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Hospital-acquired antibiotic-resistant pneumonia is one of the major causes of mortality around the world that pose a catastrophic threat. Pseudomonas aeruginosa is one of the most significant opportunistic pathogens responsible for hospital-acquired pneumonia and gained resistance to the majority of conventional antibiotics. There is an urgent need for antibiotic alternatives to control drug-resistant pneumonia and other related respiratory infections. In the present study, we explored the antibacterial potential of cineole in combination with homeopathic medicines against biofilm-forming drug-resistant P. aeruginosa . Out of 26 selected and screened homeopathic medicines, Hypericum Perforatum (HyPer) was found to eradicate biofilm-forming drug-resistant P. aeruginosa most effectively when used in combination with cineole. Interestingly, the synergistic action of HyPer and cineole was also found to be similarly effective against planktonic cells of P. aeruginosa . Further, the potential synergistic killing mechanisms of cineole and HyPer were determined by analyzing zeta membrane potential, outer membrane permeability, and DNA release from P. aeruginosa cells upon treatment with cineole and HyPer. Additionally, molecular docking analysis revealed strong binding affinities of hypericin (an active ingredient of HyPer) with the PqsA (a quorum sensing protein) of P. aeruginosa . Overall, our findings revealed the potential synergistic action of cineole and HyPer against biofilm-forming drug-resistant P. aeruginosa . Cineole and HyPer could be used in combination with other bronchodilators as inhalers to control the biofilm-forming drug-resistant P. aeruginosa ., Competing Interests: The authors declare no conflicts of interest.

Introduction: Lumbar spondylosis (LS) is a degenerative disorder of the lumbar spine. Despite substantial research efforts, no gold-standard treatment for LS has been identified. The efficacy of individualized homeopathic medicines (IHMs) in LS has remained under-researched. In this study, the efficacy of IHMs was compared with identical-looking placebos in the treatment of low back pain associated with LS., Methods: A double-blind, randomized (1:1), placebo-controlled trial was conducted at the National Institute of Homoeopathy, West Bengal, India. Patients were randomized to receive IHMs or placebos, along with standardized concomitant care for both the groups. The Oswestry low back pain and disability questionnaire (ODQ) was the primary outcome; the Roland-Morris questionnaire (RMQ) and the short form of the McGill pain questionnaire (SF-MPQ) were the secondary outcomes. Each was measured at baseline and every month for 3 months. The intention-to-treat (ITT) sample was analyzed to detect any inter-group differences using two-way repeated measures analysis of variance models overall and by unpaired t -tests at different time points., Results: Enrolment was stopped prematurely because of time restrictions; 55 patients were randomized (verum: 28; control: 27); 49 were analyzed by ITT (verum: 26; control: 23). Inter-group differences in ODQ ( F 1, 47  = 0.001, p  = 0.977), RMQ ( F 1, 47  = 0.190, p  = 0.665) and SF-MPQ total score ( F 1, 47  = 3.183, p  = 0.081) at 3 months were not statistically significant. SF-MPQ total score after 2 months ( p  = 0.030) revealed inter-group statistical significance, favoring IHMs against placebos. Some of the SF-MPQ sub-scales at different time points were also statistically significant: e.g., the SF-MPQ average pain score after 2 months ( p  = 0.002) and 3 months ( p  = 0.007). Rhus toxicodendron, Sulphur and Pulsatilla nigricans were the most frequently indicated medicines., Conclusion: Owing to failure in detecting a statistically significant effect for the primary outcome and in recruiting a sufficient number of participants, our trial remained inconclusive., Trial Registration: CTRI/2019/11/021918., Competing Interests: None declared., (Faculty of Homeopathy. This article is published by Thieme.)

