Gou Kaneko

Neoadjuvant gemcitabine plus cisplatin for muscle-invasive bladder cancer

OBJECTIVE Downstaging by neoadjuvant chemotherapy improves the survival of patients with muscle-invasive bladder cancer. In salvage setting, gemcitabine plus cisplatin has demonstrated an efficacy similar to that of methotrexate, vinblastine, doxorubicin and cisplatin with less toxicity. Therefore, the application of neoadjuvant gemcitabine plus cisplatin is also being anticipated. METHODS Twenty-two patients who received neoadjuvant gemcitabine plus cisplatin were evaluated. The rate of downstaging, chemotherapy delivery profile and toxicity data were assessed. As comparator group, nine patients who were administered with neoadjuvant methotrexate, vinblastine, doxorubicin and cisplatin were evaluated. RESULTS A mean of 1.9 cycles of neoadjuvant gemcitabine plus cisplatin were performed. Achieved drug intensity for gemcitabine and cisplatin was 83.8 and 95.4%. Downstaging to pT0 and <pT2 was achieved in 50.0 and 63.6%. Grade 3 or 4 neutropenia, anemia, thrombocytopenia and febrile neutropenia appeared in 14.3, 2.4, 21.4 and 2.4%, respectively. Grade 3 or 4 non-hematologic toxicity was not observed. Thrombocytosis developed in 26.2%. A mean of 2.3 cycles of neoadjuvant methotrexate, vinblastine, doxorubicin and cisplatin were performed. The achieved drug intensities for methotrexate, vinblastine, doxorubicin and cisplatin were 59.6, 69.8, 100 and 88.6%. In patients treated with neoadjuvant methotrexate, vinblastine, doxorubicin and cisplatin, downstaging to pT0 and <pT2 was achieved in 22.2 and 44.4%. Grade 3 or 4 neutropenia, anemia and thrombocytopenia was present in 19.1, 9.5 and 4.8%. Grade 3 nausea developed in 28.6%. CONCLUSIONS The rate of downstaging by neoadjuvant gemcitabine plus cisplatin was comparable with that by methotrexate, vinblastine, doxorubicin and cisplatin. Gemcitabine plus cisplatin was associated with less non-hematologic toxicity than methotrexate, vinblastine, doxorubicin and cisplatin.

Patterns of Interstitial Lung Disease During Everolimus Treatment in Patients with Metastatic Renal Cell Carcinoma

OBJECTIVE To elucidate the patterns of interstitial lung disease during everolimus treatment in patients with metastatic renal cell carcinoma, we reviewed seven cases of everolimus-induced interstitial lung disease. METHODS Seven patients with metastatic renal cell carcinoma, which continued to progress despite treatment with sunitinib or sorafenib, developed interstitial lung disease after treatment with everolimus. RESULTS Chest X-ray demonstrated diffuse infiltrates in lung fields, and chest computed tomography showed bilateral reticular and ground-glass opacities. Serum levels of lactate dehydrogenase (7/7), C-reactive protein (6/7), pulmonary surfactant associated protein D (1/7) and Krebs von den Lungen 6 (5/7) were elevated. The bronchoalveolar lavage fluid obtained from four patients with Grade 3 interstitial lung disease showed lymphocytosis. The transbronchial lung biopsy specimens showed interstitial lymphocytic infiltration and septal thickening of alveolar walls. In two cases with mild interstitial lung disease, the everolimus therapy was successfully continued. In four cases with Grade 3 interstitial lung disease, the drug was discontinued and steroid therapy was initiated. Pulmonary symptoms and radiological abnormalities resolved within 2 months. CONCLUSIONS Serum Krebs von den Lungen 6 was elevated compared with baseline in all cases with interstitial lung disease. Some patients who developed mild interstitial lung disease during everolimus treatment could continue to receive the treatment. Even when severe interstitial lung disease developed, withdrawal of the drug and short-term use of high-dose steroids resulted in rapid recovery. Prompt recognition of interstitial lung disease exacerbation as well as exclusion of progressive disease or infection is of primary importance.

Impact of an Adjuvant Chemotherapeutic Regimen on the Clinical Outcome in High Risk Patients with Upper Tract Urothelial Carcinoma: A Japanese Multi-Institution Experience

