LAP-BAND for BMI 30-40: 5-year health outcomes from the multicenter pivotal study.

BACKGROUND: We performed a 5-year multicenter study to evaluate the safety and effectiveness of the LAP-BAND System surgery (LBS) in patients with obesity with a body mass index (BMI) of 30-39.9 kg m(-)(2). This pivotal study was designed to support LBS application to the US Food and Drug Administration for broadening the indications for surgery and the lower BMI indication was approved with 1-year data in 2011, with the intention to complete the 5-year evaluation. OBJECTIVES: To present broad health outcome data including weight change, patient reported outcomes, comorbidity change and complications during the 5-year study. SETTING: The study was conducted at seven US private practice clinical trial sites. METHODS: We enrolled 149 BMI 30-39.9 subjects into a 5-year, multicenter, longitudinal, prospective post-approval study. Data for those completing each time point are presented. RESULTS: The predefined target of at least 30% excess weight loss was achieved by more than 76% of subjects by 1-year and at every year thereafter during the 5-year study. Mean percentage weight loss at 5 years was 15.9±12.4%. Sustained weight loss was accompanied by sustained improvement in generic and weight-specific quality of life, symptoms of depression and the prevalence of binge-eating disorder. The number of subjects with normal fasting triglyceride, high-density lipoprotein cholesterol, plasma glucose and HbA1c increased significantly between baseline and 5 years. Fifty-four months after LBS implantation, the rate of device explants without replacement was 5.4%; however, the rate of explants increased to 12.1% by month 60 owing to no cost-elective band removals offered to subjects at study exit. No deaths or unanticipated adverse device effects were reported. CONCLUSIONS: The LBS is safe and effective for people with BMI 30-39.9 with demonstrated improvements in weight loss, comorbidities and quality of life, and with a low explant rate through 5 years following treatment.

Preliminary experience with new bioactive prosthetic material for repair of hernias in infected fields.

Surgisis (Cook Surgical, Bloomington, Ind., USA) is a new four-ply bioactive, prosthetic mesh for hernia repair derived from porcine small-intestinal submucosa. It is a naturally occurring extracellular matrix which is easily absorbed, supports early and abundant new vessel growth, and serves as a template for the constructive remodeling of many tissues. As such, we believe that Surgisis mesh is ideal for use in contaminated or potentially contaminated fields in which ventral, incisional, or inguinal hernia repairs are required. From November 2000 through May 2002, 25 patients (11 male, 14 female) underwent placement of Surgisis mesh for a variety of different hernia repairs. A total of 25 hernia repairs were performed in our patient population. Fourteen procedures (56%) were performed in a potentially contaminated setting (i.e. with incarcerated/strangulated bowel within the hernia or coincident with a laparoscopic cholecystectomy/colectomy). Eleven repairs (44%) were performed in a grossly contaminated field, including one in which an infected polypropylene mesh from a previous inguinal hernia repair was replaced with Surgisis and one in which necrotic bowel was discovered within the hernial sac. Median follow-up was 15 months with a range of 1-20 months. Of the 25 total repairs, there was one wound infection complicated by enterocutaneous fistula in a patient originally operated on for ischemic bowel. The fistula was in a location independent of the Surgisis mesh. There were no mesh-related complications or recurrent hernias in our early postoperative follow-up period. Surgisis mesh appears to be a promising new prosthetic material for hernia repair, especially in contaminated or potentially contaminated fields. Obviously, long-term follow-up is still required.

Lung cancer found unresectable at thoracotomy: reappraisal of an old problem.

We review our experience with unresectable non-small cell lung cancer, after adoption of a more aggressive surgical approach, including mediastinal lymph node dissection. Cases with enlarged mediastinal lymph nodes (MLNs, cN2) that were predicted to be resectable were included. Our objective was to identify preoperative findings to prevent unnecessary thoracotomy. In 1988-1997, 192 patients had thoracotomy for non-small cell lung cancer. Fifteen cases (7.7%) were found unresectable at thoracotomy. CT scans demonstrated enlarged MLNs in 7 of 15 and enlarged hilar lymph nodes in 6 of 15 cases. The tumor abutted the hilum in 5 of 15, chest wall in 2 of 15, and mediastinal structures in 7 of 15 cases. Atelectasis was seen in 3 of 15 cases. During the same period, 63 patients with stage III disease, including 39 patients with enlarged MLNs, were resected. The unresectability rate for cN2 patients was 15.2 per cent. Five (33%) patients were physiologically unable to tolerate the required pneumonectomy [forced expiratory volume in 1 second, 1.65 liters (range, 1.15-2.07)]. There were three (20%) esophageal invasions, two (13.3%) mediastinal invasions, two (13.3%) aortic invasions, two (13.3%) metastases to the diaphragm, and one (6.6%) invasion of proximal pulmonary artery. Median survival was 4 months. Two-year actuarial survival was 8 per cent. We conclude that careful palpation and dissection were required to establish unresectability. Preliminary thoracoscopy would have prevented thoracotomy in two cases (13.3%) of diaphragmatic metastases but would not reliably establish unresectable invasion of mediastinal structures.

