado que la fluoroscopia con verde de indocianina mejora las tasas de fuga anastomótica en ensayos en fases iniciales.OBJETIVO:Nuestra hipótesis es que la utilización de fluoroscopia para asegurar la irrigación anastomótica puede disminuir la fuga anastomótica luego de una resección anterior baja.DISEÑO:Realizamos un estudio paralelo, controlado, aleatorizado 1:1. Se planificó el reclutamiento de 450-1000 pacientes durante 2 años.AMBITO:Multicéntrico.PACIENTES:Pacientes sometidos a resección definida como una anastomosis dentro de los 10cm del margen anal.INTERVENCIÓN:Pacientes que se sometieron a la evaluación estándar de la irrigación tisular contra la estándar en conjunto con la valoración de la irrigación mediante fluoroscopia con verde indocianina.PRINCIPALES VARIABLES EVALUADAS:El principal resultado fue la fuga anastomótica, y los resultados secundarios fueron la evaluación de la perfusión y la tasa de absceso posoperatorio que requirió intervención.RESULTADOS:Este estudio se cerró anticipadamente debido a la disminución de las tasas de acumulación. Un total de 25 centros reclutaron a 347 pacientes, de los cuales 178 fueron, de manera aleatoria, asignados a perfusión y 169 a estándar. Los grupos tenían datos demográficos específicos del tumor y del paciente similares. Recibieron quimio-radioterapia neoadyuvante el 63,5% de la perfusión y el 65,7% del estándar (p> 0,05). La anastomosis estuvo en un nivel promedio de 5,2 + 3,1 cm en perfusión en comparación con 5,2 + 3,3 cm en estándar (p> 0,05). Se reportó una visualización suficiente de la perfusión en el 95,4% de los pacientes del grupo de perfusión. El absceso posoperatorio que requirió tratamiento quirúrgico fue de 5,7% de los perfusion y en el 4,2% del estándar (p = 0,75). Se informó fuga anastomótica en el 9,0% de la perfusión en comparación con el 9,6% del estándar (p = 0,37). En el análisis de regresión multivariante, no hubo diferencias en las tasas de fuga anastomótica entre la perfusión y el estándar (OR 0,845; IC del 95% (0,375; 1,905); p = 0,34).LIMITACIONES:No se logró el tamaño de muestra predeterminado para reducir satisfactoriamente el riesgo de error tipo II.CONCLUSIÓN:Se puede obtener una visualización adecuada de la perfusión con ICG-F. Sin embargo, no se observaron diferencias en las tasas de fuga anastomótica entre los pacientes que se sometieron a evaluación de la perfusión versus la técnica quirúrgica estándar. En manos expertas, agregar ICG-F a la rutina de la práctica estándar no agrega ningún beneficio clínico evidente. Consulte Video Resumen en http://links.lww.com/DCR/B560. (Traducción-Dr Juan Antonio Villanueva-Herrero).

Incidence, associated risk factors, and impact of conversion to laparotomy in elective minimally invasive sigmoidectomy for diverticular disease.

BACKGROUND: Benefits of minimally invasive surgical approaches to diverticular disease are limited by conversion to open surgery. A comprehensive analysis that includes risk factors for conversion may improve patient outcomes. METHODS: The US Premier Healthcare Database was used to identify patients undergoing primary elective sigmoidectomy for diverticular disease between 2013 and September 2015. Propensity-score matching was used to compare conversion rates for laparoscopic and robotic-assisted sigmoidectomy. Patient, clinical, hospital, and surgeon characteristics associated with conversion were analyzed using multivariable logistic regression, providing odds ratios for comparative risks. Clinical and economic impacts were assessed comparing surgical outcomes in minimally invasive converted, completed, and open cases. RESULTS: The study population included 13,240 sigmoidectomy patients (8076 laparoscopic, 1301 robotic-assisted, 3863 open). Analysis of propensity-score-matched patients showed higher conversion rates in laparoscopic (13.6%) versus robotic-assisted (8.3%) surgeries (p < 0.001). Greater risk of conversion was associated with patients who were Black compared with Caucasian, were Medicaid-insured versus Commercially insured, had a Charlson Comorbidity Index ≥ 2 versus 0, were obese, had concomitant colon resection, had peritoneal abscess or fistula, or had lysis of adhesions. Significantly lower risk of conversion was associated with robotic-assisted sigmoidectomy (versus laparoscopic, OR 0.58), hand-assisted surgery, higher surgeon volume, and surgeons who were colorectal specialties. Converted cases had longer operating room time, length of stay, and more postoperative complications compared with minimally invasive completed and open cases. Readmission and blood transfusion rates were higher in converted compared with minimally invasive completed cases, and similar to open surgeries. Differences in inflation-adjusted total ($4971), direct ($2760), and overhead ($2212) costs were significantly higher for converted compared with minimally invasive completed cases. CONCLUSIONS: Conversion from minimally invasive to open sigmoidectomy for diverticular disease results in additional morbidity and healthcare costs. Consideration of modifiable risk factors for conversion may attenuate adverse associated outcomes.

