Prognostic value of a computer-aided diagnosis system involving bone scans among men treated with docetaxel for metastatic castration-resistant prostate cancer.

BACKGROUND: The bone scan index (BSI), which is obtained using a computer-aided bone scan evaluation system, is anticipated to become an objective and quantitative clinical tool for evaluating bone metastases in prostate cancer. Here, we assessed the usefulness of the BSI as a prognostic factor in patients with metastatic castration-resistant prostate cancer (mCRPC) treated using docetaxel. METHODS: We analyzed 41 patients who received docetaxel for mCRPC. The Bonenavi system was used as the calculation program for the BSI. The utility of the BSI as a predictor of overall survival (OS) after docetaxel was evaluated. The Cox proportional hazards model was used to investigate the association between clinical variables obtained at docetaxel treatment, namely PSA, patient age, liver metastasis, local therapy, hemoglobin (Hb), lactase dehydrogenase (LDH), albumin (Alb), PSA doubling time, and BSI and OS. RESULTS: The median OS after docetaxel therapy was 17.7 months. Death occurred in 22 (53.7%) patients; all deaths were caused by prostate cancer. In multivariate analysis, three factors were identified as significant independent prognostic biomarkers for OS after docetaxel; these were liver metastases (yes vs no; HR, 3.681; p = 0.026), Alb (<3.9 vs ≥ 3.9; HR, 3.776; p = 0.020), and BSI (>1% vs ≤ 1%; HR, 3.356; p = 0.037). We evaluated the discriminatory ability of our models including or excluding the BSI by quantifying the c-index. The BSI improved the c-index from 0.758 to 0.769 for OS after docetaxel. CRPC patients with a BSI >1 had a significantly shorter OS than patients with a BSI ≤ 1 (p = 0.029). CONCLUSIONS: The BSI, liver metastases and Alb were independent prognostic factors for OS after docetaxel. The BSI might be a useful tool for risk stratification of mCRPC patients undergoing docetaxel treatment.

Prognostic value of the bone scan index using a computer-aided diagnosis system for bone scans in hormone-naive prostate cancer patients with bone metastases.

BACKGROUND: The bone scan index (BSI) using a computer-aided diagnosis system for bone scans is expected to be an objective and quantitative clinical tool for evaluating bone metastatic prostate cancer. This study aimed to evaluate the pretreatment BSI as a prognostic factor in hormone-naive prostate cancer patients with bone metastases. METHODS: The study included 60 patients with hormone-naive, bone metastatic prostate cancer that was initially treated with combined androgen blockade therapy. The BONENAVI system was used for calculating the BSI. We evaluated the correlation between overall survival (OS) and pretreatment clinicopathological characteristics, including patients' age, initial prostate-specific antigen (PSA) value, Gleason scores, clinical TNM stage, and the BSI. Cox proportional hazards regression models were used for statistical analysis. RESULTS: The median follow-up duration was 21.4 months. Clinical or PSA progression occurred in 37 (61.7%) patients and 18 (30.0%) received docetaxel. Death occurred in 16 (26.7%) patients. Of these deaths, 15 (25.0%) were due to prostate cancer. The median OS was not reached. In multivariate analysis, age and the BSI were independent prognostic factors for OS. We evaluated the discriminatory ability of our models, including or excluding BSI by quantifying the C-index. The BSI improved the C-index from 0.751 to 0.801 for OS. Median OS was not reached in patients with a BSI ≤ 1.9 and median OS was 34.8 months in patients with a BSI >1.9 (p = 0.039). CONCLUSIONS: The pretreatment BSI and patients' age are independent prognostic factors for patients with hormone-naive, bone metastatic prostate cancer.

[A Case of Abdominal Wall Desmoid Tumor after Radical Nephrectomy for Renal Cancer].

