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Objective To clarify the prognostic impact of local radiotherapy on metastatic urothelial carcinoma patients treated by systemic chemotherapy. Methods Of the 228 metastatic urothelial carcinoma patients treated with systemic chemotherapy, 97 received radiotherapy mainly to metastatic sites. In patients for whom the purpose of radiotherapy was not specified, more than 50 Gy irradiation was considered to be for disease consolidation for survival analysis, while less than 50 Gy was categorized as palliation. According to the Kaplan–Meier method, we analysed overall survival from the initiation of treatment for metastatic urothelial carcinoma until death or the last follow-up, using the log-rank test to assess the significance of differences. The Cox model was applied for prognostic factor analysis. Results Overall, there was no significant difference in survival between patients with and those without radiotherapy (P = 0.1532). When analysing the patients undergoing consolidative radiotherapy separately, these 25 patients showed significantly longer survival than the 72 patients with palliative radiotherapy (P = 0.0047), with a 3-year overall survival of 43.3%. Of the present cohort, 22 underwent metastasectomy for disease consolidation, and there was no overlapping case between the metastasectomy cohort and cohort receiving consolidative radiotherapy. After controlling for four independent prognostic factors (sex, performance status, haemoglobin level and number of organs with metastasis) in our previous study, radiotherapy for disease consolidation showed a marginal value (hazard ratio = 0.666, P = 0.0966), while metastasectomy remained significant (hazard ratio = 0.358, P = 0.0006). Conclusions In the selected patients, long-term disease control could be achieved after consolidative radiotherapy for metastatic urothelial carcinoma disease. Our observations suggest that local ablative therapy (surgery or radiotherapy) could facilitate long-term disease control. However, the treatment decision should be individualized because of the lack of randomized control trials.

In selected patients, long-term systemic chemotherapy could be performed with a 1–3-month drug-free interval. Our maintenance strategy with cytotoxic drugs may become one of the options for long-term disease control., Objective Aiming to achieve long-term disease control, maintenance systemic chemotherapy (MSC) with a 1–3-month drug-free interval is continued in selected patients. We report our experience of MSC for metastatic urothelial carcinoma (UC). Methods Of 228 metastatic UC patients treated with systemic chemotherapy, 40 (17.5%, 40/228) had continuously undergone MSC. Data on the regimen, cycle number, and reason for the discontinuation of MSC were also collected. We analyzed OS from the initiation of MSC until death or the last follow-up, using the log-rank test to assess the significance of differences. Results The median number of cycles of chemotherapy was 6, and the responses were CR in 6, PR in 20, SD in 13, and PD in 1 before MSC. Gemcitabine plus CDDP or carboplatin was mainly performed as MSC (70%, 28/40). MSC was repeated quarterly in 30 (75%, 30/40), every two months in 8 (20%, 8/40), and with other intervals in 2 (5%, 2/40). Overall, a median of 3.5 cycles (range: 1–29) of MSC was performed. The reason for the discontinuation of MSC was PD in 24 (60%, 24/40), favorable disease control in 9 (22.5%, 9/40), and myelosuppression in 3 (7.5%, 3/40), and for other reasons in 2 (5%, 2/40). MSC was ongoing in 2 (5%, 2/40). The median OS was 27 months from the initiation of MSC. PS0 (P = 0.0169), the absence of lung metastasis (P = 0.0387), and resection of the primary site (P = 0.0495) were associated with long-term survival after MSC. Conclusions In selected patients, long-term systemic chemotherapy could be performed with a drug-free interval. Our maintenance strategy with cytotoxic drugs may become one of the treatment options for long-term disease control.

Objectives: With the emergence of several effective combination therapies, information on their effects at the primary site will be crucial for planning future cytoreductive nephrectomy (CN). The present study focused exclusively on changes in primary tumor sizes following treatment with nivolumab plus ipilimumab and investigated the clinical factors associated with a good response in primary tumors. Methods and materials: We retrospectively assessed 27 patients diagnosed with advanced renal cell carcinoma (RCC) who started treatment with nivolumab plus ipilimumab. Changes in tumor sizes at the primary site were described using waterfall and spider plots, respectively. We analyzed the correlation of tumor shrinkage between primary and metastatic site. The parameters analyzed between responders and non-responders according to primary tumor sizes were International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk scores, peripheral blood markers, and CRP. Results: The median age and follow-up period were 66 years and 9.3 months, respectively. The median IMDC risk score was 3 (range: 1-6). Nineteen patients were diagnosed with clear-cell RCC (ccRCC) and 8 patients with non-ccRCC. Among ccRCC patients, 9 (47.4%) achieved a significant response with a maximum reduction of 30% or more in the size of the primary tumor from baseline within 4 months, while 3 (37.5%) out of 8 patients with non-ccRCC achieved a significant response. Shrinkage of the primary tumor correlated with the metastatic tumors in both ccRCC and non-ccRCC cases. Of note, 6 patients underwent CN and no viable tumor cells were detected in the surgical specimens of 3 patients whose primary tumors shrank by approximately 50%-60% with a reduction to 4 cm or less. Among ccRCC patients, the neutrophil-to-lymphocyte ratio and monocyte-to-lymphocyte ratio were slightly lower in responders than in non-responders (P = 0.0944 and P = 0.0691). The platelet-to-lymphocyte ratio was significantly lower in responders than in non-responder (P = 0.0391). Conclusions: Significant responses in primary tumors to nivolumab plus ipilimumab were observed in 50% of ccRCC patients, while responses varied among non-ccRCC patients. Inflammation markers may be predictive factors of treatment responses in primary tumors. Although further studies are needed, the present results suggest the importance of considering CN from radiological and pathological viewpoints. (C) 2021 The Authors. Published by Elsevier Inc.

