Rectal Dissection Simulator for da Vinci Surgery: Details of Simulator Manufacturing With Evidence of Construct, Face, and Content Validity.

BACKGROUND: Apprenticeship in training new surgical skills is problematic, because it involves human subjects. To date there are limited inanimate trainers for rectal surgery. OBJECTIVE: The purpose of this article is to present manufacturing details accompanied by evidence of construct, face, and content validity for a robotic rectal dissection simulation. DESIGN: Residents versus experts were recruited and tested on performing simulated total mesorectal excision. Time for each dissection was recorded. Effectiveness of retraction to achieve adequate exposure was scored on a dichotomous yes-or-no scale. Number of critical errors was counted. Dissection quality was tested using a visual 7-point Likert scale. The times and scores were then compared to assess construct validity. Two scorer results were used to show interobserver agreement. A 5-point Likert scale questionnaire was administered to each participant inquiring about basic demographics, surgical experience, and opinion of the simulator. Survey data relevant to the determination of face validity (realism and ease of use) and content validity (appropriateness and usefulness) were then analyzed. SETTINGS: The study was conducted at a single teaching institution. SUBJECTS: Residents and trained surgeons were included. INTERVENTION: The study intervention included total mesorectal excision on an inanimate model. MAIN OUTCOME MEASURES: Metrics confirming or refuting that the model can distinguish between novices and experts were measured. RESULTS: A total of 19 residents and 9 experts were recruited. The residents versus experts comparison featured average completion times of 31.3 versus 10.3 minutes, percentage achieving adequate exposure of 5.3% versus 88.9%, number of errors of 31.9 versus 3.9, and dissection quality scores of 1.8 versus 5.2. Interobserver correlations of R = 0.977 or better confirmed interobserver agreement. Overall average scores were 4.2 of 5.0 for face validation and 4.5 of 5.0 for content validation. LIMITATIONS: The use of a da Vinci microblade instead of hook electrocautery was a study limitation. CONCLUSIONS: The pelvic model showed evidence of construct validity, because all of the measured performance indicators accurately differentiated the 2 groups studied. Furthermore, study participants provided evidence for the simulator's face and content validity. These results justify proceeding to the next stage of validation, which consists of evaluating predictive and concurrent validity. See Video Abstract at http://links.lww.com/DCR/A551.

Patterns and outcomes of colorectal cancer in adolescents and young adults.

BACKGROUND: The incidence of colorectal cancer (CRC) in the adolescent and young adult (AYA) population (aged 15-39 y) is rising. MATERIALS AND METHODS: We used the Surveillance, Epidemiology, and End Results Database to study CRC in the AYA population. We studied clinical and socioeconomic factors associated with survival. RESULTS: Of the 11,071 cases of CRC, the most common site of the primary tumor was the rectum (25%), whereas 66.6% of the diseases were left sided. Most of the patients (72%) presented with regional or metastatic disease. However, the disease-specific survival (DSS) and the overall survival of the AYA population were comparable to those of the general population (DSS; 5- and 10-y: 64.8%, 57.3%; overall survival; 5- and 10-y: 61.5% and 52.4%). On multivariate analysis, disease stage at the time of the diagnosis was the strongest predictor of mortality. After controlling for disease stage, male gender, black race, and higher grade tumors were associated with worse survival. CONCLUSIONS: The AYA population presents with advanced distal CRC but have similar survival compared with the general population.

Elderly patients with colon cancer have unique tumor characteristics and poor survival.

BACKGROUND: The incidence of colon cancer increases with age, and colon cancer predominantly affects individuals >65 years old. However, there are limited data regarding clinical and pathologic factors, treatment characteristics, and survival of older patients with colon cancer. The objective of this study was to determine the effects of increasing age on colon cancer. METHODS: Patients diagnosed with colon cancer between 1988 and 2006 were identified through the Los Angeles County Cancer Surveillance Program, in Southern California. Patients were stratified into 4 age groups: 18-49, 50-64, 65-79, and ≥80 years. Clinical and pathologic characteristics and disease-specific and overall survival were compared between patients from different age groups. RESULTS: A total of 32,819 patients were assessed. Patients aged 18 to 49 and 65 to 79 years represented the smallest and largest groups, respectively. A near equal number of males and females were diagnosed with colon cancer in the 3 youngest age groups, whereas patients who were ≥80 years old were more commonly white and female. Tumor location was different between groups, and the frequency of larger tumors (>5 cm) was greatest in youngest patients (18-49 years). The oldest patients (≥80 years) were administered chemotherapy at the lowest frequency, and disease-specific and overall survival rates decreased with increasing age. CONCLUSIONS: This investigation demonstrates that older age is associated with alterations in clinical and pathologic characteristics and decreased survival. This suggests that the phenotype of colon cancer and the efficacy of colon cancer therapies may be dependent on the age of patients.

