Biomedical subjects
Publications and source records attributed to A M Vernava.
PURPOSE: This study was conducted to report a rare cause of colonic bleeding. METHODS: Case report. CONCLUSION: Surgical resection of congenital colonic varices is associated with a low incidence of morbidity and mortality, and a favorable long-term prognosis can be expected when there is no evidence of hepatocellular disease (portal hypertension).
PURPOSE: The aim of this review is to alert the colon and rectal surgeon to the colorectal manifestations of endocrine disease. METHODS: This report was obtained by a review of the medical literature. Endocrine disease may initially present as a symptom felt to be referable to colorectal disease. Furthermore symptoms of well-established endocrine disorders may have refractory colorectal symptoms. RESULTS: Constipation is the most common gastrointestinal symptom of diabetics; however, in patients with brittle diabetes, diarrhea may be chronic and intermittent. Unexplained diarrhea, despite an exhaustive work-up for an etiology, should alert the clinician to the possibility of a pancreatic endocrine tumor. Thyroid disorders, depending on activity of the gland, may have refractory constipation, diarrhea, or steatorrhea as the only presenting symptoms. Constipation is a common symptom of hypercalcemia, secondary to hyperparathyroidism. Primary hyperparathyroidism has been associated with increased incidence of malignancies, specifically of colonic origin. In patients with acromegaly a threefold to eightfold increased risk of colon carcinoma or adenomatous polyps is seen. Chronic adrenal insufficiency may present initially as diarrhea and malabsorption. The adrenal gland is a frequent site of metastases from colorectal cancer. Pheochromocytomas may be a cause of occult gastrointestinal bleeding or ischemic colitis. CONCLUSION: Unexplained symptoms referable to the colon and rectum should alert the clinician to the possibility of an underlying endocrine disorder.
BACKGROUND: In the literature, suggested strategies for the follow-up of colon cancer patients after potentially curative resections vary widely. The optimal regimen to monitor for recurrences and new primary tumors remains unknown. The nationwide cost impact of wide practice variation is also unknown. METHODS: The 1,070 members of The Society of Surgical Oncology (SSO) were surveyed using a detailed questionnaire to measure the practice patterns of surgical experts nationwide. Respondents were asked how often they use nine separate methodologies in follow-up during years 1-5 postsurgery for TNM stage I, II, and III patients. Costs were estimated for representative less and more intensive strategies. RESULTS: Evaluable responses were received from 349 members (33%). Office visit and carcinoembryonic antigen analysis were performed most frequently. SSO members generally see patients every 3 months in years 1-2, every 6 months in years 3-4, and annually thereafter. There was wide variability in test ordering patterns and moderate variation between SSO and previously surveyed American Society of Colon and Rectal Surgeons members. The charge differential between representative less and more intensive follow-up strategies for each annual U.S. patient cohort is approximately $800 million. CONCLUSIONS: Actual practice patterns vary widely, indicating lack of consensus regarding optimal follow-up. The enormous cost differential associated with such variation is difficult to justify because there is no proven benefit of more intensive follow-up.
BACKGROUND: The factors associated with outcome of patients with nonocclusive mesenteric ischemia are poorly defined. METHODS: Over a 7-year period, 34 consecutive patients with nonocclusive mesenteric ischemia were identified. RESULTS: The mean age of the study patients was 63 years (range 31 to 94); 21 of 34 (62%) were men. The mean delay in diagnosis was 31 hours (range 7 hours to 6 days). Seven of 34 (21%) underwent preoperative visceral arteriography. Two of these 7 required surgery, and both died as a result of intestinal infarction. The remaining 27 had the diagnosis made at celiotomy. Among the 29 who were explored, 16 of 29 (55%) had intestinal infarction. Twenty-one of 29 (72%) had segmental bowel injury whereas 8 of 29 (28%) had massive injury. Among those with segmental infarction, primary anastomosis was performed in 12 of 21 patients (57%); 5 of the 12 (42%) died. Nine of 21 patients (43%) underwent delayed anastomosis; 2 of the 9 (22%) died. No patient with massive injury underwent primary anastomosis. Second-look laparotomy was performed on 22 of 29 (76%). Eleven of those 22 (50%) had a further bowel resection. Overall, 16 of 29 (55%) who underwent surgery for nonocclusive mesenteric ischemia are alive. CONCLUSIONS: Improved survival from nonocclusive mesenteric ischemia is dependent upon the identification of high-risk groups, aggressive reexploration, and delayed intestinal anastomosis.
