Reconnaissance of tumor immune microenvironment spatial heterogeneity in metastatic renal cell carcinoma and correlation with immunotherapy response.

A clearer understanding of the tumor immune microenvironment (TIME) in metastatic clear cell renal cell carcinoma (ccRCC) may help to inform precision treatment strategies. We sought to identify clinically meaningful TIME signatures in ccRCC. We studied tumors from 39 patients with metastatic ccRCC using quantitative multiplexed immunofluorescence and relevant immune marker panels. Cell densities were analyzed in three regions of interest (ROIs): tumor core, tumor-stroma interface and stroma. Patients were stratified into low- and high-marker density groups using median values as thresholds. Log-rank and Cox regression analyses while controlling for clinical variables were used to compare survival outcomes to patterns of immune cell distributions. There were significant associations with increased macrophage (CD68+ CD163+ CD206+ ) density and poor outcomes across multiple ROIs in primary and metastatic tumors. In primary tumors, T-bet+ T helper type 1 (Th1) cell density was highest at the tumor-stromal interface (P = 0·0021), and increased co-expression of CD3 and T-bet was associated with improved overall survival (P = 0·015) and survival after immunotherapy (P = 0·014). In metastatic tumor samples, decreased forkhead box protein 3 (FoxP3)+ T regulatory cell density correlated with improved survival after immunotherapy (P = 0·016). Increased macrophage markers and decreased Th1 T cell markers within the TIME correlated with poor overall survival and treatment outcomes. Immune markers such as FoxP3 showed consistent levels across the TIME, whereas others, such as T-bet, demonstrated significant variance across the distinct ROIs. These findings suggest that TIME profiling outside the tumor core may identify clinically relevant associations for patients with metastatic ccRCC.

The merits of cytology in the workup for upper tract urothelial carcinoma - a contemporary review of a perplexing issue.

INTRODUCTION: The importance of upper tract cytology for evaluating tumors is unclear. We correlated upper tract cytology with histologic findings in patients who underwent nephroureterectomy for upper tract urothelial carcinoma (UTUC) at a single tertiary care referral center. MATERIALS AND METHODS: 137 patients underwent nephroureterectomy between 2004 and 2012. 18 patients were excluded (benign tumors, atrophic kidneys with the remaining 119 patients serving as our study population). Upper tract cytology from the renal pelvis and/or ureter were retrospectively reviewed and analyzed with final pathology data in the remaining patients with UTUC. RESULTS: 57% (68/119) had preoperative upper tract cytology collected. 73% (50/68) patients had abnormal cytology (positive, suspicious) with a sensitivity of 74% (which increased to 90% if atypical included), specificity of 50% and a positive predictive value of 98%. High grade tumors were more common than expected (77% high grade vs. 20% low grade). Abnormal cytology did not predict T stage or tumor grade. Interestingly, positive upper tract cytology was found in all of the UTUC CIS specimen. CONCLUSIONS: Upper tract cytology has been utilized to support the diagnosis of upper tract urothelial carcinoma. Our data demonstrates that abnormal cytology correlates well with the presence of disease but does not predict staging or grading in these respective patients.

The merits of cytology in the workup for upper tract urothelial carcinoma - a contemporary review of a perplexing issue

Introduction The importance of upper tract cytology for evaluating tumors is unclear. We correlated upper tract cytology with histologic findings in patients who underwent nephroureterectomy for upper tract urothelial carcinoma (UTUC) at a single tertiary care referral center. Materials and Methods 137 patients underwent nephroureterectomy between 2004 and 2012. 18 patients were excluded (benign tumors, atrophic kidneys with the remaining 119 patients serving as our study population). Upper tract cytology from the renal pelvis and/or ureter were retrospectively reviewed and analyzed with final pathology data in the remaining patients with UTUC. Results 57% (68/119) had preoperative upper tract cytology collected. 73% (50/68) patients had abnormal cytology (positive, suspicious) with a sensitivity of 74% (which increased to 90% if atypical included), specificity of 50% and a positive predictive value of 98%. High grade tumors were more common than expected (77% high grade vs. 20% low grade). Abnormal cytology did not predict T stage or tumor grade. Interestingly, positive upper tract cytology was found in all of the UTUC CIS specimen. Conclusions Upper tract cytology has been utilized to support the diagnosis of upper tract urothelial carcinoma. Our data demonstrates that abnormal cytology correlates well with the presence of disease but does not predict staging or grading in these respective patients. .

