From sequence to function: using RNAi to elucidate mechanisms of human disease.

RNA interference (RNAi) has emerged as one of the most powerful tools for functionally characterizing large sets of genomic data. Capabilities of RNAi place it at the forefront of high-throughput screens, which are able to span the human genome in search of novel targets. Although RNAi screens have been used to elucidate pathway components and discover potential drug targets in lower organisms, including Caenorhabditis elegans and Drosophila, only recently has the technology been advanced to a state in which large-scale screens can be performed in mammalian cells. In this review, we will evaluate the major advancements in the field of mammalian RNAi, specifically in terms of high-throughput assays. Crucial points of experimental design will be highlighted, as well as suggestions as to how to interpret and follow-up on potential cell death targets. Finally, we assess the prospective applications of high-throughput screens, the data they are capable of generating, and the potential for this technique to further our understanding of human disease.

MEK inhibition enhances paclitaxel-induced tumor apoptosis.

The anti-cancer drug paclitaxel (Taxol) alters microtubule assembly and activates pro-apoptotic signaling pathways. Previously, we and others found that paclitaxel activates endogenous JNK in tumor cells, and the activation of JNK contributes to tumor cell apoptosis. Here we find that paclitaxel activates the prosurvival MEK/ERK pathway, which conversely may compromise the efficacy of paclitaxel. Hence, a combination treatment of paclitaxel and MEK inhibitors was pursued to determine whether this treatment could lead to enhanced apoptosis. The inhibition of MEK/ERK with a pharmacologic inhibitor, U0126, together with paclitaxel resulted in a dramatic enhancement of apoptosis that is four times more than the additive value of the two drugs alone. Enhanced apoptosis was verified by the terminal transferase-mediated dUTP nick end labeling assay, by an enzyme-linked immunosorbent assay for histone-associated DNA fragments, and by flow cytometric analysis for DNA content. Specificity of the pharmacologic inhibitor was confirmed by the use of (a) a second MEK/ERK inhibitor and (b) a transdominant-negative MEK. Enhanced apoptosis was verified in breast, ovarian, and lung tumor cell lines, suggesting this effect is not cell type-specific. This is the first report of enhanced apoptosis detected in the presence of paclitaxel and MEK inhibition and suggests a new anticancer strategy.

Biodistribution of radiolabeled lipid-DNA complexes and DNA in mice.

The tissue biodistribution and expression of [33P]DNA-1-[2-[9-(Z)-octadecenoyloxy]ethyl]]-2-[8](Z)-heptadece nyl]-3 -[hydroxyethyl]imidazolinium chloride (DOTIM):cholesterol complexes and 33P-radiolabeled DNA expressing chloramphenicol acetyl transferase (CAT; 4.7 kB) were studied after intravenous (iv) injection in ICR mice. Mice were injected with 200 microL of complex containing DNA at 3 mg/kg or DNA alone. One group received 8 microCi of radioactivity and were sacrificed at 5 and 20 min, and 1, 2, 4 and 24 h post-dose (n = 4/time point). A second group received the equivalent of 3.9 microCi of radioactivity and were sacrificed at 20 min, and 2 and 24 h for subsequent whole body autoradiographic analysis (WBA; n = 2/time point). The tissue distribution of intact DNA was assessed by Southern blot at 24 h post-dose, whereas the integrity of complexes and DNA incubated in heparinized whole blood was studied separately. In further studies, the time course of expression in lung tissue over a 48-h period was examined, and the relative lung-expression of purified open circular (OC) versus supercoiled (SC) DNA at 24 h was evaluated. Approximately 42% of the radioactivity was found in the lungs 5 min after injection and about half this percentage was found in the liver. By 2 h, only 5% remained in the lungs, but 48% was present in the liver. No other tissue accumulated >5% of the dose throughout the duration of the study. WBA radiograms confirmed the tissue distribution results and highlighted significant accumulation of radioactivity in bone over time. Southern Blot analysis demonstrated intact DNA in many tissues 24 h after dosing. In contrast, the majority of DNA incubated in blood was degraded within 2 h, although the complexes afforded some protection relative to DNA alone. The OC DNA expressed equivalently to SC DNA in lung tissue (OC = 1035 +/- 183 pg; SC = 856 +/- 257 pg/mg soluble protein, n = 6, mean +/- SEM) at 24 h, and detectable levels of CAT were present within 2 h of dosing (21.3 +/- 7.2 pg, n >/= 8, mean +/- SD). The results confirm that DNA-DOTIM:cholesterol complexes are initially deposited in the lungs after iv administration.

