Medically Treated Diverticular Abscess Associated With High Risk of Recurrence and Disease Complications.

BACKGROUND: The best management for diverticulitis with abscess formation remains unknown. OBJECTIVE: The purpose of this study was to determine the natural course and outcomes of patients with medically treated diverticular abscess. DESIGN: We conducted a retrospective review of all patients at our institution with diverticular abscess confirmed by CT from 2004 to 2014. SETTINGS: This study was conducted in a tertiary referral hospital. PATIENTS: A total of 1194 patients were treated for acute diverticulitis in 10 years; 210 patients with CT-documented diverticular abscess were analyzed (140 men (66.7%) and 70 women (33.3%); median age 45 years; range, 23-84 years). MAIN OUTCOME MEASURES: Overall recurrence and disease complication rates, as well as the need for subsequent operation after initial successful nonsurgical management, were measured, along with analysis of the whole cohort and the subgroup of patients with percutaneous drainage for diverticular abscess. RESULTS: During the initial presentation, 25 patients failed nonoperative management and required an urgent operation. A total of 185 patients were initially successfully managed without surgery and were discharged from the hospital. Of these, recurrent diverticulitis developed in 112 (60.5%) after an average time interval of 5.3 months (range, 0.8-20.0 months); 47 patients (42%) experienced more than 1 episode. The modified Hinchey stage at time of recurrence (compared with index stay) increased in 51 patients (45.6%). Seventy one (63%) of 112 recurrences showed local disease complications (recurrent abscess, fistula, stricture, or peritonitis). Fistula formation (colovesicular/colovaginal/colocutaneous) and recurrent abscess were the 2 most frequent complications. Twenty nine (26%) of 112 recurrences required an urgent operation; overall, 66 (59%) of 112 patients eventually underwent surgery at our institution. The original abscess size in patients who later developed recurrences was significantly larger than in patients who did not develop recurrence (5.3 vs 3.2 cm; p < 0.001). Paradoxically, larger abscesses also had a higher chance of successful CT-guided drainage (average size, 6.5 cm; range, 1.1-14 cm), yet CT-guided drainage did not change the overall outcome. Of 65 (31.0%) of 210 patients with CT-guided drainage, 45 (73.8%) of 61 after initial success experienced a recurrence. Furthermore, local disease complications at the time of recurrence were noted in 32 of 61 patients (52.5% of all CT-guided drainage, 71.1% of post-CT-guided drainage recurrences), and 13 (29.2%) of 45 patients with recurrence after successful CT-guided drainage subsequently required an urgent operation. LIMITATIONS: The study was limited by its retrospective noncomparative design. CONCLUSIONS: Diverticular abscesses represent complicated diverticulitis and are associated with a high risk of recurrences and disease complications. Recurrences (contrary to other series) were often more severe than the index presentation. The successful CT-guided drainage of a diverticular abscess does not appear to lower the risks of future recurrence or complication rates and frequently is only a bridge to surgery. After initial successful nonoperative management, patients with diverticular abscess should be offered interval elective colectomy (see Video, Supplemental Digital Content 1, http://links.lww.com/DCR/A216).

TAMIS-assisted laparoscopic low anterior resection with total mesorectal excision in a cadaveric series.

