Subclassification of pT3 urothelial carcinoma of the renal pelvicalyceal system is associated with recurrence-free and cancer-specific survival: proposal for a revision of the current TNM classification

Background

The clinical course of pT3 upper tract urothelial carcinoma (UTUC) is highly variable.

Objectives

The aim of the current study was to validate the clinical and prognostic importance of pT3 subclassification in the renal pelvicalyceal system in a large international cohort of patients.

Design, setting, and participants

From a multi-institutional international database, 858 renal pelvicalyceal tumors treated with radical nephroureterectomy (RNU) were systematically reevaluated by genitourinary pathologists. Category pT3 pelvic tumors were categorized as pT3a (infiltration of the renal parenchyma on a microscopic level only) versus pT3b (macroscopic infiltration of the renal parenchyma and/or infiltration of peripelvic adipose tissue).

Intervention

RNU.

Measurements

Associations of pT3 subclassifications with clinicopathologic features were assessed with the chi-square test. Prognostic impact was assessed with the log-rank test and multivariable Cox regression analyses.

Results and limitations

Of 858 patients with renal pelvicalyceal tumors, 266 (31%) had pT3 disease. Of these, 146 (54.9%) were classified as pT3a and 120 (45.1%) as pT3b. Compared with pT3a, pT3b cancers were associated with higher tumor grade, nodal disease, and tumor necrosis. Ten-year recurrence-free (pT3a 58% vs pT3b 38%; p < 0.001) and cancer-specific (pT3a 60% vs pT3b 39%; p = 0.002) survival rates were lower for patients with pT3b disease. In multivariable analyses, classification pT3b was an independent predictor of both disease recurrence (hazard ratio [HR]: 1.8, p = 0.003) and cancer-specific mortality (HR: 1.7; p = 0.02). The major limitation is the retrospective character of the study.

Conclusions

Subclassification of pT3 renal pelvicalyceal UTUC helps identify patients who are at increased risk of disease progression and cancer-related death. Further research may help assess the value of subclassification and its inclusion in future editions of the American Joint Committee on Cancer–International Union Against Cancer TNM classification system.     

Stage-Specific Impact of Tumor Location on Oncologic Outcomes in Patients With Upper and Lower Tract Urothelial Carcinoma Following Radical Surgery

BACKGROUND: Dissimilarities in management and outcomes exist between upper tract urothelial carcinoma (UTUC) and urothelial carcinoma of the bladder (UCB). OBJECTIVE: The aim of this study was to analyze the stage-specific impact of upper or lower urinary tract tumor location on oncologic outcomes. DESIGN, SETTING, AND PARTICIPANTS: Data were collected from 4335 patients with UCB treated with radical cystectomy (RC) and bilateral pelvic lymphadenectomy (PLND), 877 patients with ureteral UTUC, and 1615 with pelvicalyceal UTUC treated with radical nephroureterectomy (RNU). No patient received preoperative chemotherapy or radiation therapy. INTERVENTIONS: Patients were treated with RC and bilateral PLND or RNU. MEASUREMENTS: Outcomes were assessed according to primary tumor location. RESULTS AND LIMITATIONS: Compared to UTUC patients, UCB patients had more advanced tumor stage and higher grade, and they were more likely to harbor lymphovascular invasion (LVI) and lymph node metastasis (p<0.001). In non-muscle-invasive tumor stages, UCB patients were more likely to experience disease recurrence and mortality compared to renal pelvicalyceal tumor patients (p<0.002) but not ureteral tumors (p>0.05). In pT2 and pT3 tumors, there was no difference in outcomes between the three tumor locations. In pT4 tumors, patients with ureteral and pelvicalyceal tumors were more likely to experience disease recurrence and mortality compared to UCB patients (p<0.004). These stage-specific findings were unchanged after adjustment for the effects of age, gender, tumor grade, LVI, lymph node status, and adjuvant chemotherapy. This study is limited by its retrospective and multicenter nature. CONCLUSIONS: Stage-specific differences in outcomes exist between UCB and UTUC. The differentially worse outcomes by stage between UCB and UTUC patients underline the differences between both cancer entities and the need for individualized stage-specific management for each patient.     