Pudendal nerve latency. Does it predict outcome of anal sphincter repair?

PURPOSE: Electrophysiologic evaluation has been suggested as a means of identifying prognostic factors for patients with fecal incontinence who undergo anal sphincter repair. The purpose of this study was to evaluate the results of anal sphincter repair in patients with documented pudendal neuropathy and to determine the usefulness of electrophysiologic studies for prognostication of sphincteroplasty. METHODS: A retrospective review of a series of patients undergoing electrophysiologic studies and anterior anal sphincteroplasty was performed. Data collected included age, standardized incontinence scores (preoperative, immediately postoperative, and current follow-up), and results of pudendal nerve terminal motor latency and monopolar electromyography. Outcomes of sphincteroplasty were designated as excellent, good, fair, or poor based on incontinence scores. Prolonged pudendal nerve terminal motor latency was defined as longer than 2.2 ms and elevated as unilateral or bilateral. RESULTS: During the time period of the study (1991-1996), 15 patients had electrophysiologic studies and underwent sphincteroplasty. Twelve patients (80 percent) were available for follow-up and form the basis for this study. All patients were women, with a mean age of 45 +/- 18.6 (27-75) years and a mean follow-up of 49.7 +/- 18.6 (20.4-72.6) months. Mean duration of incontinence preoperatively was 13 +/- 16.1 (range, 1-58) years. The incontinence score was 15.8 +/- 3.5 preoperatively, 5.4 +/- 4.5 postoperatively, and 5 +/- 5.1 currently for all 12 patients. There was one patient with normal pudendal nerve terminal motor latency. In the four patients with bilateral prolonged pudendal nerve terminal motor latency, the incontinence scores were 15 +/- 4.2 preoperatively, 8.5 +/- 5.3 postoperatively, and 6 +/- 6.1 (statistically significant compared with preoperation) currently. Seven patients were found to have unilateral prolonged pudendal nerve terminal motor latency with incontinence scores of 16.3 +/- 3.5 preoperatively, 4.4 +/- 3.2 (statistically significant compared with preoperation) postoperatively, and 5.1 +/- 4.9 (statistically significant compared with preoperation) currently. Based on incontinence scores, results of the sphincteroplasty at the most current follow-up were as follows: no neuropathy, excellent in one patient; unilateral neuropathy, five with good/excellent results, two with fair/poor results; bilateral neuropathy, two with good/excellent results, two with fair/poor results (P > 0.05 bilateral vs. unilateral). By monopolar electromyographic examination, external and sphincter denervation was noted in 11 patients; their incontinence scores were 15.5 +/- 3.5 preoperatively, 5.9 +/- 4.3 (statistically significant compared with preoperation) postoperatively, and 5.5 +/- 5.0 (statistically significant compared with preoperation) currently. Monopolar electromyographic results in the puborectalis included four normal examinations and six that were unobtainable. In the two patients with puborectalis denervation, the incontinence scores were 19.5 +/- 0.7 preoperatively, 8.5 +/- 4.9 postoperatively, and 2.5 +/- 3.5 (statistically significant compared with preoperation) currently. CONCLUSIONS: Anterior anal sphincteroplasty in patients with unilateral or bilateral prolonged pudendal nerve terminal motor latency can provide significant improvement in continence with minimum morbidity. Therefore, correction of the anatomic sphincter defect should still be considered, even in patients with documented pudendal neuropathy.

Adjuvant radiation therapy in resectable rectal cancer: should local recurrence rates affect the decision?

