[Repair of Vaginal Cuff Dehiscence after Laparoscopic Radical Cystectomy with Gracilis Myocutaneous Flap].

Vaginal cuff dehiscence after total hysterectomy or total cystectomy had been increasing since laparoscopic or robotic surgery became a common surgery among gynecologists and urologists. A 52-yearold woman underwent laparoscopic radical total cystectomy for muscle invasive bladder carcinoma at Rakuwakai Otowa Hospital. She was emergently admitted with a fist-sized lump protruding from her vagina four months after surgery. Physical examination and her past history on admission disclosed vaginal cuff dehiscence after cystectomy. Computed tomographic scan and magnetic resonance imaging showed no bowel evisceration in the lump. We confirmed that the content of lump was peritoneal tissue and removed it by laparoscopic surgery. Simultaneously, we repaired the vaginal cuff dehiscence with a gracilis myocutaneous flap. There was no subsequent recurrence of vaginal dehiscence or bladder carcinoma in one-year follow-up.

Hydronephrosis severity as a predictor of postoperative renal function decline following laparoscopic radical nephroureterectomy.

BACKGROUND: This study aimed to investigate factors, including the degree of hydronephrosis, that may be associated with decreased renal function after radical nephroureterectomy (RNU). METHODS: This study included 252 patients who underwent laparoscopic RNU with an estimated glomerular filtration rate (eGFR) ≥ 30 ml/min/1.73 m2 in three institutions. We assessed the association between hydronephrosis grade and perioperative renal function and performed a stepwise multivariate linear regression analysis to identify factors associated with postoperative eGFR. Patients with preoperative eGFR ≥ 50 ml/min/1.73 m2 were divided into a training set and an independent external validation set to develop a predictive model for postoperative renal function. RESULTS: The median preoperative and postoperative eGFR were 61.1 and 46.4 ml/min/1.73 m2, respectively. The eGFR preservation rates were 66.9%, 66.6%, 88.1%, and 100.0% in groups without, with mild, moderate, and severe hydronephrosis, respectively, and this difference was statistically significant (p < 0.001). Multivariate analysis revealed that factors predictive of postoperative eGFR included sex, preoperative eGFR, clinical T stage (cT3-4), and the presence of moderate or severe hydronephrosis. Our predictive model, based on these factors, positively correlated with actual postoperative renal function, and the similarity in categories with or without renal function insufficiency between predicted and actual postoperative renal functions was 78% in both training and validation sets. CONCLUSION: Moderate or severe hydronephrosis is associated with a modest postoperative decline in renal function, while mild hydronephrosis is not. Our predictive model may be useful in predicting postoperative renal function insufficiency and guiding decision-making for perioperative medical treatment.

Preoperative risk classification for intravesical recurrence after laparoscopic radical nephroureterectomy for upper tract urothelial carcinoma in a multi-institutional cohort.

INTRODUCTION: This study aimed to identify preoperative risk factors and create a risk classification for intravesical recurrence of upper urinary tract urothelial carcinoma only after laparoscopic radical nephroureterectomy in a multi-institutional cohort. METHODS: We retrospectively analyzed 283 patients who had undergone laparoscopic radical nephroureterectomy for nonmetastatic upper tract urothelial cancer between March 2002 and March 2020. The cumulative incidence of intravesical recurrence for 224 patients without previous or concomitant bladder cancer was examined using multivariate Fine-Gray competing risks proportional hazards models. A risk stratification model was created to predict subsequent patient outcomes based on the results. RESULTS: The median follow-up duration was 33.3 months, and 71 (31.7%) patients experienced intravesical recurrence. The estimated cumulative incidence of intravesical recurrence at one and 5 years was 23.5% and 36.4%, respectively. In multivariate analysis, the presence of ureter tumors and multiple tumors were shown to be independently significant predictive factors for intravesical recurrence. Based on the results, we classified patients into three risk groups. The cumulative incidence rates of intravesical recurrence within 5 years after surgery were 24.4%, 42.5%, and 66.7% in the low-, intermediate-, and high-risk groups, respectively. CONCLUSIONS: We identified risk factors and created a risk classification model for intravesical recurrence of upper urinary tract urothelial carcinoma only after laparoscopic radical nephroureterectomy. Based on this model, an individualized surveillance protocol or adjuvant therapy could be provided.