Background: It is hypothesised that simulation enhances progression along the initial phase of the surgical learning curve. Objective: To evaluate whether residents undergoing additional simulation, compared to conventional training, are able to achieve proficiency sooner with better patient outcomes. Design, setting, and participants: This international, multicentre, randomised controlled trial recruited 94 urology residents with experience of zero to ten procedures and no prior exposure to simulation in ureterorenoscopy, selected as an index procedure. Intervention: Participants were randomised to simulation or conventional operating room training, as is the current standard globally, and followed for 25 procedures or over 18 mo. Outcome measurements and statistical analysis: The number of procedures required to achieve proficiency, defined as achieving a score of ≥28 on the Objective Structured Assessment of Technical Skill (OSATS) scale over three consecutive operations, was measured. Surgical complications were evaluated as a key secondary outcome. This trial is registered at www.isrctn.com as ISCRTN 12260261. Results and limitations: A total of 1140 cases were performed by 65 participants, with proficiency achieved by 21 simulation and 18 conventional participants over a median of eight and nine procedures, respectively (hazard ratio [HR] 1.41, 95% confidence interval [CI] 0.72–2.75). More participants reached proficiency in the simulation arm in flexible ureterorenoscopy, requiring a lower number of procedures (HR 0.89, 95% CI 0.39–2.02). Significant differences were observed in overall comparison of OSATS scores between the groups (mean difference 1.42, 95% CI 0.91–1.92; p < 0.001), with fewer total complications (15 vs 37; p = 0.003) and ureteric injuries (3 vs 9; p < 0.001) in the simulation group. Conclusions: Although the number of procedures required to reach proficiency was similar, simulation-based training led to higher overall proficiency scores than for conventional training. Fewer procedures were required to achieve proficiency in the complex form of the index procedure, with fewer serious complications overall. Patient summary: This study investigated the effect of simulation training in junior surgeons and found that it may improve performance in real operating settings and reduce surgical complications for complex procedures.

We revealed prognostic factors in metastatic urothelial carcinoma patients treated with second-line systemic chemotherapy in real-world clinical practice. Performance status, C-reactive protein level and response to prior chemotherapy were prognostic indicators., Objectives The objective of the present study was to investigate the survival outcome and prognostic factors of metastatic urothelial carcinoma patients treated with second-line systemic chemotherapy in real-world clinical practice. Methods Overall, 114 patients with metastatic urothelial carcinoma undergoing second-line systemic chemotherapy were included in this retrospective analysis. The dominant second-line chemotherapy was a paclitaxel-based combination regimen (60%, 68/114). We assessed the progression-free survival and overall survival times using the Kaplan–Meier method. The Cox proportional hazards model was applied to identify the factors affecting overall survival. Results The median progression-free survival and overall survival times were 4 and 9 months, respectively. In the multivariate analysis, an Eastern Cooperative Oncology Group performance status score greater than 0 at presentation, C-reactive protein level ≧1 mg/dl and poor response to prior chemotherapy were adverse prognostic indicators. Patients with 0, 1, 2 and 3 of those risk factors had a median overall survival of 17, 12, 7 and 3 months, respectively. Conclusions The Eastern Cooperative Oncology Group performance status at presentation, C-reactive protein level and response to prior chemotherapy were prognostic factors for metastatic urothelial carcinoma patients undergoing second-line chemotherapy. In the future, this information might help guide the choice of salvage treatment, such as second-line chemotherapy or immune checkpoint inhibitors, after the failure of first-line chemotherapy.

Objectives: During the past 2 decades, in order to improve perioperative and ontological outcomes, a minimally invasive approach, neoadjuvant chemotherapy (NAC), and an enhanced postoperative recovery program after surgery have been introduced into routine clinical practice of radical cystectomy (RC). Our aim was to examine the differences in clinical practice and postoperative complications after RC by comparing our previous and current cohorts. Materials and methods: A retrospective multi-institutional study. We collected all complications within 90 days after surgery between 2011 and 2017 (current cohort), and categorized them according to a standardized methodology. Then, we compared the outcomes with those in our previous study (previous cohort, 1997-2010). A multivariate logistic regression model was utilized to determine predictors of complications in the current cohort. Results: A total of 838 patients were newly collected (current cohort), and 919 from the previous cohort were included in the subsequent analyses. In the current cohort, the rate of performing NAC was significantly higher (13% vs. 4%, respectively, P < 0.0001), and 26% (222/ 838) underwent laparoscopic RC (LRC, without robotic assistance: n = 210, with robotic assistance: n = 12). There was no significant difference in the overall complication [69% (580/838) vs. 68% (629/919), respectively, P = 0.7284] or major complication (Grades 3-5) [25% (211/838) vs. 22% (201/919), respectively, P = 0.1022] rates between the 2 cohorts. In both cohorts, the most frequent categories were infectious, gastrointestinal, wound-related, and genitourinary. In the current cohort, the performance status (odds ratio, OR = 2.11, P = 0.0013) and operative time (OR = 1.003, P = 0.0016) remained significant predictors of major complications. NAC was not associated with any or major complications. Conclusions: Surgical complications related to RC still remain significant problems, despite the recent improvements in surgical techniques and perioperative care. NAC did not increase the complications. (C) 2021 The Authors. Published by Elsevier Inc.

There have been few reports on the effects of everolimus on the fetus, but none of six infants with documented everolimus exposure in utero had congenital malformations. A 32-year-old nulliparous woman on everolimus (5.0 mg/day) for renal angiomyolipoma (AML) due to tuberous sclerosis complex (TSC) was found to be pregnant at gestational week (GW) 7-5/7, at which time everolimus was withheld. To control AML in this patient, transarterial embolization was performed in the right and left kidneys at GW 21 and 24, respectively, and everolimus was reinitiated at GW 25. The patient gave birth at GW 37 to a normally formed infant weighing 3057 g, but who had cardiac tumors thought to be rhabdomyomas due to inherited TSC. Thus, although data are still limited, everolimus may be promising with respect to teratogenicity. Everolimus concentration in the maternal and umbilical cord blood at birth was 1.1 ng/mL and 1.0 ng/mL, respectively.

To determine the appropriate template of regional lymph node dissection (LND) at the time of laparoscopic nephroureterectomy (LNU) for patients with clinically node- negative urothelial carcinoma of the upper urinary tract.This prospective study included 45 patients undergoing LND with LNU in accordance with our prospective rules regarding the area of LND. Perioperative, pathologic, and follow-up data were collected. Micrometastasis in lymph nodes (LNs) was later evaluated by immunohistochemistry (IHC). Recurrence-free survival (RFS) was calculated with the Kaplan-Meier method.The median number of LNs removed was 14 (range 1-33). One patient with pT3 disease had node metastasis based on routine pathologic examination, and IHC revealed micrometastases in two additional patients (pT2 in one and pT3 in one). Therefore, 15% (3/20) of patients with ≥pT2 disease had node disease. After surgery, six patients experienced minor complications (Grade 1 or 2), and Grade 5 gastrointestinal bleeding after aspiration pneumonia developed in one elderly male patient on the 45th postoperative day, which was not considered to be associated with LND. At the last follow-up, lung metastasis developed in four patients (pT1 in one, pT2 in one, and pT3 in two), and presacral lymph node metastasis developed in one patient with a lower ureteral tumor (pT2), which was not included in our prospective template for a lower ureteral tumor. LN recurrence within/ near the LND area was not observed in patients with pelvic/upper ureteral carcinoma. The 2-year nonurothelial RFS rate was 84%.We consider that the present template represents regional LNs for patients with clinically node-negative pelvic/upper ureteral carcinoma, while presacral LNs may be incorporated into the regional LND template for patients with clinically node-negative lower ureteral carcinoma.