Context: Pre-hypertension remains a significant public health challenge and appropriate intervention is required to stop its progression to hypertension and/or cardiovascular diseases., Objective: To study the effects of individualized homeopathic medicines (IH) against placebo in intervening with the progression of pre-hypertension to hypertension., Design: Double-blind, randomized, two parallel arms, placebo-controlled trial., Setting: Outpatient departments of D. N. De Homoeopathic Medical College and Hospital, Kolkata, West Bengal, India., Patients: Ninety-two patients suffering from pre-hypertension; randomized to receive either IH (n = 46) or identical-looking placebo (n = 46)., Interventions: IH or placebo in the mutual context of lifestyle modification (LSM) advices including dietary approaches to stop hypertension (DASH) and brisk exercises., Main Outcome Measures: Primary - systolic and diastolic blood pressure (SBP and DBP); secondary - Measure Yourself Medical Outcome Profile version 2.0 (MYMOP-2) scores; all measured at baseline, and every month, up to 3 months., Results: After 3 months of intervention, the number of patients having progression from pre-hypertension to hypertension between groups were similar without any significant differences in between (all P>0.05). Reduction in BP and MYMOP-2 scores were non-significantly higher (all P>0.05) in the IH group than placebo with small effect sizes. Lycopodium clavatum, Thuja occidentalis and Natrum muriaticum were the most frequently prescribed medicines. No harms or serious adverse events were reported from either group. Thus, there was a small, but non-significant direction of effect favoring homeopathy, which ultimately rendered the trial as inconclusive. [Trial registration: CTRI/2018/10/016,026; UTN: U1111-1221-8251]., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: The quality of management of hyperuricemia has remained sub-optimal owing to unavoidable toxicities, limitations, and dearth of novel advances. Homeopathy has remained under-researched in hyperuricemia. We investigated the clinical effectiveness of three treatment regimens - individualized homeopathy (IH), Urtica urens mother tincture (UUMT), and both (IH + UUMT) along with lifestyle modifications in a sample of 90 patients with hyperuricemia., Methods: An open, randomized (1:1:1), 3 parallel arms (IH, UUMT, and IH + UUMT), pragmatic trial was conducted at National Institute of Homoeopathy, Kolkata. Outcome measures were serum uric acid (primary), Gout Assessment Questionnaire version 2 (GAQ2, secondary), and Measure Yourself Medical Outcome Profile version 2 (MYMOP2, secondary); all measured at baseline, and after 3 and 6 months. Intention- to-treat sample was analyzed to detect group differences by unpaired t tests., Results: Attrition rate was 8.9% (IH: 3, UUMT: 3, IH + UUMT: 2). Groups were comparable at baseline. Reductions in serum uric acid over 3 months were comparatively higher (p=0.057) in the UUMT group than others, however, the differences were narrowed over 6 months (p=0.119). Per protocol analysis of serum uric acid level revealed similar trend of significantly higher reduction in the UUMT group than the other two (3 months: p=0.001; 6 months: p=0.007). No significant differences existed in reductions of GAQ2 scores among the three groups. Few significant differences were detected in MYMOP scores over 3 months favoring IH against others (symptom 2, p=0.001 and wellbeing score, p=0.002), and also over 6 months favoring IH + UUMT against others (symptom 1, p<0.001)., Conclusion: Although all three therapies showed similar improvements, the IH + UUMT group had more positive direction of effects than IH or UUMT alone; however, no definite conclusion could be arrived at. Further trials are warranted with larger sample size. Trial registration: CTRI/2018/05/014026., (© 2020 Walter de Gruyter GmbH, Berlin/Boston.)

Background Irritable Bowel Syndrome (IBS) is a prevalent gastro-intestinal disorder characterized by recurrent abdominal pain, bloating, altered bowel function and myriad of gastro-intestinal symptoms. Dysentery compound (DC), a 'bowel nosode', is one of the homeopathic medicines to treat IBS, but remained under-researched. We hypothesized that DC would be non-inferior to individualized homeopathy (IH) in treatment of IBS. Method An open, randomized (1:1), parallel arms, pragmatic, non-inferiority, pilot trial was conducted to compare the effectiveness of DC with IH medicines in 60 IBS patients. IBS Quality of Life (IBS-QOL) questionnaire was used as the outcome measure; assessed at baseline and after 3 months. Comparative analysis was carried out on the primary outcome to detect non-inferiority by one-tailed t test at alpha=5% with a prefixed margin (Δ) of 1.0 based on assumption. Results Six subjects dropped out. Groups were comparable at baseline (all p>0.01). Though intra-group changes were higher favoring IH over DC, group differences were statistically non-significant (all p>0.01). Non-inferiority was not demonstrated by DC against IH over 3 months (mean difference= -3.3, SE=5.2, lower 95% confidence limit -11.9, t= -0.453, p=0.674). No adverse events were reported from either group. Conclusion Non-inferiority of DC against IH in treatment of IBS was not demonstrated though it appeared as safe; still, being a pilot trial, no definite conclusion could be drawn. Further exploration of both efficacy and effectiveness of either of the therapies is necessary by adequately powered trials and independent replications. Trial registration: CTRI/2017/05/008480; UTN: U1111-1196-1004.