Chronic constipation in patients with spinal cord injury (SCI) has significant impact on quality of life. To measure baseline clinical functioning, colonic transit time and anorectal manometry and the effect of cisapride on these clinical and physiological parameters, we studied 12 SCI patients. Patients initially received baseline clinical scoring, measurement of colonic transit time and anorectal manometry. Patients then received cisapride 20 mg orally three times each day. After one and three months of cisapride therapy, all measurements were repeated. The mean duration cisapride treatment was 5.2 months. Six of 12 (50 percent) reported that symptoms of constipation improved. No patient had worsening of symptoms. Prior to cisapride treatment, 23 percent of patients passed colonic transit markers by day five and 57 percent by day seven; baseline anal manometry revealed variable resting and squeeze pressures. After treatment, 33 percent of patients passed their colonic transit markers by day five and 71 percent by day seven. Six of 12 (50 percent) demonstrated a 10 percent or more increase in resting anal canal pressures. We conclude that about 50 percent of SCI patients have subjective improvement in constipation after cisapride therapy. Cisapride appears to improve both colonic and anorectal function.
Nationwide treatment results among U.S. veterans with rare anal cancers (AC) have not been previously reported. We sought to evaluate the demographics and treatment outcome of patients with rare AC in Veterans Affairs Medical Centers (VAMCs). Using national VA computer data sets, we identified all patients with the ICD-9 diagnostic code (154.2) for anal cancer from 1987-1991. Patient demographics, histopathology, tumor size, results of treatment, and survival data were sought from local tumor registrars. A total of 405 patients with AC were identified by computer search; 204 (51%) were evaluable. 164 (80%) had squamous cell carcinomas, 25 (13%) had basaloid carcinomas, 8 (4%) had melanomas and 7 (3%) had anal gland adenocarcinomas. Patients were treated either by local excision, abdominoperineal resection (APR), or primary chemoradiation. Mean follow-up was 5.1 years. Among 25 patients with basaloid tumors, 19/25 were treated with chemoradiation; 13/19 (68%) are alive, and 3/5 treated with radical surgery are living. Among the seven patients with adenocarcinoma, those treated with CR fared better than those who underwent APR. Among the 8 patients with melanoma, 3/7 (38%) underwent primary APR, and 5 (62%) were treated by local excision; 7/8 died. Rare anal tumors account for 20 per cent of all anal canal cancers in the VA population. Patients with basaloid tumors respond well to chemoradiation. Patients with anal melanoma continue to have a poor prognosis.
Two cases of laparoscopic restoration of intestinal continuity are presented. The procedures were technically straightforward and both patients did well. These cases add to a small but growing literature documenting the technical feasibility of laparoscopic intestinal surgery. The potential risks and benefits of this minimally invasive technique are discussed.
We investigated whether platelet-activating factor (PAF) alters colonic tissue levels of substance P and vasoactive intestinal peptide (VIP), two neuropeptides that regulate colonic motility. Left colons were harvested from NZ White Rabbits and underwent vascular perfusion via the inferior mesenteric artery. Strain gauge transducers were sewn onto the serosal surface of the colon to evaluate colonic motility. Colons were perfused with either buffered saline alone or with 5.0 x 10(-5) M PAF. PAF administration increased tissue VIP and substance P levels and decreased the force of colonic contractions. Pretreatment with WEB-2170 or alprazolam decreased concentrations of both tissue neuropeptides, and decreased the force of colonic contractions and minute motility index. These results suggest that both VIP and substance P are stimulated by PAF and may participate in colonic dysmotility during inflammatory states.