Objective To determine the differences in the type, incidence, and severity of 90-day morbidity after radical cystectomy between two different methods of urinary diversion, ileal conduit and neobladder. Methods We carried out a retrospective multi-institutional study by reviewing the records of 668 patients treated with open radical cystectomy, and ileal conduit (n = 493) or neobladder substitution (n = 175) between 1997 and 2010. All complications within 90 days after surgery were divided into 11 specific categories as reported by the Memorial-Sloan Kettering Cancer Center, and graded according to the modified Clavien system. Type, incidence and severity of the 90-day morbidity between the two different types of urinary diversions were compared. Results There was no significant difference in the overall complication rates between the two groups (ileal conduit: 72% [353/493], neobladder: 74% [129/175], P = 0.5909), whereas the neobladder group had fewer major (grade 3 or more) complications (13 vs 20%, respectively, P = 0.0271). The neobladder group had more infectious complications (43 vs 31%, respectively, P = 0.0037), mainly as a result of urinary tract infection, whereas the ileal conduit group had more wound-related complications (24 vs 14%, respectively, P = 0.0068), mainly as a result of surgical site infection. The 90-day mortality rates were 1.1% (2/175) in the neobladder group and 1.6% (8/493) in the ileal conduit group (P = 0.6441). Conclusions There was no significant difference in the overall complication rates between the two methods, and patients with neobladder had fewer major complications. The neobladder group had more infectious complications, whereas the ileal conduit group had more wound-related complications.

Objectives We investigated the prognosis of Japanese patients with metastatic renal cell carcinoma (RCC), and analyzed the validity of Memorial Sloan-Kettering Cancer Center (MSKCC) risk classification. Materials and methods The endpoint of the present study was overall survival. Relationships between overall survival and potential prognostic factors were assessed using the Cox proportional hazard model with a step-wise procedure. Prognostic assessment was also performed according to the MSKCC risk classification. The predictive accuracy of the MSKCC risk classification was measured employing the concordance index. Results The median survival for all patients was 22 months (95% CI, 19–28 months). The eight factors were identified as independent prognostic factor; time from initial diagnosis to metastasis, low hemoglobin (Hb), lactate dehydrogenase (LDH), corrected serum calcium (cCa), C-reactive protein (CRP), and the presence or absence of liver metastasis, bone metastasis, and lymph node metastasis. When the MSKCC risk classification was applied to patients, the median overall survival was not reached and 26 and 10 months in the patients classified as favorable, intermediate, and poor risk, respectively. The c-index was 0.73. Conclusions The prognosis of Japanese metastatic renal cell carcinoma patients may be better than that of previous studies from North America or Europe. Although there are some differences in the rate of patients in the risk groups and survival time by risk group between these patients, the MSKCC risk classification may be applicable for Japanese patients with metastatic renal cell carcinoma.

To investigate changes in renal function after retroperitoneal laparoscopic partial nephrectomy (LPN) with renal hypothermia induced by ice-slush cooling.Seventy-one patients undergoing retroperitoneal LPN with renal hypothermia were included. Perioperative outcomes were reviewed retrospectively. The total renal function was evaluated by an estimated glomerular filtration rate (eGFR) preoperatively and 6 months postoperatively in 69 patients. Split renal function (SRF) was also evaluated by 99mTc-mercaptoacetyltriglycine scintigraphy preoperatively and 6 months postoperatively in 61 patients.The median operative time was 246 minutes (range, 155-424). The median cold ischemic time, including the initial 15 minutes of hypothermia, was 57 minutes (range, 34-112). In the 21 patients whose renal temperature was monitored, median lowest renal temperature was 20.7°C (range, 12.1-27.6). The median baseline eGFR and 6-month postoperative eGFR were 77.2 mL/min/1.73 m(2) (range, 36.1-121.3) and 68.3 mL/min/1.73 m(2) (range, 33.2-103.4), and the median baseline SRF and 6-month postoperative SRF of the affected kidney were 49.3% (range, 40.3-57.6) and 40.7% (range, 13.8-54.5). Using multivariate analysis, the baseline eGFR (p0.0001) and the ischemic time (p=0.0073) were associated with the 6-month postoperative eGFR, and the 6-month postoperative SRF was only associated with a baseline SRF (p=0.0185).Ice-slush cooling could provide renal hypothermia also under LPN. The decrease in renal function was small, whereas our ischemic time was longer than experts' warm ischemic series. These observations suggested the protective effect of our cooling methods against ischemic injury.

Study Type – Therapy (outcomes) Level of Evidence 2b What's known on the subject? and What does the study add? Radical cystectomy remains associated with comparatively high perioperative morbidity and mortality, despite improvements in surgical techniques and perioperative care. At present, most studies on the complications associated with open radical cystectomy were derived from Western academic high-volume centres, and data from Japan and other Asian countries were very limited. Using the modified Clavien grading system and 11 category grouping reported from MSKCC, we observed that 68% of patients experienced at least one complication within 90 days of surgery, and 17% of patients experienced major complications (90-day mortality rate = 2%), which were compatible with reports from Western high-volume centres. As far as we know, our report is the largest one regarding perioperative morbidity and mortality in Asian patients who underwent radical cystectomy. Objective To determine the type, incidence and severity of 90-day morbidity after radical cystectomy in our institution and our affiliated hospitals in accordance with a standard reporting methodology. At present, most studies on complications associated with open radical cystectomy are derived from Western academic high-volume centres and data from Japan and other Asian countries remain very limited. Patients and Methods The study comprised a retrospective multi-institutional study. The records were reviewed of 928 patients who underwent open radical cystectomy between 1997 and 2010. All complications within 90 days of surgery were categorized into 11 specific categories and graded in accordance with the modified Clavien system. Multivariate regression models were used to determine predictors of complications. Results At least one complication was observed in 635 (68%) patients and a major (grade 3–5) complication was observed in 156 (17%) patients. The most common complication categories were infectious (30%), gastrointestinal (26%), wound-related (21%) and genitourinary (15%). The 30-day mortality rate was 0.8% and the 90-day mortality rate was 2%. A multivariate regression model showed that previous cardiovascular comorbidity and type of urinary diversion (i.e. ileal conduit or neobladder) were significant factors for any and major complications. Conclusions Surgical complication-related radical cystectomy is significant and both previous cardiovascular comorbidity and the type of urinary diversion were found to be significant factors for any and major complications. The 90-day mortality rate was 2%, which is compatible with reports from Western high-volume centres.