Hybrid neurofibroma/schwannoma is overrepresented among schwannomatosis and neurofibromatosis patients

We analyzed the histologic features of peripheral nerve sheath tumors occurring in 14 patients with schwannomatosis. Among a total of 31 tumors, 19 tumors (61%) showed schwannoma-like nodules within a neurofibroma-like tumor, corresponding to hybrid neurofibroma/schwannoma. At least 1 hybrid tumor occurred in 10 of 14 (71%) schwannomatosis patients. We then retrieved cases of hybrid tumors without documented relation to schwannomatosis from our database and identified 41 tumors arising in 23 patients. More than half of these patients (14/23) were reported to suffer from multiple peripheral nerve sheath tumors, favoring a tumor syndrome. Indeed, analysis of clinical records revealed the diagnosis of neurofibromatosis type 2 (NF2) in 26% (6/23), neurofibromatosis type 1 (NF1) in 9% (2/23), definite schwannomatosis in 4% (1/23), and possible schwannomatosis in 13% (3/23) of patients with multiple nerve sheath tumors. Our findings suggest that hybrid neurofibroma/schwannoma represents a common tumor type in schwannomatosis and shows a striking association with neurofibromatoses.     

Adult patients with sporadic polycystic kidney disease: the importance of screening for mutations in the PKD1 and PKD2 genes

Background

ADPKD is one of the most common inherited disorders, with high risk for end-stage renal disease. Numerous patients, however, have no relatives in whom this disorder is known and are unsure whether they may transmit the disease to their offsprings. The aim of this study was to evaluate whether germline mutation analysis adds substantial information to clinical symptoms for diagnosis of ADPKD in these patients.

Methods

Clinical data included renal function and presence of liver or pancreas cysts, heart valve insufficiency, intracranial aneurysms, colonic diverticles, and abdominal hernias. Family history was evaluated regarding ADPKD. Germline mutation screening of the PKD1 and PKD2 genes was performed for intragenic mutations and for large deletions.

Results

A total of 324 adult patients with ADPKD including 30 patients without a family history of ADPKD (sporadic cases) were included. PKD1 mutations were found in 24/30 and PKD2 mutations in 6 patients. Liver cysts were present in 14 patients and intracranial aneurysms in 2 patients. Fourteen patients (45%) had no extrarenal involvement. Compared to the 294 patients with familial ADPKD, the clinical characteristics and the age at the start of dialysis were similar in those with sporadic ADPKD.

Conclusion

The clinical characteristics of patients with sporadic and familial ADPKD are similar, but sporadic ADPKD is often overlooked because of the absence of a family history. Molecular genetic screening for germline mutations in both PKD1 and PKD2 genes is essential for the definitive diagnosis of ADPKD.     

Risk of Cancer-specific Mortality following Recurrence After Radical Nephroureterectomy

Purpose

To describe the natural history and identify predictors of cancer-specific survival in patients who experience disease recurrence after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC).

Methods

Of 2,494 UTUC patients treated with RNU without neoadjuvant chemotherapy, 597 patients experienced disease recurrence. A total of 148 patients (25?%) received adjuvant chemotherapy before disease recurrence. Multivariable Cox regression model addressed time to cancer-specific mortality after disease recurrence.

Results

The median time from RNU to disease recurrence was 12?months (interquartile range 5?C22). A total of 491 (82?%) of 597 patients died from UTUC, and 8 patients (1.3?%) died from other causes. The median time from disease recurrence to death of UTUC was 10?months. Actuarial cancer-specific survival estimate at 12?months after disease recurrence was 35?%. On multivariable analysis that adjusted for the effects of standard clinicopathologic characteristics, higher tumor stages [hazard ratio (HR) pT3 vs. pT0?CT1: 1.66, p?=?0.001; HR pT4 vs. pT0?CT1: 1.90, p?=?0.002], absence of lymph node dissection (HR 1.28, p?=?0.041), ureteral tumor location (HR 1.44, p?<?0.0005) and a shorter interval from surgery to disease recurrence (p?<?0.0005) were significantly associated with cancer-specific mortality. The adjusted 6-, 12- and 24-month postrecurrence cancer-specific mortality was 73, 60 and 57?%, respectively.