BACKGROUND: To demonstrate the feasibility of an innovative technique for the surgical management of rectal cancer, we performed transanal minimally invasive surgery assisted low anterior resection with total mesorectal excision (TAMIS-assisted LAR with TME) in a cadaver model. Transanal LAR via natural orifice transluminal endoscopic surgery has been reported in cadaveric series using rigid transanal platforms. This procedure has not been described using a combination of a single incision laparoscopy and TAMIS transanal endoscopic platform. We describe the first cadaveric series of TAMIS-assisted LAR with TME. METHODS: TAMIS-assisted LAR with TME was successfully performed in five fresh human cadavers. The procedure was performed using the mini-Gelpoint single incision platform and the Gelpoint Path TAMIS platform (Applied Medical, Rancho Santa Margarita, CA). The variables recorded were age, body mass index (BMI), operative time, complications, and specimen length. The grade of the TME was determined by evaluation of the specimen by photo documentation by a gastrointestinal pathologist. RESULTS: All cadavers were male with a mean age of 71 ± 8 years and mean BMI of 28 ± 3 kg/m(2). The mean operative time was 200 ± 55 min (range 128-249 min). The quality of the TME was grade I (complete) with intact mesorectum in all five cases. The mean specimen length was 36.8 ± 3.4 cm. CONCLUSIONS: TAMIS-assisted LAR with TME was feasible. A high-quality TME can be achieved using this innovative technique. Transanal endoscopic total mesorectal dissection may revolutionize the surgical management of rectal cancer. However, multicenter clinical trials are needed to further evaluate the oncologic safety and surgical outcomes of transanal endoscopic TME using various platforms before widespread application of this new technique.

Microsatellite instability, EMAST, and morphology associations with T cell infiltration in colorectal neoplasia.

BACKGROUND AND OBJECTIVES: Colorectal tumors are often observed with tumor infiltrating lymphocytes, presumably as a host-immune response, and patterns may segregate by types of genomic instability. Microsatellite unstable (MSI) colorectal cancers contain a pronounced lymphocyte reaction that can pathologically identify these tumors. Colorectal tumors with elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) have not been examined for lymphocyte patterns. METHODS: We evaluated a 108-person cohort with 24 adenomas and 84 colorectal cancers for MSI and EMAST. Immunohistochemical detection of CD4+ and CD8+ T cell infiltration were performed. Prognostic relevance was assessed by survival analysis. RESULTS: CD8+ T cell infiltration in the tumor cell nest (p = 0.013) and tumor stroma (p = 0.004) were more prominent in moderately and poorly differentiated adenocarcinoma than in adenoma and well-differentiated adenocarcinoma. CD8+ T cells in the tumor cell nest (p = 0.002) and tumor stroma (p = 0.009) were at higher density in tumors with ulcerating features compared to tumors with a sessile or polypoid appearance. MSI-H tumors showed a higher density of CD8+ T cell infiltrations in tumor cell nests (p = 0.003) and tumor stroma (p = 0.001). EMAST-positive tumors showed a higher density of CD8+ T cell infiltrations than EMAST-negative tumors both in tumor cell nest (p = 0.027) and in tumor stroma (p = 0.003). These changes were not observed with CD4+ T lymphocytes. There was no difference in cancer patient survival based on density of CD8+ cells. CONCLUSIONS: CD8+ T lymphocytes, but not CD4+ cells, were increased in tumor cell nests and the tumor stroma in both MSI and EMAST tumors, and showed higher infiltration in ulcerated tumors. CD8+ T lymphocyte infiltration is associated with both EMAST and MSI patterns, and increases with histological advancement.

John Cunningham virus T-antigen expression in anal carcinoma.

BACKGROUND: Anal carcinoma is thought to be driven by human papillomavirus (HPV) infection through interrupting function of cell regulatory proteins such as p53 and pRb. John Cunningham virus (JCV) expresses a T-antigen that causes malignant transformation through development of aneuploidy and interaction with some of the same regulatory proteins as HPV. JCV T-antigen is present in brain, gastric, and colon malignancies, but has not been evaluated in anal cancers. The authors examined a cohort of anal cancers for JCV T-antigen and correlated this with clinicopathologic data. METHODS: Archived anal carcinomas were analyzed for JCV T-antigen expression. DNA from tumor and normal tissue was sequenced for JCV with viral copies determined by quantitative polymerase chain reaction and Southern blotting. HPV and microsatellite instability (MSI) status was correlated with JCV T-antigen expression. RESULTS: Of 21 cases of anal cancer (mean age 49 years, 38% female), 12 (57%) were in human immunodeficiency virus (HIV)-positive individuals. All 21 cancers expressed JCV T-antigen, including 9 HPV-negative specimens. More JCV copies were present in cancer versus surrounding normal tissue (mean 32.54 copies/µg DNA vs 2.98 copies/µg DNA, P = .0267). There was no correlation between disease stage and viral copies, nor between viral copies and HIV-positive or -negative status (28.7 vs 36.34 copies/µg DNA, respectively, P = .7804). In subset analysis, no association was found between JCV T-antigen expression and HPV or MSI status. CONCLUSIONS: Anal carcinomas uniformly express JCV T-antigen and contain more viral copies compared with surrounding normal tissue. JCV and its T-antigen oncogenic protein, presumably through interruption of cell regulatory proteins, may play a role in anal cancer pathogenesis.