Adult prostate sarcoma: the M. D. Anderson Cancer Center Experience.

PURPOSE: Sarcoma of prostate origin is rare. Historically, long-term survival rates for adult patients with prostate sarcoma are poor. We analyzed the experience of 1 institution with prostate sarcoma during the last 3 decades. MATERIALS AND METHODS: The records of 21 patients with prostate sarcoma were reviewed to identify symptoms at presentation, diagnostic procedures, presence and development of metastases, staging evaluation, histological subtype, grade and size of the primary tumor, and treatment sequence, including surgery, and preoperative and postoperative therapies. Several clinicopathological variables were assessed for prognostic importance. RESULTS: Most patients presented with urinary obstruction. The diagnosis of prostate sarcoma was usually established with ultrasound guided biopsy or transurethral resection. Histological subtypes were leiomyosarcoma in 12, rhabdomyosarcoma in 4, malignant fibrous histiocytoma in 1 and unclassified sarcoma in 4 patients. At last followup, 8 patients had no evidence of disease after a median of 81.5 months (range 10 to 197). The remaining 13 patients died of sarcoma (median survival 18 months, range 3 to 94). The 1, 3 and 5-year actuarial survival rates for all 21 patients were 81%, 43% and 38%, respectively. Factors predictive of long-term survival were negative surgical margins (p = 0.0005) and absence of metastatic disease at presentation (p = 0.0004). Tumor size and grade, and the histological subtype of prostate sarcoma had no significant influence on actuarial survival. CONCLUSIONS: The long-term disease specific survival rate for adults with prostate sarcoma is poor. Early diagnosis and complete surgical resection offer patients the best chance for cure.

Glycolate metabolism by Hep G2 cells.

The pathways of oxalate synthesis in humans are not well defined despite their clinical significance in primary hyperoxaluria and idiopathic calcium oxalate nephrolithiasis. Furthermore, the functional roles, if any, of this synthesis have not been elucidated. This study examines pathways of oxalate synthesis from glycolate in Hep G2 cells, a human hepatoma cell line. Incubation of these cells with glycolate has revealed that a pathway may function to synthesize oxalate from glycolate that does not depend on the oxidation of glycolate to glyoxylate by glycolate oxidase. Labeling cells with 14C-glycolate and chromatographic analyses indicated that detectable amounts of 14C-glyoxylate were not formed. A radioactive peak that coeluted with oxalate on ion exclusion chromatography was the only peak yet identified. A detailed examination of glycolate metabolism in these cells should help clarify the terminal steps associated with oxalate synthesis and aid in our understanding of two-carbon metabolism.

Diagnostic and therapeutic laparoscopy for the adult cryptorchid testicle.

Laparoscopy can be utilized in the management of male patients with impalpable gonads. However, there have been few reports of its application in the management of adult men with cryptorchidism. Fourteen adult men with 15 undescended testicles were referred to our urology department over 6 years. Eight testicles from seven men could not be localized clinically or radiographically to the inguinal canal. Laparoscopy was utilized to assess for the presence and location of the gonad and to perform orchiectomy when testicular tissue was encountered. The average age of the seven men undergoing laparoscopy was 40 years. Three testicles were found proximal to the internal ring and were removed using laparoscopic techniques. The ipsilateral testicular vessels and vas deferens were visualized entering the internal ring in three cases and dense ipsilateral adhesions from previous inguinal surgery prevented adequate visualization of the cord structures in one individual, leading to four inguinal explorations in the same setting. Two inguinal orchiectomies were performed and two vanishing testicles were identified. Gonadal vessels were absent in the remaining patient as demonstrated by extensive laparoscopic dissection. The average total operative time was 105 minutes, which included additional procedures in four patients. No patient experienced an intraoperative or postoperative complication. Six of seven patients were discharged on the day of surgery. An intratesticular germ cell neoplasm was found in one of seven specimens, which stresses the importance of diagnosing and managing this uncommon problem in the adult man.