Exacerbation of rheumatoid arthritis after termination of chemotherapy for breast carcinoma.

Three women with breast carcinoma were treated with combination chemotherapy, including cyclophosphamide, 5-fluorouracil, and methotrexate, after mastectomy. Within two months of termination of chemotherapy, all 3 patients developed florid synovitis. Two patients had prior clinical manifestations consistent with rheumatoid arthritis; one patient had no antecedent history of arthritis. We suggest that this presentation may represent exacerbation of mild or subclinical rheumatoid arthritis as a consequence of withdrawal of methotrexate therapy.

Cisplatin and 5-fluorouracil infusion for metastatic colorectal carcinoma. Differences in survival in two patient groups with similar response rates.

Because of reported synergism between 5-fluorouracil (5-FU) and cisplatin (CDDP) in L1210 leukemic mice and activity of this combination in clinical studies, a trial was initiated in previously untreated patients with advanced colorectal carcinoma. Cisplatin at 20 mg/m2 and 5-FU as a continuous infusion at 1000 mg/m2 were both administered for 5 consecutive days every 4 weeks. Forty-one patients were treated at Memorial Sloan-Kettering Cancer Center (MSKCC) and 46 were treated by the Community Clinical Oncology Program (CCOP) physicians. A 50% reduction in measurable disease was seen in 12 of 35 (34%) MSKCC patients and in nine of 41 (22%) of the CCOP patients with 95% confidence intervals of 0.18 to 0.50 and 0.10 to 0.35 in the two groups, respectively. The predominant toxicities were as follows: nausea and vomiting, 32%; mucositis, 26%; leukocyte counts less than 2000 cells/mm3, 17%; platelet counts less than 25,000 cells/mm3, 8%; and severe neurotoxicity, 5%. Dose attenuation was similar in the two groups. The median survival was 16.4 months for the MSKCC group and 9.6 months for the CCOP group (P = 0.0003). Although the baseline characteristics (age, sex, performance status, and baseline lactic dehydrogenase [LDH] and alkaline phosphatase) were similar, on further examination differences between the two groups were evident. In the MSKCC group, 14% of patients with liver metastases had greater than 50% of their liver involved with tumor whereas this occurred in 41% of the CCOP group (P = 0.03). The LDH values greater than 500 U/l were observed in 10% of patients in the MSKCC group and in 37% of the patients in the CCOP group (P = 0.007). Characteristics which reflect the bulk of disease, such as the percent of liver involvement, need to be analyzed in order to evaluate purported survival differences in randomized and nonrandomized trials of colorectal carcinoma.

Phase II trial of gallium nitrate in patients with advanced malignant melanoma.

A phase II trial of gallium nitrate (250-300 mg/m2/day for 7 consecutive days) was conducted in patients with metastatic melanoma. Therapy was well-tolerated, but only one of 31 evaluable patients experienced a partial regression. Further evaluation of gallium nitrate at this dose and schedule is not warranted in patients with malignant melanoma.

Human T-cell leukemia/lymphoma syndrome.

This syndrome should be suspected in patients with clinical features of lymphadenopathy, hepatosplenomegaly, hypercalcemia, bone lesions and circulating lymphocytes with pleomorphic nuclei. Most biopsy material has morphologic characteristics of intermediate or high-grade non-Hodgkins lymphoma. Antibody titers to human T-lymphotropic virus type I confirm the diagnosis. Treatment with combination chemotherapy results in remission for most patients, but duration of response is usually short.

Activity of sequential low-dose methotrexate and fluorouracil in advanced colorectal carcinoma: attempt at correlation with tissue and blood levels of phosphoribosylpyrophosphate.

