Ranko Miocinovic

Angiotropic Lymphoma: An Immunophenotypically and Clinically Heterogeneous Lymphoma

Angiotropic lymphoma (AL) is an uncommon lymphoma often presenting with nonspecific clinical features and having a high mortality rate. Although not specifically recognized by the Revised European-American Classification of Lymphoid Neoplasms, it likely will appear as a subtype of diffuse large B-cell lymphoma in the upcoming WHO classification. Some authors may also consider it to be a subtype of cutaneous lymphomas. Recent studies have reported an immunophenotypic heterogeneity of AL, and in rare instances, an association with other NHL. To further characterize AL, we studied the immunophenotype by immunohistochemistry for CD5, CD10, CD20, bcl-2, and bcl-6 in 18 cases of B-cell AL identified at three medical centers in North America. Bcl-2 gene rearrangement status by polymerase chain reaction and Epstein Barr virus status by in situ hybridization also were evaluated.Eight men and 10 women were identified with AL (median age 71 years). Eleven patients were diagnosed in life and seven were diagnosed at autopsy. Neurologic symptoms were the most common presentation, seen in six patients. Skin was the most commonly biopsied site. All showed classic intravascular localization; in two cases, there was also a minor diffuse large cell lymphoma component observed in some organs. Most (89%) of the cases expressed bcl-2 protein; CD10, bcl-6 and CD5 were each expressed in 22% of cases. Based on CD5 and CD10 expression, three major groups were evident: CD5−, CD10− (11 cases); CD5+, CD10− (3 cases), and CD5−, CD10+ (3 cases). Even though a follicle center lymphoma preceded the AL in one patient, we did not detect bcl-2 gene rearrangement in any of these cases. All cases were negative for Epstein Barr virus. Of the five treated with chemotherapy, two achieved a complete remission.Based on these findings, we conclude that ALs are clinically and immunophenotypically heterogeneous and may represent more than one pathogenetic entity. In some instances AL may be preceded by another lymphoproliferative disorder, raising the possibility that some cases of AL may represent a transformation from another type of lymphoma. Cutaneous manifestations of AL are common; however, it appears to be a systemic lymphoma. Although often fatal, patients with AL who are diagnosed early and treated with chemotherapy may achieve remission.

Robotic Partial Nephrectomy Versus Laparoscopic Cryoablation for the Small Renal Mass

BACKGROUND Open partial nephrectomy (OPN) remains the gold standard for treatment of small renal masses (SRMs). Laparoscopic cryoablation (LCA) has provided encouraging outcomes. Robotic partial nephrectomy (RPN) represents a new promising option but is still under evaluation. OBJECTIVE Compare the outcomes of RPN and LCA in the treatment of patients with SRMs. DESIGN, SETTING, AND PARTICIPANTS We retrospectively analyzed the medical charts of patients with SRMs (≤4cm) who underwent minimally invasive nephron-sparing surgery (RPN or LCA) in our institution from January 1998 to December 2010. INTERVENTION RPN and LCA. MEASUREMENTS Perioperative complications and functional and oncologic outcomes were analyzed. RESULTS AND LIMITATIONS A total of 446 SRMs were identified in 436 patients (RPN, n=210; LCA, n=226). Patients undergoing RPN were younger (p<0.0001), had a lower American Society of Anesthesiologists score (p<0.001), and higher baseline preoperative estimated glomerular filtration rate (eGFR) (p<0.0001). Mean tumor size was smaller in the LCA group (2.2 vs 2.4cm; p=0.004). RPN was associated with longer operative time (180 vs 165min; p=0.01), increased estimated blood loss (200 vs 75ml; p<0.0001), longer hospital stay (72 vs 48h; p<0.0001), and higher morbidity rate (20% vs 12%, p=0.015). Mean follow-ups for RPN and LCA were 4.8 mo and 44.5 mo, respectively (p<0.0001). Local recurrence rates for RPN and LCA were 0% and 11%, respectively (p<0.0001). Mean eGFR decrease after RPN and LCA was insignificant at 1 mo, at 6 mo after surgery, and during last follow-up. Limitations include retrospective study design, length of follow-up, and selection bias. CONCLUSIONS Both techniques remain viable treatment options in the management of SRMs. A higher incidence of perioperative complications was found in patients undergoing RPN. However, the technique was not predictive of the occurrence of postoperative complications. Early oncologic outcomes are promising for RPN, which also seems to be associated with better preservation of renal function. Long-term follow-up and well-designed prospective comparative studies are awaited to corroborate these findings.

