Tumor Deposits in Stage III Colon Cancer: Correlation With Other Histopathologic Variables, Prognostic Value, and Risk Stratification-Time to Consider "N2c".

OBJECTIVES: National Comprehensive Cancer Network (NCCN) guidelines for stage III colon cancer define low-risk versus high-risk patients based on T (1 to 3 vs. 4) and N (1 vs. 2) status, with some variations in treatment. This study analyzes the impact of tumor deposits (TDs), T and N status, poor differentiation (PD), perineural invasion (PNI), and lymphovascular invasion (LVI) on survival. MATERIALS AND METHODS: A retrospective analysis (2010-2015) of the National Cancer Database of stage III colon cancer patients treated with both surgery and chemotherapy was conducted. Data was extracted on sex, race, age at diagnosis, Charlson-Deyo Score, histopathologic variables, and survival rates. Statistical analysis used the test of proportions, log-rank test for Kaplan-Meier curves, and Cox proportional hazard models. RESULTS: For the 42,901 patients analyzed, 5-year survival rates were similar for LNTD (59.8%) and LNTD (58.2%), but significantly worse for LNTD (41.5%) (P<0.001). The presence of LNTD was more often associated with T4 (36.9%), N2 (55.1%), PD (37.4%), PNI (34.5%), and LVI (69.1%), than LNTD or LNTD (P<0.001). The hazard ratios for each variable were: TD: 1.34; T4: 1.71; N2: 1.44; PD: 1.37; PNI: 1.11; LVI: 1.18. LN patients with ≥3 TD (N1c) had worse overall survival than those with 1 to 2 TD (P<0.01), but similar to ≥4 LNTD (N2) and 1 to 3 LNTD (N1a-b). In our model, 5-year survival ranged from 23.4% for high-risk to 78.1% for low-risk patients (P<0.001). CONCLUSION: This National Cancer Database (NCDB) analysis offers greater risk stratification and may prompt consideration of changes in American Joint Committee on Cancer (AJCC) classification (N2c, in addition to N1c) to reflect the different prognosis and guide management, as well as survivorship strategies, for TD stage III colon cancer patients.

Patterns of care for anal cancer in the United States - a comparison between academic and community cancer centers.

BACKGROUND: Management of squamous cell carcinoma of the anus (SCCA) is becoming more relevant, as its incidence increases. The purpose of this study was to investigate possible differences in patient population and care delivery for SCCA between academic and community cancer programs in the United States. METHODS: A review of available data from the American College of Surgeons Committee on Cancer National Cancer DataBase focused on gender, age, race, type of health insurance, comorbidity score, distance traveled for care, stage at diagnosis, and therapy utilization (surgery, chemotherapy, and radiation therapy) as first course of treatment (FCT). The analysis included 38,766 patients treated for SCCA. Of them, 14,422 patients received treatment at Academic Cancer Programs (ACPs), while 24,344 were treated at Community Cancer Programs (CCPs) between the years 2003 and 2013. RESULTS: Over the 11-year study period, ACPs had significantly more male patients, of younger age, a greater non-white race population, with more Medicaid or no insurance coverage, who traveled farther for cancer center care (p < 0.001). There was no difference between ACPs and CCPs with respect to Charlson co-morbidity score and stage of SCCA at diagnosis. For stage 0 patients, use of chemotherapy was 8% for ACPs, 9% for CCPs, and use of radiotherapy was 10% for ACPs and 14% for CCPs. The incidence of stage unknown was identical at both ACPs and CCPs (11.5%). CCPs had a greater overall utilization of radiation therapy as FCT for stage 0, I, II and IV patients (p < 0.001). CONCLUSIONS: Our study indicates that gender, demographic and socio-economic differences exist in the patient population with SCCA accessing different cancer programs in the US. The high incidence of stage unknown patients reflects ongoing challenges in the pre-treatment phase. A significant percentage of stage 0 patients received systemic chemotherapy and/or radiotherapy, rather than surgery alone. Despite comparable stage at diagnosis and comorbidity scores between ACPs and CCPs, there appear to be variations in treatment choices, especially with the use of radiotherapy, with associated cost and toxicity risks. Further analysis and monitoring of SCCA management in the US may lead to improved compliance with NCCN guidelines.

Challenges in Management of Squamous Cell Carcinoma of the Anus in New England and Across the United States: A Review of the National Cancer Data Base.

