Association of lung immune prognostic index with survival outcomes in patients with metastatic renal cell carcinoma treated with nivolumab plus ipilimumab.

OBJECTIVE: Lung immune prognostic index is based on derived neutrophil-to-lymphocyte ratio and lactate dehydrogenase level. Lung immune prognostic index has reported association with survival outcomes in patients with various malignancies undergoing treatment with immune checkpoint inhibitors. However, the prognostic impact of pre-treatment lung immune prognostic index in patients with metastatic renal cell carcinoma receiving nivolumab plus ipilimumab treatment remains unclear. This study examines the association between lung immune prognostic index and outcomes in this setting. METHODS: We retrospectively evaluated 156 patients with metastatic renal cell carcinoma treated with nivolumab plus ipilimumab at eight institutions. We assessed the associations between pre-treatment lung immune prognostic index and survival outcomes including progression-free survival, second progression-free survival (PFS2), cancer-specific survival and overall survival. RESULTS: Patients were classified into good (n = 84, 54%), intermediate (n = 52, 33%) and poor (n = 20, 13%) lung immune prognostic index groups. Progression-free survival did not significantly differ between lung immune prognostic index groups, but there was significant difference in PFS2, cancer-specific survival and overall survival. In multivariable Cox proportional hazard analyses, high pre-treatment lung immune prognostic index was a significant predictor of poor PFS2 (vs. good group, intermediate group: P = 0.01 and poor group: P = 0.04) and poor overall survival (vs. good group, intermediate group: P = 0.01 and poor group: P < 0.01). Moreover, the patients with poor lung immune prognostic index had significantly poorer cancer-specific survival than those with good LIPI (P < 0.01). CONCLUSIONS: High pre-treatment LIPI is suggested by our results to be a significant independent predictor of poor prognosis in patients receiving nivolumab plus ipilimumab for metastatic renal cell carcinoma.

[A Case of Granulocyte Colony-Stimulating Factor-Related Aortitis that Developed during the Treatment of Advanced Prostate Cancer with Neuroendocrine Differentiation].

An 81-year-old man with prostate cancer (cT3aN0M0), who had been undergoing hormonal therapy for 4 years and had maintained low prostate specific antigen levels, developed metastasized pelvic lymph nodes. A tissue biopsy revealed neuroendocrine differentiation of prostate cancer in the metastatic lymph nodes. Consequently, chemotherapy with carboplatin＋etoposide was initiated. During the first course, filgrastim was administered for 2 days due to a drop in his neutrophil count to 230/µl. During the second course, pegfilgrastim was administered as prophylaxis on day 4. However, on day 10 of the second course, he started to develop a fever and fatigue. Suspecting infection, antibiotics were administered, but failed to ameliorate his symptoms. On day 14, plain computed tomography revealed signs of aortic inflammation. Given the lack of improvement even after one week of antibiotic therapy, steroid treatment was initiated on the suspicion of granulocyte colony-stimulating factor (G-CSF) -induced aortitis, which rapidly improved his symptoms. Therefore, when encountering a case in which a fever remains unresponsive to antibiotics during chemotherapy with G-CSF agents, a differential diagnosis of aortic inflammation caused by G-CSF agents needs to be considered.

Molecular prevalence and zoonotic potential of trichomonads from oral cavities in household dogs.

This study investigated the molecular prevalence of oral trichomonads in household dogs. Of the 144 dogs, 21 (14.6%, 21/144) tested positive for oral trichomonads. The prevalence was significantly higher in dogs with severe gingivitis (gingival index 3: 30.0%, 8/26) than that in normal dogs (gingival index 0: 2.7%, 1/37). Therefore, an interaction between oral trichomonads and the development of periodontal disease is suggested. Of the 21 positive samples, 16 isolates were T. brixi, four isolates were T. tenax, and one was Tetratrichomonas sp. Considering T. tenax is recognized as a zoonotic agent, transmission between dogs and humans cannot be neglected.

[A Consideration for the Surgical Approach in Laparoscopic Total Pelvic Exenteration after Radiotherapy : A Case Report].