Forty-five patients with metastatic colorectal carcinoma were treated with low-dose methotrexate (MTX) and 5-fluorouracil (5-FU) given sequentially. The dose of MTX was 40 mg/m2 intravenously (IV) on days 1 and 8 followed 24 hours later by 5-FU at 600 mg/m2 IV on days 2 and 9; the drugs were recycled every 28 days. Fourteen (32%) of 43 adequately treated patients had a complete or partial response lasting a median of nine months (range, 6-15 + months). Four patients had a minor response and seven patients had stable disease for a median of nine and 10 months, respectively. Toxicity included mucositis in 28 (65%) patients, diarrhea in 18 (40%), nausea in 11 (24%), and vomiting in seven (16%). Hematologic toxicity was mild: six patients had nadir white blood cell counts less than 3.5 X 10(3) cells/microL, and seven patients had a nadir platelet count less than 100 X 10(3) cells/microL. Serial biopsies and blood samples were obtained in selected patients to evaluate the effect of MTX on tissue and lymphocyte phosphoribosylpyrophosphate (PRPP) and PRPP synthetase levels.

Phase I evaluation of a biochemically designed combination: PALA, thymidine, and 5-FU.

Fifteen patients with advanced solid tumors participated in a phase I study of a biochemically designed combination chemotherapy program which employed PALA and thymidine (TdR) with 5-FU. PALA (250-2000 mg/m2) was given 24 hours before a 90-minute iv infusion of TdR (45 g). 5-FU (100-150 mg/m2) was given as a rapid iv injection 30 minutes after beginning the TdR infusion. This three-drug treatment was repeated once weekly for 3 weeks. Neurotoxicity, manifested as dizziness, lethargy, and confusion, was dose-limiting. Myelosuppression was noted at all dose levels, as was mild to moderate mucositis and diarrhea. Further clinical evaluation of this combination does not appear to be warranted.

Mitomycin-induced hemolytic-uremic syndrome. Successful treatment with corticosteroids and intense plasma exchange.

Mitomycin has been associated with microangiopathic hemolytic anemia and renal failure. We describe a patient with the adult hemolytic-uremic syndrome due to mitomycin who was successfully treated with intense plasma exchange therapy and corticosteroid therapy. Patients receiving mitomycin should have their conditions monitored closely for acute renal failure, thrombocytopenia, and hemolytic anemia.

Preoperative chemotherapy and radiation therapy in the management of anal epidermoid carcinoma.

Management of epidermoid carcinoma of the anus has been primarily surgical in the past. Since it is a relatively rare entity, meaningful survival statistics are difficult to obtain. Five-year survival rates fall between 35 and 68% in patients treated with surgery and/or radiotherapy. Based on preliminary studies indicating promising results with the use of mitomycin C and 5-fluorouracil (5-FU) chemotherapy combined preoperatively with radiation therapy, these authors initiated a protocol in 1973 utilizing this multimodality approach. The preoperative treatment consisted of mitomycin C 15 mg/m2 IV bolus on day 1 and 5-FU 750 mg/m2/24 hours continuous infusion for five days. Radiation followed chemotherapy and consisted of 3000 rad given at 200 rad per day for 15 fractions. Of 37 patients entered on the protocol, 30 had primary disease and seven had been previously treated and had local recurrences. Median follow-up has been 28 months (range, 5-74 months). Of 31 patients with measurable lesions, 29 (94%) had major clinical responses (CR + PR) to the combined chemotherapy and radiation. Pathologic responses were also impressive with 53% (17/32) showing no evidence of residual tumor in the subsequently resected surgical specimen. Of the 37 patients treated, seven (19%) have had recurrences. The recurrence rate was 4/17 (24%) for those who had local excision following complete response to therapy as opposed to 3/18 (17%) for those treated by abdominoperineal resection. Thus it appears that the combination of preoperative mitomycin C and 5-FU with radiotherapy is effective at least in significantly downstaging this uncommon malignancy. Its ultimate effect on recurrence rate and overall patient survival awaits longer follow-up.

Phase II evaluation of 4'-epi-doxorubicin in patients with advanced colorectal carcinoma.

4'-Epi-doxorubicin (4'-epi-DX) is a new doxorubicin derivative that is more active than the parent compound against murine sarcoma virus tumors and Lewis lung carcinoma and may be less toxic. Thirty-five patients with advanced measureable colorectal carcinoma were treated with 4'-epi-DX (85 mg/m2) every 3 weeks. The major toxic effect was leukopenia less than 2000 cells/mm3 in 28% of the patients. One of 29 patients (3%) had a partial response. At this dose and schedule, 4'-epi-DX has minimal activity in colorectal carcinoma.

An in vivo evaluation of interface media used with the electric pulp tester.

Four interface media were tested with an electric pulp tester to determine whether the amount of current needed to elicit a response varies with the material. Each material was tested on the facial and linqual surfaces of anterior teeth. Clinical results showed no appreciable difference between the materials used, provided they were water or petroleum based. Facial and lingual readings were the same in about half the tests, and lingual readings were slightly lower than facial readings in 40% of the tests.