Objectives: Our goal was to identify changes in urodynamic parameters and lower urinary tract symptoms (LUTS) in men followed for1 year after radical prostatectomy (RP) compared to the preoperative measures with a specific focus on detrusor contractility. Methods: This study enrolled 43 patients who received RP (laparoscopic 27, retropubic: 16) and pressure flow studies (PFS) pre-RP as well as 12 months (M) after RP. No patients complained of urinary incontinence preoperatively. Urodynamic studies and questionnaires regarding LUTS and urinary continence were conducted before and 12 M after RP. Detrusor underactivity (DU) was defined as

Objectives: To investigate the influence of baseline renal function and dose reduction of chemotherapeutic agents on the outcome of metastatic urothelial carcinoma patients with renal impairment. Methods: A total of 57 patients with metastatic urothelial carcinoma treated by systemic chemotherapy were included in the present study. The 24 h-creatinine clearance was measured before each cycle and dose reduction was carried out according to our guidelines. Patients were divided into two groups according to baseline 24 h-creatinine clearance: fit group (60 mL/min/1.48 m2≤) and unfit group (60 mL/min/1.48 m2>). Clinical characteristics and final outcomes were compared between the two groups. Results: There was no significant difference in the total number of chemotherapy cycles of each patient between the two groups (fit group: median 5; unfit group: median 4; P = 0.7466), although dose reduction was carried out significantly more often in the unfit group than in the fit group during treatment (fit group: median 0 cycles; unfit group: median 3.5 cycles; P = 0.0016). Overall, the median survival was 16 months. There was a significant survival difference between the two groups (fit group: median 17 months; unfit group: median 10 months; P = 0.0419). On multivariate analyses, impaired renal function at the baseline remained an adverse factor (HR 2.27, P = 0.01). Conclusions: “Unfit” was a poor prognostic factor for metastatic urothelial carcinoma. The dose reduction strategy contributed to continuous treatment in the unfit group. However, its contribution to the prognosis of unfit patients is uncertain.

We evaluated the use of narrow-band imaging (NBI) cystoscopy for the detection of bladder cancer and analyzed its diagnostic efficacy in cases of carcinoma in situ (CIS) and in cases with known urine cytology results.A prospective controlled study of NBI was conducted in 104 consecutive patients with definite or suspected bladder cancer. Transurethral targeted biopsies were performed after white light imaging (WLI) and NBI cystoscopy, and the histologic outcomes were compared.A total of 313 biopsies were taken, including 161 from sites identified as potentially abnormal by NBI and/or WLI cystoscopy, and 152 from apparently normal sites. The percentage of malignancies in the sites identified only by NBI was 55.7% (39/70 places). In 26.9% of patients (28/104), bladder tumors were detected only by NBI. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and likelihood ratio of a negative test (NLR) for the detection of bladder tumors using NBI in all patients were 92.7%, 70.9%, 63.4%, 94.7%, and 0.10, respectively. The sensitivity, specificity, PPV, NPV, and NLR for the detection of CIS using NBI were 89.7%, 74.5%, 78.8%, 87.2%, and 0.14, respectively. The sensitivity, specificity, PPV, NPV, and NLR for the detection of bladder tumors using NBI in patients with positive vs negative urine cytology were 85.4% vs 98.4%, 75.7% vs 66.3%, 61.2% vs 64.5%, 92.0% vs 98.5%, and 0.19 vs 0.02, respectively.NBI is a simple and effective method for identifying bladder tumors including CIS without the need for dyes because of its high sensitivity, high NPV, and low NLR.

Objective: We conducted a Phase II trial to investigate the efficacy of combined therapy with meloxicam, a cyclooxygenase-2 inhibitor and natural interferon (IFN)-a in renal cell carcinoma patients with distant metastasis. Methods: The subjects of this study were patients with untreated renal cell carcinoma who were diagnosed from the results of imaging or pathological studies and who had measurable lesions according to the Response Evaluation Criteria in Solid Tumors (RECIST). Patients could be enrolled in the study irrespective of whether nephrectomy had been performed. Treatment involved the subcutaneous injection of natural IFN-a at 3 � 10 6 or 5 � 10 6 U three times weekly plus oral administration of meloxicam at 10 mg once daily. Results: A total of 43 patients were enrolled in the present study, included 11 patients without nephrectomy, 23 patients with a high C-reactive protein (CRP) level and 23 patients with extrapulmonary metastasis. Four patients of complete response and 12 patients of partial response were confirmed, given an overall response rate of 37.2% (95% confidence interval, 23.0‐53.3%). Stable disease for 6 months or longer was also obtained in 14 patients. The median time to progression was 14 months. Adverse events (AEs) observed were mainly flu-like symptoms due to cytokine. Although the Grade 3 or 4 AEs were fatigue, hepatic dysfunction, arthritis and gastric ulcer, all but one (gastric ulcer) were immediately improved by discontinuation of this combined therapy. Conclusions: The combination of meloxicam and natural IFN-a is considered to be an active regimen with tolerable toxicities as a first-line treatment of metastatic renal cell carcinoma.

A 72-year-old male visited our hospital with a complaint of perineal and voiding pain. An elastic hard mass was palpated by rectal examination in the cranial lesion of prostate. On CT scan and MRI it was located at the site of the right seminal vesicle. Trans-rectal needle biopsy specimen showed leiomyosarcoma. Radical cystoprostatectomy with pelvic lymph node dissection was performed at Hokkaido University Hospital. Microscopic examination of the resected specimen revealed the tumor arose from the right seminal vesicle without involvement of the bladder and the prostate gland. Three months after the operation the tumor recurred at lung and pelvic lymph node. He died 10 month postoperatively. Autopsy finding showed many visceral organs metastases without local recurrence. In the past, nine cases of leiomyosarcoma of seminal vesicle were published in the literature. Including our case, pathological diagnosis by core needle biopsy was attempted in five cases, though accurate diagnosis was made in only two cases. In our case, Immunohistological study by SMA and desmin was useful for histological diagnosis preoperatively.