Participation of Colon and Rectal Fellows in Robotic Rectal Cancer Surgery: Effect on Surgical Outcomes.

OBJECTIVES: To determine whether involvement of colon and rectal fellows has an effect on short-term surgical and oncological outcomes in robotic rectal cancer surgery. PATIENTS AND METHODS: From a dataset of 263 robotic-assisted rectal cancer operations, 114 case-matched patients over a 5-year period (January 2010-December 2015) were included in the study. Patients who underwent resection with and without fellow involvement were compared. Cases were matched according to age, body mass index, neoadjuvant therapy, and tumor location. Intraoperative, postoperative, and pathological outcomes were compared between the 2 groups. RESULTS: There was no difference in tumor grade, type of surgical procedure, presence of an anastomosis, or diverting stoma between groups. In addition, there was no difference in the incidence of intraoperative or postoperative complications between the 2 groups. Estimated blood loss was higher in the fellow group compared to the consultant group (mean difference of 70mL, p = 0.007). For pathological outcomes, there was no difference in surrogate oncological quality indicators, specifically margin positivity and lymph node yield, between the 2 groups. Furthermore, fellow involvement did not adversely affect operative time. CONCLUSION: This study demonstrates that equivalent short-term surgical and oncological outcomes can be achieved with colorectal fellow participation in the field of robotic-assisted rectal cancer surgery.

Intussusception of a small bowel large B-cell lymphoma.

Gastrointestinal tumors can rarely cause intestinal intussusception. Herein, we describe a 74 year-old male with a presumed diagnosis of Crohn's disease who presented with persistent symptoms refractory to medical management. Radiography demonstrated small bowel intussusception into the cecum. Lower endoscopy with biopsy diagnosed small bowel large Bcell lymphoma. Management included laparoscopic ileocecectomy and adjuvant R-CHOP chemotherapy. Long term outcomes of small bowel large B-cell lymphoma are related to disease stage at diagnosis, and average close to 75 %.

Dysplasia in ulcerative colitis as a predictor of unsuspected synchronous colorectal cancer.