Background: Insomnia is the most common sleep-related complaint associated with impaired day-time functioning, reduced quality of life, increased morbidity and substantial societal cost. We evaluated whether individualized homeopathy (IH) could produce significant effect beyond placebo in treatment of insomnia., Methods: In this double-blind, randomized, placebo-controlled, two parallel arms trial, 60 patients were randomized to receive either IH/verum or control/placebo (1:1). Patient-administered sleep diary (6 items; 1: latency to fall asleep, 2: minutes awake in middle of night, 3: minutes awake too early, 4: hours spent in bed, 5: total sleep time in hours, and 6: sleep efficiency) and Insomnia Severity Index (ISI) were taken as the primary and secondary outcomes respectively, measured at baseline, and after 3 months., Results: Five patients dropped out (verum: 2, control: 3). Intention to treat sample (n = 60) was analyzed. Trial arms were comparable at baseline. In the verum group, except sleep diary item 3 (P =  0.371), rest of the outcomes improved significantly (all P < 0.01). In the control group, there were significant improvements in diary item 6 and ISI score (P < 0.01) and just significant improvement in item 5 (P =  0.018). Group differences were significant for items 4, 5 and 6 (P < 0.01) and just significant (P =  0.014) for ISI score with moderate to large effect sizes; but non-significant (P > 0.01) for rest of the outcomes., Conclusion: IH seemed to produce significantly better effect than placebo. Rigorous trials and independent replications are warranted., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Among the post-immunization adverse events, especially of Diphtheria-Pertusis-Tetanus (DPT), fever is a common systemic reaction. There is anecdotal support for the use of the homeopathic medicine Arsenicum album in preventing post-vaccination fever. The investigators intended to evaluate its efficacy in preventing febrile episodes following vaccination., Methods: In the community medicine out-patient of Mahesh Bhattacharyya Homoeopathic Medical College and Hospital, West Bengal, India, between August 2014 and January 2017, a double-blind, randomized, placebo-controlled trial was conducted on 120 children (verum: 60, placebo: 60) who presented for the 2nd and 3rd dose of DPT-HepB-Polio vaccination and reported febrile episodes following the 1st dose. Intervention used was Arsenicum album 30cH 6 doses or placebo (indistinguishable from verum), thrice daily for two subsequent days. Parents were advised to report any event of febrile attacks within 48h of vaccination, either directly or over telephone., Results: The groups were comparable at baseline. Children reporting fever after the 2nd dose was 29.8% and 30.4% respectively for the homeopathy group and control group respectively [Relative Risk (RR)=1.008] with no significant difference (P=0.951) between groups. Again after the 3rd dose, children reporting fever were 31.5% and 28.3% respectively for the homeopathy group and control group respectively (RR=0.956) with no significant difference (P=0.719) between groups., Conclusion: Empirically selected Arsenicum album 30cH could not produce differentiable effect from placebo in preventing febrile episodes following DPT-HepB-Polio vaccination. [Trial registration: CTRI/2017/02/007939]., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: We evaluated the influence of several clinicopathologic variables on 5-year actuarial survival rate after curative resection of gastric adenocarcinoma., Methods: Clinical characteristics were retrieved from the records of all patients who underwent gastric resection for curative intent between 1965 and 1986 at The University of Chicago Medical Center, and follow-up was obtained from our tumor registry. Pathologic characteristics were determined from a detailed review of all available histopathologic slides., Results: One hundred seventy-eight patients underwent a curative resection during the study period at our institution. Overall 5-year actuarial survival rate was 29%. The relationship between clinicopathologic variables and 5-year survival rate was evaluated by Kaplan-Meier survival curve construction and chi-squared analysis. Lymphatic and/or capillary microinvasion (absent vs present, p < 0.001), tumor location (antrum and body vs gastroesophageal junction, p = 0.05), local extent of disease (limited to the gastric wall versus involving adjacent organs, p = 0.003), stage (absence versus presence of lymph node metastases, p < 0.001), Lauren type (intestinal versus diffuse, p < 0.01), and Ming type (expanding versus infiltrative, p < 0.02) significantly influenced survival. When a multivariate analysis with logistic regression of 5-year survival was performed, lymphatic and/or capillary microinvasion emerged as the only statistically significant, independent prognostic factor associated with long-term survival (p = 0.039). If microinvasion was omitted from the analysis, lymph node metastases (p < 0.05) and the extension to adjacent organs (p < 0.04) became the only statistically significant variables. Multiple correlation analyses suggested that microinvasion is an early histopathologic finding that correlates with a more aggressive natural history., Conclusions: Lymphatic and/or capillary microinvasion is a more powerful predictor of 5-year survival than lymph node metastases or tumor extension to adjacent organs. Correlation among clinicopathologic variables suggests that microinvasion may represent an early finding, serving as a potential marker for a biologically more aggressive tumor.

Purpose: The role of immunoscintigraphy with 111In-satumomab pendetide in the medical and/or surgical management of colorectal cancer patients was evaluated in a multicenter trial., Methods: This 103 patient study population included 46 individuals with rising serum carcinoembryonic antigen levels and otherwise negative diagnostic evaluation, 29 patients with known recurrence, presumed to be isolated and resectable, and 28 patients for whom standard diagnostic tests provided equivocal information., Results: No adverse reactions were noted following intravenous administration of 1 mg of satumomab pendetide radiolabeled with approximately 5 mCi of 111In. Thirty percent of patients developed human anti-mouse antibodies postinfusion. In the 84 patients for whom correlation with histopathologic, diagnostic, and/or clinical findings was available, antibody imaging demonstrated a sensitivity of 73 percent in patients with confirmed tumor (36/49) and negative results for all 35 patients with no evidence of malignancy. Occult disease was detected in 18 patients., Conclusion: 111In-satumomab pendetide immunoscintigraphy was helpful in the medical and/or surgical management of 45 (44 percent) patients and provided information unavailable from other diagnostic modalities.