A 71-year-old man with a right renal tumor underwent nephrectomy. The procedure was converted from laparoscopy to open surgery due to profound bleeding from the renal vein. Pathological diagnosis was clear cell carcinoma G2pT3b v1 ly1 INFα. Three years after surgery, a 5 cm tumor in the abdominal wall was found on computed tomography (CT). A mild uptake was shown on positron emission tomography/CT and as the tumor was located near the surgical wound, recurrence of the renal cell carcinoma was suspected. However, desmoid tumor was suggested by the pathological examination of the tumor biopsy. En-bloc resection of the mass was carried out and the pathological examination showed an array of proliferating and tangling atypical spindle-shaped tumor cells. Immunohistochemical staining of the tumor cells was positive for vimentin, but negative for CD34, c-kit, and s100. Pathological diagnosis was desmoid tumor. There has been no recurrence so far. Desmoid tumor, despite its extremely low incidence, should be considered in a postoperative neoplasm.

[PATHOLOGICAL COMPLETE RESPONSE WITH EVEROLIMUS FOR MULTIPLE LUNG METASTASES OF RENAL CELL CARCINOMA RESISTANT TO SUNITINIB].

A 55-year-old man was referred to our hospital because of a tumor in his right kidney. A Fluorodeoxyglucose-positron emission tomography (PET)/computed tomography (CT) scan revealed strong abnormal uptake by the tumor in the right kidney and a nodule in the right lung. The patient was diagnosed with stage IV renal cell cancer, for which he underwent transperitoneal nephrectomy. Pathological diagnosis revealed the tumor to be a renal cell carcinoma (clear cell carcinoma, G2, pT3a, v (+), INF-ß). Sunitinib was administered because of the occurrence of multiple lung metastases; however, the therapeutic effect was insufficient, and progressive disease was observed on a CT scan. Therefore, everolimus was immediately administered as a second-line therapeutic agent. After treatment, the lung metastases reduced in size, as observed on a CT scan, and partial response continued for 1 year after therapy. One metastatic lesion persisted in the right lung; therefore, he underwent right upper lobe resection after discontinuing everolimus administration. No viable tumor cells were observed on pathological diagnosis, and the patient achieved pathological complete response. 3 month after discontinuing everolimus administration, no metastatic lesions have been observed.

[A case of pneumatosis cystoides intestinalis secondary to sunitinib treatment for renal cell carcinoma].

A 78-year-old man was diagnosed as having right renal cell carcinoma (RCC) with metastasis to the right lung. He received sunitinib and the treatment reduced the size of both RCC and lung metastasis. Then he received right radical nephrectomy. The pathological diagnosis was clear cell RCC. After the initial surgery, he was diagnosed with polymyalgia rheumatic and steroid therapy was started. During follow-up, local recurrence was discovered and sunitinib was then started at a dose of 25 mg/day. Two months after the treatment, abdominal computed tomography (CT) revealed colonic pneumatosis cystoides intestinalis. Administration of sunitinib was stopped and the patient was observed carefully without pursuing surgical intervention. A follow-up CT demonstrated resolution of the colonic pnumatosis.

[Successful combination chemotherapy of gemcitabine plus nedaplatin for invasive ureteral squamous cell carcinoma].

A 77-year-old female was indicated pelvic mass and hydronephrosis when her examination of advanced gastric cancer. Computed tomography revealed left ureteral dilatation and mass around the left ureter. Laparotomy biopsy was abandoned because of her low cardiac function. Thereafter, hemorrhagic stool was observed and colonoscopy revealed hemorrhagic mucosal protrusion at sigmoid colon. This lesion was diagnosed as squamous cell carcinoma by pathology of biopsy specimen. Colonic invasion of other organ carcinoma was suspected by colonoscopic findings. Retrograde pyelogram revealed a defect of left lower ureter. Positron emission tomography revealed the mass excluding sigmoid colon and high value (SUV max was 10.3) at the mass. Therefore, it was diagnosed invasive ureteral squamous cell carcinoma and she was treated with 2 cycles of combination chemotherapy consisting of gemcitabine (800 mg/m2: day 1 and 8) and nedaplatin (60 mg/m2: day 1). During the chemotherapy, only cytopenia (grade 4: CTCAE guidelines) was observed. About 4 months after 2 courses of chemotherapy, the tumor size was reduced by almost 100% (CR; RECIST guidelines). Thereafter, recurrence of pelvic mass was not observed.