Well-differentiated thyroid carcinoma: the role of post-operative radioactive iodine administration.

Post-operative management of differentiated thyroid cancer (DTC) often involves administration of radioactive iodine (RAI) for remnant ablation or adjuvant therapy. However, given the favorable prognosis associated with DTC, the risk versus benefit ratio of RAI remains unclear. RAI is associated with substantial, albeit rare side effects, including a possible increased risk of secondary malignancy and altered fertility, which must be balanced against the magnitude of benefit for decreasing recurrence and improving survival.

IgG1 is pathogenic in Leishmania mexicana infection.

There are >2 million new cases of leishmaniasis annually, and no effective vaccine has been developed to prevent infection. In murine infection, Leishmania mexicana, which lives intracellularly in host macrophages, has developed pathways to hijack host IgG to induce a suppressive IL-10 response through FcγRs, the cell-surface receptors for IgG. To guide vaccine development away from detrimental Ab responses, which can accompany attempts to induce cell-mediated immunity, it is crucial to know which isotypes of IgG are pathogenic in this infection. We found that IgG1 and IgG2a/c induce IL-10 from macrophages in vitro equally well but through different FcγR subtypes: IgG1 through FcγRIII and IgG2a/c through FcγRI primarily, but also through FcγRIII. In sharp contrast, mice lacking IgG1 develop earlier and stronger IgG2a/c, IgG3, and IgM responses to L. mexicana infection and yet are more resistant to the infection. Thus, IgG1, but not IgG2a/c or IgG3, is pathogenic in vivo, in agreement with prior studies indicating that FcγRIII is required for chronic disease. This calls into question the assumption that macrophages, which should secrete IL-10 in response to IgG1 and IgG2a/c immune complexes, are the most important source of IL-10 generated by IgG-FcγR engagement in L. mexicana infection. Further investigations are required to better determine the cell type responsible for this immunosuppressive FcγRIII-induced IL-10 pathway and whether IgG2a/c is protective.

Prognostic and predictive roles of KRAS mutation in colorectal cancer.

The RAS gene family is among the most studied and best characterized of the known cancer-related genes. Of the three human ras isoforms, KRAS is the most frequently altered gene, with mutations occurring in 17%-25% of all cancers. In particular, approximately 30%-40% of colon cancers harbor a KRAS mutation. KRAS mutations in colon cancers have been associated with poorer survival and increased tumor aggressiveness. Additionally, KRAS mutations in colorectal cancer lead to resistance to select treatment strategies. In this review we examine the history of KRAS, its prognostic value in patients with colorectal cancer, and evidence supporting its predictive value in determining appropriate therapies for patients with colorectal cancer.

Generation of T-cell-redirecting bispecific antibodies with differentiated profiles of cytokine release and biodistribution by CD3 affinity tuning.

T-cell-redirecting bispecific antibodies have emerged as a new class of therapeutic agents designed to simultaneously bind to T cells via CD3 and to tumor cells via tumor-cell-specific antigens (TSA), inducing T-cell-mediated killing of tumor cells. The promising preclinical and clinical efficacy of TSAxCD3 antibodies is often accompanied by toxicities such as cytokine release syndrome due to T-cell activation. How the efficacy and toxicity profile of the TSAxCD3 bispecific antibodies depends on the binding affinity to CD3 remains unclear. Here, we evaluate bispecific antibodies that were engineered to have a range of CD3 affinities, while retaining the same binding affinity for the selected tumor antigen. These agents were tested for their ability to kill tumor cells in vitro, and their biodistribution, serum half-life, and anti-tumor activity in vivo. Remarkably, by altering the binding affinity for CD3 alone, we can generate bispecific antibodies that maintain potent killing of TSA + tumor cells but display differential patterns of cytokine release, pharmacokinetics, and biodistribution. Therefore, tuning CD3 affinity is a promising method to improve the therapeutic index of T-cell-engaging bispecific antibodies.