Adjuvant external beam pelvic radiotherapy (XRT) for resectable rectal cancer has been mandated by the National Cancer Institute because of reported 20 to 50 per cent reductions in local recurrence rates. However, these series' reported local recurrence rates are 18 to 39 per cent in the nonradiated patients, which seems extraordinarily high compared to the 3 to 5 per cent rates reported by surgeons advocating proctectomy with complete mesorectal excision. This fact, coupled with the high cost of XRT ($11,000-$14,000), the risk of radiation injury to small bowel and the neo-rectum, and the failure of XRT to provide any survival advantage, raises questions as to the precise role of XRT for rectal cancer. The purpose of this study was to perform a review of 212 consecutive patients undergoing curative resection via low anterior resection (LAR) or abdominoperineal resection (APR) for rectal cancer between 1989 and 1993, focusing on local and distant recurrence rates and survival. The choice of surgery alone (SUR), preoperative radiation (PRE) (45 Gy), or postoperative radiation (POST) (45-50 Gy) was at the surgeon's discretion. There were no significant differences in male:female ratio (SUR, 83:60; PRE, 14:8; POST, 34:13) or type of procedure (SUR-LAR, 112:APR, 31; PRE-LAR, 5:APR, 17; POST-LAR, 30:APR, 17) between the groups. There were no significant differences in age between the preoperative and postoperative radiation groups (PRE, 64.0 +/- 2.4; POST, 59.2 +/- 1.7); however, age was significantly different (P < 0.05) between the surgery-alone and the postoperative radiation groups (SUR, 68.5 +/- 0.8; POST, 59.2 +/- 1.7). With a median follow-up of 49 months, there were no significant differences in local recurrence (SUR, 4.2%; PRE, 4.5%; POST, 2.1%); however, there was a significantly longer survival for the SUR group compared to the other groups (SUR, 45.9 months; PRE, 36.4 months; POST, 39.3 months; P < 0.05 least significant difference). The PRE group also had shorter survival compared to the other groups when only Stage II and III lesions were studied (S, 40.0 months; PRE, 28.3 months; POST, 39.3 months). Local recurrences based on TNM stage were: T1N0 (S, 0 of 27; PRE, 0 of 3); T2N0 (S, 4 of 4S; PRE, 0 of 7); T2N1 (S, 0 of 9; POST, 1 of 5); T3,4N0 (S, 2 of 37; PRE, 1 of 9; POST, 0 of 10); and T3,4N1,2 (S, 0 of 21; PRE, 0 of 3; POST, 0 of 30). The results of this series support the contention that proctectomy with complete mesorectal excision yields a 4.2 per cent local recurrence rate without the need for adjuvant XRT. In this series, if all the patients had received adjuvant radiation, an additional $2.2 million would have been added to the costs of medical care. Therefore, the potential risks, costs, and benefits of adjuvant pelvic XRT for rectal cancer must be weighed against optimal benchmarks for local recurrence rate for surgery alone.

Long-term outcome after ileocecal resection for Crohn's disease.

The decision to operate on ileocecal Crohn's disease is usually tempered by concern for early recurrence and the potential for multiple small bowel resections that will render the patients a gastroenterological cripple. However, delays in surgical management may unnecessarily prolong the patient's disease state and risk complications from both medications and unchecked disease. The aim of this study was to report the long-term clinical outcome of patients undergoing ileocecal resection for Crohn's disease between 1970 and 1993. One hundred eighty-one patients underwent ileocecal resection for Crohn's disease during the study period, with a median follow-up of 14.3 years. The mean age at the first resection was 32.7 +/- 0.9 years, and the male female ratio was 79:102. The indications for the initial resection were intractability in 119 (68.4%), obstruction in 45 (25.9%), enteric fistula in 27 (15.5%), perforation in 16 (9.2%), intra-abdominal abscess in 7 (4.0%), and hemorrhage in 5 (2.9%). Postoperative complications included prolonged ileus in 13 (7.5%), pneumonia/atelectasis in 15 (8.6%), wound infection in 11 (6.3%), urinary tract infection in 10 (5.7%), intra-abdominal abscess in 7 (4.0%), and wound dehiscence in 1 (0.6%). There were no operative mortalities. Fifty-six (30.9%) developed a recurrence requiring further surgery, with the mean time interval between initial ileocecal resection and operation for recurrence being 72.3 +/- 7.6 months. A second recurrence developed in 19 patients (10.5%) with a mean time interval of 52.3 +/- 8.3 months. The most frequent sites of first recurrence were the preanastomotic ileum in 49 (87.3%), the postanastomotic colon in 10 (17.9%), other colonic sites in 16 (28.6%), and other small bowel sites in 2 (3.6%) and other sites in 4 (7.1%). The types of resection for first recurrence were ileal resection in 28 (50%), right hemicolectomy in 17 (30.4%), segmental colectomy in 6 (10.7%), total proctocolectomy in 3 (5.4%), and proximal small bowel resection in 2 (3.6%). The long-term follow-up of this patient cohort indicated that 125 (69.1%) had only one resection, 37 (20.4%) required two resections, 15 (8.3%) required three resections, 4 (2.2%) required four resections. The results indicate that ileocecal resection of Crohn's disease had a high rate of disease control obtained with low morbidity, and a low frequency of three or more bowel resections (2.2%). Therefore, surgical resection of ileocecal Crohn's disease should not be unduly delayed for fear of risking short bowel syndrome. This approach should minimize overall disease-related patient morbidity by avoiding long periods of chronic illness.

