Findings on Colonoscopy after Diverticulitis: A Multicenter Review.

Diverticular disease is a common problem where patients with diverticulosis have a 1-4 per cent risk of acute diverticulitis. Current guidelines recommend a colonoscopy after.the resolution of acute diverticulitis. The aim of this study was to evaluate the yield of significant findings on colonoscopy after an episode of diverticulitis. This is a retrospective analysis of patients who underwent colonoscopy after an episode of diverticulitis between November 2005 and August 2017 at three major teaching hospitals. Advanced adenomas were defined as adenomas ≥1 cm, serrated adenomas, and tubulovillous or villous adenomas. A total of 584 patients (298 males; 51%) underwent colonoscopy for a history of diverticulitis after resolution of acute symptoms. Colonoscopy was complete in 488 patients (84%). Among these 488 patients, 446 had diverticular disease, 31 had advanced adenomas, and four had adenocarcinomas. Colonoscopies were incomplete in 96 patients (16%). Forty-six of those patients underwent surgery. The overall incidence of advanced adenomas and adenocarcinomas was 32 (5.4%) and nine (1.5%), respectively. In our study, the prevalence of advanced adenomas and adenocarcinomas was relatively high compared with the average risk individuals. Our findings support that patients after an episode of diverticulitis should continue to get a colonoscopy.

Anal Adenocarcinoma: Outcomes in an Uncommon Malignancy.

Adenocarcinoma is an uncommon malignancy of the anal canal. Although it is recognized as an aggressive disease, optimal management and long-term outcomes are not well established. Patients diagnosed with anal adenocarcinoma were identified from a cancer database. Their charts were reviewed for patient and disease characteristics, management, and outcomes. Eighteen patient charts from 1997 to 2012 were reviewed. Nine patients presented with stage II disease, five with stage III, three with stage IV, and one was inadequately staged before chemoradiation. One patient refused treatment, one patient went straight to abdominoperineal resection, 13 patients underwent initial chemoradiation therapy, and three underwent palliative chemotherapy. Of the 13 patients who received neoadjuvant therapy, eight underwent subsequent radical resection; three progressed during neoadjuvant and became unresectable, one had complete pathologic response and was observed, and one did not complete neoadjuvant and was lost to follow-up. Two patients with stage II disease were disease free over eight years, and one was disease free after 26 months; four patients had persistent or recurrent local disease, and 10 developed metastatic disease. Seven patients died with disease at a median 16 months, and the other seven were alive with disease at a median follow-up of 10 months. Patients with anal adenocarcinoma present at advanced stages, and cure is rare. Although chemoradiation followed by abdominoperineal resection is the most common management strategy, the potential for curative resection and long-term disease free survival is minimal, regardless of stage at presentation.

Excess of proximal microsatellite-stable colorectal cancer in African Americans from a multiethnic study.

PURPOSE: African Americans (AA) have the highest incidence of colorectal cancer compared with other U.S. populations and more proximal colorectal cancers. The objective is to elucidate the basis of these cancer disparities. EXPERIMENTAL DESIGN: Of note, 566 AA and 328 non-Hispanic White (NHW) colorectal cancers were ascertained in five Chicago hospitals. Clinical and exposure data were collected. Microsatellite instability (MSI) and BRAF (V600E) and KRAS mutations were tested. Statistical significance of categorical variables was tested by the Fisher exact test or logistic regression and age by the Mann-Whitney U test. RESULTS: Over a 10-year period, the median age at diagnosis significantly decreased for both AAs (68-61; P < 0.01) and NHWs (64.5- 62; P = 0.04); more AA patients were diagnosed before age 50 than NHWs (22% vs. 15%; P = 0.01). AAs had more proximal colorectal cancer than NHWs (49.5% vs. 33.7%; P < 0.01), but overall frequencies of MSI, BRAF and KRAS mutations were not different nor were they different by location in the colon. Proximal colorectal cancers often presented with lymphocytic infiltrate (P < 0.01) and were diagnosed at older ages (P = 0.02). Smoking, drinking, and obesity were less common in this group, but results were not statistically significant. CONCLUSIONS: Patients with colorectal cancer have gotten progressively younger. The excess of colorectal cancer in AAs predominantly consists of more proximal, microsatellite stable tumors, commonly presenting lymphocytic infiltrate and less often associated with toxic exposures or a higher BMI. Younger AAs had more distal colorectal cancers than older ones. These data suggest two different mechanisms driving younger age and proximal location of colorectal cancers in AAs.