Objectives: To evaluate the prognostic role of different clinico-pathological parameters in node-positive patients treated by radical cystectomy. Methods: A retrospective multi-institutional study of 435 patients who underwent radical cystectomy between 1990 and 2005 was carried out. Of them, pathological lymph node (LN) metastases were found in 83 patients. Sixty of these 83 patients, whose clinical information and follow-up data were available, were included in the analysis. Twenty-five patients had undergone adjuvant chemotherapy, whereas 35 had not. A Cox proportional hazards model was used to determine the impact of the following clinico-pathological parameters on patient survival: number of resected LNs, number of positive LNs, LN density (defined as the ratio of the number of positive LNs divided by the total number of resected LNs) and adjuvant chemotherapy. Results: Median follow-up for surviving patients was 41 months (range 4–138) after surgery. The median survival time for all patients was 22 months (95% confidence interval, 15–42 months). At multivariate analysis, LN density of 25% or less, adjuvant chemotherapy and pure urothelial carcinoma were independently significant predictors of survival. Conclusions: Lymph node density predicts survival in patients with node-positive bladder cancer.

OBJECTIVES To determine the role of lymph-node (LN) dissection in patients undergoing surgery for upper urinary tract (UUT) cancer. PATIENTS AND METHODS We reviewed the clinicopathological data from 312 patients with UUT cancer treated predominantly by nephroureterectomy. The relationship between clinical characteristics and cancer-specific survival (CSS) was analysed, focusing on node-related information. RESULTS In all, 166 patients had LN dissection while 146 did not (pNx). Multivariate analysis showed that T stage, grade and pN status were significant variables for CSS. The difference in survival between the pN0 and pNx groups remained significant in a multivariate analysis. The median (range) number of LNs removed was 6 (1–65). There was no significant difference in CSS between the 72 patients with fewer than six LNs removed and the 78 with six or more removed. CONCLUSIONS LN dissection is important for postoperative stratification of patients with UUT cancer because node-positive disease was one of the variables with a significant adverse effect on survival. In addition, the significant difference in survival between the pN0 and pNx groups might indicate a therapeutic benefit of LN dissection, although removing more LNs did not uniformly increase the probability of CSS.

Objective: Epstein-Barr virus (EBV) has been implicated in the genesis of a variety of human cancers. We aimed to confirm the presence and define the role of EBV in bladder cancer. Methods: A total of 39 bladder cancer specimens were analyzed. Ten urinary bladder tissues obtained at autopsy were used as a normal control. EBV-encoded RNA (EBER) was evaluated by in situ hybridization (ISH). Frozen material available from 18 EBER-positive cases was analyzed by using reverse transcription-polymerase chain reaction for BZLF1, an early lytic gene product. The expression of CD20, CD3, ZEBRA (BZLF1 product) and transforming growth factor β1 (TGFβ-1) was assessed using an immunohistochemical technique. Results: Infiltration of EBER-expressing lymphocytes was detected in 26 of 39 bladder cancer cases (66.7%). A small fraction of the tumor cells as well as the infiltrating lymphocytes were positive in two cases. All normal urinary bladder specimens showed negative results. The incidence of EBV-positive lymphocyte infiltration was significantly higher for advanced stage cancers than those in earlier stages (Ta-152% vs T2-4 93%, P = 0.013). The presence of BZLF1 mRNA was demonstrated in seven out of the 18 EBER-positive cases. Conclusions: Infiltration of EBV-harboring lymphocytes occurs in a large subset of bladder cancers cases. It is more frequently associated with advanced stages. EBV infection in tumor cells is very limited. Our findings suggest that EBV-positive lymphocytes might play a role in bladder cancer progression.

Background: Due to variations in location and size, laparoscopic surgery for paraaortic or paracaval neurogenic tumors is challenging. We evaluated the surgical outcomes, as well as surgical tips and tricks. Methods: Between 2000 and 2015, 25 procedures were performed in 24 patients. One patient underwent second surgery due to the recurrence of paraganglioma. Data were collected on the tumor diameter, tumor location, perioperative outcomes, pathology, and last known disease status. Regarding the operative procedures, we reviewed the operative charts or videos to identify surgical tips and tricks. Results: The median tumor diameter was 5.0 cm (range, 1.5-10). The tumor location was suprahilar in 10, hilar in 6, and infrahilar in 9. Regarding the approach, a transperitoneal approach was selected in 24 cases and retroperitoneal approach in 1. The median operative time and blood loss were 208 minutes (range, 73-513) and 10 mL (range, 0-1,020), respectively. No patient required blood transfusion or conversion to open surgery. Pathological examination revealed paraganglioma in 12, ganglioneuroma in 7, and schwannoma in 6. At the last follow-up, 23 patients were free of disease, while one patient developed metastatic multiple recurrence of paraganglioma 54 months after the second laparoscopic surgery. A review of the surgical records revealed several tips and tricks, including taping the vena cava/ renal vein (n=2) being helpful for detaching a retrocaval tumor from these great vessels, or rotating the kidney to provide a favorable operative view of tumors behind the renal hilum (n=2). In recent cases, 3D-CT was helpful for preoperative planning. Conclusion: Laparoscopic resection of paraaortic or paracaval neurogenic tumors is feasible in experienced hands. Surgeons should be familiar with detaching maneuvers around great vessels and the mobilization of adjacent organs. Careful preoperative planning is mandatory.

INTRODUCTION AND OBJECTIVES: We present a case report of our initial experience with laparoendoscopic single-site surgery (LESS) combined with cystoscopy for primary bladder paraganglioma. METHODS: A 41 years old woman consulted for headache and palpitation after micturition for 10 years. Ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI), and cystoscopy revealed a solitary 2cm mass lesion in the top of the bladder (Fig.1,2). High levels of noradrenaline were found both in plasma and urine. 123IMIBG scintigraphy showed an abnormal accumulation in the bladder. Thus, paraganglioma of the bladder was diagnosed. A LESS partial cystectomy combined with cystoscopy was performed. OCTOport ,>R was inserted through 2cm skin incision through the umbilicus, and one 2-mm port was added (Fig.3,j. Cystoscopic guidance was helpful to determine the excision line of the tumor during laparoscopic surgery,@,iFig.4,j. RESULTS: She has been free from symptom after operation. Histological examination of the resected specimen showed a paraganglioma. CONCLUSIONS: LESS partial cystectomy combined with cystoscopy for bladder paraganglioma can easily identify the margins of tumor and is safe technique.