What is the learning curve for laparoscopic colectomy?

Learning curves have been described for a variety of laparoscopic procedures including cholecystectomy, tubal ligation, and diagnostic laparoscopy. Although multiple series of laparoscopic colectomies have appeared, there is little information regarding the learning curve associated with this advanced procedure. The purpose of this study is to present a single team's experience with laparoscopic colon resection to allow the description of our learning curve. The data collected included age, sex, operating room time, recovery of bowel function, days to clear liquid, hospital stay, conversion, complications, indication for operation, and site of resection. Sixty consecutive patients were analyzed and divided into three groups: First 20, Second 20, and Third 20. There were no significant differences between the three groups with respect to age, male versus female ratio, indications for surgery, or site of resection. However, the complexity of surgical procedures and the incidence of previous major abdominal surgery increased steadily with experience. The incidence of pulmonary complications was 30 per cent in the First 20 group and decreased to 5 per cent for the next two groups. The conversion rate was 20 per cent for the First 20 group, 45 per cent for the Second 20 group, and decreased to 10 per cent for the Third 20 group.(ABSTRACT TRUNCATED AT 250 WORDS)

Superior nitrogen balance after laparoscopic-assisted colectomy.

BACKGROUND: Although early resumption of enteral feeding after gastrointestinal surgery results in improved nitrogen balance and lower infectious complications, no postoperative nutritional data after laparoscopic-assisted colectomy exists. OBJECTIVE: The authors prospectively compared nitrogen balance after laparoscopic-assisted colectomy versus open colectomy. METHODS: This is a series of colon resections (open, N = 10; laparoscopic-assisted, N = 9) at the Ferguson-Blodgett Hospital, Grand Rapids, Michigan, between January and March 1993. Nitrogen intake and 24-hour urine collections were performed on postoperative days 1, 3, and 7 for the analysis of total urinary nitrogen and urinary 3 methylhistidine-(3mH). RESULTS: The time to passage of flatus (4.7 +/- 0.6; 2.0 +/- 0.2), resumption of oral intake (6.1 +/- 0.7; 1.4 +/- 0.2; p < 0.05, Student's test), first bowel movement (5.2 +/- 1.0; 3.0 +/- 0.3; p < 0.05, Student;s t test), and discharge (10.3 +/- 1.3; 4.1 +/- 1.8; p < 0.05, Student's t test) occurred significantly earlier in the laparoscopic-assisted colectomy group. Overall hospital charges were lower in the laparoscopic-assisted colectomy group ($11,572 +/- $823 vs. $13,961 +/- $1050). The operative time was higher in the laparoscopic-assisted colectomy group (176 +/- 12 hours vs. 105 +/- 17 hours, p < 0.05,Student's test). Blood loss was higher in the open group (805 +/- 264 mL vs 217 +/- 32 mL, p < 0.05, Student's test). Urinary nitrogen losses were similar between the two groups; however, significantly more patients in the laparoscopic-assisted colectomy group achieved net positive nitrogen on day 3 (6/9; 0/10; p < 0.05, Fisher's exact test), and day 7 (9/9; 4/10; p < 0.05, Fisher's exact test). Infectious complications occurred less frequently in the laparoscopic-assisted colectomy group (0/9 vs. 4/10; p < 0.05, Fisher's exact test). CONCLUSIONS: Patients undergoing laparoscopic-assisted colectomy can achieve early resumption of enteral nutrition with earlier return to positive nitrogen balance compared with open colectomy. This may offer benefits of fewer infectious complications and lower cost of care.