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Acute mesenteric ischemia represents one to two percent of all gastrointestinal illnesses. There are three possible causes of acute arterial mesenteric ischemia: embolism, thrombosis, and nonocclusive mesenteric insufficiency. The key to early diagnosis is a high index of suspicion. The classic clinical picture of obvious cardiac disease, sudden onset of severe abdominal pain and gastrointestinal emptying, is not always present. Serum markers and plain films are often nondiagnostic but may suggest acute arterial mesenteric ischemia. Angiography establishes the diagnosis and allows for planning of aortomesenteric bypass, if indicated. Papaverine is immediately instilled to decrease splanchnic vasoconstriction. Embolic and thrombotic disease is treated by laparotomy with re-establishment of visceral perfusion. Only after blood flow is restored is nonviable bowel resected. Clinical methods of assessing intestinal viability include Doppler scanning, intravascular dyes, and tissue oximetry. The decision to perform a second-look laparotomy is made prior to closure of the abdomen. Pharmacologic treatment is the mainstay of nonocclusive ischemia. Surgery is reserved for clinical deterioration. Survival is dependent on the cause and extent of occlusion as well as the rapidity of diagnosis and therapy. Bowel necrosis results in mortality rates between 80 percent and 95 percent.
UNLABELLED: The incidence of Clostridium difficile colitis has increased during recent years, presumably because of liberal use of broad-spectrum antibiotic regimens. METHODS: A retrospective review to determine patterns of C. difficile colitis development, morbidity, and treatment results was undertaken. During an 18-month period, 90 patients were diagnosed with C. difficile colitis by fecal toxin assays. Patient demographics, symptoms, previously administered antibiotic regimens, diagnostic evaluations, treatment modalities, morbidity, and mortality were identified, entered into a computer data base, and analyzed. RESULTS: The mean age was 58 years; males outnumbered females 1.2:1. Among 90 patients, 41 (46 percent) developed C. difficile colitis after surgical procedures. Eighty (89 percent) patients received antibiotic therapy before developing C. difficile colitis: 35 (44 percent) for documented infections and 45 (56 percent) as empiric or prophylactic therapy. Cephalosporins, penicillins, quinolones, vancomycin, and aminoglycosides were the most frequently administered antibiotic classes prior to C. difficile colitis diagnosis. Ten (11 percent) patients developed C. difficile colitis without previous antibiotic therapy. Eighty-two (91 percent) patients presented with diarrhea, while eight (9 percent) had fever only. Primary C. difficile colitis treatment for both groups included vancomycin (66 percent), metronidazole (24 percent), or both drugs (10 percent). Ten (11 percent) patients received no treatment. No patient developed toxic colitis or megacolon. Colonoscopy was performed in four (4 percent) patients; pseudomembranes were identified in one (25 percent) patient. There was one C. difficile colitis recurrence after treatment, but no C. difficile colitis-associated morbidity. Mortality (14 patients, 16 percent) was not related to C. difficile colitis, but to underlying illness. No difference in patient age, sex, previous antibiotic administration, serum albumin, total days hospitalized, duration of C. difficile colitis antibiotic therapy, C. difficile colitis treatment regimens, or mortality was identified between nonsurgical and surgical patients. The white blood cell count was significantly lower in the nonsurgical group however. Clostridium difficile colitis developed most commonly after antibiotic administration with symptoms of diarrhea, but did occur without previous antibiotic administration or diarrhea. CONCLUSION: Despite the clinical setting, C. difficile colitis had no associated morbidity and treatment was highly effective. Mortality was related to underlying medical illness, not C. difficile colitis.