Objective: The authors review their experience, evaluating the incidence and examining the various modalities employed in the diagnosis and treatment of patients with Crohn's disease complicated by fistulae., Summary Background Data: Although common, internal and external fistulae in Crohn's disease may pose challenging problems to the surgeon., Methods: Of 639 patients who underwent surgical treatment at the University of Chicago between 1970 and 1988 for complications of Crohn's disease, 222 patients (34.7%) were found to have 290 intra-abdominal fistulae., Results: A fistula was diagnosed preoperatively in 154 patients (69.4%), intraoperatively in 60 (27%), and only after examination of the specimen in 8 (3.6%). The fistula represented the primary or single indication for surgical treatment in 14 patients (6.3%) and one of several indications in the remaining patients. Of 165 patients with an abdominal mass or abscess, 69 (41.8%) had a fistula. All patients underwent resection of the diseased intestinal segment; 160 (73.1%) with primary anastomosis and the remaining 62 with a temporary or permanent stoma. The fistula was directly responsible for a stoma in only 16 patients (7.2%) and was never responsible for a permanent stoma. Resection of the diseased bowel achieved en bloc removal of the fistula in 145 cases. Removal of 93 additional fistulae required resection of the diseased bowel segment along with closure of a fistulous opening on the stomach or duodenum (n = 14), bladder (n = 35), or rectosigmoid (n = 44). When the fistula drained through a vaginal cuff (n = 4), the opening was left to close by secondary intention; when the fistula opened through the abdominal wall (n = 46), the fistulous tract was debrided. In the remaining two entero-salpingeal fistulae, en bloc resection of the involved salpinx accomplished complete removal of the fistula. There was a dehiscence of one duodenal and one bladder repair; 14 patients (6%) experienced postoperative septic complications and one patient died., Conclusions: Fistulae are diagnosed preoperatively in 69% of cases and can be suspected in as many as 42% of patients with an abdominal mass. Fistulae are the primary or single indication for surgical treatment and are directly responsible for a stoma only in a few patients. Treatment, based on resection of the diseased bowel and extirpation of the fistula, can be accomplished with minimal morbidity and mortality.

Objective: To document the functional results of 50 consecutive patients who underwent hand-sewn ileal J pouch-anal restorative proctocolectomy for ulcerative colitis between 1988 and 1991 (mean follow-up, 18.1 months; range, 6 to 48 months)., Design: Patients recorded their observations daily over 1 week. The patients completed these weekly diaries every 3 months for the first year and then at 18, 24, 36, and 48 months after ileostomy closure., Study Participants: Fifty patients (mean age, 31 years; 24 males)., Setting: The University of Chicago (Ill)., Results: Stool frequency at 3, 6, 12, and 24 months was 6.3 +/- 2.1, 5.5 +/- 2.4, and 5.1 +/- 1.9, and 5.9 +/- 1.6 per day, respectively, without urgency. Fifty-four percent were perfectly continent; 18% had occasional spotting (one or two leaks per week); 12% had minor leakage (three to seven per week); and 16% had major leakage (more than seven per week). In these three groups, loss of solid feces never occurred in 84%, 88%, and 65% of patients, respectively. Females had more severe incontinence than males, but continence improved over time for both sexes. Twenty-two percent of female patients developed dyspareunia; no males developed impotence, but 19% had retrograde ejaculation. The probability of experiencing pouchitis increased with time from 15% at 6 months to 40% at 12 months, and 50% after 24 months., Conclusions: These results represent an accurate assessment of patient function after ileal J pouch-anal anastomosis. We encourage the use of a prospective, patient-completed protocol to obtain a realistic assessment of functional results.

We report on 14 cases of intestinal adenocarcinoma complicating Crohn's disease, seven occurring in the small bowel and seven in the large bowel. In both locations, two-thirds of patients were male. The average ages at the time of diagnosis of Crohn's disease and of cancer were similar between the two groups of patients: 28 and 48 years, respectively. The diagnosis of cancer was suspected or obtained preoperatively in only four cases of large bowel cancer; in two patients with large bowel cancer and five with small bowel cancer, the diagnosis was made at laparotomy. In the remaining cases, only careful histologic examination revealed the carcinoma. Six small bowel cancers were located in the ileum, and five colonic cancers were distal to the splenic flexure. Two small bowel and one large bowel cancer were multifocal and had surrounding mucosal dysplasia. All tumors, except one small bowel cancer, underwent resection. Survival correlated with stage of tumor at resection; no patient with regional or distant metastasis survived five years, in comparison with an 83 percent five-year actuarial survival rate of patients with tumor confined to the intestinal wall. Mean survival was six months for patients with small bowel cancer in comparison with 65 months for patients with large bowel cancer, reflecting a tendency toward more advanced lesions in the small bowel cancer group.

A stapling technique for construction of an ileal J-pouch is presented. The technique is simple, minimizes the chances for pelvic contamination and avoids midpouch enterotomies. By postponing the performance of the apical enterotomy until after the pouch is in the definitive position, the apical enterotomy is placed exactly where needed to facilitate the subsequent ileoanal anastomosis.

