David Margel

Transanal endoscopic microsurgery: experience with 75 rectal neoplasms.

PURPOSE: The aim of this study was to describe a single institutions experience with transanal endoscopic microsurgery in patients with benign and malignant rectal tumors. PATIENTS: Between January 1992 and April 1998, 75 patients with a mean follow up of 38 months, underwent transanal endoscopic microsurgery excision of benign (46) or malignant (29) rectal tumors, located 3 to 18 cm from the dentate line. RESULTS: A total of 3 of 46 (6.5 percent) patients with benign tumors underwent conversion to radical surgery owing to tumor size. During the follow-up period, benign tumor recurrence was observed in four (9 percent) patients, three of whom were managed by repeat transanal endoscopic microsurgery, whereas one required radical surgery. Histologic staging of malignant tumors was T1 (10), T2 (10), and T3 (9). Seven patients with either inadequate resection margins or T3 tumors were complimented with radical surgery. Of the remaining 22 patients, 11 received adjuvant radiation therapy whereas 11 had no further treatment. Four (18 percent) had recurrent disease, which was managed by repeat transanal endoscopic microsurgery in two, radical surgery in one, and laser ablation in one. No cancer-related deaths were observed during the follow-up period. There was one operative mortality in a cardiac-crippled patient. Postoperative complications were mainly of a minor character and included fever, urinary retention, and bleeding; none of which required reintervention. Rectourethral fistula developed in one patient who underwent repeat transanal endoscopic microsurgery excision for a T3 malignancy. Fecal soiling was transient in three patients and persisted in two. CONCLUSION: Transanal endoscopic microsurgery excision is a safe and precise technique that is well tolerated even in high operative risk patients. Transanal endoscopic microsurgery may become a procedure of choice for benign rectal tumors and selected early malignant neoplasms.

Neutrophil-to-lymphocyte ratio predicts progression and recurrence of non–muscle-invasive bladder cancer

OBJECTIVE Neutrophil-to-lymphocyte ratio (NLR) predicts advanced stage disease and decreased survival in patients undergoing radical cystectomy for urothelial carcinoma of the bladder. The predictive value of NLR in non-muscle-invasive bladder cancer (NMIBC) has not been well studied. We aimed to evaluate whether NLR predicted disease recurrence and progression in NMIBC. MATERIALS AND METHODS The medical records of 122 consecutive, newly diagnosed, patients with NMIBC treated with transurethral tumor resection, between the years 2003 and 2010, were reviewed. Patients with hematological malignancies (n = 4) and without preoperative NLR (n = 11) were excluded. Cutoff points for NLR were tested separately for recurrence and progression using the standardized cutoff-finder algorithm. Univariate and multivariate Cox regression analyses were used to evaluate the association between NLR and disease recurrence and progression. RESULTS The study cohort comprised 91 men and 16 women at a median age of 68 years. The median NLR was 2.85 (interquartile range: 2-3.9). In total, 68 patients (64%) had an NLR>2.41. Patients with NLR>2.41 were more often men (P = 0.02) and had T1 category tumors (P = 0.034). Analyzed as a continuous variable, higher NLR showed a weak positive association with high tumor grade (R = 0.21, P = 0.028). The median follow-up for patients without disease recurrence was 40 months (interquartile range: 23-51). The estimated 3-year progression-free survival rate in patients with an NLR>2.41 was 61%, compared with 84% in patients with an NLR≤2.41 (P = 0.004). On multivariate analysis, an NLR>2.41 (hazard ratio [HR] = 3.52; 95% CI: 1.33-9.33; P = 0.012) and high-risk tumors compared with low-intermediate-risk tumors (HR = 4.83; 95% CI: 1.31-17.77; P = 0.018), as defined by the European Organization for Research and Treatment of Cancer risk tables, were associated with disease progression. An NLR>2.43 (HR = 1.75; 95% CI: 1.05-2.92; P = 0.032) and treatment with intravesical instillations (HR = 0.49; 95% CI: 0.28-0.85; P = 0.011) were associated with disease recurrence on multivariate analysis. CONCLUSIONS NLR is an independent predictor of disease progression and recurrence in patients with NMIBC without hematological malignancies. Prospective studies are required to validate the role of NLR as a prognostic marker in NMIBC.

Presence of detrusor muscle in bladder tumor specimens--predictors and effect on outcome as a measure of resection quality.