UNLABELLED: The follow-up of patients after potentially curative resection of colon cancer has important clinical and financial implications for patients and society, yet the ideal surveillance strategy is unknown. PURPOSE: The aim of this study was to determine the current follow-up practice pattern of a large, diverse group of experts. METHODS: The 1,663 members of The American Society of Colon and Rectal Surgeons were asked, via a detailed questionnaire, how often they request nine discrete follow-up evaluations in their patients treated for cure with TNM Stage I, II, or III colon cancer over the first five posttreatment years. These evaluations were clinic visit, complete blood count, liver function tests, serum carcinoembryonic antigen (CEA) level, chest x-ray, bone scan, computerized tomographic scan, colonoscopy, and sigmoidoscopy. RESULTS: Forty-six percent (757/1663) completed the survey and 39 percent (646/1663) provided evaluable data. The results indicate that members of The American Society of Colon and Rectal Surgeons generally conduct follow-up on their patients personally after performing colon cancer surgery (rather than sending them back to their referral source). Routine clinic visits and CEA levels are the most frequently performed items for each of the five years. The large majority (> 75 percent) of surgeons see their patients every 3 to 6 months for years 1 and 2, then every 6 to 12 months for years 3, 4, and 5. Approximately 80 percent of respondents obtain CEA levels every 3 to 6 months for years 1, 2, and 3, and every 6 to 12 months for years 4 and 5. Colonoscopy is performed annually by 46 to 70 percent of respondents, depending on year. A chest x-ray is obtained yearly by 46 to 56 percent, depending on year. The majority of the members of The American Society of Colon and Rectal Surgeons do not routinely request computerized tomographic scan or bone scan at any time. There is great variation in the pattern of use of complete blood count and liver function tests. Members of The American Society of Colon and Rectal Surgeons from the United States tend to follow their patients more closely than do those living in other countries. The intensity of follow-up does not markedly vary across TNM Stages I to III. CONCLUSION: The surveillance strategies reported here rely most heavily on clinic visits and CEA level determinations, generally reflecting guidelines previously proposed in the current literature.
PURPOSE: The aim of this study was to determine how frequently pruritus ani (PA) is a symptom secondary to benign or malignant colon and anorectal pathology. METHODS: One hundred nine patients with PA as the only presenting symptom were prospectively evaluated over a two-year period. All patients underwent anoscopy, rigid proctoscopy, and colonoscopy and were treated for PA. Patient data were entered into a computer data base and analyzed. RESULTS: The mean age was 52.1 years; males outnumbered females 2:1. The mean duration of symptoms was 6.1 weeks. Mean coffee intake was four cups per day. Forty-five percent of patients smoked and 45 percent drank alcohol daily. Thirty-five percent had an abnormal proctosigmoidoscopy or colonoscopy. Twenty-seven (25 percent) patients had primary pruritus and 82 (75 percent) patients had coexisting colon or anorectal pathology. The PA-associated neoplasia included rectal cancer (11 percent), anal cancer (6 percent), adenomatous polyps (4 percent), and colon cancer (2 percent). Hemorrhoids (20 percent) and anal fissures (12 percent) were the most common pruritus-related anorectal diseases. Among the 23 percent of patients with PA and neoplasia, pruritic symptoms were present longer compared with those with PA and anorectal disease < 0.001 and primary pruritus (P < 0.0001). All patients with primary PA were initially treated with dietary fibers, steroid cream, and drying agents. The recurrence rate for primary pruritus was twice that for anorectal disease (P < 0.0001). CONCLUSIONS: PA responds to treatment in 89 percent of patients, while 11 percent are refractory to treatment. Symptoms suggestive of pruritus ani, especially those of long duration, should alert the surgeon to the potential for proximal colon and anorectal neoplasia.
Antibiotic-associated colitis is caused by Clostridium difficile toxin. However, the pathophysiology of this entity is poorly understood. The aim of this study was to determine the effects of C. difficile toxin on colonocyte cyclooxygenase and phospholipase A2 (PLA2) activity. A transformed colonocyte cell line (Caco-2) was grown to confluency on 6 well plates. The cells were stimulated with graded concentrations of C. difficile toxin. In separate experiments, the cells were pretreated for one hour prior to stimulation with the cyclooxygenase inhibitor, indomethacin, or the glucocorticoid, dexamethasone. The culture media was collected one hour following C. difficile stimulation. Prostaglandin E2 (PGE2), 6-keto prostaglandin F1 alpha (6KPGF), thromboxane B2 (TxB2) and leukotriene B4 (LTB4) levels were determined in the media by an ELISA. Platelet activating factor (PAF) concentration was determined by a RIA. C. difficile toxin stimulated PGE2 and 6KPGF levels in a dose dependent fashion but failed to stimulate TxB2, LTB4 or PAF. Prostanoid production was inhibited by indomethacin dose dependently but was not inhibited by dexamethasone. The presence of indomethacin resulted in production of PAF. Our results show that the effects of C. difficile toxin on colonocytes are mediated by cyclooxygenase activity. The increase in PAF formation associated with indomethacin administration suggests that the prostanoids modulate PLA2 activity and inhibit PAF formation.