Treatment of advanced hemorrhoidal disease: a prospective, randomized comparison of cold scalpel vs. contact Nd:YAG laser.

PURPOSE: Recently, laser technology has been advocated for the treatment of hemorrhoids. However, there has been little scientific evaluation of the use of the Nd:YAG laser for excisional treatment of hemorrhoidal disease. The purpose of this study was to perform a prospective randomized study of the Nd:YAG laser vs. scalpel excision, when performing a standard Ferguson-closed hemorrhoidectomy. METHODS: Patients presenting for internal-external hemorrhoidectomy were eligible for study. Hemorrhoidectomies were performed under epidural or caudal blocks. The standard Ferguson closed hemorrhoidectomy technique was used. Data evaluated included: age, sex, estimated blood loss, operative time, postoperative pain scores, postoperative analgesic use, wound healing, and time for return to work. Eighty-six patients were eligible for study (laser, N = 51; scalpel, N = 35). RESULTS: There were no significant differences between the groups, except for a greater degree of wound inflammation and dehiscence at the 10 day postoperative visit for the laser group (laser, 1.7 +/- .2; scalpel, 0.8 +/- .2; P < 0.05, t-test). The use of the Nd:YAG laser added $480 per case; as a result, the treatment cost for the laser group was $15,360 higher than that of the conventional group. CONCLUSION: The results indicate that there are no patient care advantages associated with the use of the Nd:YAG laser for excisional hemorrhoidectomy compared with scalpel excision. As new technology becomes available, surgeons must rigorously assess therapeutic efficacy and cost-benefit ratio before deciding to employ this technology for patient care.

Rectopexy.

Many surgical procedures have been described for the management of full-thickness rectal prolapse. Currently, the three procedures most frequently used are anterior resection with or without suture rectopexy, transabdominal mesh fixation without resection, and perineal proctosigmoidectomy. Only the latter procedure avoids a laparotomy, and the mesh fixation technique has a high incidence of severe constipation postoperatively. Recently, there have been two reports of laparoscopic mesh fixation for rectal prolapse which were successful. However, the long-term concerns are probably very similar. Therefore, the purpose of this paper is to report a series of 6 laparoscopic-assisted anterior resections performed for rectal prolapse at Ferguson-Blodgett Hospital from January 1, 1992 through October 30, 1992. There were no perioperative mortalities and the only complication was a port site bleed which required re-exploration. The mean time for resumption of oral intake was 2.75 +/- 1.5 days and the length of hospital stay was 4.0 +/- 0.8 days. No early recurrences (< 1 yr) have been noted in this series. The authors feel that laparoscopic-assisted anterior resection is a safe and effective method of treating full-thickness rectal prolapse, thereby avoiding a laparotomy and reducing hospital stay.

Open colectomy versus laparoscopic colectomy: are there differences?

Laparoscopic colectomy has been increasingly reported as an option for the treatment of colonic pathology. However, there is very little information regarding perioperative morbidity and the cost effectiveness of this technique. The purpose of this study is to review our first year of experience with laparoscopic colon resection. Data collected includes: age, technique (open laparotomy, laparoscopic, laparoscopic/converted open), Karnofsky score, complications, specimen size/nodes, OR time, hospital stay, and cost. This is a consecutive series of 140 elective colonic resections including 102 open laparotomies (O) and 38 laparoscopic (L) cases. The indications for surgery have included adenocarcinoma col/rect (O = 59, L = 9), diverticular disease (O = 10, L = 10), adenomatous polyp (O = 3, L = 7), IBD (Crohn's, CUC) (O = 15, L = 4), rectal prolapse (O = 3, L = 4), and other (O = 12, L = 4). There were no significant differences with respect to age (O = 60.7 +/- 1.5; L = 54.8 +/- 3.8; C = 66.1 +/- 3.1), perioperative morbidity (O = 11%; L = 15%; C = 17%). The laparoscopic and laparoscopic converted cases required significantly more time compared to the open laparotomy group (O = 2.1 +/- 0.2 hours; L = 2.9 +/- 0.2; C = 3.4 +/- 0.2). There were significantly less intraoperative blood loss associated with laparoscopic procedures compared with either open or converted groups of patients (O = 687 +/- 54 cc; L = 157 +/- 19; C = 491 +/- 50).(ABSTRACT TRUNCATED AT 250 WORDS)

Endoscopic tattooing of the colon: clinical experience.