Microsatellite alterations at selected tetranucleotide repeats are associated with morphologies of colorectal neoplasias.

BACKGROUND & AIMS: Elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) occurs during microsatellite instability (MSI) that is not associated with major defects in DNA mismatch repair (MMR) but rather the reduced (heterogenous) expression of the MMR protein hMSH3; it occurs in sporadic colorectal tumors. We examined the timing of development of EMAST during progression of colorectal neoplasias and looked for correlations between EMAST and clinical and pathology features of tumors. METHODS: We evaluated tumor samples from a cohort of patients that had 24 adenomas and 84 colorectal cancers. EMAST were analyzed after DNA microdissection of matched normal and tumor samples using the polymorphic tetranucleotide microsatellite markers MYCL1, D9S242, D20S85, D8S321, and D20S82; data were compared with clinical and pathology findings. Traditional MSI analysis was performed and hMSH3 expression was measured. RESULTS: Moderately differentiated adenocarcinomas and poorly differentiated adenocarcinomas had higher frequencies of EMAST (56.9% and 40.0%, respectively) than well-differentiated adenocarcinomas (12.5%) or adenomas (33.3%) (P = .040). In endoscopic analysis, ulcerated tumors had a higher frequency of EMAST (52.3%) than flat (44.0%) or protruded tumors (20.0%) (P = .049). In quantification, all tumors with >3 tetranucleotide defects lost MSH3 (>75% of cells); nuclear heterogeneity of hMSH3 occurred more frequently in EMAST-positive (40.0%) than in EMAST-negative tumors (13.2%) (P = .010). CONCLUSIONS: EMAST is acquired during progression of adenoma and well-differentiated carcinomas to moderately and poorly differentiated carcinomas; it correlates with nuclear heterogeneity for hMSH3. Loss of hMSH3 corresponds with multiple tetranucleotide frameshifts. The association between EMAST and ulcerated tumors might result from increased inflammation.

Recent smoking is a risk factor for anal abscess and fistula.

BACKGROUND: Smoking is a risk factor for inflammatory, fistulizing cutaneous diseases. It seems reasonable that smoking might be a risk factor for anal abscess/fistula. OBJECTIVE: This study aimed to test the hypothesis that recent smoking is a risk factor for development of anal abscess/fistula. DESIGN: This is a case-control study. SETTINGS: This study was conducted at a Department of Veterans Affairs general surgical clinic. PATIENTS: Included in the study were 931 patients visiting the general surgical clinic over a 6-month period. INTERVENTIONS: A tobacco use questionnaire was administered. MAIN OUTCOME MEASURES: Patients with anal abscess/fistula history were compared with controls, who had all other general surgical conditions. To investigate the temporal relation between smoking and the clinical onset of anal abscess/fistula, we compared the group consisting of current smokers and former smokers who had recently quit, against the group consisting of nonsmokers and former smokers who had quit a longer time ago (ie, not recently). We excluded patients with IBD and HIV. RESULTS: Cases and controls were comparable in age (57 and 59 y) and sex (93% and 97% male). After exclusions, there were 74 anal abscess/fistula cases and 816 controls. Among the anal abscess/fistula cases, 36 patients had smoked within 1 year before the onset of anal abscess/fistula symptoms, and 38 had not smoked within the prior year; among controls, 249 had smoked within 1 year before seeking surgical treatment, and 567 had not (OR 2.15, 95% CI 1.34-3.48, 2-tail P = .0025). Using a 5-year cutoff for recent smoking, the association was less pronounced but still significant (OR 1.72, 95% CI 1.03-2.86, P = .0375), and the association was insignificant at 10 years (OR 1.34, 95% CI 0.78-2.21, P = .313). LIMITATIONS: Limitations of the study included self-selection bias, recall bias, convenience sample, and noninvestigation of the dose-response relationship. CONCLUSIONS: Recent smoking is a risk factor for anal abscess/fistula development. As in other smoking-related diseases, the influence of smoking as a risk factor for anal abscess/fistula diminishes to baseline after 5 to 10 years of smoking cessation. Anal abscess/fistula can be added to the list of chronic, inflammatory cutaneous conditions associated with smoking.