A 66-year-old woman underwent concurrent chemoradiotherapy (CCRT) for stage IIA cervical cancer. However, two recurrent masses were detected at the vaginal stump 6 years after CCRT, and we performed laparoscopic total pelvic exenteration to obtain a complete cure. Because the terminal ileum appeared white secondary to the effects of radiotherapy, we constructed an ileal conduit using the ileum, approximately 40 cm toward the mouth from the ileocecum. We performed transperineal resection of the vagina and urethra and intersphincteric resection as anal-preservation surgery along with transverse colostomy. We used a right short gracilis myocutaneous flap to reconstruct the pelvic floor and perineum. The operation time was 816 min, and the estimated blood loss was 1,168 ml. On histopathological examination of the resected specimen, the parauterine tissue showed a positive surgical margin. Patients with recurrent cervical cancer after CCRT show poor prognosis. Complete resection with a negative margin is associated with more favorable prognosis in patients with recurrent pelvic masses. Compared with an open procedure, laparoscopic pelvic exenteration is safe and feasible in these patients. Selection of an optimal surgical approach, urinary diversion, and pelvic floor reconstruction is important for complete resection and prevention of perioperative complications.

[Spontaneous Resolution of Renal Artery Pseudoaneurysm after Robotic-Assisted Partial Nephrectomy].

Partial nephrectomy (PN) for small renal tumors has become increasingly common. Complications of PN include renal artery pseudoaneurysm (PA), a potentially life-threatening condition. However, the true incidence and natural history of PA after PN remain unclear. Therefore, we conducted a retrospective study of the radiographic characteristics of robotic-assisted partial nephrectomy (RAPN) observed during the postoperative period. We selected 36 consecutive patients with renal carcinoma who underwent RAPN at our institution between December 2016 and May 2019. Patients with contraindications for the use of contrast medium were excluded. A total of 31 eligible patients underwent computed tomography angiography (CTA) during the early postoperative period after RAPN and the incidence of PA was evaluated. Among the patients with PASs, asymptomatic PAs were followed without intervention and their clinical course was assessed using CTA at 1 to 3 months postoperatively. PA was identified in 5 out of 31 (16.1%) patients after RAPN. Median duration between PN and the first CTA was 6 days (range, 1-8). Median PA size was 13 mm (range, 8-17). All (100%) PAs were asymptomatic and resolved spontaneously, as verified by CTA during the late postoperative period. Median duration between identification of PA on early postoperative CTA and subsequent resolution was 92 days (range, 35-106). Our findings indicated that asymptomatic PA after PN can be followed without intervention.

[Needle Lost during Robot-Assisted Laparoscopic Radical Prostatectomy : A Case Report].

A 66-year-old man, who presented with prostate cancer, underwent robot-assisted laparoscopic radical prostatectomy. During surgery, a suture needle was lost after an assistant surgeon removed it from the AirSeal® access port. We were not able to find the needle using a portable radiograph with no contrast optimization. After disassembling the device, the needle was found in the groove of the port top. It should be acknowledged that the needle can become stuck in the AirSeal® port, even though it does not have a valve structure. An X-ray radiograph, with an appropriate gradation setting could be useful to retrieve suture needles.

The third national Japanese antimicrobial susceptibility pattern surveillance program: Bacterial isolates from complicated urinary tract infection patients.

The antimicrobial susceptibility patterns of bacterial pathogens isolated from patients with complicated urinary tract infections were analyzed using national surveillance data. The data consisted of 881 bacterial strains from eight clinically relevant species. The data were collected for the third national surveillance project from January 2015 to March 2016 by the Japanese Society of Chemotherapy, the Japanese Association for Infectious Disease, and the Japanese Society of Clinical Microbiology. Surveillance was undertaken with the cooperation of 41 medical institutions throughout Japan. Fluoroquinolone required a MIC90 of 2-64 mg/L to inhibit the 325 Escherichia coli strains tested and the proportion of levofloxacin resistant E. coli strains increased to 38.5% from 29.6% in 2011 and 28.6% in 2008. The proportion of levofloxacin resistant strains of Pseudomonas aeruginosa and Enterococcus faecalis decreased from previous reports and the proportion of multidrug-resistant P. aeruginosa and carbapenem-resistant Enterobacteriaceae remained low. Among methicillin-resistant Staphylococcus aureus (MRSA) strains, strains with reduced susceptibility to vancomycin (minimum inhibitory concentration, 2 µg/mL) increased to 14.7% from 5.5%. Bacterial strains that produced extended-spectrum ß-lactamase included E. coli (79 of 325 strains, 24.3%), Klebsiella pneumoniae (9 of 177 strains, 7.7%), and Proteus mirabilis (6 of 55 strains, 10.9%). The proportion of extended-spectrum ß-lactamase producing E. coli and K. pneumoniae strains increased from previous surveillance reports.