INTRODUCTION AND OBJECTIVES: Surgeonand hospitalcase volume are identified as factors related with outcomes of surgical procedures. Radical cystectomy (RC), due to its major impact on the patient, might substantially benefit from centralization if this assumption were true. We aim to test this hypothesis in Spain, a country in which no lower limit nor centralization for radical cystectomy exists. METHODS: We performed a retrospective cohort review of patients undergoing RC in Spain during 2011 and 2012, accessing data from inpatient discharge forms (CMBD) of every patient operated on of radical cystectomy. CMBD is a mandatory file that is submitted to the Ministry of Health and provides information on patient’s demographics as well as morbidity and cause of discharge including death. Hospitals were stratified into volume quartiles depending on their 2-year cumulative cystectomy volume (very lowvolume 58). Hospitals were also categorized according to their size in beds and teaching facilities. A comparison with data in the literature was made. RESULTS: We analyzed 5,594 RCs in 266 centers of Spain during 2011 and 2012 (2,701 RCs in 2011 and 2,893 RCs in 2012). Mean age was 66.5 9.8 years and 84.7% were males. Mean hospital stay was 20.7 16.6 days. Mortality rate at 30, 60 and 90 days was 2.8%, 4.7% and 5.9%, respectively. 90-day mortality rate for very-low, low, medium and high-volume centers was 5.9%, 5.9%, 7% and 5.1%, respectively (p1⁄40.2). Hospital size and teaching facilities were not associated with mortality. A statistically significant difference was noted in the complications and readmission rate. These results compare favorably with reported multicenter series in the literature with 90-day mortality rate ranging from 4.2 to 7.9%. CONCLUSIONS: Our data do not support an urgent need for regionalization of radical cystectomy in our country. However, initiatives to improve surgical outcomes of radical cystectomy within individual national setting should be explored.

We previously reported that gelsolin gene expression is reduced in various tumors. In an effort to gain further insights into the mechanism of gelsolin downregulation in tumors, we examined the in vivo properties of the gelsolin promoter in urinary bladder cancer cell lines. Neither mutation nor hypermethylation were responsible for gene silencing at the promoter. After exposure to trichostatin A (TSA), a histone deacetylase inhibitor, gelsolin promoter activity was markedly enhanced in the cancer cells not in cells derived from normal tissue. Chromatin immunoprecipitation (ChIP) assays revealed that both histones H3 and H4 were hypoacetylated in the promoter region of the cancer cells, and the accumulation of acetylated histones were detected by TSA treatment. In vivo footprinting analysis revealed the presence of dimethylsulfate (DMS) hypersensitive site in the untranslated region around nucleotide -35 only in the cancer cells but not in cells derived from normal tissue, and analysis of KMnO4 reactive nucleotides showed that the stem loop structure could be formed in vivo of the cancer cells. This novel stem loop structure may play a part in regulating the transcription of the gelsolin gene in the cancer cells. .. These results suggest that nucleosome accessibility through histone deacetylation and structural changes (DMS hypersensitivity and stem loop structure) in the promoter region form the basis of the mechanism leading to the silencing of gelsolin gene in human bladder cancer.

To investigate the suppressive effect of dominant negative H-ras mutant N116Y on transformed phenotypes, we established two N116Y ras mutant stable transfectant clones (C5, C13) of human bladder cancer cell line, UMUC-2. These N116Y ras mutant transfectants, especially the C5 cells, showed a dramatic change of cellular morphology and significantly reduced growth in soft agar compared to their control. Furthermore, phosphorylation of the Jun NH2-terminal kinase (JNK) was significantly decreased in these transfectants compared to the control. These results suggest that the N116Y-induced suppression of transformed phenotypes in UMUC-2 cells is associated with inhibition of JNK phosphorylation.

Patients with an adrenal tumor usually undergo laparoscopic adrenalectomy. However, an alternative treatment approach might be needed in some patients with adrenal metastasis from malignancy or with severe complications. Real-time tracking radiotherapy (RTRT) with a gold marker is considered one of the feasible treatment options because this system can reduce the adverse effects of organ movement such as that in the adrenal gland or kidney. A 64-year-old patient with hormone refractory prostate cancer presented with clinically isolated adrenal metastasis. The patient underwent RTRT treatment with an implanted gold marker in the right adrenal metastasis. There were no adverse events. Although disease progression with elevated prostate-specific antigen occurred 8 months later, there was no further growth of the right adrenal metastasis before he died. From our experience, RTRT with an implanted gold marker might be feasible for the treatment of isolated adrenal metastasis from malignancies including prostate cancer.

Our previous studies demonstrated that introduction of a dominant negative H-ras mutant, N116Y, inhibits the growth of various types of cancer cells in vitro. In this study, we tested the efficacy of N116Y in blocking the growth of esophageal cancer cells using an adenoviral vector. Infection with N116Y adenovirus, (AdCMV-N116Y), in which N116Y expression is driven by the cytomegalovirus promoter, significantly reduced the in vitro growth of all esophageal cancer cell lines studied. Esophageal cancer cells that contained wild-type K-ras and H-ras (TE8, SGF3, SGF7) were more sensitive to AdCMV-N116Y than HEC46 cells that expressed mutant K-ras protein. Most importantly, direct injection of AdCMV-N116Y into TE8- or SGF3-induced tumors in nude mice suppressed their growth significantly. To examine the suppressive mechanism of N116Y, cell cycle profile and the activation of extracellular signal-regulated kinase 2 (Erk2) were examined by flow cytometry and Western blot analysis, respectively. In TE8 cells, progression into S phase was clearly blocked after infection with AdCMV-N116Y. Infection with AdCMV-N116Y did not strongly suppress the activation of Erk2 after EGF stimulation in serum-starved HEC46 cells, whereas it completely suppressed activation in TE8, SGF3 and SGF7 cells. Our observations suggest that N116Y reduces growth of human esophageal cancer cells and suppresses the activation of Erk2; they also indicate that N116Y is a potential candidate gene for human esophageal cancer gene therapy.