PURPOSE Current guidelines do not yet provide any recommendations for adjuvant chemotherapy in patients with upper tract urothelial carcinoma managed with radical nephroureterectomy. We evaluated whether an adjuvant chemotherapeutic regimen would affect the clinical outcome in patients with high risk upper tract urothelial carcinoma. MATERIALS AND METHODS We identified 873 patients who had undergone radical nephrouretectomy for localized upper tract urothelial carcinoma at 14 Japanese institutions between 1993 and 2011. We assessed whether the type of regimen, such as methotrexate, vinblastine, doxorubicin and cisplatin, and gemcitabine and cisplatin, in an adjuvant setting, could affect the subsequent clinical outcome of patients with upper tract urothelial carcinoma. RESULTS On multivariate analysis pathological T stage, tumor grade, lymphovascular invasion and lymph node involvement were prognostic factors for recurrence-free survival and cancer specific survival. We defined 229 patients with 3 or more of these factors as the high risk group. In an analysis according to adjuvant regimen, Kaplan-Meier curves showed that the 1 and 2-year recurrence-free survival rates in the methotrexate, vinblastine, doxorubicin and cisplatin treated group were 71.4% and 47.9%, which were significantly higher than in the gemcitabine and cisplatin treated group (48.2% and not reached, p=0.022) or those not treated with adjuvant chemotherapy (53.4% and 39.6%, p=0.039). Similar results were observed in terms of cancer specific survival. CONCLUSIONS Our study showed that pT3-4, tumor grade 3, positive lymphovascular invasion and lymph node involvement were independent risk factors for disease mortality in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy. In the high risk group methotrexate, vinblastine, doxorubicin and cisplatin adjuvant chemotherapy contributed to improve subsequent mortality compared to gemcitabine and cisplatin or no adjuvant chemotherapy.

Visceral obesity is associated with better recurrence-free survival after curative surgery for Japanese patients with localized clear cell renal cell carcinoma

OBJECTIVE To investigate the prognostic significance of visceral obesity to predict recurrence after curative surgery for Japanese patients with localized renal cell carcinoma. METHODS The data of 285 patients who underwent curative surgery for localized renal cell carcinoma were retrospectively reviewed. Median follow-up was 36.7 months. The association between visceral obesity and recurrence-free survival rate was evaluated using the Kaplan-Meier method and Cox regression models. Visceral fat area at the level of the umbilicus measured using pre-operative computed tomography was used as an index of visceral obesity. RESULTS Twenty-nine patients (10.2%) experienced recurrence. Five-year recurrence-free survival rates were 91.3% in high visceral fat area group (≥ 120 cm(2)) and 76.9% in low visceral fat area group (<120 cm(2)) (P = 0.037); however, visceral fat area was not an independent predictor of recurrence-free survival in multivariate analysis. In the patients with clear cell renal cell carcinoma, 28 patients (11.6%) experienced recurrence. Five-year recurrence-free survival rates were 88.7% in high visceral fat area group and 71.0% in low visceral fat area group (P = 0.043), and visceral fat area was an independent predictor of recurrence-free survival (hazard ratio: 1.974, P = 0.042) as well as C-reactive protein, Fuhrman nuclear grade, tumor size and microvascular invasion. In patients with organ confined clear cell renal cell carcinoma in particular, visceral fat area was also a useful and independent predictor of recurrence-free survival (hazard ratio: 2.807, P = 0.038). Body mass index was not useful in either cohort. CONCLUSIONS High visceral fat area was a positive predictive biomarker for better recurrence-free survival after curative surgeries for localized clear cell renal cell carcinomas; however, body mass index was not a predictor.

Unidirectional barbed suture for vesicourethral anastomosis during laparoscopic radical prostatectomy

We investigated the impact of unidirectional barbed suture (UBS) for vesicourethral anastomosis (VUA) during laparoscopic radical prostatectomy.

How does visceral obesity affect surgical performance in laparoscopic radical nephrectomy

OBJECTIVE In a previous study, we described the relationship between operating time and obesity, particularly visceral obesity, in laparoscopic surgery. Operating time in laparoscopic surgery is affected by the experience and technique of the surgeon. Here, we investigated whether a difference in the surgeons experience affects the operating time for laparoscopic radical nephrectomy in patients with visceral obesity. METHODS From January 2006 to February 2012, 167 laparoscopic radical nephrectomies were performed at our institution. Visceral fat area was measured at the level of the umbilicus using computed tomography. A visceral fat area ≥ 100 cm(2) was used as the definition of visceral obesity. All laparoscopic radical nephrectomies were performed by six surgeons. Two of the six surgeons perform 50 cases or more laparoscopic surgeries every year and they were defined as the expert group. We analyzed the relationships between clinical findings, methods, surgeon experience, body mass index or visceral fat area and operating time. RESULTS The expert and non-expert surgeons performed 77 and 90 laparoscopic radical nephrectomies, respectively, and the median operating time was 167.0 ± 44.0 and 227.5 ± 60.6 min. Twenty-five patients underwent laparoendoscopic single-site nephrectomy by the expert surgeons. For all surgeons, visceral obesity was a significant factor for prolonged operating time. Multivariate analysis showed that visceral obesity and clinical T stage were independent risk factors for prolonged operating time for the non-expert surgeons [P = 0.004, hazard ratio (HR): 5.15, P = 0.037, HR:10.41]. However, for the expert surgeons, clinical T stage was the only independent risk factor for prolonged operating time (P = 0.039, HR: 4.33). CONCLUSION Visceral obesity was a factor of prolonged operating time in laparoscopic radical nephrectomy. The non-expert surgeons were particularly affected by visceral obesity.