Feasibility of laparoscopic adrenalectomy for metastatic adrenal tumors in selected patients: a retrospective multicenter study of Japanese populations.

BACKGROUND: Because of the small numbers of cases in single centers, the indications for and survival benefits of adrenalectomy for adrenal metastasis remain unclear. We evaluated the outcomes of laparoscopic adrenalectomy for patients with adrenal metastasis. METHODS: We retrospectively analyzed the records of 67 patients who underwent laparoscopic adrenalectomy for metastatic disease from 2003 to 2017 at 11 hospitals. Associations of clinical, surgical, and pathologic features with overall survival (OS) and positive surgical margins were evaluated using univariate and multivariate Cox regression analyses and univariate logistic regression analysis. RESULTS: Lung cancer (30%) and renal cell carcinoma (30%) were the most common primary tumor types. Intraoperative complications were observed in seven patients (10%) and postoperative complications in seven (10%). The surgical margin was positive in 10 patients (15%). The median OS was 3.8 years. Univariate analysis showed that the tumor size, episodes of extra-adrenal metastasis before adrenalectomy, extra-adrenal metastasis at the time of adrenalectomy, and positive surgical margins were significantly associated with shorter OS (p = 0.022, p = 0.005, p < 0.001, and p = 0.022, respectively). Multivariate analysis showed that extra-adrenal metastasis at the time of adrenalectomy and positive surgical margins remained statistically significant (p = 0.022 and p = 0.049, respectively). In the univariate analysis, the tumor size was significantly associated with positive surgical margins (p = 0.039). CONCLUSIONS: Laparoscopic adrenalectomy for adrenal metastasis can be safely performed in selected patients, and patients with isolated adrenal metastasis and negative surgical margins seem to have more favorable outcomes.

Impact of tumor size on patient survival after radical nephrectomy for pathological T3a renal cell carcinoma.

PURPOSE: We recently reported the results from a multi-institutional retrospective outcome study involving 814 patients with renal cell carcinomas (RCCs) who had undergone radical surgery and whose diagnoses were confirmed via a central pathological review. This study aimed to clarify the impact of tumor size on survival outcomes in patients with pT3aN0M0 RCC after radical nephrectomy using this cohort. METHODS: Using the Kaplan-Meier method, overall survival (OS), cancer-specific survival (CSS) and relapse-free survival (RFS) were estimated for 103 pT3aN0M0 patients. The differences in the OS, CSS and RFS according to tumor size were evaluated using the log-rank test. To identify independent prognostic factors that affected each survival outcome, clinicopathological factors were examined using univariate and multivariate analyses, and the Cox proportional hazards model. RESULTS: The OS, CSS and RFS rates for 26 patients with pT3a RCCs ≤4 cm were significantly better than those for 77 patients with pT3a RCCs that were 4-7 cm or >7 cm (P = 0.0064, 0.0169 and 0.0001, respectively). Tumor size and venous invasion were independent prognosticators for OS, CSS and RFS. The OS and CSS for patients with pT3a tumors ≤4 cm were comparable with those for patients with pT1 RCCs, and the RFS for patients with pT3a RCCs ≤4 cm was similar to that for patients with pT1b RCCs. CONCLUSIONS: Tumor size significantly influenced the prognosis for patients with pT3aN0M0 RCC. This study's results suggest that the postoperative management of pT3a RCCs could be individualized according to tumor size.

Asymmetric oxidation of 1,3-propanediols to chiral hydroxyalkanoic acids by Rhodococcus sp. 2N.