This retrospective study was aimed at defining the morbidity and mortality of a radical resection for adenocarcinoma of the rectum complemented by a wide pelvic lymphadenectomy. Twenty-seven consecutive patients with rectal carcinoma who underwent a surgical resection with conventional (Group I) or wide (Group II) pelvic lymphadenectomy were analyzed. Group I consisted of 10 patients (three women and seven men; mean age, 71 years) with tumors between 6 and 14 cm (mean, 10.6 cm) from the anal verge. Group II consisted of 17 patients (eight women and nine men; mean age, 67 years) with tumors between 3 and 14 cm (mean, 9 cm) from the anal verge. The choice of lymphadenectomy in association with colorectal resection was left at the discretion of the surgeon. There were no deaths within 60 days of operation. Mean intraoperative blood loss was the same in the two groups, although three patients (18 percent) required blood transfusions of over two liters during the performance of a wide pelvic lymphadenectomy in comparison with only one (10 percent) during conventional pelvic lymphadenectomy. The rate of early postoperative complications and the average length of postoperative hospital study were each similar between the two groups. After a wide pelvic lymphadenectomy, three (18 percent) patients developed a neurogenic bladder, requiring intermittent self-catheterization, and they all recovered within one, four, and eight months, respectively. Of the 16 males, three from Group I and four from Group II were sexually active and potent before surgical treatment; after recovering from surgery, only two patients from Group I regained their sexual potency. We conclude that the performance of a wide pelvic lymphadenectomy did not increase the intraoperative or early postoperative complication rate, the mean intraoperative blood loss, or the length of postoperative hospital stay. Technical refinements are currently under study to obviate the neurologic long-term complications.

Thirty-six pancreatic patients with massive gastrointestinal bleeding have now been identified as having pancreaticoduodenal and gastroduodenal artery aneurysms as causative. In the past decade, seven of the patients have been encountered at the authors' institution and seven presented in the literature. Of these 14, there was a predilection for men (85%) with an average age of 48.1 years, who had complications of pancreatitis (75%), that is, abscess or pseudocyst. Eleven of these patients underwent surgery with an 81 per cent survival rate. Previous reports had shown a 47 per cent survival rate in 19 similar patients. Embolization of the aneurysm was attempted in four patients with two successes. The authors believe that early diagnosis by arteriography and early operative intervention were responsible for the improved survival. A high index of suspicion in this patient population is crucial for early diagnosis and improvement in survival.

Between 1970 and 1988, 1379 patients with Crohn's disease were treated at the University of Chicago. Of these, 639 (mean age, 32.5 years; 322 men, 317 women) required at least one surgical procedure. The most common indications for operation were failure of medical treatment (n = 215, 33%), presence of a fistula (n = 154, 24%), and bowel obstruction (n = 141, 22%). A fistula was the most common intraoperative Crohn's-related complication. In 582 patients (92%), a resection was necessary, with primary anastomosis in 416 (65%), a temporary stoma in 124 (20%), and a permanent stoma in 42 (7%). The remaining 57 patients underwent diverse procedures (stricturoplasty, bypass, and so on). Two patients (0.3%) died. Follow-up data was obtained in 95%. One hundred eighteen patients developed recurrence requiring reoperation. The recurrence rate was 20% at 5 years and 34% at 10 years. The recurrence involved a permanent stoma or a previous anastomosis in 62 patients (afferent limb in 46, efferent in 16). In the 391 patients without previous surgery for Crohn's disease, a covariate analysis was performed to determine those variables significantly associated with recurrence. Variables included demographic data, findings at operation, surgical procedures, and histopathologic characteristics. The analysis revealed that the number of sites involved was the only variable that was significantly associated with the intra-abdominal recurrence rate (p less than 0.001). The annualized risk of recurrence was 1.6% for patients with single-site involvement and 4% for those with multiple-site involvement. Perineal disease was associated with a significantly higher risk of local recurrence than any other site (p less than 0.02). A subanalysis of 236 patients with single-site involvement but no previous operation allowed us to study the influence of site on indications for surgery and type of operative procedure. Failure of medical treatment was the most common indication for all sites. In contrast the site involved influenced the procedure: resection and primary anastomosis was feasible in 88% of jejunoileal and terminal ileal cases and a temporary ileostomy was necessary in only 12%. No patients with small bowel localization required a permanent stoma. A resection with primary anastomosis was feasible in only 32% of patients with colonic disease. The remaining two thirds of patients required either a temporary or a permanent stoma. It is concluded that multisite involvement is associated with 2.5 times the rate of recurrence of single-site disease, while the presence of perineal disease has a significantly higher incidence of local recurrence.(ABSTRACT TRUNCATED AT 400 WORDS)

As reported in the Bulletin at various times over the past several years, the American College of Surgeons has frequently been called upon by federal agencies and commissions to provide clinical information and advice on issues that are associated with implementation of the Medicare physician payment system reforms mandated by the Omnibus Budget Reconciliation Act of 1989 (OBRA '89). In doing so, the College has often relied on the expertise of Fellows who are deeply committed both to the practice of general surgery and to the College. The purpose of this article is to provide a review of the College's participation in activities related to implementation of the Medicare reforms, as viewed by some of the general surgeons who shared in those efforts.

