[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.

Expression of androgen receptor in non-muscle-invasive bladder cancer predicts the preventive effect of androgen deprivation therapy on tumor recurrence.

Our recent retrospective study revealed a significantly reduced risk of bladder cancer (BC) recurrence in men who received androgen deprivation therapy (ADT) for their prostate cancer. However, whether androgen receptor (AR) signals contributed to the preventive effect of ADT remained unclear because ADT could reduce serum estrogens as well. The purpose of this study is to investigate the associations between the expression of AR/estrogen receptors (ERs) and BC recurrence in patients treated with ADT. We immunohistochemically stained 72 BCs and 42 corresponding normal urothelial tissues. AR/ERα/ERß were positive in 44(61%)/22(31%)/39(54%) tumors and 35(83%)/24(57%)/34(81%) corresponding normal urothelial tissues, respectively. There were no statistically significant correlations between AR/ERα/ERß expression and clinicopathological features of BC. With a median follow-up of 31.3 months, 12 (43%) of 28 patients with AR-negative tumor versus 11 (23%) of 44 patients with AR-positive tumor experienced BC recurrence. Thus, patients with AR-positive tumor had a significantly lower risk of BC recurrence (P=0.031), compared with those with AR-negative tumor. Meanwhile, the expression of ERα/ERß in tumors and that of AR/ERα/ERß in normal urothelial tissues were not significantly correlated with BC recurrence. A multivariate analysis revealed AR positivity in tumors as an independent prognosticator (hazard ratio: 0.27; 95% confidence interval: 0.11-0.67) for BC recurrence. These results indicate that ADT prevents BC recurrence via the AR pathway, but not via the ERα/ERß pathways.

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.

[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 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.

Androgen deprivation therapy prevents bladder cancer recurrence.

Although accumulating preclinical evidence indicates the involvement of androgen receptor signals in bladder cancer (BC) development, its clinical relevance remains unclear. We aimed to evaluate the predictive role of androgen deprivation therapy (ADT) in BC recurrence in prostate cancer (PC) patients. We retrospectively reviewed 20,328 patients with PC diagnosed during 1991-2013 and identified 239 (1.2%) men having primary BC. After excluding ineligible patients, 162 patients made up a final cohort. With a median follow-up of 62 months, 38 (50%) of 76 control patients without ADT experienced BC recurrence, while 19 (22%) of 86 did in ADT group. Thus, patients having received ADT for their PC showed a significantly lower risk of BC recurrence (5-year actuarial recurrence-free survival: 76% v 40%; P < 0.001) and also had a significantly smaller number of recurrence episodes (5-year cumulative recurrence: 0.44 v 1.54; P < 0.001), compared to the control patients. A multivariable analysis revealed ADT as an independent prognosticator (hazard ratio, 0.29; 95% confidence interval, 0.17-0.49) for BC recurrence. This is the first clinical study showing that ADT significantly reduces the risk of BC recurrence.

[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 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.

An evaluation to define the role of repeat transurethral resection in a treatment algorithm for non-muscle-invasive bladder cancer.

OBJECTIVE: Repeat transurethral resection (ReTUR) is an effective treatment for non-muscle-invasive bladder cancer (NMIBC) to prevent disease recurrence or progression. It also has an important role in stratifying patients according to histopathological results. Therefore, the end point of ReTUR should be considered in a treatment algorithm. We evaluated positive ReTUR to define its role in a treatment algorithm for NMIBC. MATERIALS AND METHODS: A second TUR was performed in 111 patients between July 2006 and February 2010. A third TUR was performed in 31 patients with T1/a/is tumors at the second TUR. The incidence of residual disease was calculated according to the NMIBC risk levels proposed by the International Bladder Cancer Group. We used ReTUR as a general term to indicate second and third TURs. RESULTS: Residual disease at the second TUR was detected in 51% of the patients; it was observed in 17%, 45%, and 65% patients in the low-, intermediate-, and high-risk disease groups, respectively (P = 0.01). Residual disease at the third TUR was detected in 48% patients; it was observed in 18% and 65% patients in the intermediate- and high-risk disease groups, respectively (P = 0.06). CONCLUSION: The incidence of residual disease correlated with the risk levels for NMIBC. In the intermediate-risk disease group, nearly complete resection was accomplished after the third TUR. However, in the high-risk disease group, a high incidence of residual disease was identified even after the third TUR. Our results provide important data that may be useful in establishing an end point in a treatment algorithm for NMIBC.

[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.

Plasma free amino acid profiling of five types of cancer patients and its application for early detection.

BACKGROUND: Recently, rapid advances have been made in metabolomics-based, easy-to-use early cancer detection methods using blood samples. Among metabolites, profiling of plasma free amino acids (PFAAs) is a promising approach because PFAAs link all organ systems and have important roles in metabolism. Furthermore, PFAA profiles are known to be influenced by specific diseases, including cancers. Therefore, the purpose of the present study was to determine the characteristics of the PFAA profiles in cancer patients and the possibility of using this information for early detection. METHODS AND FINDINGS: Plasma samples were collected from approximately 200 patients from multiple institutes, each diagnosed with one of the following five types of cancer: lung, gastric, colorectal, breast, or prostate cancer. Patients were compared to gender- and age- matched controls also used in this study. The PFAA levels were measured using high-performance liquid chromatography (HPLC)-electrospray ionization (ESI)-mass spectrometry (MS). Univariate analysis revealed significant differences in the PFAA profiles between the controls and the patients with any of the five types of cancer listed above, even those with asymptomatic early-stage disease. Furthermore, multivariate analysis clearly discriminated the cancer patients from the controls in terms of the area under the receiver-operator characteristics curve (AUC of ROC >0.75 for each cancer), regardless of cancer stage. Because this study was designed as case-control study, further investigations, including model construction and validation using cohorts with larger sample sizes, are necessary to determine the usefulness of PFAA profiling. CONCLUSIONS: These findings suggest that PFAA profiling has great potential for improving cancer screening and diagnosis and understanding disease pathogenesis. PFAA profiles can also be used to determine various disease diagnoses from a single blood sample, which involves a relatively simple plasma assay and imposes a lower physical burden on subjects when compared to existing screening methods.

[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.

[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.