Rectal Cancer Complete Response Outcomes in a Community-Based Hospital Comparable with Large Cancer Centers When Multidisciplinary Approach to Rectal Cancer Is Used.

Achievement of pathologic complete response (pCR) in patients with locally advanced rectal cancer correlates with improved prognosis relative to non-pCR counterparts. Such correlations are not well established in the context of a community-based hospital. This study aims to examine pCR rates, recurrences, and survival data for locally advanced rectal cancer patients in community settings. A single-center retrospective chart review was performed at a community-based hospital. Study population consisted of 119 patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy, followed by surgical resection. Patients with a history of metastasis, inflammatory bowel disease, hereditary cancer syndromes, concurrent or prior malignancy, and emergent surgery were excluded. Twenty-four patients (20.2%) achieved pCR. Across both groups, all demographics and perioperative characteristics were comparable. The five-year survival was 73.7 per cent in the non-pCR group and 95.8 per cent in the pCR group (P = 0.0243). At five years, 27.7 per cent of the non-pCR group had a recurrence, as compared with none in the pCR group (P = 0.0018). Based on our study, we believe that a multidisciplinary approach to rectal cancer used at a community-based hospital can achieve oncological outcomes and survival benefits similar to those of larger academic tertiary care institutions.

Repair of a recurrent traumatic rectovaginal fistula using vaginal wall plication to reinforce a rectal wall advancement flap.

BACKGROUND: Rectovaginal fistulas (RVF) can cause significant physical discomfort and psychological distress for patients and remain amongst the most challenging disorders for surgeons. METHODS: A 28-year-old female with a history of a traumatic cloaca repaired 12 years prior was diagnosed with a recurrent RVF and underwent repair using a rectal wall advancement flap reinforced with posterior vaginal wall plication. This case is used to demonstrate surgical technique. The study adhered to the prescribed ethical guidelines. Informed consent was obtained from the patient to use the video recording of her operation for educational purposes. RESULTS: The patient had an uneventful postoperative course. The fistula was fully healed without any signs or symptoms of recurrence at 8 weeks follow-up exam. Her protective ileostomy was successfully closed. CONCLUSIONS: Transanal repair of a RVF through creation of a rectal advancement flap and plication of redundant vaginal wall can be used to treat appropriately selected patients with significant tissue defects.

Elective versus emergency surgery for ulcerative colitis: a National Surgical Quality Improvement Program analysis.

BACKGROUND: It is unclear whether advances in the medical management of ulcerative colitis (UC) have altered outcomes for medically intractable disease. Therefore, it is essential to understand the current impact of elective versus emergency surgery for UC. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was used to compare outcomes for elective versus emergency UC surgery between 2005 and 2010. RESULTS: Four thousand nine hundred sixty-two patients were eligible for study (94% elective and 6% emergent). Emergency surgery patients were significantly older and frequently underwent open surgery. Emergency cases were associated with a higher frequency of cardiac, pulmonary, and renal comorbidities; postoperative complications; longer hospital stays; and higher rates of return to the operating room. CONCLUSIONS: In the era of advanced UC medical therapy, the need for emergency surgery still exists and is associated with substantial morbidity and mortality. Data are needed to determine if earlier selection of surgery would be beneficial.

Timing of chemotherapy and survival in patients with resectable gastric adenocarcinoma.

AIM: To evaluate the timing of chemotherapy in gastric cancer by comparing survival outcomes in treatment groups. METHODS: Patients with surgically resected gastric adenocarcinoma from 1988 to 2006 were identified from the Los Angeles County Cancer Surveillance Program. To evaluate the population most likely to receive and/or benefit from adjunct chemotherapy, inclusion criteria consisted of Stage II or III gastric cancer patients > 18 years of age who underwent curative-intent surgical resection. Patients were categorized into three groups according to the receipt of chemotherapy: (1) no chemotherapy; (2) preoperative chemotherapy; or (3) postoperative chemotherapy. Clinical and pathologic characteristics were compared across the different treatment arms. RESULTS: Of 1518 patients with surgically resected gastric cancer, 327 (21.5%) received perioperative chemotherapy. The majority of these 327 patients were male (68%) with a mean age of 61.5 years; and they were significantly younger than non-chemotherapy patients (mean age, 70.7; P < 0.001). Most patients had tumors frequently located in the distal stomach (34.5%). Preoperative chemotherapy was administered to 11.3% of patients (n = 37) and postoperative therapy to 88.7% of patients (n = 290). An overall survival benefit according to timing of chemotherapy was not observed on univariate or multivariate analysis. Similar results were observed with stage-specific survival analyses (5-year overall survival: Stage II, 25% vs 30%, respectively; Stage III, 14% vs 11%, respectively). Therefore, our results do not identify a survival advantage for specific timing of chemotherapy in locally advanced gastric cancer. CONCLUSION: This study supports the implementation of a randomized trial comparing the timing of perioperative therapy in patients with locally advanced gastric cancer.