BACKGROUND: Endoscopic surveillance of patients with ulcerative colitis aims to prevent cancer-related morbidity through the detection and treatment of dysplasia. The literature to date varies widely with regard to the importance of dysplasia as a marker for colorectal cancer at the time of colectomy. OBJECTIVE: The aim of this study was to accurately characterize the extent to which the preoperative detection of dysplasia is associated with undetected cancer in patients with ulcerative colitis. DESIGN/PATIENTS/SETTING: A retrospective chart review was conducted of patients undergoing surgery for colitis within the Mayo Clinic Health System between August 1993 and July 2012. MAIN OUTCOME MEASURES: Patient demographics and pre- and postoperative dysplasia were tabulated. The relationship between pre- and postoperative dysplasia/cancer in surgical pathology specimens was assessed. RESULTS: A total of 2130 patients underwent abdominal colectomy or proctocolectomy; 329 patients were identified (15%) as having at least 1 focus of dysplasia preoperatively. Of these 329 patients, the majority were male (69%) with a mean age of 49.7 years. Unsuspected cancer was found in 6 surgical specimens. Indeterminate dysplasia was not associated with cancer (0/50). Preoperative low-grade dysplasia was associated with a 2% (3/141) risk of undetected cancer when present in random surveillance biopsies and a 3% (2/79) risk if detected in endoscopically visible lesions. Similarly, 3% (1/33) of patients identified preoperatively with random surveillance biopsy high-grade dysplasia harbored undetected cancer. Unsuspected dysplasia was found in 62/1801 (3%) cases without preoperative dysplasia. LIMITATIONS: This study is limited by its retrospective nature and by its lack of evaluation of the natural history of dysplastic lesions that progress to cancer. CONCLUSIONS: The presence of dysplasia was associated with a low risk of unsuspected cancer at the time of colectomy. These findings will help inform the decision-making process for patients with ulcerative colitis who are considering intensive surveillance vs surgical intervention after a diagnosis of dysplasia.

Colectomy for endoscopically unresectable polyps: how often is it cancer?

BACKGROUND: Colonoscopy has an established role in reducing the burden of colorectal cancer through early detection and removal of polyps. For endoscopically unresectable polyps, colectomy is generally indicated to prevent malignant transformation or to remove cancer already present. OBJECTIVE: This study aimed to determine the incidence of malignancy and the factors predictive of malignancy in surgically resected benign polyps. DESIGN/PATIENTS/SETTING: This study was a retrospective chart review of patients undergoing a colectomy for a colonic polyp (no preoperative diagnosis of cancer) in 4 hospitals within the Mayo Clinic Health System. MAIN OUTCOME MEASURES: Patient characteristics, endoscopic location and size, and preoperative and operative polyp pathology were tabulated. Correlations between these features and the finding of invasive carcinoma on surgical pathology were assessed. RESULTS: A total of 750 patients met our inclusion criteria. Patients were predominantly male (55.2%) with an average age of 69.4 ± 9.8 years. A majority of polyps were located in the right colon (70.9%). Invasive cancer was identified in 133 patients (17.7%). Multivariate analysis revealed polyps in the left colon (adjusted OR 2.13, 95% CI (1.22-3.72)), and those with high-grade dysplasia (adjusted OR 4.60, 95% CI (2.91-7.27)) were more likely to harbor carcinoma. Age, sex, polyp dimension, and villous features were not predictive of malignancy. Of the patients with cancer, 31 (23.3%) had nodal disease. LIMITATIONS: This study is limited by its retrospective nature, the change in terminology and technique over time, and the partially subjective nature of an endoscopically unresectable polyp. CONCLUSIONS: The finding that polyp size and villous features do not strongly predict malignancy differs from previous endoscopic studies. This study confirms that polyps located in the left colon or with high-grade dysplasia are more likely to harbor cancer. The results of this study suggest that endoscopically unresectable polyps are best treated by radical oncologic resection.

Persistent ischiorectal fistula with supralevator origin secondary to a chronic tubo-ovarian abscess: report of a case and review of the literature.

BACKGROUND: Chronic tubo-ovarian abscess is an uncommon finding in postmenopausal women. This abscess may rupture or fistulize to adjacent organs into the ischiorectal space. CASE: A gravida three, para three, postmenopausal woman with extensive sigmoid diverticulosis presented with perianal fistula of 2 years' duration. Magnetic resonance imaging showed the tract to have a supralevator origin adjacent to the sigmoid colon. She had no recent instrumentation other than preoperative colonoscopy. Intraoperatively, the fistula tract origin was noted to be from a right tubo-ovarian abscess. She was treated with right salpingo-oophorectomy and tract excision/sealing. At 4-month follow-up, the fistula tract was healed with no further drainage. CONCLUSIONS: Tubo-ovarian abscess should be considered in the differential diagnosis of supralevator fistula in postmenopausal women when no other source can be localized.

Identification of patients with high-risk stage II colon cancer for adjuvant therapy.