BACKGROUND: Management of squamous cell carcinoma of the anus (SCCA) is becoming more relevant, as its incidence continues to increase. The purpose of this study was to evaluate regional and national data to assess trends in epidemiology, access to cancer center care, and overall management strategies in SCCA. STUDY DESIGN: A review of available data from the American College of Surgeons Committee on Cancer National Cancer Data Base focused on incidence, sex, age, stage at diagnosis, distance traveled for care, and utilization of therapy as first course of treatment (FCT). The analysis included 40,817 patients treated for SCCA at 1513 cancer centers in the United States, of which 2347 patients were treated at 109 cancer centers in New England, between the years 2003 and 2013. RESULTS: Over the 11-year period, incidence of SCCA increased by 76% in the United States and by 83.8% in New England. Stage was unknown in 11.7% of all US cases, significantly higher than more common cancers, for example, breast (4.3%), prostate (6%), or colon (7.8%) (P<0.001). Patients in southern New England, compared with northern New England, traveled <10 miles more often (53.4% vs. 38.1%) (P<0.001), and>25 miles less often (14.3% vs. 28.7%) (P<0.001). Cases of early stage SCCA (0, I) were more frequent in southern New England (29.2%) than northern New England (21.7%) (P=0.0025), whereas more advanced stage (II to IV) cases occurred less frequently in southern New England (60.1%) than northern New England (72%) (P<0.001). Overall, the most common FCT was chemoradiotherapy, utilized in 49.3% of cases, followed by chemoradiotherapy plus surgery in 19.4% of cases. Stage unknown patients were treated with chemoradiotherapy in 34.6% of cases, with surgery alone in 20.2%, and with chemoradiotherapy plus surgery in 15.4% of cases. CONCLUSIONS: The incidence of SCCA is steadily increasing. Its frequency of stage unknown is significantly higher than other common cancer sites. Travel distance and stage at diagnosis data may reflect regional differences in cancer center care access. Although chemoradiotherapy remains the most commonly utilized FCT, challenges in accurate staging and inconsistent use of additional prognostic variables may affect optimal treatment.

'Natural orifice' transcolostomy full-thickness excision of colonic tumour.

This technical note describes a novel technique, not previously found in the surgical or endoscopic literature: A combined endoscopic and surgical approach to perform a full-thickness excision of a colonic tumour. At the time of colonoscopy via stoma, a large sessile polyp in the descending colon was detected but could not be safely resected endoscopically. The lesion was exteriorised by prolapsing the distal colon through the colostomy, then excised surgically with adequate margins in a full-thickness fashion. This approach was more complete than an endoscopic approach and less invasive than a segmental colectomy and redo colostomy. It may prove useful to surgical endoscopists facing a similar clinical situation in their practice.

Solitary Pouch Ulcer: A New Clinical Entity?

Solitary rectal ulcer syndrome is a well-known clinical entity, likely secondary to a defecatory dysfunction. In patients who have undergone restorative proctocolectomy with ileoanal reservoir, it is conceivable that a similar pathophysiology may lead to "solitary pouch ulcer," but such a syndrome has not been reported to date. This article reports 2 such cases and clinical success with lasting symptomatic relief through local therapy and behavior modification rather than anti-inflammatory.

CT scan findings do not predict outcome of nonoperative management in small bowel obstruction: Retrospective analysis of 108 consecutive patients.

OBJECTIVES: The study purpose was to investigate the ability of Emergency Department CT scan to predict the need for operative intervention in patients hospitalized for small bowel obstruction (SBO) likely secondary to adhesions (ASBO) and initially managed nonoperatively. DESIGN: Retrospective case series. Statistical analysis was done with independent-samples t-test and chi-square to identify correlation between variables and outcome of nonoperative management. SETTING: Tertiary care academic medical center. PATIENTS AND METHODS: Of 200 consecutive patients hospitalized for SBO, 108 were included in the study with a diagnosis of ASBO and received initial nonoperative management. Exclusion criteria were need for emergency surgery (e.g. peritonitis) or other diagnoses (e.g. neoplasms, hernias, Crohn's disease). CT findings such as transition point, small bowel faeces, high grade obstruction, and abnormal vascular course were correlated with failure of nonoperative management. RESULTS: Only 18 patients (16.7%) required operative intervention, while the other 90 (83.3%) were successfully discharged after nonoperative care. There was no correlation between CT scan findings and treatment outcome. CONCLUSIONS: Emergency Department CT scan findings do not significantly alter management decisions in patients admitted for ASBO and managed initially with nonoperative care.

A bariatric surgery center of excellence: operative trends and long-term outcomes.