Atypical Oncologic Failure After Laparoscopic Radical Nephroureterectomy in a Japanese Multicenter Study.

Objectives: To investigate the recurrence patterns and the atypical oncologic failure (AOF) defined as the presence of atypical recurrences, such as retroperitoneal carcinomatosis or port-site recurrence, after laparoscopic radical nephroureterectomy (LRNU). Methods: LRNU performed at three institutions were included in this retrospective study. The primary endpoints were the first recurrence site and recurrence-free survival. The recurrence sites were classified as atypical recurrences, such as retroperitoneal carcinomatosis or port-site recurrence, as well as distant, local, and intravesical. The Kaplan-Meier curves were obtained to elucidate the time until recurrence and survival. Results: A total of 283 patients were included in the final analysis. Postoperative pathology was T3 or higher in 112 (40%) patients. The median follow-up period was 31 months, and the 3-year recurrence-free, cancer-specific, and overall survival rates were 69.6%, 78.1%, and 72.0%, respectively. The first recurrence sites involved distant, local, atypical, and intravesical recurrences in 51 (18%), 36 (13%), 14 (5%), and 94 (33%) patients, respectively. Of the 14 patients with AOF, 12 had pathologically locally advanced tumors, but seven patients had a preoperative diagnosis of clinical stage T2 or less. Conclusion: A small number of AOF cases were found after LRNU for patients with upper tract urothelial carcinoma. Careful patient selection is critical for AOF prevention.

Clinical outcomes following laparoscopic radical nephroureterectomy in octogenarians.

BACKGROUND: This study aimed to compare the incidence of postoperative complications occurring within 30 days of surgery between octogenarians and younger patients and identify preoperative risk factors for the incidence of postoperative complications. Moreover, we also compared the oncological outcomes between octogenarians and younger patients. METHODS: This retrospective study included 283 patients who underwent laparoscopic radical nephroureterectomy for upper tract urothelial carcinoma from 2002 to 2020. The patients were divided into octogenarians and younger patients (age: < 80 years), and their clinical characteristics, perioperative parameters, and postoperative complications were evaluated. The predictors of postoperative complications were evaluated using logistic regression models. Recurrence-free survival, cancer-specific survival, and overall survival were measured using the Kaplan-Meier method. RESULTS: Twelve (17.1%) octogenarians and 40 (18.7%) younger patients had postoperative complications. No significant difference in the incidence of postoperative complications was observed between octogenarians and younger patients (p = 0.14). A high body mass index was a significant risk factor for complications (p = 0.03). The 5-year recurrence-free survival, cancer-specific survival, and overall survival rates for octogenarians and younger patients were 72% and 64% (p = 0.31), 76% and 63% (p = 0.63), and 43% and 63% (p = 0.06), respectively. CONCLUSION: Laparoscopic radical nephroureterectomy can be performed in octogenarians with complication rates similar to those in younger patients. Similarly, the outcomes of laparoscopic radical nephroureterectomy for oncological control do not differ significantly between octogenarians and younger patients. This procedure is safe and effective for selected octogenarians.

[Renal Pseudoaneurysm Developed after Flexible Transurethral Lithotripsy : A Case Report].

A 73-year-old woman was referred to our hospital for treatment of a 12 mm stone in the right ureteropelvic junction and pyonephrosis. A double-J ureteral stent was indwelled for right hydronephrosis and emphysematous pyelonephritis. After antibiotic treatment, flexible transurethral lithotripsy (f-TUL) was performed and all the stones were disintegrated and extracted without any complications. On the day after f-TUL, severe back pain occurred, and computed tomography revealed subcapsular hematoma and renal pseudoaneurysm. Angiography and selective embolization of the bleeding artery were performed to control the bleeding.

