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Biomedical subjects

J R Monson

Publications and source records attributed to J R Monson.

At least 109 records · Page 6Linked to original sources

Recent progress in the use of monoclonal antibodies for imaging and therapy.

Despite their availability since 1975, monoclonal antibodies (MAbs) have failed to make a significant impact in the clinical treatment of patients outside of diagnostic assays for the measurement of tumor markers. Recently, however, studies have appeared demonstrating that MAb-directed imaging techniques may have a meaningful role to play in the diagnosis and treatment of patients with solid tumors such as colorectal cancer and malignant melanoma. Furthermore, second generation MAbs are appearing that mediate more specific binding characteristics, and experimental studies have suggested that genuine antitumor activity may not be far away. Finally, the recent development of newer molecules, such as chimeric and human antibodies, may lead to significant advances in MAb use. Specifically, allergic reactions to murine antibodies can be reduced or avoided altogether, and repeated doses can be administered safely. These newer MAbs appear to mediate cell lysis more efficiently and have been combined with chemotherapeutic agents and cell toxins. Greater understanding of host responses to MAbs and the development of anti-idiotype and anti-anti-idiotype antibodies have led to clinical trials that, it is hoped, will confirm the place of MAb therapy in clinical oncology.

Antibodies, Monoclonal↗

Laparoscopic assisted surgery of the colon. Operative technique.

Laparoscopic cholecystectomy is the most common major abdominal operation performed endoscopically. Other surgical procedures performed endoscopically include hysterectomy, hernia repair, Nissen fundoplication, and vagotomy. More recently, laparoscopic colectomy has been described (1,2). We have performed over fifty laparoscopic assisted colonic procedures, the results of which have been published (2). In this paper we describe the technique of two laparoscopic assisted procedures in colonic surgery--right and left hemicolectomy.

Anastomosis, Surgical↗

Preliminary results of laparoscopic repair of perforated duodenal ulcers.

A consecutive series of six patients admitted with perforated anterior duodenal ulcer were operated on using a laparoscopic technique. Only one operation was unsuccessful and required conversion to conventional open laparotomy. The remaining five patients had a completed laparoscopic omental patch repair with peritoneal washout. There was no mortality, and two patients developed a chest infection postoperatively. Early mobilisation and discharge from the hospital (mean, 6 days) were notable features in this series. In conclusion, laparoscopic repair of uncomplicated perforated duodenal is a safe and effective technique.

Duodenal Ulcer↗

Taurolidine inhibits tumour necrosis factor (TNF) toxicity--new evidence of TNF and endotoxin synergy.

The use of recombinant tumour necrosis factor (TNF) in the treatment of solid tumours has been limited by life threatening toxicity. In addition TNF may be a major mediator of the effect of endotoxins. Recent evidence suggested that a synergism between endotoxin (at the picogram level) and TNF may contribute to this toxicity. The use of the anti-endotoxin taurolidine may reduce TNF toxicity by interfering with this synergy. C57/BL6 mice (n = 140) received toxic doses (12 micrograms/mouse IV) of TNF. Four groups were studied. Group A received taurolidine 200 mg/kg IV 30 minutes before TNF, group B received TNF followed 30 minutes later by taurolidine 200 mg/kg IV, group C received an identical volume (0.5 ml) of normal saline 30 minutes prior to TNF, and group D taurolidine 200 mg/kg IP 45 minutes before TNF. The mortality rate of those mice receiving intravenous taurolidine 30 minutes prior to TNF was 8.8%. This was significantly less (P < 0.005) than the mortality rate achieved in groups B, C and D (33% vs 39.4% vs 50%). Further experiments employing an MTT (3-(4,5-dimethylthinzol-2-microliters)-2,5-diphenyl tetrazolinm bromide) assay showed that this was not due to direct interaction of taurolidine with TNF but is likely to be due to interference with the synergistic effects of endotoxin and TNF. It was also demonstrated in cotherapy studies in a murine model that taurolidine did not reduce the anti-tumour efficacy of TNF against the TNF sensitive mouse fibrosarcoma cell line Meth-A sarcoma.

Animals↗

Changes in immunological parameters during interleukin 2 and interferon 2 alpha treatment of recurrent renal cell carcinoma and malignant melanoma.