Conclusions

Approximately 80?% of patients who experience disease recurrence after RNU die within 2?years after recurrence. Patients with non-organ-confined stage, absence of lymph node dissection, ureteral tumor location and/or shorter time to disease recurrence died of their tumor more quickly than their counterparts. These factors should be considered in patient counseling and risk stratification for salvage treatment decision making.     

Fungal periprosthetic hip and knee joint infections clinical experience with a 2-stage treatment protocol

Fungal periprosthetic joint infections are a rare entity in orthopedic surgery, and there exist no guidelines according to which these infections can be successfully managed. Between 2004 and 2009, 7 patients with fungal periprosthetic joint infections (4 total hip arthroplasties and 3 total knee arthroplasties) have been treated with a 2-stage protocol and implantation of antibiotic-loaded cement spacers. Most of the infection was caused by Candida species. Systemic antifungal agents were administered for 6 weeks in 6 cases and 6 months in 1 case. The mean spacer implantation time was 12 weeks. At a mean follow-up of 28 months (5-70 months), no persistence of infection or reinfection could be observed. A 2-stage treatment protocol with implantation of an antibiotic-loaded cement spacer is an efficient option in the treatment of fungal periprosthetic infections.     

Reduction of ischemia/reperfusion injury by antithrombin III after experimental pancreas transplantation

BACKGROUND: Graft pancreatitis is a major complication after pancreas transplantation. Antithrombin III (AT III) is an anticoagulatory and anti-inflammatory substance. The aim of our study was to evaluate a prophylactic application of AT III in experimental pancreas transplantation. METHODS: Pancreas transplantation was performed in rats. Cold ischemia time (University of Wisconsin solution at 4 degrees C) was 12 hours. After 4 hours of reperfusion, pancreatic enzymes were assessed and the pancreas was evaluated by intravital microscopy and histologic and immunohistochemical examination. Recipients were allocated randomly to 2 groups: 1 control group (n = 6) and 1 group in which recipients received 125 IU AT III/kg 30 minutes before reperfusion (n = 6). Six animals that did not undergo transplantation served as healthy controls. RESULTS: Enzyme levels showed no differences between the 2 transplantation groups but were significantly (P <.05) higher than in the control group. Histologic damage was significantly less evident in animals that received AT III compared with transplantation animals that did not receive AT III. During intravital microscopy, animals receiving AT III showed significantly higher capillary and venular erythrocyte velocities compared with untreated transplantation animals. The leukocyte-endothelium interaction in postcapillary venules was decreased significantly in animals with AT III treatment. CONCLUSIONS: AT III pretreatment decreases tissue damage by attenuating microcirculatory disturbances and leukocyte adherence in experimental graft pancreatitis by its anti-inflammatory and anticoagulatory properties.     

Primary Lymphedema of the Lower Limb: The Clinical Utility of Single Photon Emission Computed Tomography/CT

ObjectiveThe aim of this prospective study was to determine whether the additional use of the single photon emission computed tomography/CT (SPECT/CT) technique improves the diagnostic value of planar lymphoscintigraphy in patients presenting with primary lymph edema of the lower limb.ResultsIn comparison to pathological planar scintigraphic findings, the addition of SPECT/CT provided relevant additional information regarding the presence of dermal backflow (86%), the anatomical extent of lymphatic disorders (64%), the presence or absence of lymph nodes (46%), and the visualization of lymph vessels (4%).ConclusionAs an adjunct to planar lymphoscintigraphy, SPECT/CT specifies the anatomical correlation of lymphatic disorders and thus improves assessment of the extent of pathology due to the particular advantages of tomographic separation of overlapping sources. The interpretation of scintigraphic data benefits not only in baseline diagnosis, but also in physiotherapeutical and microsurgical treatments of primary lymphedema.