Nonpalpable lesions of the colon can be difficult to locate intraoperatively. We have demonstrated in an experimental study in dogs that the colon can be endoscopically "tattooed" by injecting dye through a flexible needle into the wall of the colon. At laparotomy, the resulting "tattoo" is then visible on the serosal surface of the bowel. This technique allows precise surgical localization of endoscopically identified lesions simply by visualizing the dye. Our initial clinical experience tattooing 15 colonic lesions in 12 patients is presented. In all patients, the endoscopically injected dye (1 per cent indocyanine green) was easily visualized on the serosal surface of the colon at surgery. The dye remained at the site of injection for at least 36 hours allowing tattooing to be performed the day before surgery. No significant complications were encountered with only one patient developing an inflammatory reaction at the site of injection. This experience demonstrates the clinical utility of endoscopic tattooing of the colon to permit accurate intraoperative localization of small or nonpalpable lesions.

Short-chain fatty acid enemas: a cost-effective alternative in the treatment of nonspecific proctosigmoiditis.

The purpose of this study was to perform a randomized, prospective comparison of corticosteroid enemas (CS--100 mg of hydrocortisone/60 cc P.R. q.h.s.; n = 12), mesalamine enemas (5-ASA--4 g/60 cc P.R. q.h.s.; n = 19), and short-chain fatty acid enemas (SCFA--60 cc P.R. b.i.d.; n = 14) for the treatment of proctosigmoiditis. Patients presenting to the Ferguson Clinic with the diagnosis of idiopathic proctosigmoiditis were evaluated for age, sex, prior history of proctitis, duration of symptoms prior to presentation, endoscopic scoring, and mucosal biopsies. Clinical evaluation was performed at two-week intervals for six weeks, with repeat biopsies taken at six weeks. There was no significant difference with respect to age, male/female ratio, past history of proctosigmoiditis, length of colorectum involved at the time of initial presentation, symptom resolution, and endoscopic and histologic improvement among the three treatment groups. Recovery occurred in a similar proportion in each of the three groups: CS, 10/12; 5-ASA, 17/19; and SCFA, 12/14. The cost of six weeks of treatment was: CS, $71.82; 5-ASA, $347.28; and SCFA, $31.50. This study indicates that SCFA enemas are equally efficacious to CS or 5-ASA enemas for the treatment of proctosigmoiditis at a significant cost savings.

The necessity of routine pathologic evaluation of hemorrhoidectomy specimens.

Unsuspected carcinoma of the anus found on routine pathologic analysis of specimens taken at hemorrhoidectomy is a rare occurrence. Rates of 1 to 2 per cent are quoted, but without the support of objective data. During the past 20 years, 21,257 hemorrhoidectomies have been performed at Ferguson Hospital. During that time period, only one instance of unsuspected carcinoma of the anus was diagnosed solely by microscopic analysis of a specimen that was taken at hemorrhoidectomy. Based on this information, we recommend selective rather than routine pathologic evaluation of hemorrhoidectomy specimens. All patients should undergo careful anorectal examination prior to hemorrhoidectomy. Repeat examination should be performed with the patient under anesthesia and all excised tissue should be visually and manually inspected by the operating surgeon. Any suspicious areas as based on preoperative evaluation, examination under anesthesia or inspection of excised tissue should be sent for gross and microscopic evaluation.

Transanal excision of large, rectal villous adenomas.