Rectal adenocarcinoma is said to have a poorer outcome than colon adenocarcinoma when compared on the basis of Dukes' staging. However a new staging system, determined by a multivariate analysis of 147 patients with rectal adenocarcinoma, has revealed three other variables significantly related to outcome. Therefore this study analyzed the authors' experience with colonic carcinoma during the same time period as they had studied for rectal carcinoma to determine whether the new staging system is valid for colon carcinoma as well, and, if so, to compare the outcome of patients with colon and rectal carcinoma on the basis of this new staging. A total of 603 patients with 611 colonic adenocarcinoma were operated on at the University of Chicago Medical Center between 1965 and 1981. Two hundred seventy-nine adenocarcinomas (45.7%) were located proximal to the splenic flexure and 332 (54.3%) were located between the splenic flexure and the rectosigmoid. Four hundred sixty-two patients underwent segmental colectomy, 46 subtotal colectomy, 26 total colectomy, 18 proctocolectomy, 5 abdominal-perineal resection, 1 appendectomy, while 20 had local excision of the tumor through colotomy and 25 had permanent diverting stoma as the only procedure. The operative mortality rate was 6.1% in the whole group, but was only 2.7% in the group of potentially curable patients. Complete follow-up was obtained in all patients. To validate a previous staging system for Dukes' B and C rectal adenocarcinoma, the authors investigated the correlation between 5-year survival for colonic carcinoma patients and all relevant variables that they had considered potentially meaningful in the previous study with rectal adenocarcinoma. The resulting multivariate analysis using Cox regression showed that the four variables found previously to be significantly related to outcome for rectal adenocarcinoma patients (stage, race, tumor morphology, and vascular and/or lymphatic microinvasion) were the only four variables significantly (p less than 0.05) associated with outcome for colonic adenocarcinoma patients. In addition, by using the results of their previous staging system for rectal adenocarcinoma patients, they 'predicted' the 5-year survival rates of the colon adenocarcinoma patients, divided in 16 staging subgroups. In subgroups of at least 15 patients, the rectal staging system predicted the outcome to within 1 to 6 percentage points of the observed outcome of the colonic adenocarcinoma patients. Thus this study validates this staging system, incorporating stage, race, tumor morphology, and microinvasion to predict 5-year survival rate more accurately than Dukes' staging alone for both colon and rectal adenocarcinoma.(ABSTRACT TRUNCATED AT 400 WORDS)

A total of 853 patients with 861 colorectal adenocarcinomas were operated on at our institution between 1965 and 1981. Complete follow-up information was obtained in all but six patients (99.4%), and all available histologic slides were reviewed to determine pathologic stage and characteristics. Six hundred fifty-one patients (76.3%) underwent a potentially curative procedure, and their operative mortality rate was 2.8%. Of the 627 patients available for analysis, 50 (8%) had a local recurrence. The median time to local recurrence was 18 months, and only 16% of local recurrences were diagnosed 5 years after the original resection. Median survival of patients with a local recurrence was 3 1/2 years from the original resection, and 16 patients (32%) survived 5 years or longer. A multivariate logistic regression analysis was conducted to examine the influence of several clinical and pathologic characteristics on local recurrence among Dukes' stages B and C adenocarcinomas (n = 539) after exclusion of patients with synchronous tumors (n = 8), postoperative deaths (n = 18), loss to follow-up (n = 6), or incomplete data (n = 11). This analysis revealed that the local recurrence rate was significantly related to depth of invasion (B1 + C1 = 0%; B2 + C1 = 10%; p less than 0.01), site of origin (right plus transverse colon = 6%; left plus rectosigmoid colon = 10%; rectum = 12%; p less than 0.05), and lymphatic or capillary microinvasion (absent, 6%; present, 14%; p less than 0.05). This analysis attempts to identify patients at high risk for development of local recurrent disease to select candidates for postoperative adjuvant therapy.

Total parenteral nutrition (TPN) is a well-established means of nutritional support in the critically ill patient who is unable to maintain adequate oral intake. A complication of long-term parenteral nutrition is gallbladder disease. Cholecystitis is often difficult to diagnose in patients with multisystem disease and has a dour prognosis when there is delay in diagnosis and operative treatment. An awareness of the risk factors for cholecystitis, including TPN, in the critically ill patient is the sine qua non of early diagnosis. If cholecystitis is suspected, the diagnosis may be established by ultrasonography, tomography, and scintigraphy. Immediate cholecystectomy is the treatment of choice.

We have reviewed several tumor markers that our advocates feel are now clinically useful, involve current assay technology, and are based on already available information. These include, in selected instances, estrogen receptors for breast cancer, thyrocalcitonin for medullary cancer of the thyroid, prostatic acid phosphatase for cancer of the prostate, alpha-fetoprotein for hepatocellular cancer, and carcinoembryonic antigen for monitoring colon cancer. We have considered the potential use of measurement of serum proteases and protein degradation products due to their activity as possible future areas of development, and we have explored measurement of tissue aryl hydrocarbon hydroxylase to identify populations at risk of cancer resulting from chemical carcinogenesis. It is clear that the study of tumor markers is already improving patient care in some specific areas and offers exciting potential for the future.

From 1966 through 1970 we performed resections in 216 patients with carcinoma of the large bowel. The relative five year survival for all patients was 65.5%. The relative five year survival for all potentially curable patients was 80.4%. Patients with positive lymph nodes and full-thickness penetration of their tumors had a five year survival of 70.5% and a 10 year survival of 60.5%. In performing this study we have tested the principles of wide anatomical resection and radical lymphadenectomy. For their specific influences on survival we have also examined stage, site, age, sex, race, margins, local recurrence, hypogastric lymph node dissection, serosal penetration and various aspects of nodal status. The information derived from these parameters has confirmed our hypothesis that survival is directly related to radical anatomical resection and lymphadenectomy. For rectal cancer, extensive resection also reduces the incidence of local recurrence. We are persuaded that the principles of operation for large-bowel cancer are valid and that they merit universal adoption.