PURPOSE: Adjuvant therapy for Stage II colon cancer remains controversial but may be considered for patients with high-risk features. The purpose of this study was to assess the prognostic significance of commonly reported clinicopathologic features of Stage II colon cancer to identify high-risk patients. METHODS: We analyzed a prospectively maintained database of patients with colon cancer who underwent surgical treatment from 1990 to 2001 at a single specialty center. We identified 448 patients with Stage II colon cancer who had been treated by curative resection alone, without postoperative chemotherapy. RESULTS: With median follow-up of 53 months, 5-year disease-specific survival for this cohort was 91 percent. Univariate and multivariate analyses identified three independent features that significantly affected disease-specific survival: tumor Stage T4 (hazard ratio (HR), 2.7; 95 percent confidence interval (CI), 1.1-6.2; P = 0.02), preoperative carcinoembryonic antigen > 5 ng/ml (HR, 2.1; 95 percent CI, 1.1-4.1; P = 0.02), and presence of lymphovascular or perineural invasion (HR, 2.1; 95 percent CI, 1-4.4; P = 0.04). Five-year disease-specific survival for patients without any of the above poor prognostic features was 95 percent; five-year disease-specific survival for patients with one of these poor prognostic features was 85 percent; and five-year disease-specific survival for patients with > or = 2 poor prognostic features was 57 percent. CONCLUSIONS: Patients with Stage II colon cancer generally have an excellent prognosis. However, the presence of multiple adverse prognostic factors identifies a high-risk subgroup. Use of commonly reported clinicopathologic features accurately stratifies Stage II colon cancer by disease-specific survival. Those identified as high-risk patients can be considered for adjuvant chemotherapy and/or enrollment in investigational trials.

Is nonsmall cell type high-grade neuroendocrine carcinoma of the tubular gastrointestinal tract a distinct disease entity?

Although small cell carcinoma of the gastrointestinal (GI) tract is well-recognized, nonsmall cell type high-grade neuroendocrine carcinoma (HGNEC) of this site remains undefined. At the current time, neither the World Health Organization nor American Joint Committee on Cancer includes this condition in the histologic classifications, and consequently it is being diagnosed and treated inconsistently. In this study, we aimed at delineating the histologic and immunophenotypical spectrum of HGNECs of the GI tract with emphasis on histologic subtypes. Guided primarily by the World Health Organization/International Association for the Study of Lung Cancer criteria for pulmonary neuroendocrine tumors, we were able to classify 87 high-grade GI tract tumors that initially carried a diagnosis of either poorly differentiated carcinoma with or without any neuroendocrine characteristics, small cell carcinoma, or combined adenocarcinoma-neuroendocrine carcinoma into the following 4 categories. The first was small cell carcinoma (n=23), which had features typical of pulmonary small cell carcinoma, although the cells tended to have a more round nuclear contour. The second was large cell neuroendocrine carcinoma (n=31), which had a morphology similar to its pulmonary counterpart and showed positive immunoreactivity for either chromogranin (71%) or synaptophysin (94%) or both. The third was mixed neuroendocrine carcinoma (n=11), which had intermediate histologic features (eg, cells with an increased nuclear/cytoplasmic ratio but with apparent nucleoli), and positive immunoreactivity for at least 1 neuroendocrine marker. The fourth was poorly differentiated adenocarcinoma (n=17). In addition, 5 of the 87 tumors showed either nonsmall cell type neuroendocrine morphology (n=3) or immunohistochemical reactivity for neuroendocrine markers (n=2), but not both. Further analysis showed that most HGNECs arising in the squamous lined parts (esophagus and anal canal) were small cell type (78%), whereas most involving the glandular mucosa were large cell (53%) or mixed (82%) type; associated adenocarcinomas were more frequent in large cell (61%) or mixed (36%) type than in small cell type (26%); and focal intracytoplasmic mucin was seen only in large cell or mixed type. As a group, the 2-year disease-specific survival for patients with HGNEC was 25.4% (median follow-up time, 11.3 mo). No significant survival difference was observed among the different histologic subtypes. In conclusion, our study demonstrates the existence of both small cell and nonsmall cell types of HGNEC in the GI tract, and provides a detailed illustration of their morphologic spectrum. There are differences in certain pathologic features between small cell and nonsmall cell types, whereas the differences between the subtypes of nonsmall cell category (large cell versus mixed) are less distinct. Given the current uncertainty as to whether large cell neuroendocrine carcinoma is as chemosensitive as small cell carcinoma even in the lung, our data provide further evidence in favor of a dichotomous classification scheme (small cell vs. nonsmall cell) for HGNEC of the GI tract. Separation of nonsmall cell type into large cell and mixed subtypes may not be necessary. These tumors are clinically aggressive. Prospective studies using defined diagnostic criteria are needed to determine their biologic characteristics and optimal management.