OBJECTIVES To identify predictors of the absence of detrusor muscle in bladder tumor specimens and analyze its effect on clinical outcome as an indicator of resection quality. METHODS The bladder cancer database of a tertiary medical center was queried for patients who underwent complete transurethral resection of bladder tumor (TURBT) between 2008 and 2009. Study end points were absence of detrusor muscle in the surgical specimen and its association with disease recurrence/progression. RESULTS Detrusor muscle in the surgical specimen was found in 265 of the 332 study patients (79%). The likelihood of finding muscle increased with higher clinical stage (Odds Ratio [OR]-1.8), higher tumor grade (OR-3), larger tumor size (OR-3.2), multifocal disease (OR-1.7), and nonpapillary morphology (OR-2.3). History of bladder cancer, surgeons experience, and tumor location in the bladder had no effect. In the whole study population, neither tumor recurrence nor disease progression was associated with absence of detrusor muscle. In patients with T1 tumors, absence of detrusor muscle in the specimen was associated with higher early recurrence rate but not worse long-term outcome. CONCLUSIONS Absence of detrusor muscle in TURBT specimens is not determined by the technical difficulty of the procedure or surgical experience. Surgeons are more prone to obtain deep muscle in large, nonpapillary-appearing tumors, likely reflecting efforts to attain accurate staging in these cases. The presence or absence of detrusor muscle may serve as a surrogate of resection quality in patients with T1 tumors, but its general applicability to the overall population of patients undergoing TURBT remains questionable.

A Novel Technique to Improve the Processing of Minute Ureteroscopic Biopsies

To examine the ability of a new specimen handling technique to improve histopathological yield of ureteroscopic biopsies, performed in patients with suspected upper tract urothelial carcinoma (UTUC). In a bi-center retrospective study we compared the results of the new tissue handling technique (group 1) with the standard technique (group 2). In the new technique, to achieve maximal tissue preservation, the specimen is mounted on filter paper prior to embedding in paraffin. Multivariate analysis was performed to determine which factors are associated with optimal histological results. We further compared the biopsies with the final specimen in a subgroup of patients who underwent nephroureterectomy (NU). Of 55 ureteroscopic biopsies, 1 biopsy from group 1 (new technique) and 3 biopsies from group 2 (standard technique) were inadequate for pathological examination. 51 UTUC specimens were analyzed. Tumor grade and stage were determined in 85% and 63% of the patients in group 1 and in 83% and 25% of group 2 (p=0.85 and p=0.007). Orientation was preserved in 82% of group 1 and 42% of group 2 (p=0.003). On multivariate analysis biopsy technique and biopsy diameter were found to predict stage determination (p=0.01 and p=0.007) and tissue orientation (p=0.005 and p=0.04). Among patients who underwent NU, stage concordance between the biopsy and final pathology was observed in 56% and 27% of the patients in group 1 and 2, respectively. The new processing technique for small UTUC forceps biopsies decreases the rate of biopsies with insufficient material and improves biopsy interpretation.

Malignant Abnormalities in Male BRCA Mutation Carriers: Results From a Prospectively Screened Cohort

This study evaluates the use of a comprehensive screening protocol for prostate, breast, colorectal, and pancreatic cancer and skin malignant abnormalities in male BRCA carriers.

Earlier Age of Breast Cancer Onset in Israeli BRCA Carriers-Is it a Real Phenomenon?

Data on genetic anticipation in breast cancer are sparse. We sought to evaluate age at diagnosis of breast cancer in daughters with a BRCA mutation and their mothers. A review of all carriers of the BRCA mutation diagnosed with breast cancer at the Genetics Institute of a tertiary medical center in 2000–2013 yielded 80 women who could be paired with a mother with breast cancer who was either a carrier of the BRCA mutation or an obligate carrier according to pedigree analysis. Age at diagnosis, type of mutation (BRCA1, BRCA2), year of birth, and ethnicity were recorded. Paired t‐test was used to analyze differences in age at cancer diagnosis between groups and subgroups. Mean age at diagnosis of breast cancer was 50.74 years (range 22–88) in the mothers and 43.85 years (range 24–75) in the daughters. The difference was statistically significant (p < 0.001). These findings were consistent regardless of type of BRCA mutation, ethnicity, or mothers year of birth. However, on separate analysis of pairs in which the mother was diagnosed before the age of 50 years, there was no significant difference in mean age at diagnosis between mothers and daughters (~42 years for both). Daughters who carry a BRCA mutation are diagnosed with breast cancer at an earlier age than their carrier mothers, with the exception of pairs in which the mother was diagnosed before the age of 50 years. Future breast‐screening guidelines may need to target specific subpopulations of BRCA mutation carriers.