Neoadjuvant Systemic Therapy or Early Cystectomy? Single-center Analysis of Outcomes After Therapy for Patients With Clinically Localized Micropapillary Urothelial Carcinoma of the Bladder

OBJECTIVES To analyze the treatment outcomes of patients with micropapillary bladder cancer (MPBC). MPBC is a rare variant of urothelial carcinoma with aggressive clinical behavior. Radical cystectomy is considered the standard approach for treatment of patients with localized disease; however, the role of perioperative systemic therapy has been poorly defined. MATERIAL AND METHODS A retrospective review identified 38 consecutive patients who had been treated at our institution for MPBC from 2000 to 2010. The patient data were analyzed for the pre- and postoperative clinicopathologic features, treatment course, and cancer-specific survival. RESULTS The median follow-up of surviving patients after cystectomy was 17 months (range 2-75). At the initial transurethral biopsy, 28 patients (74%) had clinical Stage T2N0 or less. In this group, 26 (93%) of 28 were upstaged to nonorgan-confined and/or lymph node-positive disease. Overall, 32 patients (86%) had evidence of lymph node metastasis on the final pathologic examination. All patients with cTis-T1 who had undergone initial bladder-sparing therapy with bacille Calmette-Guérin had pathologically advanced disease at cystectomy. All 15 patients who had received perioperative cisplatin-based chemotherapy died of metastatic disease. The 5-year overall survival rate was 40% (95% confidence interval 16-64). CONCLUSIONS MPBC is an aggressive disease with a high likelihood of regional lymph node metastasis at the initial presentation. Although radical cystectomy plays a critical role in treatment, systemic neoadjuvant chemotherapy might be a more appropriate strategy than immediate cystectomy. Because of the poor response to current chemotherapy agents, the development of new and effective drugs for this subset of patients could be needed.

Outcomes of laparoscopic and robotic radical cystectomy in the elderly patients.

OBJECTIVE To compare the perioperative outcomes of laparoscopic/robotic radical cystectomy (LRRC) for urothelial cancer of bladder (UCB) between elderly (≥ 70 years) and younger (<70 years) patients. MATERIALS AND METHODS A retrospective review of 146 patients who underwent LRRC between 2003 and 2010 at 2 academic institutions (Cleveland, Ohio, United States and Toulouse, France) was performed. Of these, 74 patients were classified as elderly (≥ 70 years) and 72 patients were considered younger (<70 years). Perioperative outcomes, final pathology results, overall survival (OS), and cancer specific survival (CSS) were compared between the 2 groups. RESULTS Both groups had similar clinical stage at diagnosis, American Society of Anesthesiologists score, body mass index, and gender distribution. Ileal conduit-type diversion was favored in the older vs younger group, 84% vs 36%, respectively. Overall conversion rate to open procedures was 4% in both groups. Perioperative complication rate was not significantly different between the younger and older patients. Positive margin rate was 5% in both groups. The 5-year OS for older and younger patients was 75% and 87%, respectively (P = .03), and the 5-year CSS for the 2 groups was 51% and 54%, respectively (P = .7). CONCLUSION Laparoscopic/robotic radical cystectomy in the elderly does not have worse perioperative complications or pathologic outcomes compared with younger patients and therefore can be offered as treatment option in select older patients.

Acceptance and Durability of Surveillance as a Management Choice in Men with Screen-detected, Low-risk Prostate Cancer: Improved Outcomes with Stringent Enrollment Criteria