Immunohistochemical expression of folate receptor alpha in colorectal carcinoma: patterns and biological significance.

Folate receptor alpha (FRalpha) has emerged as a potential cancer therapy target with several folate-linked therapeutic agents currently undergoing clinical trials. In addition, FRalpha expression in tumors may offer prognostic significance. Most studies on FRalpha expression used reverse transcriptase polymerase chain reaction or cytofluorimetric assays. The applicability of such methods to paraffin-embedded tissues is limited. The aims of this study were to assess the feasibility of immunohistochemistry in detecting FRalpha expression and to assess the patterns and clinical significance of FRalpha expression in colorectal tissues. We used tissue microarrays containing 152 normal colorectal mucosa samples, 42 adenomas, 177 primary, and 52 metastatic colorectal carcinomas. Our results showed that staining for FRalpha on colorectal tissues was simple and easy to read. FRalpha positivity was more frequent in carcinomas (33% in primaries and 44% in metastases) than in normal mucosa or adenoma (7% in both) (P < .001). Positive staining in primary carcinomas correlated with younger age (n = 130) (P = .008), presence of distant metastasis (n = 130) (P = .043), and non-high-frequency microsatellite instability status (as detected by the standard polymerase chain reaction method using the 5 National Cancer Institute-recommended markers) (n = 77) (P = .006). Positive staining in primary carcinomas also correlated with a worse 5-year disease-specific survival (P = .04) on univariate but not multivariate analysis. Thus, our data show that there is selective expression of FRalpha in some colorectal cancers, providing a foundation for investigating the use of folate conjugates for imaging and therapy of colorectal tumors. Furthermore, our results suggest that a possible association exists between FRalpha expression and the microsatellite instability status in colorectal carcinoma. The significance of such an association as well as the prognostic value of FRalpha expression deserves further exploration.

Individualized prediction of colon cancer recurrence using a nomogram.

PURPOSE: Estimates of recurrence after curative colon cancer surgery are integral to patient care, forming the basis of cancer staging and treatment planning. The categoric staging system of the American Joint Committee on Cancer (AJCC) is commonly used to convey risk by grouping patients based on anatomic elements. Although easy to implement, there remains significant heterogeneity within each stage grouping. In the era of multimodality treatment, a more refined tool is needed to predict recurrence. METHODS: An institutional database of 1,320 patients with nonmetastatic colon cancer was used to develop a nomogram to estimate recurrence after curative surgery. Prognostic factors were assessed with multivariable analysis using Cox regression, whereas nonlinear continuous variables were modeled with cubic splines. The model was internally validated with bootstrapping, and performance was assessed by concordance index and a calibration curve. RESULTS: The colon cancer recurrence nomogram predicted relapse with a concordance index of 0.77, improving on the stratification provided by either the AJCC fifth or sixth staging scheme. Factors in the model included patient age, tumor location, preoperative carcinoembryonic antigen, T stage, numbers of positive and negative lymph nodes, lymphovascular invasion, perineural invasion, and use of postoperative chemotherapy. CONCLUSION: Using common clinicopathologic factors, the recurrence nomogram is better able to account for tumor and patient heterogeneity, thereby providing a more individualized outcome prognostication than that afforded by the AJCC categoric system. By identifying both the high- and low-risk patients within any particular stage, the nomogram is expected to aid in treatment planning and future trial design.