Management of anastomotic leak: lessons learned from a large colon and rectal surgery training program.

BACKGROUND: Anastomotic leak is a dreaded surgical complication that can lead to significant morbidity and mortality. Despite its prevalence, there is no consensus on the management of anastomotic leak. This study aimed to review the management of anastomotic leak in the Division of Colon and Rectal Surgery at two institutions. METHODS: This is a retrospective review of all anastomotic leaks occurring after surgery in the Division of Colon and Rectal Surgery at two teaching institutions during 1997-2008. RESULTS: Altogether, 103 leaks occurred in 1,707 anastomoses (6 %), with a median time to diagnosis of 20 days (2-1,400 days). The 90-day mortality rate was 3 %. The majority of cases were managed nonoperatively (73 %), and the majority of leaks were from an extraperitoneal anastomosis (67 %). Success (i.e., radiographic demonstration of a healed leak, restored gastrointestinal continuity) occurred in 54 % of operatively managed leaks and 57 % of nonoperatively managed leaks (56 % overall). Operative management differed by leak location. In 91 % of patients with intraperitoneal leaks, the anastomosis was resected. In 76 % of patients with extraperitoneal leaks, diversion and drainage alone was performed without manipulating the anastomosis. Nonoperative management was successful for 57 % of extraperitoneal leaks and 58 % of intraperitoneal leaks. There was no significant difference in the success rates based on type of management (operative/nonoperative) for either extraperitoneal or intraperitoneal leaks. CONCLUSIONS: Anastomotic leak continues to result in patient morbidity and mortality. Its diverse presentation requires tailoring management to the patient. Nonoperative and operative treatments are viable options for intraperitoneal and extraperitoneal leaks based on patient presentation.

Hydrophilic interaction chromatography with aerosol-based detectors (ELSD, CAD, NQAD) for polar compounds lacking a UV chromophore in an intravenous formulation.

In this work, a high performance liquid chromatography (HPLC) method is reported for the separation and quantitation of a drug substance that is highly polar and lacking a chromophore in a mannitol intravenous (IV) formulation. Three polar stationary phases operated in hydrophilic interaction chromatography (HILIC) mode were evaluated in conjunction with an Alltech 800 ELSD detector. These columns were evaluated with respect to chromatographic properties such as buffer, pH and organic concentrations to identify the best stationary phase. The chromatographic method was then validated for the determination of mGlu2/3 receptor agonist (-)-(1R, 4S, 5S, 6S)-4-Amino-2-sulfonylbicyclo [3.1.0] hexane-4,6-dicarboxylic acid (LY404039) content in a mannitol IV formulation with respect to linearity (R(2) of 0.9997), repeatability (%RSD of 0.36%), accuracy, solution stability (99.56% after 24h), specificity, intra-assay precision (%RSD 0.48%) and limit of detection (LOD, ∼50 µg/mL). In addition to the Alltech 800 ELSD detector, several other aerosol-based detectors were investigated for reproducibility, linearity and LOD. These additional detectors consisted of an Alltech 3300 evaporative light scattering detector (ELSD), a nano quantity analyte detector (NQAD) and a charged aerosol detector (CAD). Based on the data from this report, a feasible isocratic LC method was achieved using a TSKgel Amide-80 column with mobile phase conditions of 30% water with 0.2% trifluoroacetic acid (TFA) and 70% acetonitrile (ACN) using any of the four aerosol-based detectors for detection and quantitation.

Ligation of intersphincteric fistula tract: early results of a pilot study.