Immunological parameters were studied in patients with either advanced renal cell cancer (n = 7) or advanced malignant melanoma (n = 6) during treatment with a low-dose continuous intravenous treatment with human recombinant interleukin-2 (hr IL-2) and recombinant interferon alpha-2a. Before treatment, natural killer (NK) cell activity was found to be significantly lower in these patients than in 10 normal controls. However, the numbers of NK cells in circulation were equivalent; following incubation of the patients' peripheral blood mononuclear cells (PBMC) with IL-2 for three days normal lymphokine activated killer (LAK) cell activities were induced. Thus, in-vitro incubation with IL-2 appeared to overcome a defect in NK activity. We next examined the effect of IL-2/IFN alpha therapy on in-vitro LAK induction. Treatment significantly increased in-vitro LAK activity in eight of nine patients tested, although in-vivo LAK cell activity was not altered during treatment. The numbers of NK cells (CD16+ CD56+) in peripheral blood showed a significant increase in seven of ten patients as a result of treatment. The three patients who showed the best clinical response also showed the highest increase in expression of these phenotypic markers. T cells were found to be activated in 8/10 patients as indicated by increased co-expression of CD3 with CD25 after completion of 4-day continuous intravenous infusion of IL2. Four days before the start of treatment, cancer patient PBMC stimulated with concanavalin A (con A) produced significantly greater amounts of TNF compared to normal controls. In-vitro inducible TNF was found to decrease following treatment. Since IL-2 production and lymphocyte proliferation in response to Con A were normal in the patient group and were not altered by treatment, the reduction in TNF levels seemed not to be a general inhibitory effect. Further study of these and other changes in the immune system during IL-2/IFN alpha treatment may help to understand how these immunoregulators cause tumour destruction and to predict their usefulness in individual patients.

Adult↗

Primary adenocarcinoma in an ileostomy: a late complication of surgery for ulcerative colitis.

In the 1950s the treatment of ulcerative colitis was revolutionized by Brooke by way of a colectomy combined with an eversion ileostomy. This procedure is known to be associated with a number of complications that include skin excoriation, stenosis, intestinal obstruction, retraction or prolapse of the stoma, abscess and fistula formation, and ileitis. However, adenocarcinoma arising in the abnormally placed small intestinal mucosa 20 years or more after the initial operation is being increasingly recognized and reported. This article describes one such case and includes an extensive review of the current world literature on the subject of adenocarcinoma arising as a late complication of operation for ulcerative colitis.

Adenocarcinoma↗

Prospective evaluation of laparoscopic-assisted colectomy in an unselected group of patients.

Laparoscopic technology is likely to have an increasing impact on surgical procedures that have previously required an open approach. We have prospectively evaluated laparoscopic colectomy in 40 patients requiring elective colonic excision mainly for malignant disease. 33 of 40 patients had a successfully completed laparoscopic colectomy, although there was one postoperative death. Seven operations were unsuccessful and required conversion to conventional open laparotomy. Morbidity was low with no wound infections and only two chest infections in the 32 survivors. Early mobilisation and discharge from hospital (mean 8 days) was a notable feature. Previous abdominal surgery was not an absolute contraindication to laparoscopic colectomy. However, the inability to palpate the colon directly to confirm the site of laparoscopically impalpable lesions leads us to recommend contrast radiology to confirm the location of colonoscopically diagnosed lesions before laparoscopically assisted colectomy. Preliminary pathological assessment of resected tumour specimens revealed a satisfactory tumour clearance. We conclude that laparoscopic colectomy is a feasible operation in most patients and leads to a substantial patient benefit without compromising the chance of a surgical cure of cancer.

Adult↗

Is the relationship between angiogenesis and metastasis in breast cancer real?

The suggested link between angiogenesis in breast cancer and metastasis remains unsubstantiated. We tested this relationship in primary breast carcinomas from 37 patients with a median follow-up 9.5 years (Cohort 1) and 50 patients with a median follow-up of 1.5 years (Cohort 2). Angiogenesis was assessed by counting vessel density after immunohistochemical staining of vascular endothelium for factor VIII. Patients were grouped according to whether metastasis (defined as spread to axillary lymph nodes, distant sites or both) had occurred. The mean +/- SD scores in Cohort 1 when metastasis was absent and present, respectively, were 15.6 +/- 4.9 (n = 21) and 14.1 +/- 3.7 (n = 16). In Cohort 2 the scores were 15.4 +/- 5.8 (n = 26) and 14.5 +/- 4.9 (n = 24). There was no significant difference between these scores in either cohort. Multivariate analysis demonstrated lymph node involvement (P < 0.001) and tumour size (P < 0.001) but not angiogenesis score (P > 0.05) to predict distant metastasis. This evidence argues against any prognostic significance of angiogenesis in breast carcinoma.

Aged↗

Intraoperative radiotherapy for unresectable cholangiocarcinoma--the Mayo Clinic experience.