Oncological Outcomes of Retroperitoneal Lymph Node Dissection During Retroperitoneal Laparoscopic Radical Nephroureterectomy for Renal Pelvic or Upper Ureteral Tumors: Matched-Pair Analysis.

Objectives: The aim of this study was to investigate the oncological outcomes and recurrence patterns in clinically node-negative patients with renal pelvic and/or upper or middle ureteral tumors after template-based retroperitoneal lymph node dissection (RPLND) in conjunction with retroperitoneal laparoscopic radical nephroureterectomy (LRNU). Materials and Methods: A total of 283 patients who received LRNU with and without RPLND at three Japanese institutions were enrolled. The template for RPLND included the renal hilar and para-aortic lymph nodes (LNs) (left side) and renal hilar, paracaval, retrocaval, and intra-aortocaval LNs (right side). The LNs and kidneys were removed en bloc. The primary endpoint was set as recurrence-free survival. All RPLND cases were matched one-to-one with no-RPLND cases using a propensity score matching approach, and 47 matched pairs were included in analyses. Results: Compared with the control group, significant differences were not observed in the RPLND group in terms of operation time, blood loss, postoperative complication rate, and pathological findings. The estimated 5-year recurrence-free survival was significantly higher in the RPLND group (86.8%) compared with the group without RPLND (64.2%) (p = 0.014). The estimated 5-year cancer-specific survival showed a similar tendency; however, it did not reach a statistically significant difference (87.5% vs 71.3%, respectively; p = 0.168). As for the first recurrence site, the RPLND group showed a lower incidence of distant recurrence, while no significant difference was observed in the rate of regional LN recurrence. Conclusions: This study suggests that template-based RPLND in conjunction with retroperitoneal LRNU efficiently improves recurrence-free survival by reducing distant recurrences.

Complications and their management following retroperitoneal lymph node dissection in conjunction with retroperitoneal laparoscopic radical nephroureterectomy.

OBJECTIVES: To describe the detailed perioperative complications and their management after retroperitoneal lymph node dissection with retroperitoneal laparoscopic radical nephroureterectomy for patients with upper tract urothelial carcinoma at three institutions. METHODS: Retroperitoneal lymph node dissection was performed on patients with upper tract urothelial carcinoma located at the pelvis and/or upper or middle ureter, and its template included the renal hilar and para-aortic lymph nodes (left side) and the renal hilar, paracaval, retrocaval, and intra-aortocaval lymph nodes (right side). The lymph nodes and kidneys were removed en bloc. The primary endpoint was postoperative complication rates, and the secondary endpoints were intraoperative findings and chylous leakage management. The associations of retroperitoneal lymph node dissection with postoperative complications were examined using logistic regression with propensity score techniques. RESULTS: Eighty-eight (31%) and 195 (69%) patients underwent and did not undergo retroperitoneal lymph node dissection, respectively. There was no significant difference in postoperative complications and other perioperative findings in the entire cohort, except for prolonged operation time. Retroperitoneal lymph node dissection was not statistically significantly associated with total and serious complications in propensity score analyses. Postoperative chylous leakage could be conservatively managed even though it is common in patients with retroperitoneal lymph node dissection (14/88 (16%)). The incidence of chylous leakage was significantly lower in patients whose lymphatic vessels were meticulously clipped completely during retroperitoneal lymph node dissection (5.3% vs 24%; P = 0.017). CONCLUSION: There was no association between retroperitoneal lymph node dissection with laparoscopic radical nephroureterectomy and postoperative complications. However, chylous leakage is often observed after retroperitoneal lymph node dissection and careful management is highly required. The use of clips during retroperitoneal lymph node dissection is recommended to minimize chylous leakage risk.

[A Case of Prostate Cancer with High Levels of Prostate-Specific Antigen Undetected by Prostate Biopsy].