Aim To clarify prognostic factors of metatstatic urothelial carcinoma treated by systemic chemotherapy in real-world clinical practice in the Japanese population. Materials and methods A total of 228 patients with metastatic urothelial carcinoma undergoing systemic chemotherapy between 2000 and 2013 were included in the present multi-institutional study. The gemcitabine plus cisplatin regimen was administered as first-line chemotherapy to 131 patients, whereas methotrexate, vinblastine, doxorubicin, and cisplatin or its modified regimen was given to 71 patients. Of the 228 patients, 119 received at least 2 different regimens and 22 underwent resection of metastases (metastasectomy). Multivariate survival analysis was performed using the Cox proportional hazards model. The characteristics included were age, sex, Eastern Cooperative Oncology Group performance status (PS), primary site, pathology of primary site, hemoglobin levels, lactate dehydrogenase levels, C-reactive protein levels, corrected calcium levels, estimated glomerular filtration rate levels, history of prior chemotherapy, metastatic sites, resection of primary site, number of metastatic organs, and metastasectomy. Results The median overall survival (OS) time was 17 months. On multivariate analysis, female sex, good Eastern Cooperative Oncology Group PS at presentation, hemoglobin level≥10 g/dl, and single organ metastasis were significant independent predictors of prolonged OS. For the survival effect of metastasectomy, the median OS time of the 22 patients with metastasectomy was 53 months, which was significantly longer when compared with patients not undergoing metastasectomy (15 mo). After adjustment for the 4 aforementioned prognostic factors, metastasectomy still remained significant (hazard ratio: 0.364, P = 0.0008). Conclusions Female sex, more favorable PS at presentation, hemoglobin level>10 g/dl, and single organ metastasis were favorable prognostic factors. In addition, metastasectomy was associated with long-term disease control.

What's known on the subject? and What does the study add? Radical cystectomy remains associated with comparatively high perioperative morbidity and mortality, despite improvements in surgical techniques and perioperative care. At present, most studies on the complications associated with open radical cystectomy were derived from Western academic high-volume centres, and data from Japan and other Asian countries were very limited. Using the modified Clavien grading system and 11 category grouping reported from MSKCC, we observed that 68% of patients experienced at least one complication within 90 days of surgery, and 17% of patients experienced major complications (90-day mortality rate = 2%), which were compatible with reports from Western high-volume centres. As far as we know, our report is the largest one regarding perioperative morbidity and mortality in Asian patients who underwent radical cystectomy.To determine the type, incidence and severity of 90-day morbidity after radical cystectomy in our institution and our affiliated hospitals in accordance with a standard reporting methodology. At present, most studies on complications associated with open radical cystectomy are derived from Western academic high-volume centres and data from Japan and other Asian countries remain very limited.The study comprised a retrospective multi-institutional study. The records were reviewed of 928 patients who underwent open radical cystectomy between 1997 and 2010. All complications within 90 days of surgery were categorized into 11 specific categories and graded in accordance with the modified Clavien system. Multivariate regression models were used to determine predictors of complications.At least one complication was observed in 635 (68%) patients and a major (grade 3-5) complication was observed in 156 (17%) patients. The most common complication categories were infectious (30%), gastrointestinal (26%), wound-related (21%) and genitourinary (15%). The 30-day mortality rate was 0.8% and the 90-day mortality rate was 2%. A multivariate regression model showed that previous cardiovascular comorbidity and type of urinary diversion (i.e. ileal conduit or neobladder) were significant factors for any and major complications.Surgical complication-related radical cystectomy is significant and both previous cardiovascular comorbidity and the type of urinary diversion were found to be significant factors for any and major complications. The 90-day mortality rate was 2%, which is compatible with reports from Western high-volume centres.

Objective: We reviewed the outcomes of metastatic renal cell carcinoma patients with the primary tumor in situ who initially underwent interferon-a-based immunotherapy to evaluate the effect of this therapy on metastatic sites as well as primary kidney tumor and survival. Methods: Thirty-one patients, for whom upfront cytoreductive nephrectomy was considered to be inappropriate because of poor performance status and far-advanced disease, were the subject of the present study. Tumor response and reduction in the size of metastatic sites and primary kidney tumor were assessed. Overall survival distributions were estimated using the Kaplan–Meier method with the significance determined using the log-rank test. Results: Partial response was observed in 11 patients, yielding an overall response rate of 35%. Seventeen patients had regression or stabilization of metastatic sites, while progression of metastatic sites was observed in the remaining 14 patients. Regarding the maximum response of primary kidney tumor, a reduction in kidney primary tumor size was observed in 42% of the patients and the mean reduction rate in these patients was 18.2% (range: 3 – 36%). Furthermore, the reduction in the size of metastatic sites was significantly associated with that in the size of primary kidney tumor (R 2 ¼ 0.432, P , 0.0001). The median survival for the 31 patients was 17 months. The median survival was 42 months in patients with regression or stabilization of metastatic sites and 7 months in those without (P , 0.001). Conclusions: The present study suggests that metastatic sites as well as primary kidney tumor respond to interferon-a-based immunotherapy in metastatic renal cell carcinoma patients with primary tumor in situ.

To investigate the influence of baseline renal function and dose reduction of chemotherapeutic agents on the outcome of metastatic urothelial carcinoma patients with renal impairment.A total of 57 patients with metastatic urothelial carcinoma treated by systemic chemotherapy were included in the present study. The 24 h-creatinine clearance was measured before each cycle and dose reduction was carried out according to our guidelines. Patients were divided into two groups according to baseline 24 h-creatinine clearance: fit group (60 mL/min/1.48 m(2) ≤) and unfit group (60 mL/min/1.48 m(2)). Clinical characteristics and final outcomes were compared between the two groups.There was no significant difference in the total number of chemotherapy cycles of each patient between the two groups (fit group: median 5; unfit group: median 4; P=0.7466), although dose reduction was carried out significantly more often in the unfit group than in the fit group during treatment (fit group: median 0 cycles; unfit group: median 3.5 cycles; P=0.0016). Overall, the median survival was 16 months. There was a significant survival difference between the two groups (fit group: median 17 months; unfit group: median 10 months; P=0.0419). On multivariate analyses, impaired renal function at the baseline remained an adverse factor (HR 2.27, P=0.01)."Unfit" was a poor prognostic factor for metastatic urothelial carcinoma. The dose reduction strategy contributed to continuous treatment in the unfit group. However, its contribution to the prognosis of unfit patients is uncertain.

impairment of deflection angle (minus 95, 123 and 114 degrees, respectively). In all 3 ureterorenoscopes flow rates and angle of deflection were least impaired by BIGopsy. Insertion of the BIGopsy device in any ureterorenoscope reduced the field of view by at least 20% compared to a maximum of 12% reduction caused by the other forcipes. CONCLUSIONS: The various biopsy devices differ in the impairment of irrigation flow rates, degree of deflection and reduction of field of view. The Cook BIGopsy forceps allows for the least impairment of irrigation flow in single-channel flexible ureterorenoscopes due to a smaller diameter and does not significantly impair deflection. However, a smaller field of view may hamper tissue acquisition.