[A case of pneumomediastinum during BEP (bleomycin, etoposide, cisplatin) chemotherapy for testicular cancer].

We report a case of drug-induced pneumomediastinum by bleomycin in testicular cancer, which is extremely rare ; to our knowledge, only 3 cases have been reported. A 28-year-old man presented with a left testicular mass. He underwent radical left inguinal orchiectomy that demonstrated a seminoma, pT3N0M0. Ten months after surgery, para-aortic lymph node metastasis appeared, and he received three cycles of bleomycin, etoposide and cisplatin (BEP) chemotherapy. On day 13 of the fourth course of BEP, he complained of snowball crepitation of the neck and computed tomography revealed subcutaneous emphysema, extensive mediastinal air, and intraspinal air accumulation without pneumothorax. The pneumomediastinum and subcutaneous emphysema tended to deteriorate until 15 days after the onset of pneumomediastinum, but fortunately he had no signs or symptoms of infection. These findings resolved spontaneously after 1 month.

[A case of retroperitoneal bronchogenic cyst treated by laparoscopic surgery].

A 51-year-old woman was referred to our hospital because of continuing back pain for 2 weeks. Computed tomography revealed a mass 30x40 mm in diameter adjacent to the left adrenal gland. We performed laparoscopic surgery in order to relieve the symptoms and make a diagnosis. Because there was adhesion between the mass and gastric wall, the mass was resected together with the gastric wall. Histopathological findings revealed the cyst with ciliated columunar epithelium and the final diagnosis was retroperitoneal bronchogenic cyst. There was no evidence of malignancy and the back pain disappeared.

[Retrospective analysis of predicting biochemical recurrence after initial radical prostatectomy].

We evaluated clinical outcomes of radical prostatectomy in 244 patients who had undergone radical prostatectomy as initial treatment from January 2000 to December 2011, and were followed up for more than 6 months. Biochemical recurrence after prostatectomy was defined as prostate-specific antigen (PSA) level of at least 0. 2 ng/ml. We evaluated potential risk factors for significant associations with biochemical recurrence. Median follow-up period after prostatectomy was 49 months (range, 6-144). Of the total, 192, 31, and 20 patients were at pathological stage pT2, pT3a, and pT3b, respectively. In 83 patients with the positive surgical margin, apexes were mostly in the positive area. Of the 68 patients with PSA recurrence, PSA non-relapse rate was 66.6% for 5 years. Multivariate analysis was performed for seminal vesicle invasion, PSA nadir, surgical margins, and Gleason score. Thirty-two patients with PSA recurrence underwent salvage radiotherapy, and the biochemical recurrence rate at 5 years was 73.8%. The group in which the PSA level before salvage radiotherapy was ＜0.5 ng/ml had a low rate of biochemical recurrence. We must consider the recurrence of poorly differentiated or non-confined cancer after radical prostatectomy. These results suggest that early use of salvage radiotherapy is effective for patients with biochemical recurrence after radical prostatectomy.

[A case of retroperitoneal angiosarcoma effectively treated with recombinant interleukin-2].

Angiosarcoma is rare and highly malignant vascular neoplasm, and primary retroperitoneal angiosarcoma is extremely rare. Preoperative diagnosis is very difficult because there are no specific imaging features, and definitively effective treatment has not yet been established. We recently treated a patient with primary retroperitoneal angiosarcoma in which a prompt and exact diagnosis was difficult to obtain. One month after surgery, local recurrence appeared, but salvage immunotherapy using recombinant interleukin-2 (rIL-2) showed good efficacy, and the patient obtained complete response. Here we report this rare case of angiosarcoma. A 60-year-old woman with abdominal pain was diagnosed with a left retroperitoneal mass on CT scan. The tumor was about 9 cm in diameter and positioned above the left kidney. Further study using MRI, 131I-MIBG scintigraphy, and enhanced CT suggested chronic expanding hematoma and the patient underwent surgical resection. Histopathological diagnosis was primary retroperitoneal angiosarcoma based on positive staining for VIII factor, CD31, CD34, and p53. One month after surgery, FDG-PET revealed local recurrence adjacent to the psoas major. We initiated salvage immunotherapy using rIL-2. The patient was treated effectively and achieved complete response. She is alive and well 19 months after surgery and rIL-2 treatment.