Rhodococcus sp. 2N was found as a 1,3-propanediols-oxidizing strain from soil samples through enrichment culture using 2,2-diethyl-1,3-propanediol (DEPD) as the sole carbon source. The culture condition of the strain 2N was optimized, and the highest activity was observed when 0.3% (w/v) DEPD was added in the culture medium as an inducer. Chiral HPLC analysis of the hydroxyalkanoic acid converted from 2-ethyl-2-methyl-1,3-propanediol (EMPD) revealed that the strain 2N catalyzed the (R)-selective oxidation of EMPD. The reaction products and intermediates from DEPD and EMPD were identified by nuclear magnetic resonance analyses, and the results suggested that only one hydroxymethyl group of the propanediols was converted to carboxy group via two oxidation steps. Under optimized conditions and after a 72-h reaction time, the strain 2N produced 28 mM (4.1 g/L) of 2-(hydroxymethyl)-2-methylbutanoic acid from EMPD with a molar conversion yield of 47% and 65% ee (R).

[Use of Vacuum-Assisted Closure Therapy in the Treatment of Postoperative Inguinal Lymphocele after Lymphadenectomy for a Vulvar Apocrine Adenocarcinoma : A Case Report].

A 79-year-old man with vulvar apocrine adenocarcinoma and right inguinal lymph node metastasis underwent wide excision and free skin graft reconstruction of the primary lesion and right inguinal lymphadenectomy. However, left inguinal lymph node metastasis was noted after 11 months, and left inguinal lymphadenectomy was performed. Twelve days postoperatively, the patient developed left inguinal lymphocele. The lymphocele was drained percutaneously and compressed, but lymph secretion persisted and lymphocele skin necrosis was observed. Therefore, debridement and vacuum-assisted closure (VAC) therapy were performed in cooperation with the department of plastic surgery. Subsequently, lymph secretion declined and eventually stopped. The lymphocele scar was reconstructed with a free skin graft, and after further observation for 8 months, right lymph node swelling was noted. Nevertheless, on the left inguinal site, neither lymphocele recurrence nor inguinal lymph node metastasis was observed. In conclusion, VAC therapy might be beneficial in the treatment of postoperative inguinal lymphocele after lymphadenectomy.

[The Safety of Laparoscopic Radical Cystectomy during Initial Phases in a Japanese Multicenter Cohort].

We evaluated the safety of laparoscopic radical cystectomy (LRC) during initial phases and its learning curve in a Japanese multicenter cohort by studying 436 patients who underwent LRC with no robot assistance at 10 institutions in Japan. We divided the patients into three groups according to cumulative surgical volume at each institution (first 10 cases, 11-30 cases, after 31 cases in each institution), and compared perioperative and pathologic variables among the three groups. The first, second, and third groups included 100, 166, 170 patients, respectively. The preoperative variables were similar in the three groups except for the rate of neoadjuvant chemotherapy. The methods of LRC procedure, such as urinary diversion, the extent of lymph node dissection, and concomitant urethrectomy or nephroureterectomy, were similar in the three groups. Mean operative time was 629, 562 and 531 minutes, respectively, and mean blood loss was 755, 650 and 435 ml, respectively. Both values decreased over time with the institution's experience. There was no significant difference among the three groups in the rate of positive surgical margin, the number of retrieved lymph nodes, and the rate of intra- and postoperative complications. LRC was safely performed during initial phases with an acceptable complication rate and without compromising oncological results, although operative time was longer and blood loss increased.

[Distant Metastasis in Patients with Non-Muscle Invasive Bladder Cancer without Local Recurrence : Report of Two Rare Cases].