Surgical management of ulcerative colitis in the era of biologicals.

PURPOSE: Proctocolectomy has been a curative option for patients with severe ulcerative colitis. In recent years, there has been a growing use of medical salvage therapy in the management of patients with moderate to severe ulcerative colitis. We aimed at reviewing the role of surgical management in a time of intensified medical management on the basis of published trial data. The aim was to determine the efficacy of aggressive medical versus surgical management in achieving multifaceted treatment goals. METHODS: A comprehensive search of Pubmed, Medline, the Cochrane database was performed. Abstracts were evaluated for relevance. Selected articles were then reviewed in detail, including references. Recommendations were then drafted based on evidence and conclusions in the selected articles. RESULTS: The majority of patients with UC will not need surgery. However, steroid-refractoriness and steroid-dependence signal a subset of patients with more challenging disease. Biological therapy has been shown to achieve short-term improvement and temporarily reduce the need for a colectomy. However, there is a substantial financial and medical price to pay because a high fraction of these salvaged patients will still need a curative colectomy but may be exposed to the negative impact of prolonged immunosuppression, chronic illness, and a higher probability to require 3 rather than 2 operations. Proctocolectomy with ileo-anal pouch anastomosis-performed in 1, 2, or 3 steps depending on the patient's condition-remains the surgical procedure of choice. Even though it has its share of possible complications, it has been associated with excellent long-term outcomes and high levels of satisfaction, such that in the majority of patients they become indistinguishable from unaffected normal individuals. CONCLUSIONS: The current data demonstrate that use of medical salvage therapy in the treatment of UC will likely continue to grow and evolve. Consensus is being developed to better define and predict failure of medical therapy and clarify the role of the different treatment modalities. For many patients, sacrificing the nonresponsive diseased colon is an underused or unnecessarily delayed chance to normalize their health and life. Biologicals in many instances may have to be considered the bridge to that end.

Use of the American College of Surgeons NSQIP Surgical Risk Calculator for Laparoscopic Colectomy: how good is it and how can we improve it?

BACKGROUND: The American College of Surgeons NSQIP risk calculator was developed from multi-institutional clinical data to estimate preoperative risk. The impact of outliers has the potential to greatly affect predictions. Although the effect of outliers is minimized in large series, their impact on the individual provider or institution could be profound. No previous study has assessed the risk calculator for a single institution or provider, including outliers. Our goal was to evaluate the accuracy of the predicted outcomes at a single institution. STUDY DESIGN: Laparoscopic colectomies performed by two colorectal surgeons at a tertiary referral center were prospectively evaluated using the risk calculator. Predicted outcomes were compared with actual outcomes for length of stay (LOS), complications, return to the operating room, and death. Main outcomes measures were differences in actual vs predicted outcomes. RESULTS: One hundred and sixteen patients were included. Actual LOS was higher than predicted (mean ± SD 4.22 ± 5.49 days vs predicted 4.11 ± 1.18 days; p = 0.0001). Four outliers with multiple complications had an LOS >3 SDs from the mean. After removing these, observed LOS was significantly shorter than predicted (adjusted LOS mean ± SD 3.31 ± 2.30 days vs predicted 4.05 ± 1.14 days; p = 0.002). Occurrence of any complication was significantly lower than predicted (17.3% vs 19.4%; p = 0.05). Rates of major complications (13.2% vs 19.4%; p = 0.009) and surgical site infections (9.8% vs 11.8%; p = 0.006) were also significantly lower than predicted. There were no significant differences in death, urinary tract infection, renal failure, and reoperation rates. CONCLUSIONS: Although the risk calculator was effective for evaluating average surgical-risk patients, it does not accurately predict outcomes in a small percentage of patients when one or more serious complications occur. Addition of surgeon- and patient-specific data via the American College of Surgeons case-logging system could better adjust for these areas.