OBJECTIVE To analyze the acceptance rate and durability of surveillance among contemporary men with low-risk prostate cancer managed at a large, US academic institution. METHODS Patients with low-risk parameters on initial and repeat biopsy were offered surveillance regardless of age. Regular clinical evaluation and repeat prostate biopsy were recommended every 1-2 years, and intervention was recommended based on adverse clinical and pathologic parameters on follow-up. Acceptance rate of active surveillance, freedom from intervention, and freedom from recommended intervention were measured. RESULTS AND LIMITATIONS Of 202 low-risk patients, 86 (43%) chose immediate treatment and 116 (57%) underwent repeat biopsy for consideration of surveillance. Intervention was recommended after initial repeat biopsy in 27 (23%) men because of higher-risk features, leaving a total of 89 men on surveillance. Over a median follow-up of 33 months, 16 men were ultimately treated and 8 were recommended to undergo treatment because of adverse clinical features on subsequent evaluations. Of the men on surveillance, the 3-year freedom from intervention and freedom from recommended intervention was 87% (95% CI, 78-93) and 93% (95% CI, 85-97), respectively. CONCLUSIONS Acceptance of surveillance (57%) in low-risk patients in this series is substantially higher than previous reports, and approximately one-third of these patients are ultimately managed by surveillance using stringent criteria. The risk of reclassification to a more aggressive cancer over short-term follow-up in appropriately selected patients is low.

Presacral and Retroperitoneal Lymph Node Involvement in Urothelial Bladder Cancer: Results of a Prospective Mapping Study

PURPOSE We evaluated the incidence of positive lymph nodes in the presacral and retroperitoneal regions in patients who underwent radical cystectomy and extended pelvic lymph node dissection for urothelial bladder cancer. MATERIALS AND METHODS As part of a prospective mapping study, 143 patients underwent radical cystectomy and extended pelvic lymph node dissection for urothelial bladder cancer between 2006 and 2010. Lymph nodes from 6 separate regions were labeled, including bilateral pelvic and common iliac, presacral and retroperitoneal. We evaluated pathological features, treatment outcomes and cancer specific survival in patients with or without lymph node positive disease in the presacral and retroperitoneal regions. RESULTS A median of 37 lymph nodes (IQR 27-49) were removed. Overall 52 (36%) patients had positive lymph nodes, of whom 24 (46%) had metastatic disease in the presacral or retroperitoneal region. Four patients (3%) had an isolated solitary positive lymph node in these 2 templates. Two-year overall survival in patients without vs with presacral/retroperitoneal lymph node positive disease was 44% (95% CI 24-64) vs 25% (95% CI 5-45) (p = 0.11). In contrast, 2-year cancer specific survival in the 2 groups was 55% (95% CI 33-77) and 29% (95% CI 7-51), respectively (p = 0.02). CONCLUSIONS A substantial proportion of patients have lymph node positive disease in the presacral and retroperitoneal regions, including some with isolated and/or solitary lymph node involvement. While the limited positive lymph node burden in these templates suggests a potential therapeutic role for extending the anatomical boundaries of lymph node dissection, patient survival was poor. Extended lymph node dissection provides important staging information but to our knowledge the therapeutic benefit has yet to be definitively proved.

Robotic Partial Nephrectomy for Small Renal Masses in Patients With Pre-existing Chronic Kidney Disease

OBJECTIVE To assess the outcomes of robotic partial nephrectomy in patients with pre-existing chronic kidney disease (CKD). MATERIALS AND METHODS Patients who underwent robotic partial nephrectomy for renal tumors between 2007 and 2011 were identified from our prospectively maintained institutional database. Perioperative as well as short-term oncological and functional outcomes were assessed. A comparative analysis was performed between patients with pre-existing CKD (estimated glomerular filtration rate [eGFR] 15-60 mL/min, group 1, n = 52) and patients with eGFR >60 mL/min (group 2, n = 303). RESULTS Group 1 patients were older (median 68 vs 57 years, P < .001), with higher American Society of Anesthesiology (ASA) score (3 vs 2, P < .001) and a higher Charlson comorbidity index (7 vs 4, P < .001). Warm ischemia time (WIT) was similar in both groups (18 vs 18 minutes, P = .52). Group 1 had a higher postoperative complication rate (40.4% vs 21.1%, P = .003). Pathologic and oncological data were similar. After a median follow-up of 3 months (interquartile: 1-10), deterioration of eGFR was lower in group 1 patients (-5% vs -12%, P = .004). No endstage renal disease was noted in either group. There was significantly less CKD upstaging in group 1 than in group 2 (11.5% vs 33.9%, P = .001). After multivariate analysis, preoperative eGFR and WIT were independent predictors of latest eGFR. Less than 15% of patients with normal baseline renal function developed CKD stage III or higher. CONCLUSION Despite a high risk of surgical complications, robotic partial nephrectomy only marginally affects renal function in patients with pre-existing CKD.