Thirteen patients with unresectable cholangiocarcinomas were treated with external beam radiation therapy (ERT) and intraoperative radiation therapy (IORT) in combination with biliary stenting. Local treatment failure occurred in 50% of the patients treated with curative intent and an additional two patients developed distant recurrent disease. Patient morbidity was primarily related to biliary sepsis and gastrointestinal complications. There was minimal morbidity related to the IORT. Although the median survival of 16.5 months seemed to be an improvement over our previous results for ERT alone or ERT with 5-fluorouracil, the survival data are still discouraging. Further improvements in treatment will require better means of biliary bypass and increased tumour response perhaps by the use of radiosensitizers or hyperthermia in conjunction with radiation therapy.

Adult↗

A phase 2 trial of recombinant interleukin-2 and 5-fluorouracil in patients with metastatic colorectal carcinoma.

The toxicity and efficacy of sequential 5-fluorouracil (5-FU) and recombinant interleukin-2 (IL-2) were evaluated in 12 patients with metastatic colorectal carcinoma. This combination of 5-FU and IL-2 produced a 10% partial response rate with 40% of patients remaining in stable disease while on therapy. No clear improvement in survival was demonstrable. In contrast to the disappointing response rates the overall level of toxicity was very low with no treatment related deaths. It is concluded that modifications in treatment schedules are required before further similar studies are commenced.

Adult↗

Total gastrectomy for advanced cancer. A worthwhile palliative procedure.

Subtotal gastric resection usually provides the best palliation in advanced gastric cancer; however, if total gastrectomy (TG) is required there is doubt about its benefit. The authors reviewed 53 consecutive patients undergoing TG for advanced gastric adenocarcinoma between 1980 and 1989. Indications for TG were tumor location in 30% and extent of tumor in 70%, including nine patients (17%) with linitis plastica. Four patients (8%) died postoperatively, and six patients required reoperation for postoperative complications. The median postoperative hospital stay was 13 days. The median survival was 19 months, and 13 patients (24%) lived for more than 2 years. The quality of life was graded in survivors as good in 59%, satisfactory in 28%, and poor in 13% of patients. It was concluded that TG is a worthwhile procedure for selected patients, even in the presence of advanced disease, providing prolongation of good quality of life with low morbidity and mortality.

Adenocarcinoma↗

Radical resection for carcinoma of the ampulla of Vater.

One hundred four consecutive patients who underwent radical resection for ampullary cancer between 1965 and 1989 were retrospectively reviewed. Frequent clinical findings included jaundice (67%), significant (greater than 10%) weight loss (42%), and anemia (27%). Eighty-seven patients (84%) underwent a subtotal pancreatectomy, and 17 patients (16%) underwent a total pancreatectomy. The postoperative mortality was 5.7% (six patients), and reoperation for postoperative complications was required in six patients. The 5- and 10-year survival rates were 34% and 25%, respectively. Eight patients died of tumor recurrence more than 5 years after resection. Patient survival was significantly impaired by microscopic lymphatic invasion, regional nodal metastasis, tumor grade, and the epithelium of origin. In a multivariate analysis, only microscopic lymphatic invasion significantly reduced patient survival. Radical resection for ampullary cancer can be performed with a low morbidity and mortality and should remain the procedure of choice for ampullary carcinoma.

Adenocarcinoma↗

Thyroid dysfunction can predict response to immunotherapy with interleukin-2 and interferon-2 alpha.

Thyroid dysfunction is a well-recognised side-effect of treatment with interleukin-2 (IL2). We assessed the correlation between the development of abnormal thyroid function and tumour response in 13 patients receiving IL2 and interferon-2 alpha (IFN2 alpha) for advanced malignancy. Seven patients had normal thyroid function during treatment, and all of these patients have since died of progressive disease. Of six patients who did develop thyroid dysfunction during treatment, one patient has died of progressive disease. However, statistically we were unable to confirm a definite correlation between the development of thyroid dysfunction and survival in this small group of patients.

Adult↗

Clinical experience with the combined use of recombinant interleukin-2 (IL2) and interferon alfa-2a (IFN alpha) in metastatic melanoma.