[A CASE OF RENAL CELL CARCINOMA WITH SMALL INTESTINE METASTASIS DURING NIVOLUMAB PLUS IPILIMUMAB].

A 71-year-old man with a history of hoarseness and right upper extremity numbness was referred to our department for evaluation of an intrathoracic mass that was detected on chest radiography and a right kidney tumor observed on computed tomography (CT). Histopathological examination of percutaneous kidney biopsy and bronchoscopic lung biopsy specimens revealed renal clear cell carcinoma with multiple lung metastases. The patient showed a poor risk based on the International Metastatic renal cell carcinoma Database Consortium score, and nivolumab plus ipilimumab were initiated as first-line therapy. His symptoms gradually improved, following four courses of nivolumab plus ipilimumab treatment, and CT revealed shrinkage of all lesions. However, he developed diarrhea, rash, anemia, and elevated serum C-reactive protein levels (CRP) following this therapy. Diarrhea and rash were considered immune-related adverse events, and he was treated with oral prednisolone and topical corticosteroid. Nivolumab administration was discontinued because anemia worsened together with elevated serum CRP levels despite improvement in diarrhea. He subsequently developed constipation and abdominal bloating, following further treatment for 4 months. CT revealed intestinal tumor-induced intussusception, necessitating partial resection of the small intestinal tumor, which was histopathologically diagnosed as metastases. Both anemia and elevated CRP improved postoperatively. Currently, all metastatic lesions other than the resected intestine have continued to respond to treatment over 12 months after initiation of nivolumab plus ipilimumab therapy.

Prognosis of patients with T1 bladder cancer after en bloc transurethral resection of bladder tumor stratified by invasion to the level of the muscularis mucosa.

PURPOSE: To evaluate the prognosis of patients with pT1 bladder cancer who underwent en bloc resection of bladder tumors (ERBTs), stratified by invasion to the muscularis mucosa (MM) level. METHODS: Among 64 specimens obtained by ERBT with bipolar energy from patients with pT1 bladder cancer, MM was detected in 61 specimens. Thus, 61 specimens were included in this retrospective study. Patients were stratified by invasion to the MM level (pT1a, invasion above the MM level; pT1b, invasion within the MM level; and pT1c, invasion beyond the MM level). In specimens with discontinuous MM, invasion to the MM level was predicted from the dispersed MM in the specimen. The primary endpoints were progression-free survival (PFS) and cancer-specific survival (CSS). RESULTS: Progression occurred in 2/39 patients with pT1a (5.1%), 1/6 patients with pT1b (16.7%), and 6/16 patients with pT1c cancer (37.5%). Cancer death occurred in 1/39 patients with pT1a (2.6%), 0/7 patients with pT1b, and 3/16 patients with pT1c cancer (18.8%). Patients with pT1a or pT1b cancer had a significantly better prognosis than those with pT1c cancer. On univariate analysis, tumor size ≥ 3 cm and pT1c were significantly associated with shorter PFS. On multivariate analysis, only pT1c was independently associated with shorter PFS. CONCLUSION: This is the first study evaluating the prognosis by T1 substaging based on invasion to the MM level using ERBT specimens. ERBT provided high-quality specimens for diagnosing the MM and showed poor prognosis in pT1c bladder cancer. ERBT could be an appropriate surgical approach for an accurate diagnosis and prognosis of the T1 bladder cancer substage.

[Two cases of pellagra associated with chemotherapy of docetaxel, estramustine, dexamethasone].