A 79 year-old-man visited our hospital with right back pain. Computed tomography suggested external iliac and para-aortic lymphadenopathy. Serum prostate specific antigen (PSA) increased to 335 ng/ml and prostate cancer was highly suspected. We performed transperineal prostate biopsies two times, but could not detect prostate carcinoma cells. Multiparametric magnetic resonance imaging (MRI) indicated no suspicious malignant lesions in the prostate. Laparoscopic biopsy of the right obturator lymph nodes was performed and histological examination, including immunohistochemical staining with PSA, confirmed lymphnode metastasis from prostate cancer. After endocrine therapy was started, serum PSA levels declined and lymph nodes shrunk. In cases of negative prostate biopsies despite high serum PSA levels, aggressive indication for biopsy of metastatic lesion and histological inspection is highly recommended.

[A Case of Hemodialysis-Associated Pelvic Amyloidoma Mimicking Renal Cancer-Associated Etiology].

Patients with renal insufficiency receiving long-term hemodialysis often develop so-called hemodialysis amyloidosis characterized by systemic ß 2-microglobulin amyloid lesions, while patients with renal cell carcinoma may develop amyloid A(AA) amyloidosis. Herein, we present a 67-year-old man on thirty-yearlong hemodialysis who was diagnosed to have left renal cell carcinoma coincident with a large spaceoccupying lesion adjacent to the psoas muscle in the pelvic cavity. An ultrasound-guided percutaneous needle biopsy was performed at the time of laparoscopic radical nephrectomy. The pathological work-up on the needle biopsy specimen revealed that the lesion was not an AA amyloidoma but a ß2-microglobulin amyloidoma, which is a rare manifestation of hemodialysis amyloidosis.

[A case of Mycoplasma hominis infection after bladder injury during cesarean section].

A 21-year-old female patient underwent emergency cesarean section and a postoperative hematoma occurred at the site of the uterine incision. The patient underwent laparotomy for hemostasis. An 3 cm perforation at the posterior wall of the bladder was identified. The bladder was repaired in two layers with an absorbable suture. Three days later she developed a fever of over 38 degrees C. Despite therapy with several antimicrobial agents, her fever persisted and the wound was opened. Computed tomography scan revealed an abscess at the site where the hematoma had formed. We present a case of severe wound infection that was caused by Mycoplasma hominis infection after cesarean section. Bladder perforation associated with cesarean section is uncommon. Mycoplasma hominis should be considered as a causative organism if an antimicrobial resistant infection occurs at the surgical site after a cesarean section.

[A case of prostate cancer with disseminated carcinomatosis of bone marrow which responded to Zoledronic acid].

A 76-year-old man underwent radical prostatectomy under the diagnosis of stage C prostate cancer (cT3bN0M0, Gleason score 3＋4) in 1999. Endocrine treatment for postoperative biochemical failure started in 2001. He was admitted to our hospital because of general fatigue and multiple bone pain with a prostate specific antigen (PSA) level of 1,141 ng/ml in August 2009. On admission, no metastasis was detected on bone scintigraphy or computed tomography. Bone marrow biopsy was finally performed for the assessment of bone metastasis after PSA further increased to 8,679 ng/ml with the manifestation of severe anemia and thrombocytopenia. The biopsy findings disclosed disseminated carcinomatosis of bone marrow (DCBM). Treatment with Zoledronic acid (ZA) not only mitigated bone pain, but also rapidly improved of PSA and hematological findings. Although the prognosis of a patient with DCBM is generally considered to be very poor, ZA contributed to the improvement for the survival of the patient in the present case.

Mercaptoacetyltriglycine-3 renogram is not superior to estimated glomerular filtration rate measurement for the prediction of long-term renal function after nephrectomy.

OBJECTIVE: To evaluate the clinical usefulness of effective renal plasma flow (ERPF) measured using preoperative mercaptoacetyltriglycine-3 (MAG3) renogram for the prediction of chronic renal insufficiency after nephrectomy. METHODS: A total of 47 patients underwent preoperative MAG3 renal scintigraphy and subsequent unilateral nephrectomy. Correlations between the 5-year postoperative estimated glomerular filtration rate (eGFR) and the preoperative ERPF of the contralateral kidney (cERPF), ERPF of the diseased kidney (dERPF), total ERPF (tERPF), cERPF to dERPF ratio, serum creatinine (sCr) level, eGFR, as well as the influence of preoperative comorbidities (diabetes, hypertension) on the postoperative eGFR, were evaluated with both univariate and multivariate analyses. RESULTS: Multiple linear regression analysis showed that preoperative cERPF significantly correlated with postoperative eGFR. However, a much stronger correlation was observed between the preoperative and postoperative eGFR. Multiple logistic regression analysis showed that only preoperative eGFR was a significant predicator of the development of advanced-stage chronic kidney disease (CKD). CONCLUSIONS: Preoperative MAG3 renogram is not superior to eGFR measurement as a prognostic indicator of long-term renal function after unilateral nephrectomy.