The purpose of this study is to demonstrate that a transanal excisional approach can be successfully used in most cases of large, benign, rectal villous adenomas with acceptable rates of recurrence and complications in comparison with historic controls. A retrospective review of all cases of benign, large, rectal villous adenomas at this institution from 1975 to 1985 was performed. A total of 122 patients had large, benign, rectal villous adenomas excised. All except five were treated by transanal excision. Thirty-eight percent of lesions were more proximal than 8 cm from the anal verge. The average follow-up was 55 months. Twenty-seven percent of patients were treated for residual disease after a known incomplete initial treatment or an adenoma at the same location within 6 months of the original treatment. Thirty percent of patients were treated for recurrent adenoma 6 months after complete initial treatment. Two patients (1.7 percent) with recurrences were found to have invasive carcinoma. Both patients had excisional therapy, and one had additional radiation therapy for these carcinomas. Ten postoperative hemorrhages and two perforations occurred as symptomatic or serious complications. This renders a 10 percent complication rate for the study group, which is lower than reported by others using the Kraske or trans-sphincteric approach to the rectum. Because of the expected higher recurrence rate, regular follow-up is necessary for this type of therapy. In conclusion, this study demonstrated that transanal excision of large, benign, rectal villous adenomas can be a safe and effective method of treatment.

Is colonoscopic screening appropriate in asymptomatic patients with family history of colon cancer?

Colonoscopy has been advocated by some investigators as the most appropriate means of screening asymptomatic patients with a positive family history of colorectal cancer. However, results of such screening have been widely disparate. The purpose of this study was to evaluate the yield of colonoscopy in a cohort of completely asymptomatic individuals with one or two first-degree relatives with a history of colorectal cancer and to compare this yield with that of colonoscopy in a group of patients with apparent anal bleeding. Patients with possible genetic disorders, such as familial polyposis, were excluded. A total of 160 asymptomatic patients and a comparison group of 137 patients with nonacute anorectal bleeding underwent colonoscopy. Colonoscopy was completed in 143 of the 160 study patients (89 percent) and in all of the comparison patients and did not result in any complications. Twenty-two adenomas were found in 17 study patients (10.6 percent); 16 of the 22 adenomas were less than 1 cm in size. In the comparison group, eight adenomas were identified (5.8 percent of patients). No cancers were identified. The difference in polyp frequency between groups was not significant. The relatively low yield of colorectal neoplasms discovered at colonoscopy in this study may in part be due to the small sample size or to the strict criteria used to define these asymptomatic patients but does not lend strong support to the notion that colonoscopy is an appropriate first step in screening the asymptomatic patient with one or two first-degree relatives with colon cancer.

Anorectal and colonic disease and the immunocompromised host.

The immunocompromised host is becoming increasingly ubiquitous in the authors' patient population. There are growing numbers of long-term transplant recipients, and combination chemotherapy is producing many long-term survivors. Of greatest concern is that the number of patients with human immunodeficiency virus (HIV) causing immunosuppression is increasing. The literature is reviewed to produce a current summary of conditions affecting the anorectum and colon and arising as a direct consequence of the immunocompromised host. Pathophysiology and theoretic considerations are mentioned where applicable and current therapy is discussed. The conditions are classified under infectious, neoplastic, iatrogenic, and congenital. Although the colorectal surgeon will encounter most of these conditions sometime during a career, many are infrequent, and a current review is provided herein to provide categorization and updated information.

Gallstone obstruction of the colon. Report of two cases and review of management.

Gallstone ileus is a distinctly unusual cause of colonic obstruction. Two patients, with associated biliary-colonic fistulas, are described. The clinical features and approximate management of this entity are discussed.

Surgical treatment of chronic anal fissure. A retrospective study of 1753 cases.

This is a retrospective study of 1753 cases of chronic anal fissures treated by five varying methods over a five-year period from January 1976 to December 1980. Results showed that the incidence of recurrent fissures was higher in those treated by anal fissurectomy with sphincterotomy. There was also a significant difference in operative time, length of hospital stay, patient discomfort, and incidence of urinary retention among these operative methods. Generally, lateral anal sphincterotomy and multiple anal sphincterotomies showed a lesser incidence of these factors. A simpler procedure, such as lateral anal sphincterotomy or multiple anal sphincterotomies, is the treatment of choice for chronic anal fissure. However, a chronic anal fissure associated with symptomatic enlarged hemorrhoids may have a similar result when treated with hemorrhoidectomy and fissurectomy as a combined procedure.