A multicentre study of IL2 and IFN alpha has been performed in 58 patients with metastatic melanoma. The scheme consisted of IL2 3.0 BRMP MU/m2/d as a continuous infusion for 4 d combined with subcutaneous administration of IFN alpha 6 MU/m2/d, day 1 + 4. The cycle was repeated every 2 weeks for a maximum duration of 26 weeks. 54 patients were evaluable for response. One (2%) achieved a complete and 10 (19%) a partial response. 19 (35%) patients were stable and 24 (44%) showed progressive disease. Common side-effects included fever, chills, fatigue, skin rash, anorexia, nausea and diarrhoea. Hypothyroidism was noted in 10% of the patients. These results show that this regimen of IL2 and IFN alpha is active but, in contrast to what could be expected, not superior to IL2 alone possibly due to suboptimal dosing. In an ongoing study in Rotterdam and Nijmegen, a more intense schedule was chosen, consisting of three daily i.v. doses of IL2 4.5 BRMP MU/m2 and IFN alpha 3.0 MU/m2 for 5 d. This regimen is repeated at intervals of 3 weeks for a total of three cycles. Presently, nine patients have been entered. One patient achieved a complete response, four a partial response (overall 56%), three had stable disease and one progressed. Toxicity was severe and treatment was prematurely stopped in five patients: myocardial infarction (one patient), atrial fibrillation (one patient), negative T waves and myocardial hypokinesia (one patient) and psychosis (two patients). This regimen can only be justified if the therapeutic results are superb, which has yet to be awaited.

Adolescent↗

Combined ultrasound-guided extracorporeal shockwave lithotripsy and MTBE instillation in the treatment of common bile duct stones.

We report on our initial experience in the treatment of 4 patients with common bile duct stones with extracorporeal shockwave lithotripsy, either alone or in combination with methyl-tert-butyl ether. In four patients, common bile duct stones were successfully fragmented employing a second-generation ultrasound-guided piezoelectric lithotripter (EDAP LT-01). In two of these patients direct application of methyl-tert-butyl ether to the gallstone was utilized to assist in dissolution. There was no mortality or morbidity attributable to either treatment modality. In this first report of this combination of treatments we conclude that ESWL probably has a complementary role to play in the management of patients with common bile duct stones.

Adult↗

Cholecystectomy is safer without drainage: the results of a prospective, randomized clinical trial.

Drainage after cholecystectomy remains routine despite the lack of scientific supportive data. Numerous clinical studies in the past have attempted to address this controversy but have failed to resolve the issue for different reasons. These include retrospective design, inclusion of only selected cases, and randomization before surgery. In this study 479 patients undergoing cholecystectomy were randomly allocated to a drainage group (a high-pressure suction drain in Morison's pouch for 48 hours) or a nondrainage group. Randomization was performed at the time of peritoneal closure. All patients undergoing cholecystectomy, both elective and urgent, were included and the operations were performed by all grades of surgeons. There were two deaths from cardiopulmonary causes, both in the drainage group. No patient required reoperation in either group. The incidence of both wound infections (15 vs 5; p less than 0.05) and chest infections (56 vs 19, p less than 0.02) was significantly higher in the drainage group. Three hundred fifty-six patients underwent abdominal ultrasonography 72 hours after surgery. The number of subhepatic fluid collections thus detected was significantly higher in the patients who received a drain (17 vs 6, p less than 0.05). None of these collections was clinically significant. The postoperative hospital stay was longer in the patients with drains (10.3 vs 9.1 days), but this difference failed to reach statistical significance. We conclude from this study that the use of a drain after cholecystectomy serves no useful purpose and is potentially harmful. This practice should be abandoned.

Cholecystectomy↗

Piezoelectric lithotripsy and soft tissue injury. Safety limits in the experimental and clinical setting.

Controversy surrounds the capacity of extracorporeal shock wave lithotripsy to cause soft tissue injury. This study examines the influence of different dosages of shock waves on the gall bladder in both humans and an animal model. Sixty one guinea pigs were divided into groups and subjected to different numbers of shock waves (6,000, 24,000, and 48,000) at different frequencies (2.5, 5.0, 10, 20 shock waves per second) and sacrificed at different intervals. Soft tissue damage after lithotripsy seemed to be related to the number of shock waves administered. In addition, repeated administration of low dose lithotripsy (at weekly intervals for six weeks) did not seem to produce a cumulative injury. Finally, in the animals sacrificed one month after receiving high dose lithotripsy, no soft tissue damage was evident, indicating satisfactory healing. Thirty patients were subjected to either high dose (36,000 shock waves) or low dose (6,000 shock waves) lithotripsy 24 hours before elective cholecystectomy. Both macroscopic and microscopic evidence of soft tissue injury were detected in a significantly higher percentage of patients who received a high dose in a single treatment (p less than 0.05). The group who received repeated low dose lithotripsy showed no evidence of cumulative injury. We conclude that low dose lithotripsy produces minimal soft tissue injury and is safe when repeated up to six times at weekly intervals.

Animals↗