Distant metastasis is rare in patients with non-muscle invasive bladder cancer (NMIBC). We describe two cases of NMIBC with distant metastasis diagnosed in the follow-up period after transurethral resection (TUR), with neither intravesical recurrence nor progression to muscle-invasive disease. Case 1 : A 77-yearold man was referred to our hospital for treatment of a bladder tumor with the complaint of asymptomatic gross hematuria. TUR of the bladder tumor was performed. Pathological examination revealed high grade urothelial carcinoma pT1. Second TUR was performed and pathological examination confirmed high grade urothelial carcinoma pT1 with lymphovascular invasion. The patient received standard BCG therapy and subsequently developed left leg pain and lumbago 10 months after initial diagnosis. Magnetic resonance imaging, computed tomography, and bone scintigraphy demonstrated no local recurrence, but revealed multiple bone and liver metastases. The patient died 15 months after initial diagnosis. Case 2 : A 70-year-old man was referred to our hospital for treatment of an incidental bladder tumor. TUR of the bladder tumor was performed and pathological examination confirmed high grade urothelial carcinoma pT1. Second TUR was performed and pathological examination revealed no residual tumor cells. 18Fflurodeoxyglucose (FDG) positron emission tomography/computed tomography confirmed increasing uptake of 18F-FDG in the retroperitoneal lymph nodes, 18 months after initial diagnosis. The patient underwent laparoscopic lymphadenectomy. Pathological examination demonstrated metastasis of the bladder cancer. Combined chemotherapy was initiated with gemcitabine and cisplatin consecutively. To date the patient survives without progression or new distant metastases after four cycles of chemotherapy.

[Misdirection of an Indwelling Urethral Catheter into the Ureter in a Female Patient with Neurogenic Bladder : A Case Report].

We report a case of misdirection of an indwelling urethral catheter into the ureter. An 86-year-old women with neurogenic bladder had been undergoing chronic indwelling urethral catheter exchange for 1 year. She was referred to our hospital owing to lower abdominal pain and gross hematuria. A computed tomographic scan showed an indwelling urethral catheter in the right ureter. Retrograde ureterography showed that the ureter had no leakage and the catheter was removed under fluoroscopic guidance. Urethral catheterization is a common procedure. We reviewed 23 cases of an indwelling urethral catheter entering the ureter and we consider that this misdirection occurs particularly among female patients with neurogenic bladder.

[Two Cases of Inflammatory Myofibroblastic Tumor of the Urinary Bladder].

We describe two cases of inflammatory myofibroblastic tumor (IMT) of the urinary bladder. Case 1 : A 55-year-old man complained of urinary frequency. Transurethral biopsy of the bladder tumor was performed ; pathological examination revealed IMT. After steroid therapy for 1 year, the tumor was markedly reduced in size. Laparoscopic partial cystectomy was performed. The patient has now been free from recurrence for 3 years after the surgery. Case 2 : A 61-year-old man presented with gross hematuria. Transurethral biopsy of the bladder tumor revealed IMT. Despite steroid therapy for 6 months, the tumor size increased. Laparoscopic partial cystectomy and vesicoureteroneostomy were performed. The patient has now been free from recurrence for 1 year and 11 months after the surgery. IMT of the urinary bladder often responds well to steroid therapy. We experienced two cases of IMT. One showed a good response to steroid therapy and the other showed a poor response to steroid therapy. In both cases, we performed laparoscopic partial cyctectomy and the patients have remained free from recurrence IMT of the urinary bladder may have a good prognosis after complete surgical resection.

[Lymph Node Metastasis to the Prostatic Anterior Fat Pad in the Patients Treated with Prostatectomy].

We investigated the prostatic anterior fat pad (PAFP) for the presence of lymph nodes and lymph node metastases after excision during radical prostatectomy for the treatment of prostate cancer. From November 2013 to May 2017, 215 patients underwent radical prostatectomy for localized prostate cancer at our institution. PAFP was removed and sent for pathological analysis routinely to evaluate the presence of lymph nodes and lymph node metastases. Of the 215 patients, 20 (9.3%) had lymph nodes in the PAFP. Among the 20 patients with lymph nodes in the PAFP, 2 patients (10.0% ; 0.9% of all patients) were positive for metastatic prostate cancer. These patients did not have positive nodes elsewhere among the pelvic lymph nodes. There was no significant difference in the clinicopathological features between the patients with lymph nodes in the PAFP and those with no lymph nodes in the PAFP. The present findings are similar to those in the Western population. Considering the very low rate of lymph node metastasis in PAFP, it is necessary to discuss which patients should be selected for pathological analysis of PAFP.

[A Case of Primary Sigmoid Colon Lymphoma Presenting with Sigmoidovesical Fistula in a Patient with a Long History of Ulcerative Colitis].