Comparison of long-term outcomes of penile prostheses and intracavernosal injection therapy.

PURPOSE: Intracavernosal injection therapy is one of the most popular therapies for erectile dysfunction today. Yet, most clinicians consider intracavernosal injection a palliative treatment for erectile dysfunction because of the high patient initiated dropout rate. In contrast, penile prostheses appear to offer a more permanent cure for erectile dysfunction. We compare the long-term outcomes of both therapies in contemporaneously treated patients and determine the reasons for failure of each. MATERIALS AND METHODS: Telephone survey and chart review was conducted on the first 115 patients treated with intracavernosal injection and 65 patients undergoing insertion of a penile prosthesis during the same period at our institution. Mean patient age was 57 and 60 years, respectively, and mean followup of all patients was 5.4 years (range of 3.3 to 16). RESULTS: An equal percentage of patients were lost to followup in both groups, including 19% of the intracavernosal injection group and 18% of the penile prosthesis group. Of the intracavernosal injection patients 6 (6%) died during followup and 10 (19%) of the prosthetic patients died (p < 0.05). At the time of contact only 41% of the patients were still using intracavernosal injection. In contrast, 70% of the patients were still sexually active with the prosthesis (p < 0.01). Mean duration of use of the penile prosthetics was 63 months compared to 37 months for intracavernosal injection (p < 0.001). The most common reasons for discontinuing intracavernosal injection were inadequate erections (16 cases), lack of spontaneity (14), side effects (12), lack of partner (10), loss of sexual interest (6) and spontaneous return of normal erections (4). More than half of the patients (61%) who discontinued intracavernosal injection remain sexually active with other therapies, including penile prosthesis in 11, vacuum devices in 4, vascular surgery in 1 and oral medication in 1, and 14 without any therapy. We could not identify any significant clinical parameters that would accurately predict which patients most benefited by the long-term use of intracavernosal injection therapy. In contrast, only 6 patients discontinued use of the implant because of complications (infection, erosion and malfunction) and 7 for reasons independent of the implant (that is lack of partner, loss of sexual interest and co-morbidity). CONCLUSIONS: Intracavernosal injection serves as only a palliative therapy for the majority of patients with erectile dysfunction but there exists a core group who derives long-term satisfaction with its use. The majority of patients who discontinue intracavernosal injection remain sexually active yet do not progress to more invasive or effective therapies. The reason for discontinuing therapies for erectile dysfunction is often unrelated to the actual therapeutic modality. Our findings suggest that further improvements in intracavernosal injection therapy and the development of alternative methods of delivery of vasoactive agents will have only a limited impact on the overall outcome of therapy for erectile dysfunction and that increased attention to issues separate from the erection is warranted.

Is radiographic evaluation of the chest necessary following flank surgery?

PURPOSE: We determined whether routine postoperative chest radiography is warranted after flank surgery to assess for pneumothorax. MATERIALS AND METHODS: A retrospective study of 253 adult flank operations performed during a 6-year period was conducted. RESULTS: Incidental pleurotomy occurred in 63 cases (24.9%). The performance of rib resection and the level of rib removed as well as female gender had a significant impact on this occurrence. Pleurotomy was treated by a simple evacuation technique and tube thoracostomy was not necessary. Only 2 patients (0.8%) had a postoperative pneumothorax without intraoperative recognition of pleurotomy, which resolved without intervention. CONCLUSIONS: Routine postoperative chest radiography to assess for pneumothorax following open flank surgery is not necessary.