Relationship of EMAST and microsatellite instability among patients with rectal cancer.

BACKGROUND: Elevated microsatellite instability at selected tetranucleotide repeats (EMAST) is a genetic signature identified in 60% of sporadic colon cancers and may be linked with heterogeneous expression of the DNA mismatch repair (MMR) protein hMSH3. Unlike microsatellite instability-high (MSI-H) in which hypermethylation of hMLH1 occurs followed by multiple susceptible gene mutations, EMAST may be associated with inflammation and subsequent relaxation of MMR function with the biological consequences not known. We evaluated the prevalence of EMAST and MSI in a population-based cohort of rectal cancers, as EMAST has not been previously determined in rectal cancers. METHODS: We analyzed 147 sporadic cases of rectal cancer using five tetranucleotide microsatellite markers and National-Cancer-Institute-recommended MSI (mononucleotide and dinucleotide) markers. EMAST and MSI determinations were made on analysis of DNA sequences of the polymerase chain reaction products and determined positive if at least two loci were found to have frame-shifted repeats upon comparison between normal and cancer samples from the same patient. We correlated EMAST data with race, gender, and tumor stage and examined the samples for lymphocyte infiltration. RESULTS: Among this cohort of patients with rectal cancer (mean age 62.2 ± 10.3 years, 36% female, 24% African American), 3/147 (2%) showed MSI (three males, two African American) and 49/147 (33%) demonstrated EMAST. Rectal tumors from African Americans were more likely to show EMAST than Caucasians (18/37, 49% vs. 27/104, 26%, p = 0.014) and were associated with advanced stage (18/29, 62% EMAST vs. 18/53, 37%, non-EMAST p = 0.02). There was no association between EMAST and gender. EMAST was more prevalent in rectal tumors that showed peri-tumoral infiltration compared to those without (30/49, 60% EMAST vs. 24/98, 25% non-EMAST, p = 0.0001). CONCLUSIONS: EMAST in rectal cancer is common and MSI is rare. EMAST is associated with African-American race and may be more commonly seen with metastatic disease. The etiology and consequences of EMAST are under investigation, but its association with immune cell infiltration suggests that inflammation may play a role for its development.

Expectant management of anal squamous dysplasia in patients with HIV.

PURPOSE: Anal squamous dysplasia is commonly found in patients with HIV infection. There is no satisfactory treatment that eradicates this premalignant lesion with low morbidity and low recurrence. This study reviews a series of patients with HIV and an abnormal anal examination who had squamous dysplasia and who have been followed with physical examination alone and with repeat biopsies as necessary for new or suspicious lesions. METHODS: We reviewed the charts of 40 HIV-positive men who had squamous dysplasia of the anal canal and anal margin, focusing on history, physical findings, histologic diagnosis, and the occurrence of invasive squamous-cell carcinoma. RESULTS: Forty HIV-positive men (mean age, 39 years) were followed for anal squamous dysplasia. Biopsies revealed dysplasia, which was usually multifocal. The grade of dysplasia varied, but 28 of 40 patients had at least one area of severe dysplasia. All patients had a follow-up period greater than one year (mean, 32 months; range, 13-130 months). Three patients developed invasive carcinoma while under surveillance, and these were completely excised or cured with chemoradiation. CONCLUSIONS: Extensive excision for dysplasia in the context of HIV confers high morbidity and questionable benefit, and other treatments are of uncertain value. In a group of patients followed expectantly, most did not develop invasive cancer, and in those who did, early cancers could be identified and cured. Physical examination surveillance for invasive carcinoma may be acceptable for following patients with HIV and biopsy-proven squamous dysplasia.