To obtain accurate disease staging, we routinely perform regional lymph node dissection (LND) in conjunction with laparoscopic nephroureterectomy (NU) to treat urothelial carcinoma of the upper urinary tract. The present study evaluated the feasibility and usefulness of LND in laparoscopic NU.Thirty-nine patients undergoing laparoscopic NU with regional LND were included in the present study. We evaluated the number of lymph nodes (LNs) resected, pathological node status, adverse events, and survival data. Node count was compared with that of 41 patients who underwent open NU between 1990 and 2008.The median number of LNs removed was 10 (range, 2-59) in the laparoscopic NU group and 10 (range, 1-65) in the open NU group (Mann-Whitney U-test, p = 0.82). Pathological examination demonstrated positive LNs in four patients (10.3%) and three of the four patients received adjuvant chemotherapy. Although chylous drain discharge was detected just after resuming dietary intake in eight patients, it resolved without significant problem. Five-year overall survival by stage was 100% for pT2 ≥ disease, 55% for pT3 disease, and 0% for pT4 disease.LND can be performed safely and effectively during laparoscopic nephroureterectmy. We consider that accurate node staging and subsequent stratification are mandatory for disease management.

Purpose: Interportal adjustment was applied to patients with prostate cancer using three fiducial markers and two sets of fluoroscopy in a real-time tumor-tracking radiotherapy (RTRT) system. The incidence of table position adjustment required to keep intrafractional uncertainty within 2.0 mm was investigated in this study. Methods and Materials: The coordinates of the center of gravity of the three fiducial markers were measured at the start of every portal irradiation in intensity-modulated radiotherapy (IMRT) with seven ports. The table position was adjusted to the planned position if the discrepancy was larger than 2.0 mm in the anterior-posterior (AP), cranial-caudal (CC), or left-right (LR) directions. In total, we analyzed 4541 observations in 20 patients who received 70 Gy in 30 fractions (7.6 times a day in average). Results: The incidence of table position adjustment at 10 minutes from the initial set-up of each treatment was 14.2%, 12.3%, and 5.0% of the observations in the AP, CC, and LR directions, respectively. The accumulated incidence of the table position adjustment was significantly higher at 10 minutes compared to that at 2 minutes for AP (p = 0.0033) and CC (p = 0.0110) but not LR (p = 0.4296). An adjustment greater than 5 mm was required at least once in the treatment period in 11 (55%) patients. Conclusions: Interportal adjustment of table position was required in more than 10% of portal irradiations during the 10-minute period after initial setup to maintain treatment accuracy within 2.0 mm.

Pheochromocytoma (PCC) and paraganglioma (PGL) are tumors of the autonomic nervous system. The former is a tumor that occurs in only adrenal glands, and the latter can be found in the head and neck or in the thorax and abdomen. In PCC and PGL, genetic mutations account for approximately 30% of functional (secrete catecholamines) and nonfunctional cases. In addition to RET, VHL and NF-1, genes encoding succinate dehydrogenase complex subunit B (SDHB), subunit C (SDHC), and subunit D (SDHD) are recognized as susceptibility genes for PCC and PGL. Recently, PCC and PGL caused by genetic mutations of SDHB, SDHC and SDHD were established as hereditary pheochromocytoma paraganglioma syndrome (HPPS). Approximately 15% of all PCCs and PGLs are recognized as HPPS. Among these three susceptibility genes, SDHB and SDHD are known to be strongly related to HPPS. The aim of this study was to analyze SDHB and SDHD mutations in PCC and PGL patients. Among 18 patients, we identified a novel heterozygous nonsense mutation at codon 168 resulting in a CAG (glutamine) to TAG (stop) substitution (Q168X) in the SDHB gene in a patient diagnosed with solitary sporadic PGL. A number of studies have reported that SDHB mutation-associated disease demonstrates a higher rate of malignancy. However, all seven patients diagnosed with malignancy in this study did not have genetic mutation of SDHB and only one patient with no malignant sign had genetic mutation of SDHB. Further accumulation of cases is necessary to confirm the association between SDHB mutation and malignant potential.

Aim To determine the role of lymph node dissection (LND) in the treatment of urothelial carcinoma (UC) of the upper urinary tract (UUT). Patients and methods [Study-1] A retrospective multi-institutional study evaluated 293 patients undergoing predominantly nephroureterectomy for UC of the UUT. Of 293 patients, 267 patients had pure UC and 26 demonstrated other histological components. Regarding the pathological node status, 130 patients had pN0 disease, 141 patients had pNx disease and 22 patients had pN+ disease. The sites of initial recurrence and time to first recurrence were reviewed. The sites of recurrence were classified as locoregional or distant recurrence. The relationship between node status and future recurrence was analyzed. [Study-2] Fifty-one patients treated by nephroureterectomy at Hokkaido University Hospital were included. All had LND and all LNs were negative on hematoxylin and eosin staining. We re-evaluated the presence of micrometastasis in LND specimens by anti-cytokeratin immunohistochemistory. Results [Study-1] Of 293 patients, 76 developed disease relapse. Regional lymph node recurrence was the most common site (34 patients). On multivariate analyses that adjusted for the effect of tumor stage and tumor grade, pNx (skipping LND) was an adverse factor not only for locoregional recurrence, but also for distant relapse. [Study-2] Immunohistochemistry identified micrometastases in 7 (14%) of 51 patients. Regarding survival, 5 of these 7 patients with micrometastases were alive at last follow-up. Conclusions On relapse analysis, skipping LND was an adverse factor not only for locoregional recurrence, but also for distant relapse. Immunohistochemistry detected micrometastases in about 14% of patients previously diagnosed as pN0. These findings further support a potential therapeutic benefit of LND by eliminating micrometastases.