A case of laparoscopic excision of a huge retroperitoneal cystic lymphangioma.

Retroperitoneal cystic lymphangioma is a rare benign tumor. Most patients eventually experience some symptoms that necessitate therapeutic intervention. Excision is the treatment of choice, and some cases of laparoscopic resection have been reported. We report another case of a huge retroperitoneal cystic lymphangioma that was successfully excised laparoscopically with the SAND balloon catheter. Large cystic lymphangioma was downsized by puncturing and aspirated with the SAND balloon catheter. Laparoscopic surgical technique should be considered for treatment of selected cystic lesions of retroperitoneal origin.

Differential control of allo-antigen-specific regulatory T cells and effector T cells by anti-CD4 and other agents in establishing transplantation tolerance.

Donor-specific graft tolerance can be established by a combination of allo-antigen exposure and manipulation of T cell function, for example by donor-specific transfusion (DST) under the cover of a non-depleting anti-CD4 mAb. Yet, the cellular basis of this graft tolerance is still obscure. This report shows that T cell-deficient BALB/c nude mice reconstituted with naive unfractionated T cells are specifically tolerized to DBA/2 skin grafts by DST and anti-CD4 mAb treatment, whereas those transferred with T cell suspensions depleted of all Foxp3(+)CD25(+)CD4(+) natural regulatory T cells (Tregs) are not. The treatment inhibits Mls-1(a) allo-antigen-specific expansion of CD4(+) non-Tregs expressing Vbeta6 TCR subfamily but leaves the expansion of Vbeta6-expressing Tregs unaffected, allowing the latter to selectively expand and establish donor-specific tolerance. Furthermore, anti-CD4 mAb inhibits in vitro the selective expansion of allo-antigen-specific CD4(+) non-Tregs but not natural Tregs, as observed with in vitro anti-CD154 [CD40 ligand (CD40L)] mAb or rapamycin treatment. The results collectively indicate that the differential effect of biologicals and pharmacological substances on the expansion of allo-antigen-specific Tregs and effector T cells and resulting dominance of the former can be a key general mechanism underlying dominant transplantation tolerance.

Genetic polymorphisms in glutathione S-transferase T1 affect the surgical outcome of varicocelectomies in infertile patients.

Glutathione S-transferases (GSTs), superoxide dismutase 2 (SOD2) and NAD(P)H:quinone oxidoreductase 1 (NQO1) are anti-oxidant enzyme genes. Polymorphisms of GSTs, SOD2 and NQO1 have been reported to influence individual susceptibility to various diseases. In an earlier study, we obtained preliminary findings that a subset of glutathione S-transferase T1 (GSTT1)-wt patients with varicocele may exhibit good response to varicocelectomy. In this study, we extended the earlier study to determine the distribution of genotype of each gene in the infertile population and to evaluate whether polymorphism of these genes affects the results of surgical treatment of varicocele. We analyzed 72 infertile varicocele patients, 202 infertile patients without varicocele and 101 male controls. Genotypes of GSTs were determined by polymerase chain reaction (PCR). Genotyping of SOD2 and NQO1 was performed using the PCR-restriction fragment length polymorphism (PCR-RFLP) method. A significantly better response to varicocelectomy was found in patients with the GSTT1-wt genotype (63.2%) and NQO1-Ser/Ser genotype (80.0%) than in those with GSTT1-null genotype (35.3%) and NQO1-Pro/Pro or NQO1-Pro/Ser genotype (45.2%), respectively. The frequencies of glutathione S-transferase M1/T1, SOD2 and NQO1 genotypes did not differ significantly among the varicocele patients, idiopathic infertile patients and male controls. GSTT1 genotype is associated with improvement of semen parameters after varicocelectomy. As the number of patients with NQO1-Ser/Ser genotype was not sufficient to reach definite conclusions, the association of NQO1 genotype with varicocelectomy requires further investigation.