An ileosigmoid fistula complicating Crohn's disease of the small bowel has been considered a perplexing entity, but in practice does not pose a serious operative problem. The presence of such a fistula does not signify that the sigmoid colon is a primary site of Crohn's disease. The operative treatment of this entity is simple and usually does not require resection of the sigmoid colon. Rather the sigmoid colon defect may easily be treated by simple closure, or by minimal partial resection and closure. Temporary diversion of the fecal stream is occasionally indicated because of local inflammation. Forty-four of the 48 patients treated in this manner had successful resolution of their problem. Four patients were found to have primary Crohn's disease of the colon and required further treatments in addition to closure of the fistula.

Cancer of the colon and rectum appear to be epidemic in the US, with 150,000 cases expected during 1988. Two thirds of these patients are over age 60, and two thirds also have either full penetration of the bowel wall or metastases to regional lymph nodes. Mass screening via tests for occult blood in the stool is invaluable for detecting early carcinomas of the colon and rectum. Digital examination, endoscopy, and barium contrast radiographs help to confirm the diagnosis. Tumors of the colon and rectum are best treated operatively with appropriate lymphadenectomy and adequate margins, both proximally and distally, to guard against local recurrence. Certain factors, such as mucinous tumors, microinvasion, and non-exophytic tumors of the rectum have been shown to have a propensity for local recurrence. Local treatment by fulguration or electrocoagulation is advocated only for tiny tumors confined to a polyp, or for the extremely elderly or poor-risk patient. Radiation therapy appears to be an appropriate adjuvant to the treatment of rectal cancer either preoperatively or postoperatively.

S-shaped ileal reservoirs (SSRs) and double-barreled ileal reservoirs (DBRs) of equal size were placed 6 or 2 cm from the anus and evaluated over 1 year for their ability to improve the functional incontinence noted after an ileoanal anastomosis (IAA). Compared to straight IAA, both reservoirs prolonged intestinal transit (235 minutes versus 135 minutes, P less than 0.001) and alleviated frequency without causing nutritional abnormalities. The capacity of the reservoirs was greater than that of a comparable length of distal ileum in dogs (n = 6) with straight IAA (304 +/- 16 ml versus 102 +/- 2 ml, P less than 0.001). The SSRs (n = 9), in contrast to the DBRs (n = 10), developed excessive volume capacity (360 +/- 30 ml versus 254 +/- 104 ml, P less than 0.01) and obstructive complications. Reservoirs with 6 cm efferent conduits (n = 13), in contrast to those with a 2 cm efferent conduit (n = 6), underwent marked dilatation (334 +/- 24 ml versus 238 +/- 13 ml, P less than 0.005). Electromyography and manometry revealed the DBRs to be more contractile than the SSRs but less than ileum proximal to the anus in dogs with a straight IAA. Ileal reservoirs improve results after IAA. Reservoirs should be complaint and yet contractile (e.g., DBR) so as to discourage excessive dilatation, which is the harbinger of obstruction. Ileal conduits facilitate reservoir placement, but if longer than 2 cm they excessively impeded reservoir emptying, predisposing to excessive reservoir dilatation and obstruction. A DBR with a 2 cm efferent conduit results in continence without obstructive problems.

To gain a better understanding of the biologic development of rectal adenocarcinomas, the authors evaluated the level of ras gene protein product (p21) in the available material of 74 Dukes' B adenocarcinomas, 64 Dukes' C adenocarcinomas, and 60 lymph-node metastases resected at the University of Chicago Medical Center between 1965 and 1981. Pathologic slides and archival paraffin blocks were retrieved for confirmation of the original diagnosis and measurement of p21 content. P21 titers were obtained using the RAP-5 monoclonal antibody in a semiquantitative immunohistochemical assay. Titer was expressed as the highest dilution giving definitive staining using the avidin-biotin peroxidase method. The analysis indicated that a higher percentage of Dukes' stage C rectal adenocarcinomas had high (greater than or equal to 1:40,000) p21 titers than Dukes' B adenocarcinomas (68.8 vs. 51.4 percent, respectively, P less than 0.05). In view of recent data suggesting that ras oncogene expression confers invasive and metastatic capabilities to NIH 3T3 cells, the authors believe this study offers evidence that overexpression of ras oncogene with overproduction of p21 protein product may be an important prerequisite for the acquisition of metastatic capabilities in the early stages of colon cancer.