BACKGROUND: Surgery remains the most effective intervention for obesity and its comorbidities. However, the long-term efficacy of bariatric procedures is rarely reported. This study addresses operative trends, efficiency, and long-term outcomes from a large bariatric program. STUDY DESIGN: Data were prospectively collected on 3,460 patients undergoing 3,503 operations from January 2004 to March 2013. Primary procedures included Roux-en-Y gastric bypass (RY; n = 2,966), adjustable band (AB; n = 352), and sleeve gastrectomy (SG; n = 118). There were 67 revisional procedures (RP). Mean operative time, hospital length of stay, major 30-day morbidity/mortality, follow-up compliance, and weight loss per procedure at follow-up were recorded. RESULTS: Mean operative times decreased to the following: RY, 53 minutes; AB, 35 minutes; SG, 46 minutes; and RP, 71 minutes. Mean length of stay was reduced to the following: RY, 1.53 days; AB, 0.97 days; SG, 2.12 days; and RP, 2.68 days. Major complications were mortality, 0.09%; leak, 0.51%; bleed, 2.37%; pneumonia, 0.63%; venous thromboembolism, 0.40%; and reoperation, 2.34%. The complication rate was lowest for AB and highest for SG (p < 0.05). Adjustable band was the initial procedure in 73% of cases requiring RP. Follow-up compliance was 93% at 1 year, 79% at 3 years, 71% at 5 years, and 33% at 9 years. Adjustable band offered significant weight loss at 1 and 3 years (p < 0.0001), but less than RY or SG (p < 0.0001). Excess weight loss was not significantly different between RY and SG at 1 year. Significant weight loss with RY persisted at 7 to 9 years (p < 0.0001). CONCLUSIONS: Our bariatric program experienced an increase in SG and RP and a decrease in AB. Optimization of care reduced operative time and length of stay. All procedures achieved significant weight loss in the first year. Adjusted band had the lowest morbidity, but inferior weight loss and greater need for revision. Long-term weight-loss data are only available for RY.

Distal margins in radical resections for rectal cancer after chemoradiation therapy: how short is long enough?

BACKGROUND: The purpose of our study was to assess the impact of distal margin length on outcome in patients with rectal cancer treated with neoadjuvant chemoradiation therapy (CRT) followed by radical resection. METHODS: Fifty-three consecutive patients were evaluated. The selection criteria included: adenocarcinoma of the mid- or distal rectum, locally advanced stage, absence of distant metastases, and preoperative CRT followed by proctectomy with total mesorectal excision. The operations included low anterior resection in 33 patients (62%) and abdominoperineal resection in 20 (38%). The outcome measures were: tumor regression, complete pathologic response, length of distal resection margins, status of radial margins and recurrence rate. RESULTS: Forty-eight patients (91%) had tumor regression, and 11 (21%) had a complete pathologic response. Distal resection margins were tumor-free in all patients, ranging in length from 0.1 to 7.4 cm (mean = 2.2). Follow-up (mean = 48.8 months) was current in 50 of 53 patients (94%). There was no locoregional recurrence. CONCLUSIONS: Distal resection margins shorter than 1-2 cm appear to be equivalent to longer margins in patients who undergo CRT followed by proctectomy with total mesorectal excision. These findings may lead to greater utilization of sphincter-saving procedures in rectal cancer.

Stapled revision of complete colorectal anastomotic obstruction.

Colonic and rectal anastomotic strictures occur with an incidence ranging from 3% to 30%. Several factors, such as defunctionalization, anastomotic leak, ischemia, radiation, and neoplasms, have been implicated in their pathogenesis. Management of large bowel strictures is generally based on their cause, location, and appearance. Various methods have been described, including endoscopic techniques (eg, balloon dilatation and/or stents) and operative revision. Postoperative rectal strictures usually respond well to direct dilatation, without the need for endoscopic balloons. If surgical revision is necessary, morbidity can be significant, as in any reoperative procedure. We hereby present a novel surgical method of revision for a complete anastomotic obstruction, which proved effective and avoided extensive operative dissection, mobilization, and re-resection.

Role of caveolae in the pathogenesis of cholesterol-induced gallbladder muscle hypomotility.

Muscle cells from human gallbladders (GB) with cholesterol stones (ChS) exhibit a defective contraction, excess cholesterol (Ch) in the plasma membrane, and lower binding of CCK-1 receptors. These abnormalities improved after muscle cells were incubated with Ch-free liposomes that remove the excess Ch from the plasma membrane. The present studies were designed to investigate the role of caveolin-3 proteins (Cav-3) in the pathogenesis of these abnormalities. Muscle cells from GB with ChS exhibit higher Ch levels in the plasma membrane that were mostly localized in caveolae and associated with parallel increases in the expression of Cav-3 in the caveolae compared with that in GB with pigment stones (PS). The overall number of CCK-1 receptors in the plasma membrane was not different between muscle cells from GB with ChS and PS, but they were increased in the caveolae in muscle cells from GB with ChS. Treatment of muscle cells from GB with ChS with a Galpha(i3) protein fragment increased the total binding of CCK-1 receptors (from 8.3 to 11.2%) and muscle contraction induced by CCK-8 (from 11.2 to 17.3% shortening). However, Galpha(q/11) protein fragment had no such effect. Moreover, neither fragment had any effect on muscle cells from GB with PS. We conclude that the defective contraction of muscle cells with excessive Ch levels in the plasma membrane is due to an increased expression of Cav-3 that results in the sequestration of CCK-1 receptors in the caveolae, probably by inhibiting the functions of Galpha(i3) proteins.