Avoiding androgen deprivation therapy in men with high-risk prostate cancer: the role of radical prostatectomy as initial treatment.

OBJECTIVE To examine the ability of surgery as initial management in avoiding androgen deprivation therapy (ADT) in patients with high-risk localized prostate cancer. MATERIALS AND METHODS A total of 267 men were identified from a cohort of patients treated by radical prostatectomy (RP) between January 1998 and June 2004. Patients were included if they presented with clinical stage ≥T2b and/or prostate-specific antigen (PSA) ≥15 ng/mL, and/or Gleason score ≥8. Information on biochemical recurrence, distant metastasis, cancer-specific survival, and use of ADT was obtained from a prospectively maintained database. RESULTS The median follow-up was 6.7 years (range, 1-146 months). Biochemical recurrence (BCR), distant metastasis (DM), and prostate cancer-specific mortality (PCSM) were observed in 112 (42%), 28 (10%), and 15 (6%) patients, respectively. Salvage treatment was performed in 95 (85%) of 112 patients with BCR. Only 71 (27%) of 267 men were subjected to ADT. Overall, 8-year probabilities of freedom from BCR, DM, PCSM, and ADT were 46% (95% CI, 38-54), 87% (95% CI, 84-90), 93% (95% CI, 91-95), and 71% (95% CI, 65-77), respectively. CONCLUSIONS RP provides excellent long-term clinical outcomes for patients with high-risk localized prostate cancer and avoids the use of ADT in approximately 70% of these patients.

High-Grade Prostatic Intraepithelial Neoplasia

High-grade prostatic intraepithelial neoplasia (HGPIN) has been established as a precursor to prostatic adenocarcinoma. HGPIN shares many morphological, genetic, and molecular signatures with prostate cancer. Its predictive value for the development of future adenocarcinoma during the prostate-specific antigen screening era has decreased, mostly owing to the increase in prostate biopsy cores. Nevertheless, a literature review supports that large-volume HGPIN and multiple cores of involvement at the initial biopsy should prompt a repeat biopsy of the prostate within 1 year. No treatment is recommended for HGPIN to slow its progression to cancer.

Utility of Intraoperative Frozen Section During Robot-Assisted Partial Nephrectomy: A Single Institution Experience

BACKGROUND AND PURPOSE Intraoperative frozen section (FS) analysis has been regarded as a paramount tool for immediate evaluation of tumor margin status during partial nephrectomy procedures. The aim of this study was to assess the utility of FS during robot-assisted partial nephrectomy (RAPN). PATIENTS AND METHODS A retrospective review of our Institutional Review Board-approved prospectively maintained minimally invasive partial nephrectomy database yielded 342 consecutive RAPN procedures from June 2007 to September 2011. Of these, the initial 128 cases underwent FS evaluation, whereas the following 214 cases did not. Patient demographics, perioperative outcomes, and final pathology results were analyzed and compared between the two groups. RESULTS Body mass index, Charleson Comorbidity Index, tumor size, renal score, preoperative creatinine level, and estimated glomerular filtration rate (eGFR) were similar between both groups. Operative time was significantly longer in the no-FS group (193 vs 180 min; P=0.04). Warm ischemia time (median 19 vs 19 min), estimated blood loss (150 vs 200 mL), postoperative creatinine level (1.0 vs 1.1 mg/dL), and postoperative eGFR (75.6 vs 75.9) were similar between the no-FS group and FS group, respectively. Complications occurred in 32 (15.0%) and 31 (24.2%) cases in no-FS and FS, respectively (P=0.06). Final pathology results demonstrated seven cases of positive margins, 1 (1%), in the FS group and 6 (3%) in the no-FS group (P=0.19). Of the cases with positive margins at final pathology analysis, a R.E.N.A.L. score of 3/3 was found on closeness to renal sinus. Overall, three intraoperative positive margins were noted in the FS group (2.3%): One patient underwent radical nephrectomy and one reresection; one case was managed with observation only. CONCLUSION Routine application of FS analysis during RAPN seems to provide a limited benefit. FS might be advisable for tumors with sinus invasion because they seem to carry a higher likelihood of positive surgical margin at final pathology determination.