BACKGROUND: Transsphincteric fistulotomy is associated with a variable degree of fecal incontinence that is directly related to the thickness of the sphincter mechanism overlying the fistula. Staged fistulotomy with seton or the use of cutting seton designed to reduce the proportionate incontinence rates have failed to do so. This has resulted in attempts to find novel sphincter-sparing techniques in the past 2 decades including draining seton, fibrin sealant, anal fistula plug, dermal advancement, and endorectal advancement flaps. These operations have a variable success rates of 30% to 80% reported in the literature. OBJECTIVE: In 2007, Rojanasakul from Thailand demonstrated a novel technique, ligation of intersphincteric fistula tract, and reported a 94% success rate in a small series. Since then, a few other small cohorts of patients have been reported in the literature with success rates varying from 57% to 82%. An institutional review board-approved study was proposed to measure our results and compare them with the published data. DESIGN: This study was undertaken to evaluate the success of ligation of intersphincteric fistula tract procedures in a group of unselected transsphincteric fistulas deemed unsuitable for lay-open fistulotomy. SETTING: The procedure was performed in 3 different settings: a public institution, a major university hospital, and a large private hospital. PATIENTS: A total of 40 patients underwent 41 ligation of intersphincteric fistula tract procedures performed by 6 Board-certified colon and rectal surgeons. RESULTS: In a mean follow-up of 18 weeks, 74% of the patients achieved healing. In patients who underwent ligation of intersphincteric fistula tract as their primary procedure, the healing rate was 90%. The limitation of this study is its "case series" nature and the short mean follow-up period of 18 weeks. CONCLUSION: Ligation of intersphincteric fistula tract has had excellent success in transsphincteric fistulas in multiple small series. A larger number of patients and longer follow-up period are needed to validate the early favorable results.

A systematic approach to development of liquid chromatographic impurity methods for pharmaceutical analysis.

A strategy for developing chromatographic methods designed to determine impurities and degradation products in active pharmaceutical ingredients and drug products is presented. Selectivity is achieved by evaluating a chromatographic space comprised of 12 stationary/mobile phase combinations. Stationary phases predicted to be orthogonal based on their hydrophobic subtraction model parameters used. The particle sizes, column dimensions, and gradient times chosen provide high peak capacities and allow operation at backpressures that can be achieved with standard instrumentation. The mobile phases utilized are compatible with MS detection and cover a wide range of pH, solvent strength, and solvent selectivity. Analyte detection is accomplished using a combination of diode array and mass spectroscopic detectors which allow mixtures of project compounds to be injected and selectively detected. Automation of data acquisition and processing is accomplished using AutoChrom software from ACD\Labs. The strategy is illustrated with detailed data from two case studies and summary data from nineteen pharmaceutical projects.

Evaluating the performances of quantitative structure-retention relationship models with different sets of molecular descriptors and databases for high-performance liquid chromatography predictions.

Quantitative structure-retention relationship (QSRR) models were studied for two databases: one with 151 compounds and the other with 1719 compounds. In both cases, the three modeling methods employed (multiple linear regression, partial least squares, and random forests) provided similar prediction results with regard to root-mean-square error of prediction. The reversed-phase retention related seven molecular descriptors provided better models for the smaller dataset, while the use of over 2000 molecular descriptors generated better models for the larger dataset. The QSRR models were then validated with a mixture of an active pharmaceutical ingredient and its four process/degradation impurities. Finally, classification of compounds based on similar logD profiles before QSRR modeling improved chromatographic predictability for the models used. The results showed that database composition had a desirable effect on prediction accuracy for certain input molecules.

New techniques in the treatment of common perianal diseases: stapled hemorrhoidopexy, botulinum toxin, and fibrin sealant.

There have been several recent advances in the treatment of common perianal diseases. Stapled hemorrhoidopexy is a procedure of hemorrhoidal fixation, combining the benefits of rubber band ligation into an operative technique. The treatment of anal fissure has typically relied upon internal sphincterotomy; however, it carries a risk of incontinence. The injection of botulinum toxin represents a new form of sphincter relaxation, without division of any sphincter muscle; morbidity is minimal and results are promising. For the treatment of fistula in a fistulotomy remains the gold standard, however, it carries significant risk of incontinence. Use of fibrin sealant to treat fistulae has been met with variable success. It offers sealing of the tract, and then provides scaffolding for native tissue ingrowth.

Very high-pressure capillary liquid chromatography assisted by voltage.