NK2 receptor-mediated spontaneous phasic contractions in normal and ulcerative colitis human sigmoid colon.

Human colonic circular muscle produces spontaneous phasic contractions that are reduced in ulcerative colitis. How the spontaneous phasic contractions develop and why they decrease in ulcerative colitis are not known. We found that spontaneous phasic contractions of normal sigmoid circular muscle strips were significantly reduced by 90-min incubation with tetrodotoxin (10(-5) M), which blocked neurokinin A release in basal conditions and in response to electrical stimulation. In addition, spontaneous contraction of human sigmoid colon was significantly decreased by the NK2 receptor antagonists MEN10376 (Asp-Tyr-D-Trp-Val-D-Trp-D-Trp-Lys-NH2) and NK2ra (Bz-Ala-Ala-D-Trp-Phe-D-pro-Pro-Nle-NH2) but not by atropine or by the NK1 antagonist FK888 (N2-[(4R)-4-hydroxyl-1-(1-methyl-1H-indol-3-yl)carbonyl-l-prolyl]-N-methyl-N-phenylmethyl-3-(2-naphthyl)-l-alaninamide), suggesting that NK2 receptors are involved in their development. The spontaneous phasic contractions were abolished by thapsigargin and cyclopiazonic acid and significantly decreased by the protein kinase C inhibitor chelerythrine and by the calmodulin inhibitor CGS9343B (1,3-dihydro-1-[1-[(4-methyl-4H,6H-pyrrolo[1,2-a]-[4,1]-benzoxazepin-4-yl)methyl]-4-piperidinyl]-2H-benzimidazol-2-one (1:1) maleate), suggesting that spontaneous phasic contractions may be mediated by Ca2+ release from intracellular stores and by a protein kinase C- and calmodulin-dependent pathway. In strips from patients with ulcerative colitis, spontaneous contractions were significantly reduced, and this reduction was partially restored by the hydrogen peroxide scavenger catalase. Neurokinin A release, however, was not affected. We conclude that spontaneous phasic contractions of human sigmoid circular smooth muscle may be mediated by activation of NK2 receptors, calcium release from intracellular stores, and activation of calmodulin and protein kinase C. In ulcerative colitis patients, spontaneous phasic contractions are decreased, and this decrease may be in part due to overproduction of hydrogen peroxide affecting sigmoid circular muscle.

Production of IL-1beta, hydrogen peroxide, and nitric oxide by colonic mucosa decreases sigmoid smooth muscle contractility in ulcerative colitis.

We have previously shown that sigmoid circular muscle cells from patients with ulcerative colitis (UC) exhibit reduced contraction and Ca2+ signaling in response to the neurotransmitter neurokinin A (NKA) and that IL-1beta and H2O2 may contribute to these reduced responses in UC. In addition, we have found that nitric oxide (NO) levels were significantly increased in UC circular muscle. To establish the site of origin for IL-1beta, H2O2, and NO, we assembled an in vitro system in which normal or UC mucosa were sealed between two chambers filled with oxygenated Krebs solution. Because the mucosa consists of full-thickness mucosa and submucosa, it is expected that whatever is released into the undernatant from the submucosal side may diffuse to the circular muscle layer in the intact colon. Treatment of normal sigmoid circular muscle cells for 2 h with undernatants collected from the UC submucosal side (UCS) significantly decreased contraction induced by NKA and thapsigargin and the NKA- and caffeine-induced Ca2+ signal in Ca2+-free medium. In addition, UC mucosa released into the undernatant on its submucosal side significantly more H2O2, IL-1beta, and NO than normal mucosa. The reduction in contraction and Ca2+ signal induced by UCS was partially reversed by pretreatment with an IL-1beta antibody or with catalase. The NO scavenger hemoglobin partially prevented UCS-induced reduction in contraction and Ca2+ signaling in response to NKA but not the reduced response to thapsigargin or caffeine. Sodium nitroprusside inhibited NKA but not the caffeine-induced Ca2+ signal. We conclude that in UC the mucosa releases IL-1beta, H2O2, and NO, which may contribute to the impaired Ca2+ release and altered sigmoid muscle contractility.