Tuberculosis and trimethoprim-sulfamethoxazole.

The sulfonamides were the first drugs with antituberculous effects. Their use was abandoned and basically forgotten with the advent of streptomycin and isoniazid combination treatment. There is a widespread belief, apparently based on testing a single isolate on questionable media, that Mycobacterium tuberculosis is resistant to trimethoprim-sulfamethoxazole (TMP-SMX). We saw a complex immunocompromised patient with tuberculosis who was initially treated with TMP-SMX without antituberculous drugs and defervesced on this treatment. An isolate of M. tuberculosis from this patient was found to be sensitive to TMP-SMX. We examined how frequently M. tuberculosis is sensitive to TMP-SMX. Isolates were tested for susceptibility to TMP-SMX on supplemented Middlebrook 7H10 plates. We found that 43 of 44 (98%) isolates of M. tuberculosis were susceptible to the combination of < or = 1 microg/ml of TMP and 19 microg/ml of SMX (< or = 1/19 microg/ml). Thus, the vast majority of our M. tuberculosis isolates were susceptible to TMP-SMX at an MIC similar to that for Mycobacterium kansasii, Mycobacterium marinum, and sensitive rapidly growing mycobacteria, organisms successfully treated with TMP-SMX as part of the treatment regimen. It is possible that TMP-SMX may be useful in treating patients with multiple-drug-resistant and extended drug-resistant tuberculosis. We feel that a clinical trial looking at the effectiveness of TMP-SMX as an antituberculous drug is worthwhile.

Comparing the Gleason prostate biopsy and Gleason prostatectomy grading system: the Lahey Clinic Medical Center experience and an international meta-analysis.

BACKGROUND: The accuracy of the prostate biopsy Gleason grade to predict the prostatectomy Gleason grade varies tremendously in the literature. OBJECTIVES: Determine the accuracy and distribution of the prostate biopsy Gleason grade and prostatectomy Gleason grade at LCMC (Lahey Clinic Medical Center) and worldwide. DESIGN, SETTING, AND PARTICIPANTS: Participants included 2890 patients who had not received preoperative hormones, and for whom preoperative and postoperative Gleason sums were available. Participants underwent radical prostatectomy at LCMC, an academic referral center, from 1982-2007. Studies for the meta-analysis were selected from Medline: 1994-2007. Search criteria included keywords "Gleason," "biopsy," and "prostatectomy," >/=200 patients, and whether the biopsy and prostatectomy Gleason scores categorized into the predefined Gleason grades. The meta-analysis included 15 studies and the LCMC database for 14,839 total patients. MEASUREMENTS: Gleason scores 2-6, 7, and 8-10 were converted to low, moderate, and high grade, respectively. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value were calculated. The kappa statistic and chi-square were used to compare biopsy and prostatectomy grades. RESULTS AND LIMITATIONS: The percentage of patients in whom the prostatectomy grade was accurately predicted, upgraded, and downgraded was 58%, 36%, and 5% at LCMC and 63%, 30%, and 7% in the meta-analysis, respectively. The PPV for low-, moderate-, and high-grade cancer was 54%, 70%, and 60% for LCMC and 62%, 70%, and 50% for the meta-analysis, respectively. The sensitivity decreased with increasing Gleason grade (low, moderate, and high) for LCMC (91%, 38%, 28%) and the meta-analysis (90%, 40%, 33%), respectively. The distribution of low-, moderate-, and high-grade cancer on biopsy (69%, 25%, and 6%) and prostatectomy specimen (47%, 44%, and 9%) demonstrated only "fair" agreement (kappa, 0.37). CONCLUSIONS: Patients and practitioners need to be cognizant of significant upgrading for low-grade disease and the downgrading for high-grade disease.

Progression of laparoscopic radical prostatectomy: improved outcomes with the extraperitoneal approach and a running anastomosis.

PURPOSE: To compare the operative and perioperative outcomes of patients undergoing either a transperitoneal or an extraperitoneal laparoscopic radical prostatectomy (TLRP or ELRP) with either an interrupted or a running urethrovesical anastomosis (IUVA or RUVA). PATIENTS AND METHODS: From January 2003 through December 2004, 265 patients underwent LRP by one surgeon at the Lahey Clinic Medical Center. They were divided into three groups according to the operative approach (TLRP or ELRP) and the suture anastomosis (IUVA or RUVA): group 1 = TLRP and IUVA (N = 58; 21.6%), group 2 = TLRP and RUVA (N = 35; 13.1%), and group 3 = ELRP and RUVA (N = 172; 64.2%). RESULTS: Group 3 had statistically better outcomes, as judged by operative time (222, 191, and 170 minutes for groups 1, 2, and 3, respectively; P < 0.0001), postoperative analgesic use (39.6, 30.4, and 18.9 mg of narcotic; P < 0.0001), length of stay (3.76, 2.74 days, and 1.67 days; P < 0.0001), leak on postoperative cystogram (17.9%, 11.4%, and 3.5%; P = 0.001), and complication rate (32.8%, 11.4%, and 9.9%; P < 0.0001). The groups had similar estimated blood loss (168, 145, and 176 mL) and positive surgical-margin rates (15.5%, 14.3%, and 14.5%). CONCLUSIONS: We demonstrate improved surgical outcome for ELRP with RUVA in regard to operative time, analgesic use, length of stay, leak rate, and complication rate. Long-term follow-up will determine whether a difference exists in disease recurrence, continence, and erectile function.

Incomplete renal tumor destruction using radio frequency interstitial ablation.

PURPOSE: We evaluate the efficacy of temperature based radio frequency ablation as a potential treatment modality for small (less than 3.5 cm.) renal tumors. MATERIALS AND METHODS: We treated 15 patients with a total of 20 tumors with radio frequency ablation through an open surgical approach immediately before partial nephrectomy. All tumors were biopsied before radio frequency ablation treatment. Tumors were heated to 90 to 110C for 6 to 16 minutes (mean 9.1). Tumor ablation was monitored by direct vision and ultrasound. Partial nephrectomy was performed in standard fashion. All specimens were stained with hematoxylin and eosin, and 5 specimens were stained for nicotinamide adenine dinucleotide (NADH) diaphorase activity. RESULTS: Tumors ranged from 1.5 to 3.5 cm. (mean 2.4) in greatest dimension. All 20 specimens had evidence of morphologically unchanged tumor and normal renal parenchyma on standard hematoxylin and eosin staining. Of the 5 specimens 4 stained positively for NADH in areas confirmed to be tumor in hematoxylin and eosin stained neighboring sections. There was 1 intraoperative renal pelvic thermal injury requiring pyeloplasty and 2 postoperative caliceal leaks requiring stent placement. CONCLUSIONS: In our series radio frequency therapy did not result in total tumor destruction when specimens were examined with hematoxylin and eosin or NADH staining. We believe that radio frequency interstitial tumor ablation of renal cell carcinoma without subsequent tissue resection should continue to be an investigational treatment modality for those who would otherwise undergo partial or radical nephrectomy.