Capillary liquid chromatography at moderately high pressures and capillary electrochromatography (CEC) have been combined to drive the mobile phase through capillary columns packed with small diameter particles. In a column packed with 1.5 microm nonporous particles, linear velocities near 3mm/s were observed when combining inlet pressures of 690 bar (10,000 psi) and an applied voltage of 25 kV. Optimum linear velocity for the column was achieved using a pressure-voltage combination of 350 bar (5000 psi) and 5 kV. Separation efficiencies at near optimum linear velocity agreed with those predicted by the van Deemter equation for liquid chromatography. Retention factors were observed to decrease under pressure-voltage combination as the voltage was increased; such a behavior has been attributed to Joule heating effects.

Endometriosis-induced acute small and large bowel obstruction: rare clinical entities.

The extragonadal manifestations of intestinal endometriosis necessitating immediate abdominal surgical exploration are, to date, sparsely represented within the literature. We present two cases of acute complete small and large bowel obstruction secondary to endometriosis, requiring emergent laparotomy; and review the pertinent literature.

Upper gastrointestinal bleeding caused by a "hypophrenic" diverticulum of the distal esophagus.

Distal esophageal diverticula are uncommon acquired anomalies of the distal thoracic esophagus. We report a case of an elderly man presenting with a history of upper gastrointestinal bleeding secondary to a distal esophageal diverticulum arising from the intra-abdominal portion of the esophagus. To our knowledge, this is the first report of upper gastrointestinal bleeding from a subdiaphragmatic esophageal diverticulum. We propose the term "hypophrenic diverticulum of the esophagus" for this disease entity, and we would like to bring it to the attention of readers of The American Surgeon.

Treatment of fistulas-in-ano with fibrin sealant in combination with intra-adhesive antibiotics and/or surgical closure of the internal fistula opening.

PURPOSE: The treatment of fistulas-in-ano with fibrin sealant injection has been moderately successful. Failures can be caused by persistent infection within the tract or early expulsion of the clot. In an attempt to improve the success rate, we examined three modifications of the sealant procedure: the addition of cefoxitin to the sealant, surgical closure of the primary opening, or both. METHODS: A prospective, randomized, clinical trial was performed in which patients were treated with Tisseel-VH fibrin sealant according to previously published procedures. In addition, patients were randomized to receive intra-adhesive cefoxitin, surgical closure of the primary opening, or both modifications. Cefoxitin, 100 mg, was added to the sealant for patients randomized to receive intra-adhesive antibiotics. For the appropriate patients, the primary fistula opening was closed with a 3-0 absorbable suture. If fistulas failed to heal, patients were offered a single retreatment with sealant. RESULTS: Twenty-four patients were treated in the cefoxitin arm, 25 in the closure arm, and 26 in the combined arm. Median duration of fistulas was 12 months. Patients were followed for a mean of 27 months postoperatively. There was no postoperative incontinence or complications related to the sealant itself. Initial healing rates were 21 percent in the cefoxitin arm, 40 percent in the closure arm, and 31 percent in the combined arm (P = 0.35). One of five patients in the cefoxitin arm, one of seven patients in the closure arm, and one of six patients in the combined arm were successfully retreated; final healing rates were 25, 44, and 35 percent respectively (P = 0.38). CONCLUSIONS: Treatment of fistula-in-ano with fibrin sealant with closure of the internal opening was somewhat more successful than sealant with cefoxitin or the combination, however this did not achieve statistical significance. None of the three modifications were more successful than historic controls at our institution treated with sealant alone. Therefore, the addition of intra-adhesive cefoxitin, closure of the internal opening, or both are not recommended modifications of the fibrin sealant procedure.

Beyond fulfilling the core competencies: an objective structured clinical examination to assess communication and interpersonal skills in a surgical residency.

OBJECTIVE: The Accreditation Council for Graduate Medical Education (ACGME) has challenged program directors to assess their residents' core competencies, including communication and interpersonal skills (CIS). We report our institution's experience using a series of standardized patient encounters in an objective structured clinical examination (OSCE) to evaluate CIS in surgical residents. METHODS: Standardized patients rated the residents' ability to maintain a patient-centered approach across 6 challenging communication tasks. Residents received verbal feedback from the patients after each encounter and completed a survey indicating their experience and comfort with each task. Individual and group reports documented resident competency and provided aggregate information for curriculum review. Formal grades were not assigned. RESULTS: Twenty-two residents in 2 surgical residency programs piloted the assessment. The Generalizability of the assessment was 0.81. Scores of second- and third-year residents were not significantly different. Residents found the program to be helpful and able to assess their skills. CONCLUSIONS: The standardized patient-based OSCE is an effective method to assess communication and interpersonal skills and provides useful information for curriculum review.