The benefit of laparoscopic partial nephrectomy in high body mass index patients

OBJECTIVE The aims of the present study were to evaluate the effect of body mass index on the surgical outcomes of open partial nephrectomy and laparoscopic partial nephrectomy, and to analyze whether higher body mass index patients may derive greater benefit from laparoscopic partial nephrectomy. METHODS We reviewed 110 patients who underwent open partial nephrectomy and 47 patients who underwent laparoscopic partial nephrectomy at our institution. We analyzed the data to determine what kind of factor would be associated with prolonged operative time, increased estimated blood loss and prolonged ischemic time, and compared the result of open partial nephrectomy with that of laparoscopic partial nephrectomy. RESULTS A statistically significant correlation was observed between body mass index and operative time or estimated blood loss in open partial nephrectomy. Multivariate analysis also demonstrated that body mass index was an independent predictor for prolonged operative time and higher estimated blood loss in open partial nephrectomy, but not in laparoscopic partial nephrectomy. In the normal body mass index group (body mass index<25.0 kg/m2), although mean operative time in the laparoscopic partial nephrectomy group was significantly longer than that in the open partial nephrectomy group, the difference was relatively small. In the high body mass index group (body mass index≥25.0 kg/m2), the mean operative time of the two groups was not statistically different. The estimated blood loss of open partial nephrectomy was significantly higher than that of laparoscopic partial nephrectomy in both groups. In both operative procedures, tumor size was an independent predictor for prolonged ischemic time in multivariate analysis. CONCLUSIONS Body mass index was an independent predictor for prolonged operative time and higher estimated blood loss in open partial nephrectomy but not in laparoscopic partial nephrectomy. Laparoscopic partial nephrectomy was less influenced by body mass index and had a greater benefit, especially in high body mass index patients.

Two cases of bowel perforation associated with sunitinib treatment for renal cell carcinoma

Sunitinib, a multitargeted tyrosine kinase inhibitor, is widely used in the treatment of carcinoma. Adverse events associated with this treatment, including fatigue, diarrhea, and hematotoxicity, have been reported in clinical trials. Bowel perforation is a surgical emergency that requires immediate treatment depending on the location and progression of the tumor. We report 2 cases of bowel perforation during sunitinib treatment. The patients presented with diffuse peritonitis, and emergency exploratory laparotomy was performed. We speculate that the underlying mechanisms were decrease in capillary density of the normal mucosa in case 1 and tumor shrinkage because of sunitinib treatment in case 2. To the best of our knowledge, this is the first study to report the pathological findings implicating bowel perforation due to sunitinib treatment. Further investigations are needed to clarify the risk factors for intestinal perforations associated with sunitinib treatment.

The combination therapy of prednisolone and tacrolimus for severe painful bladder syndrome/interstitial cystitis.

A 47-year-old woman visited our hospital with complaints of frequent urination and intensive pelvic pain. Painful bladder syndrome/interstitial cystitis (PBS/IC) was suspected based on her symptoms. Hydrodistention was performed, and crack and petechial hemorrhage were found, and she was treated with tricyclic antidepressants and antihistamine. However, these treatments were ineffective. An allergy or autoimmune reaction was suspected as the pathogenesis due to eosinophilia and elevation of serum IgE levels. The patient was then treated with immunosuppressive agents. Although her symptoms were not sufficiently improved by single-agent therapy with prednisolone or tacrolimus, they were completely improved by their combined administration. This is the first case to report the effectiveness of combination therapy consisting of prednisolone and tacrolimus to treat PBS/IC.

A case of intraepithelial squamous cell carcinoma arising from urethral caruncle

A 62-year-old female patient had occasional bleeding from a mass in the urethral meatus. She had been conservatively treated with steroid ointment at another hospital for 1 year, but the bleeding had persisted. The patient was therefore referred for further treatment. A reddish mass, measuring 5 mm in diameter was noted at the posterior lip of the urethral meatus. The mass was diagnosed to be a urethral caruncle and was removed. Microscopically, the squamous epithelium, which covered the urethral caruncle, was found to be keratinized, with the proliferation of atypical cells with swollen nuclei in the entire mucosal layer. The mass was finally diagnosed to be intraepithelial squamous cell carcinoma arising from the urethral caruncle.The occurrence of intraepithelial squamous cell carcinoma arising from a urethral caruncle is extremely rare. A search of the English literature revealed only 1 other case report.