Seven male Rhesus monkeys, with demonstrated gastric hypersecretory response to 50% distal small bowel resection, were studied. This increase in gastric acid output had persisted for more than 6 months. Precise, anatomical antrectomy without vagotomy was performed and intestinal continuity restored by gastroduodenostomy. Complete abolition of basal acid secretion and of the secretory response to histamine occurred. These effects could not be reversed by continuous (5 hour) infusions of pentagastrin at 0.2 microgram/kg hr-1 or 2 microgram/kg hr-1. The dose response curve to gastrin pentapeptide was altered; maximum secretion was greatly reduced and occurred at 10 microgram/kg hr-1. Neither basal serum gastrin or basal serum GIP was significantly reduced by antrectomy. These findings indicate that in this animal model the antrum is essential in the genesis of the hypersecretory state. If these findings are relevant to man precise antrectomy may be the procedure of choice for symptomatic acid hypersecretion after small bowel resection or disease.

Primary squamous-cell and adenosquamous-cell carcinoma of the colon are uncommon and their characteristics not well known. This paper reports the clinical features and pathologic findings of two colonic adenosquamous carcinomas and reviews other reports of adenosquamous and squamous carcinoma of the colon from the English medical literature. Including these two cases, 63 cases have been reported since 1927. Of these, six occurred in patients with ulcerative colitis, three occurred at the colonic opening of chronic colocutaneous fistulas, and concomitant schistosomiasis was present in two patients. Synchronous squamous-cell carcinoma of the colon was present in 3.2 percent of cases and 10 percent had either antecedent, synchronous, or metachronous adenocarcinoma of the colon. These lesions appeared to be distributed uniformly throughout the colon. The five-year survival after resective therapy for primary squamous-cell and adenosquamous-cell carcinoma of the colon calculated with life table analysis is 50 percent for Dukes' B lesions, 33 percent for Dukes' C lesions, and 0 percent for Dukes' D lesions.

Ras oncogenes are a specific family of genes believed to play a role in malignant transformation and tumor growth in humans. To gain a better understanding of the role these oncogenes may play in malignant transformation, we evaluated the levels of a ras gene protein product (p21) in formaldehyde-fixed, paraffin-embedded specimens of normal human colonic mucosa, hyperplastic polyps, tubular adenomas, villous adenomas, and epithelium from a patient with ulcerative colitis. The p21 protein content was measured using the RAP-5 monoclonal antibody in a semiquantitative immunohistochemical assay. The titer value was expressed as the highest dilution of antibody giving definite staining using the avidin-biotin peroxidase method. Differences in p21 titer values among all classes of polyps were significant (hyperplastic polyps values were less than tubular adenomas values, which were less than villous adenoma values). The p21 titers obtained from ulcerative colitis specimens were similar to those obtained from villous adenomas. We conclude that the levels of ras oncogene protein product increase with the malignant potential of benign human colonic conditions. These findings suggest that the ras oncogene protein product may play an important role in the malignant transformation of benign lesions of the human colon. If these findings are confirmed, as technology progresses to allow molecular probes to measure gene products in biopsy specimens, high-risk patients could be monitored and treated before actual malignant transformation occurs.

Hypercalcemia as a complication of carcinoma of the colon is uncommon (1). It usually occurs in the presence of anorectal or rectal carcinoma that metastasizes to the lumbosacral vertebrae (2-4). Hypercalcemia complicating colon carcinoma in the absence of bone metastases--so-called humoral hypercalcemia of malignancy or paraneoplastic hypercalcemia--is rare. Only two such cases associated with adenocarcinoma of the colon (5,6) and two cases associated with adenosquamous carcinoma of the distal colon (rectum and sigmoid) (7) have been reported. We describe the first reported case of an adenosquamous carcinoma of the cecum and ascending colon that was accompanied by severe humoral hypercalcemia. The hypercalcemia was associated with a parathyroid hormone (PTH)-like substance.

Thirty-three carcinomas of the colon and rectum occurring in patients with ulcerative colitis have been compared with matched controls from a population without colitis. There is no difference in length of survival between the patients in the two groups. More extensive tumor spread in the control group is due to the method of selection.

A technique for the placement of a transhepatic stent at the time of biliary-enteric anastomosis, which prevents the stent from interfering with the performance of the anastomosis is described herein. This technique obivates the need to pass the transhepatic catheter after the posterior portion of the hepaticojejunostomy has been completed.

The histologic materal from the original lesion of 113 patients suffering from Clinical Stage I and Clinical Stage II malignant melanomas were reviewed in an attempt to correlate depth of invasion with prognosis and to test whether or not current methods of microstaging were a valid guide to therapy. Both the microstaging methods of Clark and Breslow were eminently successful in indicating the prognosis of the patient, but were of no greater utility than other histologic parameters such as mitotic activity, perineural, vascular, or lymphatic invasion, or the presence of superficial ulceration. The value of elective node dissection for the treatment of primary malignant melanoma is uncertain. Deterents against empiric dissection are its low yield of occult metastases, its inability to prevent recurrence in a substantial portion of patients independent of the status of the nodes, and the difficulty in demonstrating an improved survival rate when this method of therapy is employed. Neither Clark's nor Breslow's methods or microstaging appeared to yield adequate criteria by which to choose node dissection. A simplified method of microstaging is proposed utilizing well defined anatomic levels, and yields statistically valid criteria for the performance of elective node dissection. Using this method, elective node dissection is advocated solely for those tumors that clearly invade the reticular dermis. Patients with tumors restricted to the papillary dermis do not appear to be benefited by empiric node dissection.