Very high pressure HPLC with 1 mm id columns.

Theoretical calculations and experimental data indicate that very high pressure HPLC can be performed using 1 and 1.5 mm id columns, and contrary to previous beliefs, the frictional heating generated does not appear to be detrimental to the separation.

Hand-sewn versus stapled intestinal anastomoses in a chronically steroid-treated porcine model.

Chronic steroid treatment is known to delay wound healing; however, there are no trials examining stapled intestinal anastomoses in subjects chronically treated with steroids. The current study compares mechanically stapled to manually sutured intestinal anastomoses in a steroid-treated porcine model. Twenty adult male pigs were treated with daily prednisolone (0.5 mg/kg IM) for 14 days. The pigs were divided between hand-sewn and stapled groups. All pigs underwent a laparotomy with construction of a jejunojejunostomy, an ileocecostomy, and a colocolostomy. Pigs were sacrificed on postoperative day 4. Bursting pressure, collagen content, and inflammatory scores were used to evaluate each anastomosis. Bursting pressure was greater for the hand-sewn group at the jejunojejunostomies only (1.52 vs 0.79 psi; P < 0.001). The collagen content and microscopic inflammatory scores were not significantly different at any location. The mean gross inflammatory score was greater for the hand-sewn colocolostomies only (5.20 vs 4.00; P < 0.01). Stapled ileocecostomies and colocolostomies appear to heal as well as hand-sewn anastomoses. This may not be true of the jejunojejunostomies as evidenced by the decreased bursting pressures. These data may provide evidence in support of the use of stapled anastomoses in steroid-treated patients.

Retrorectal cyst: a rare tumor frequently misdiagnosed.

BACKGROUND: The rarity of retrorectal cysts and their nonspecific clinical presentations often lead to misdiagnoses and inappropriate operations. In recent years, several such patients have been referred to our institutions for evaluation and treatment of misdiagnosed retrorectal cysts. A review of these patients is presented. STUDY DESIGN: Medical records of the colorectal surgery divisions at two institutions were reviewed. Patients found to have previously misdiagnosed retrorectal cysts were identified. Preliminary diagnoses, radiologic examinations, operative procedures, and final diagnoses were obtained. RESULTS: Seven patients with retrorectal cysts who had been misdiagnosed before referral were identified. These patients had been treated for fistulae in ano, pilonidal cysts, perianal abscesses; psychogenic, lower back, posttraumatic, or postpartum pain, and proctalgia fugax before the correct diagnosis was made. Patients underwent an average of 4.1 operative procedures. Physical examination in combination with CT scanning made the correct diagnosis in all patients. All patients underwent successful resection through a parasacrococcygeal approach, and six of seven did not require coccygectomy. The resected tumors included four hamartomas, two epidermoid cysts, and one enteric duplication cyst. CONCLUSIONS: Retrorectal cysts are a rare entity that can be difficult to diagnose without a high index of clinical suspicion. A history of multiple unsuccessful procedures should alert the clinician to the diagnosis of retrorectal cyst. Once suspected, the correct diagnosis can be made with physical examination and a CT scan before a definitive surgical procedure.

Organo-silica nano-particles used in ultrahigh-pressure liquid chromatography.

A simple one-step process was used to synthesize uniform, spherical organosilica nano-particles containing octadecyl moieties. These nano-particles, having a diameter of 670 nm, were slurry packed into fused-silica capillary tubes of 50 microm internal diameter and tested for use in ultrahigh-pressure liquid chromatography (UHPLC) at inlet pressures of about 50,000 psi (approximately 3,500 bar), providing for the use of HPLC with nano-particle packed columns. The retention characteristics of a column packed with the organo-nano-particles were shown to be stable under acidic (pH < 1) and basic (pH > 11) conditions. Fast analysis times and relatively high separation efficiencies (approximately 500,000 plates m(-1)) were obtained under the conditions used.