An 81-year-old male with hormone refractory prostate cancer, received chemotherapy of Docetaxel, Estramustine and dexamethasone as an outpatient. After 4 courses of chemotherapy, he was admitted to our hospital in December 2007 because of general fatigue, appetite loss and erythema of the back of hands and face. He was diagnosed with pellagra. Nicotinic acid was administered and the symptoms disappeared. An 80-year-old male with hormone refractory prostate cancer, received chemotherapy of Docetaxel, Estramustine and dexamethasone without admission. After 8 courses of the chemotherapy, appetite loss appeared. In January 2008, medical examinations revealed nails peeling off, facial erythema and erosion of the back of his hands. He was diagnosed with pellagra. Nicotinic acid was administered and the symptoms disappeared. Pellagra, a nicotinic acid deficiency disease, is rarely observed clinically nowadays. However, it may occur in the patients, undergoing chemotherapy without admission.

[Clinical study of penis-conserving treatment for carcinoma of penis].

We retrospectively reviewed 9 patients with squamous cell carcinoma of the penis who were treated with penis preservation between April 1988 and January 2008. Six patients had recurrence and 4 patients died of cancer. Patients treated with penis preservation had a significantly higher. Future studies are needed on a larger number of cases.

[A clinical study for intravesical recurrence after surgical therapy of urotherial carcinoma of the upper urinary tract].

To identify the risk factors for developing subsequent bladder carcinoma in patients undergoing surgical management of urothelial carcinoma (UC) of the upper urinary tract, we retrospectively studied 119 (median age 69, 81 males and 38 females) patients who underwent surgical resection at Yokohama Municipal Citizen's Hospital, Yokosuka Kyousai Hospital and Chigasaki Municipal Hospital from August 1980 to September 2006. After a median follow up of 37.7 months, 42 cases (35.3%) developed recurrent bladder cancer and the intravesical recurrence-free survival rate at 5 years (Kaplan-Meier method) was 57.7%. Bladder cancer was significantly more common in patients who had smaller primary tumors (less than 3 cm: p0.0444) by univariate analysis. This factor was also identified as independent predictor for the intravesical recurrence by multivariated analysis (p0.0495, Hazard ratio 2.099). In 42 intravesical recurrence cases, invasive recurrence was seen in 9 cases (21.4%). Invasive recurrence appeared to occur in the patients who were older and had longer interval by intravesical recurrence.

[Low-dose docetaxel, estramustine and dexamethasone combination chemotherapy for hormone-refractory prostate cancer].

The objective of this study was to evaluate the efficacy and safety of low-dose docetaxel, estramustine and dexamethasone combination chemotherapy in patients with hormone-refractory prostate cancer (HRPC). Sixty-nine patients with HRPC were enrolled. Docetaxel was given at a dose of 25 mg/m(2) on days 1 and 8 every 3 weeks, oral estramustine 280 mg twice daily on days 1 to 3 and 8 to 10, and oral dexamethasone 1 mg daily throughout the course. Cycles were repeated every 21 days. Treatment was continued until disease progression or excessive toxicity. Patients were evaluated for response and toxicity. Patients received a median of eleven cycles (range : 1-25). Prostatic-specific antigen (PSA) was decreased greater than 50% in 53 (77%) out of 69 patients and median duration of PSA response was 10.2 months. Median time to progression and overall survival 10.2 and 24 months, respectively. Grade 1-2 fatigue was the most common toxicity observed in 10 (15%) patients. Grade 3-4 toxicities were observed in five (7%) patients (2 thrombosis, 2 bilirubin elevation, and 1 aspartate transaminase/alanine transaminase elevation). Low-dose docetaxel, estramustine and dexamethasone combination chemotherapy is an effective and well tolerated treatment for Japanese HRPC patients.

[The relationship between inflammatory bowel disease (IBD) and complications of urinary and male genital tracts].

Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) that may often involve organs other than those of the gastrointestinal tract. We investigated retrospectively the frequency, diagnosis and treatment of urinary and male genital complications of CD and UC. From February 1998 to July 2007, 93 patients with CD and 75 patients with UC consulted our department for urinary and male genital complications. Thirty, 19 and 16 of the 93 patients with CD were diagnosed as having fistulas to the urinary and male genital systems, urolithiasis and hydronephrosis, respectively. Fifteen, 14 and 13 of the 75 patients with UC were diagnosed as having urolithiasis, urinary tract infection (UTI) and lower urinary tract symptoms (LUTS), respectively. Fistula to the urinary and male genital systems in CD occurred more often in men. In 22 CD patients who had undergone surgical operation and were definitively diagnosed as fistula, the positive rate of cystogram (CG) was 38.1% (8/21). They presented with pyuria (10 cases), pneumaturia (7), hematuria (7), fecaluria (2) and urorrhea (2). Cystoscopy was performed in 20 patients. Fistula opening in the urinary bladder was found in only 2 patients. Other findings in the bladder were edema (14 cases), redness of mucosa (6) and debris (3). Hydronephrosis in CD occurred in 16 patients. Placing a percutaneus nephrostomy (PNS) or ureteral stent was performed in 11 patients and surgical therapy was performed in 12 patients. Only two of the 34 patients with urolithiasis (CD 19, UC 15 cases) underwent ESWL and/or TUL. Almost all patients with UTI in UC were treated with antibiotics and improved, but one patient died from Fournier's Gangrene due to erirectal abscess.

[A clinical study concerning survival of operative cases for the transitional cell carcinoma of the upper urinary tract].

To identify prognostic factors influencing survival in transitional cell carcinoma (TCC) of the upper urinary tract, we retrospectively studied 189 (median age 70, 130 males and 59 females) patients who underwent surgical resection at our 3 hospitals from August 1980 to September 2006. After a median follow up of 47.8 months, 45 cases (23.8%) died of cancer and the 5-year and 10-year disease-specific survival rate (Kaplan-Meier method) was 70.5 and 67.1%. Because lymphatic and vascular involvements, pattern of infiltration and location of tumor had loss of data, only the univariate analysis was done. They were observed to be significantly different by the univariate analysis. The significant prognostic factors for survival using Cox-proportional hazard models were tumor stage, tumor grade, lymph node metastasis, and surgical margin status. Adjuvant chemotherapy was not the prognostic factor in our multivariate analysis.

[Neoadjuvant and adjuvant chemotherapy with methotrexate, cisplatin and bleomycin for advanced penile cancer: a case report].

A 58-year-old male consulted our hospital because of penile swelling and pain with bilateral inguinal lymphadenopathy. Pathological examination of the penile tumor and right superficial inguinal lymph node biopsy demonstrated moderately differentiated squamous cell carcinoma with lymph node metastasis. We diagnosed the tumor inoperable radically and adjuvant chemotherapy with methotrexate, cisplatin and bleomycin was administered, followed by partial penectomy and left superficial lymphadenectomy. The surgical specimens showed few viable tumor cells. This combination chemotherapy is suggested to be effective for the treatment of advanced penile cancer.

[Carcinoma of penis: report of 59 cases and review of literature].

PURPOSE: To analyze the characteristics and prognostic factor of penile cancer, we retrospectively reviewed the clinicopathological data of patients with a diagnosis of penile cancer treated. PATIENTS AND METHODS: The records of 59 patients (median age 66, ranged from 47 to 91) with squamous cell carcinoma of the penis reffered between April 1988 and January 2006 were reviewed. The importance of tumor size and stage, differentiation, type of infiltration, vascular invasion, patient age, lymph node metastasis, distant metastasis and type of therapy were assessed using univariate and multivariate analyses. RESULTS: After a mean follow up of 37.7 months, 13 cases (22.0%) died of cancer and 5-year survival was 67.4%. Multivariate analysis demonstrated that, type of operation (p = 0.0471, Hazard ratio 3.364), vascular invasion (p = 0.0014, Hazard ratio 5.921) were associated with survival. CONCLUSION: Vascular invasion and type of operation were related to survival. Our findings indicate that correct pathological diagnosis and appropriate treatment may lead to prolonged survival.