Platelet-activating factor (PAF) is an endogenous phospholipid which may be an important mediator of shock and inflammation. Recent evidence suggests that PAF plays a role in the development of ischemic colitis and inflammatory bowel disease. Its effects are mediated by second messengers, including the arachidonic acid metabolites. Using an ex vivo isolated left colon rabbit perfusion model, our aims were to determine whether exogenously administered trinitrobenzene sulfonic acid (TNB), which produces experimental colitis, stimulates both PAF and eicosanoid release in the colon, and if so, whether this effect can be blocked by a PAF antagonist. Colonic inflammation was induced by the intracolonic administration of 0.25 ml of 50% ethanol containing 30 mg of TNB. Tissue and perfusate concentrations of the eicosanoids, [prostaglandin E (PGE2), 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and thromboxane B2 (TXB2), leukotriene B4 (LTB4)] and the autocoid PAF were measured by ELISA. During TNB infusion there was a significant increase in tissue levels of PAF compared to control colons. Additional studies performed pretreating the colons with the PAF receptor antagonist WEB-2170 prior to TNB infusion blocked PAF release. TNB stimulated release of luminal eicosanoids except LTB4 and suppressed release of tissue prostanoids. Pretreatment with WEB-2170 prior to TNB inhibited luminal eicosanoids, and inhibited PGE2 and prostacyclin, but not TX tissue suppression. Inhibition of TNB-stimulated PAF release by WEB-2170 suggests that PAF may play a role in TNB-induced colitis and this phenomenon may mediate tissue injury.
OBJECTIVE: The outcomes of patients with squamous cell carcinoma of the anal canal treated by either sphincter-preserving procedures or radical surgery were evaluated, with the goals of identifying factors predicting treatment failure and quantifying results of salvage therapy in patients with recurrent disease. BASIC PROCEDURES: A population-based study on all patients in all 159 hospitals of the Department of Veterans Affairs (VA) from 1987 to 1991 was carried out. Data were compiled from several national computerized VA data sets. Supplementary information from local tumor registrars also was obtained, including demographic information, discharge summaries, operative reports, pathology reports, and medical oncology and radiation oncology summaries. From these sources, information on tumor histology, tumor stage, tumor grade, presence of regional or distant metastases, surgical procedures, use of chemotherapy and radiation therapy (RT), toxicity of chemotherapy and RT, development of recurrent disease, treatment of recurrence, survival, and cause of death were obtained. MAIN FINDINGS: Four hundred five patients with anal cancer were identified by computer search, and 204 (51%) were evaluable; 164 of 204 (80%) had squamous cell carcinoma, 137 of whom (84%) were treated with sphincter-preserving procedures, and 27 of whom (16%) were treated by by radical surgery. One hundred fourteen of 138 (83%) were treated by multimodality therapy, which we defined as local excision followed by chemotherapy and RT. The mean dose of RT among patients treated by multimodality therapy was 4200 +/- 540 cGy and 82% of those treated with multimodality therapy received 5-FU/mitomycin C. Recurrent disease was diagnosed in 43 of all 149 patients (29%) with potentially curable disease. (stages I-III) Multivariate analysis revealed that stage at diagnosis (p = 0.04) and method of treatment (p = 0.03) were the sole predictors of recurrence. Fifty-three percent of patients who underwent salvage abdominoperineal resection (APR) are alive, whereas only 19% who underwent salvage chemotherapy with or without RT are alive. PRINCIPAL CONCLUSIONS: These data indicate that multimodality therapy currently is being employed in the majority of patients with squamous cell carcinoma of the anal canal in the VA system. Tumor stage and method of treatment appear to affect the likelihood of development of recurrent disease. Salvage APR has curative potential. Results with salvage chemotherapy and RT are disappointing.
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