Paradoxical puborectalis contraction and increased perineal descent.

Paradoxical puborectalis contraction and increased perineal descent are two forms of functional constipation presenting as challenging diagnostic and treatment dilemmas to the clinician. In the evaluation of these disorders, the clinician should take special care to exclude anatomic disorders leading to constipation. Physical examination is supplemented by additional diagnostic modalities such as cinedefecography, electromyography, manometry, and pudendal nerve tefninal motor latency. Generally, these investigations should be used in combination with the two playing the more relied upon techniques. Treatment is typically conservative with biofeedback playing a principal role with favorable results when patient compliance is emphasized. When considering paradoxical puborectalis contraction, failure of biofeedback is usually augmented with botulinum toxin injection. Increased perineal descent is generally treated with biofeedback and perineal support maneuvers. Surgery has little or no role in these conditions. The patient who insists on surgical intervention for either of these two conditions should be offered a stoma.

Limitations of early rectal cancer nodal staging may explain failure after local excision.

Successful selection of patients with rectal cancer for local excision requires accurate preoperative lymph node staging. Although endorectal ultrasound is capable of detecting locally advanced disease, its ability to correctly identify nodal metastases in early rectal lesions is less well described. This study examines the accuracy of endorectal ultrasound in determining nodal stage based on depth of penetration of the primary lesion (T stage). Between 1998 and 2003, endorectal ultrasound was performed on 938 consecutive patients; 134 had biopsy-proven rectal cancers and were treated with radical resection, without neoadjuvant therapy. Lymph node metastases were measured pathologically and correlated with endorectal ultrasound and clinicopathologic features. Accuracy and specificity of endorectal ultrasound nodal staging was determined. The overall accuracy of endorectal ultrasound nodal staging for the study cohort was 70 percent, with a 16 percent false-positive rate and 14 percent false-negative rate. Endorectal ultrasound was more likely to overlook small metastatic lymph node deposits. The size of lymph node metastasis and accuracy of endorectal ultrasound nodal staging was related to T stage. The specificity of endorectal ultrasound nodal staging, or the ability to identify patients who were node-negative, was dependent on T stage. Early rectal lesions are more likely to have lymph node micrometastases not detected by endorectal ultrasound. The ability of endorectal ultrasound to correctly identify patients without lymph node metastasis is dependent on the T stage of the primary lesion. The limitations of endorectal ultrasound in accurately staging nodal disease in early rectal lesions may, in part, explain the relatively high recurrence rates seen after local excision.

Novel xenograft model expressing human hepatocyte growth factor shows ligand-dependent growth of c-Met-expressing tumors.

c-Met, a receptor tyrosine kinase responsible for cellular migration, invasion, and proliferation, is overexpressed in human cancers. Although ligand-independent c-Met activation has been described, the majority of tumors are ligand dependent and rely on binding of hepatocyte growth factor (HGF) for receptor activation. Both receptor and ligand are attractive therapeutic targets; however, preclinical models are limited because murine HGF does not activate human c-Met. The goal of this study was to develop a xenograft model in which human HGF (hHGF) is produced in a controllable fashion in the mouse. Severe combined immunodeficient mice were treated with adenovirus encoding the hHGF transgene (Ad-hHGF) via tail vein injection, and transgene expression was determined by the presence of hHGF mRNA in mouse tissue and hHGF in serum. Ad-hHGF administration to severe combined immunodeficient mice resulted in hHGF production that was (a) dependent on quantity of virus delivered; (b) biologically active, resulting in liver hypertrophy; and (c) sustainable over 40 days. In this model, the ligand-dependent human tumor cell line SW1417 showed enhanced tumor growth, whereas the ligand-independent cell lines SW480 and GTL-16 showed no augmented tumor growth. This novel xenograft model is ideal for investigating c-Met/HGF-dependent human tumor progression and for evaluating c-Met targeted therapy.

Molecular co-expression of the c-Met oncogene and hepatocyte growth factor in primary colon cancer predicts tumor stage and clinical outcome.