Induction of tolerance by adoptive transfer of Treg cells.

Naturally arising CD4+CD25+ regulatory T (Treg) cells can be exploited to establish immunologic tolerance to allogeneic transplants. In vivo exposure of CD4+CD25+ T cells from normal naive mice to alloantigen in a T cell-deficient environment elicits spontaneous expansion of alloantigen-specific CD4+CD25+ natural Treg cells, which are able to suppress allograft rejection mediated by subsequently transferred naive T cells, leading to long-term graft tolerance. Similar antigen-specific expansion of natural Treg cells can also be achieved in vitro by stimulating CD4+CD25+ T cells from normal animals with alloantigen in the presence of high doses of interleukin-2. The expanded CD4+CD25+ Treg cells are even capable of suppressing secondary mixed leukocyte reaction in vitro and, by in vivo transfer, establishing antigen-specific long-term graft tolerance. Thus, in vivo or in vitro, direct or indirect ways of alloantigen-specific expansion of naturally arising CD4+CD25+ Treg cells can establish antigen-specific dominant tolerance to allogeneic transplants.

Control of immune responses by antigen-specific regulatory T cells expressing the folate receptor.

Immune responses can be enhanced or dampened by differential manipulation of Foxp3-expressing CD25(+)CD4(+) natural regulatory T (Treg) cells versus other naive or activated T cells. By searching for a molecule capable of distinguishing these populations, we here found that natural Treg cells constitutively expressed high amounts of folate receptor 4 (FR4). The expression of FR4 and CD25 also separated antigen-stimulated CD4(+) non-Treg cells into the FR4(hi)CD25(-) and FR4(lo)CD25(+) populations, which were different in proliferation and cytokine secretion upon restimulation. These distinctions showed that antigenic stimulation activated and expanded antigen-specific natural Treg cells as well as effector and memory T cells. Accordingly, FR4(hi)CD25(+)CD4(+) T cells enriched from alloantigen-stimulated T cells suppressed graft rejection. Administration of FR4 monoclonal antibody specifically reduced Treg cells, provoking effective tumor immunity in tumor-bearing animals, whereas similar treatment of normal young mice elicited autoimmune disease. Thus, specific manipulation of FR4(hi)CD25(+)CD4(+) Treg cells helps control ongoing immune responses.

GSTT1 and GSTM1 polymorphisms are associated with improvement in seminal findings after varicocelectomy.

To identify the best candidates for varicocelectomy, we evaluated the genetic polymorphism in glutathione S-transferase (GST) T1 and M1 in 38 infertile men with high-grade varicocele testis who underwent varicocelectomy. The response rate to varicocelectomy is significantly higher in patients with the GSTT1-wt genotype than the GSTT1-null genotype, and the response rate became higher in combination with the GSTM1 genotype.

[Small intestinal metastases from renal cell carcinoma: a case report and literature review].

We report a case of small intestinal metastasis from renal cell carcinoma (RCC) in a 57-year-old female. The patient had undergone partial nephrectomy for a right RCC (pT1aN0M0) in June 1997. She later developed multiple metastases, in the lungs, brain, and bone, and was admitted with nausea, vomiting, and appetite loss in April 2003. She presented with melaena a few weeks after her admission and a computed tomographic scan revealed a small bowel mass that was not definitively diagnosed. We removed the mass surgically, and the histological features confirmed the diagnosis as metastatic RCC. The patient recovered and could consume, but died of brain metastases 102 days after the surgery. Metastasis of RCC in the small bowel is a rare entity clinically. To our knowledge, this is only the 20th case of small intestinal metastasis from RCC reported in the Japanese and English literature.