Laparoscopic versus open colon resections in California: a cross-sectional analysis.

Laparoscopic surgery is associated with decreased hospital length of stay, improved perioperative morbidity, and faster return to work compared with open procedures. Despite these benefits, laparoscopy has not been universally adopted with recent implementation estimates ranging from 10 to 30 per cent. The purpose of this study was to analyze the adoption of laparoscopic techniques for colon resections in California in 2009 based on institutional colectomy volume status. A total of 14,736 patients from 320 hospitals was analyzed. The laparoscopic to open case ratios for the low (zero to 17 cases/year), medium (18 to 50 cases/year), and high (greater than 50 cases/year) volume centers were: 0.32, 0.50, and 0.92, respectively. Although the data confirmed that a laparoscopic approach reduced length of stay (LOS) regardless of volume, lower adopters of laparoscopic colectomy had a longer overall total LOS, likely related to preponderance of open cases. Therefore, the data show that higher-volume institutions appear to have implemented laparoscopic colectomy for more of their case volume, and this adoption may account for the better institutional outcomes observed in these centers.

Milan Criteria and UCSF Criteria: A Preliminary Comparative Study of Liver Transplantation Outcomes in the United States.

The application of orthotopic liver transplantation (OLT) for patients with hepatocellular cancer (HCC) necessitates highly selective criteria to maximize survival and to optimize allocation of a scarce resource. The objective of this study was to compare the outcomes of OLT for HCC in patients transplanted under Milan and UCSF criteria. The United Network of Organ Sharing (UNOS) database was queried for patients who had undergone OLT for HCC from 2002 to 2007, and 1,972 patients (Milan criteria, n = 1, 913; UCSF criteria, n = 59) were identified. Patients were stratified by pretransplant criteria (Milan versus UCSF), and clinical and pathologic factors and overall survival were compared. There were no differences in age, gender, diabetes mellitus, body mass index, and hepatitis B, or C status between the two groups. Overall survival was similar between the Milan and UCSF cohorts (1-, 2-, 3-, and 4-year survival rates: 88%, 81%, 76%, and 72% versus 91%, 80%, 68% and 51%, respectively, P = 0.21). Although the number of patients within UCSF criteria was small, our results nevertheless suggest that patients with HCC may have equivalent survival when transplanted under Milan and UCSF criteria. Long-term followup may better determine whether UCSF criteria should be widely adopted.

Portocaval hemitransposition in pediatric liver transplant recipients: a single-center experience.

Few studies have reported a series of patients who have undergone portocaval hemitransposition at the time of orthotopic liver transplantation (OLT). Furthermore, no series report the outcome of pediatric patients who required the procedure. This work analyzes the experience with portocaval hemitransposition in the pediatric liver transplant population at a single center since the initial description of the procedure. We carried out a retrospective analysis of all pediatric liver transplants performed in our institution during the 8-year period from January 1, 1997, to December 31, 2004. Of 320 pediatric patients who received OLT during the study period, 7 underwent portocaval hemitransposition (2.2%). Five of the patients had biliary atresia. Four grafts were whole cadaveric livers, while the remaining 4 were left lateral segments from either in situ cadaveric split (n = 3) or living donation (n = 1). One patient received a whole cadaveric allograft and was retransplanted with a segment 2/3 graft; in both cases portocaval hemitransposition was utilized. Average warm ischemia time was 54 +/- 16 minutes. Three patients had primary nonfunction of the allograft; 2 were retransplanted with successful outcome, and the remaining patient died before retransplantation. Another patient died from recurrent disease. Four of 7 are long-term survivors and demonstrate good liver function as long as 8 years posttransplant. In conclusions, long-term survival is possible following OLT with portocaval hemitransposition in pediatric patients. However, rates of primary graft nonfunction can be high. Appropriate selection of recipient and type of donor graft are essential for good outcomes. Portocaval hemitransposition should be used cautiously and as a last resort to establish portovenous inflow.