INTRODUCTION/HYPOTHESIS: Over-expression of the c-Met receptor tyrosine kinase has been described in a variety of cancers and implicated in tumor progression. Unlike some solid tumors, current evidence indicates that c-Met activation in colon cancer is unrelated to gene mutation, is ligand dependent, and occurs via a paracrine fashion. We hypothesize that over-expression of the c-Met receptor and its ligand, hepatocyte growth factor (HGF) in the tumor microenvironment is associated with tumor progression and metastases. METHODS: Primary tumor c-Met and HGF mRNA expression was analyzed in 60 colon adenocarcinomas. Receptor and ligand expression was analyzed for correlation and association with clinicopathologic features and outcome. RESULTS: Compared to adjacent normal mucosa, 69% and 48% of tumors showed a greater than 2- and greater than 10-fold elevation in c-Met mRNA, respectively. Elevated HGF mRNA was noted in 47% of tumors with 19% having a greater than 10-fold increase. Tumor c-Met expression was correlated with HGF expression, and a cohort of 33 patients could be defined with both low c-Met and HGF expression. Compared with the 27 tumors with either high c-Met or HGF, the cohort with low c-Met and HGF expression had fewer nodal and distant metastases as well as improved overall survival (HR=2.3, p<0.05). CONCLUSION: Evaluation of the c-Met receptor in context of ligand, HGF, allows identification of a metastatic phenotype that correlates with advanced stage and poor survival. c-Met and HGF co-expression in the tumor microenvironment could be useful in the molecular staging of colon cancer and viable therapeutic targets.

Surgical salvage of recurrent rectal cancer after transanal excision.

PURPOSE: This study examines surgical salvage of locally recurrent rectal cancer following transanal excision of early tumors. METHODS: Through retrospective review of a colorectal database we identified 50 patients who underwent attempted surgical salvage for local recurrence following initial transanal excision of T1 or T2 rectal cancer. Eight patients had resectable synchronous distant disease. Clinicopathologic variables were associated with extent of surgery required for salvage and outcome. RESULTS: Salvage procedures included abdominoperineal resection (31), low anterior resection (11), total pelvic exenteration (4), and transanal excision (3). One patient had unresectable disease at exploration, requiring diverting ostomy. Of the 49 patients who underwent successful salvage, 27 (55 percent) required an extended pelvic dissection with en bloc resection of one or more of the following structures: pelvic sidewall and autonomic nerves (18); coccyx or portion of sacrum (6); prostate (5); seminal vesicle (5); bladder (4); portion of the vagina (3); ureter (2); ovary (1); and uterus (1). Complete pathologic resection (R0) was accomplished in 47 of 49 patients. Of the eight patients with distant and local recurrence, two underwent synchronous resection and six had delayed metastasectomy. With a median follow-up of 33 months, 29 patients had recurred or died of disease at the time of this analysis. Five-year disease-specific survival was 53 percent. Factors predictive of survival included evidence of any mucosal recurrence on endoscopy, low presalvage carcinoembryonic antigen, and absence of poor pathologic features (lymphovascular and perineural invasion). Patients who required an extended pelvic resection had a worse survival rate. CONCLUSION: Pelvic recurrence following transanal excision of early rectal cancer is often locally advanced, requiring an extended pelvic dissection with en bloc resection of adjacent pelvic organs to achieve salvage. The long-term outcome in patients undergoing resection is less than expected, considering the early stage of their initial disease. When contemplating local excision for early rectal cancer, the risk of local recurrence, the extent and morbidity of surgery required for salvage, and the modest cure rate following salvage should be considered.

Surgical management of locally advanced and locally recurrent colon cancer.

Locally advanced and locally recurrent colon cancers pose a surgical challenge with tumors extending into surrounding structures and organs. Anticipation of the need for an extended surgical resection, often with multivisceral en bloc organ removal, is critical for surgical planning. For both primary and recurrent tumors, postsurgical long-term survival is achievable but only after complete resection. The role of neoadjuvant and adjuvant therapy continues to be redefined in this era of biologic chemotherapeutics, and multimodality therapy holds promise in aiding resection and improving postsalvage survival.