A 73-year-old male patient with a 16-year history of ulcerative colitis presented to our hospital with a history of pneumaturia and fever. Cystoscopy and a computed tomography scan showed sigmoidovesical fistula. Colonoscopy showed a necrotic tumor along with sigmoidovesical fistula. A biopsy was not sufficient to make a definitive diagnosis of the tumor. Total colectomy with ileostomy and partial cystectomy were performed. A pathological examination showed diffuse large B-cell lymphoma of the sigmoid colon. On postoperative day 35, delayed dehiscence of the bladder wall was detected and a biopsy of the bladder wall showed lymphoma. Standard systemic chemotherapy (R-THP-COP) was administered and the defect of the bladder was closed. Three years and 2 months postoperatively, the patient has no local recurrence or distant metastasis.

[An Increase in Cases of Bladder Tamponade Due to Cystitis Among Elderly Women and Clinical Background Factors].

Bladder tamponade is thought to be caused mainly by bladder cancer or radiation cystitis. However, in women, it may often be caused by cystitis in clinical settings. This has not been noted in previous reports of bladder tamponade in Japan. Thus, we retrospectively analyzed the clinical features of 83 male and 41 female patients with bladder tamponade. Seventy-four patients were treated at Nishi-Kobe Medical Center between April 2005 and March 2015, and 50 were treated at Shizuoka City Shizuoka Hospital between November 2008 and March 2015. The patients'median age was 80 years. The cause of bladder tamponade was urological malignancies in 33 of the 83 male patients (40%), benign prostatic hyperplasia in 20 of the 83 male patients (24%), and cystitis in 33 of the 41 female patients (80%). Compared with the men, the women with bladder tamponade were significantly older and the proportion of patients with cerebrovascular disease, diabetes, and dementia was higher. In addition, more women were nursing home residents, with a higher rate of voiding with diapers and antithrombotic use than men. Causative strains of cystitis were diverse, and some were antibiotic resistant. Most of the cases of bladder tamponade in the women occurred in the elderly and were caused by cystitis. In an aging society, increases in the incidences of chronic, complicated cystitis due to impaired independent micturition, dysuria, and systemic diseases such as diabetes, and increased use of antithrombotic drugs may contribute to bladder tamponade in women.

[A Case of Hyperammonemia Caused by Urinary Tract Infection Due to Urease-Producing Bacteria].

We present here a rare case of hyperammonemia without liver dysfunction or portal-systemic shunting. The patient was an 80-year-old woman with a history of neurogenic bladder. She was admitted to a nearby hospital for vomiting, diarrhea and consciousness disturbance. Two days after admission, she was transferred to our hospital because of persistant consciousness disturbance. Laboratory data revealed hyperammonemia, but there was no indication of liver dysfunction. Moreover abdominal computed tomography did not reveal any clear finding of liver disease or portal-systemic shunting, but we noted multiple large bladder diverticula. Antibiotic therapy, tracheal intubation, ventilator management and bladder catheterization were performed. The patient's level of consciousness improved rapidly. Urinary culture revealed Bacteroides ureolyticus (urease-producing bacteria). The patient was diagnosed with hyperammonemia and a urinary tract infection due to urease-producing bacteria. Thus, physicians should be aware that obstructive urinary tract infections due to urease-producing bacteria can also be the cause of hyperammonemia.

[A Case of ACD-Associated RCC with Lymph Node Metastasis and Contralateral Renal Carcinoma after Nephrectomy].

A 59-year-old man who had undergone hemodialysis for 13 years was diagnosed with left renal cell carcinoma (RCC),cT1aN0M0,in 2010. He had a laparoscopic left nephrectomy,and the pathological diagnosis at that time was clear cell carcinoma,pT1a (multifocal). At 1 year after surgery,he was diagnosed with a left renal hilar lymph node metastasis and a new right RCC,cT1aN0M0. Consequently,he underwent a right nephrectomy and retroperitoneal lymph node dissection in 2012. Pathologic diagnosis by the current classification of the right renal tumor was acquired cystic disease-associated renal cell carcinoma (ACD-associated RCC),and that of the left hilar lymph node was metastatic RCC with sarcomatoid change. According to the revised classification the pathological diagnosis of the left renal tumor was ACD-associated RCC. There has been no evidence of recurrence or metastasis for 3 years after the second operation. The specific classification of dialysis-related renal tumors and their characteristics should be standard knowledge for urologists.