Latrophilin-3 as a downstream effector of the androgen receptor induces urothelial tumorigenesis.

Emerging evidence indicates that androgen receptor (AR) signaling plays a critical role in the pathogenesis of male-dominant urothelial cancer. Meanwhile, latrophilins (LPHNs), a group of the G-protein-coupled receptor to which a spider venom latrotoxin is known to bind, remain largely uncharacterized in neoplastic diseases. The present study aimed to determine the functional role of LPHN3 (encoded by the ADGRL3 gene), in association with AR signaling, in urothelial tumorigenesis. In human normal urothelial SVHUC cells, AR overexpression and androgen treatment considerably increased the expression levels of ADGRL3/LPHN3, while chromatin immunoprecipitation assay revealed the binding of AR to the promoter region of ADGRL3. In SVHUC or SVHUC-AR cells with exposure to a chemical carcinogen 3-methylcholanthrene, LPHN3 activation via ligand (e.g., α-latrotoxin, FLRT3) treatment during the process of the neoplastic/malignant transformation or LPHN3 knockdown via shRNA virus infection induced or reduced, respectively, the oncogenic activity. In N-butyl-N-(4-hydroxybutyl)nitrosamine-treated female mice, α-latrotoxin or FLRT3 injection accelerated the development of bladder tumors. Immunohistochemistry in surgical specimens further showed the significantly elevated expression of LPHN3 in non-muscle-invasive bladder tumors, compared with adjacent normal urothelial tissues, which was associated with a marginally (p = 0.051) higher risk of disease recurrence after transurethral resection. In addition, positivity of LPHN3 and AR in these tumors was strongly correlated. These findings indicate that LPHN3 functions as a downstream effector of AR and promotes urothelial tumorigenesis.

Prostate Cancer Risk Stratification by Simple Scoring of the Current pT3 Lesions: A Proposal for a New Pathologic T-Staging System.

Cancer spread beyond the prostate, including extraprostatic extension (other than seminal vesicle or bladder invasion; EPE)/microscopic bladder neck invasion and seminal vesicle invasion (SVI) currently classified as pT3a and pT3b lesions, respectively, does not uniformly indicate poor oncologic outcomes. Accurate risk stratification of current pT3 disease is therefore required. We herein further determined the prognostic impact of these histopathologic lesions routinely assessed and reported by pathologists, particularly their combinations. We assessed consecutive 2892 patients undergoing radical prostatectomy for current pT2 (n = 1692), pT3a (n = 956), or pT3b (n = 244) disease at our institution between 2009 and 2018. Based on our preliminary findings, point(s) were given (1 point to focal EPE, microscopic bladder neck invasion, or unilateral SVI; 2 points to nonfocal/established EPE or bilateral SVI) and summed up in each case. Our cohort had 0 point (n = 1692, 58.5%; P0), 1 point (n = 243, 8.4%; P1), 2 points (n = 657, 22.7%; P2), 3 points (n = 192, 6.6%; P3), 4 points (n = 76, 2.6%; P4), and 5 points (n = 32, 1.1%; P5). Univariate analysis revealed associations of higher points with significantly worse biochemical progression-free survival, particularly when P4 and P5 were combined. In multivariable analysis (P0 as a reference), P1 (hazard ratio [HR], 1.57; P = .033), P2 (HR, 3.25; P < .001), P3 (HR, 4.01; P < .001), and P4 + P5 (HR, 5.99; P < .001) showed significance for the risk of postoperative progression. Meanwhile, Harrell C-indexes for the current pT staging, newly developed point system, and the Cancer of the Prostate Risk Assessment post-Surgical (CAPRA-S) score were 0.727 (95% CI, 0.706-0.748), 0.751 (95% CI, 0.729-0.773), and 0.774 (95% CI, 0.755-0.794), respectively, for predicting progression. We believe our data provide a logical rationale for a novel pathologic T-staging system based on the summed points, pT1a (0 point), pT1b (1 point), pT2 (2 points), pT3a (3 points), and pT3b (4 or 5 points), which more accurately stratifies the prognosis of prostate cancer.

Latrophilins as Downstream Effectors of Androgen Receptors including a Splice Variant, AR-V7, Induce Prostate Cancer Progression.

Latrophilins (LPHNs), a group of the G-protein-coupled receptor to which a spider venom latrotoxin (LTX) is known to bind, remain largely uncharacterized in neoplastic diseases. In the present study, we aimed to determine the role of LPHNs in the progression of prostate cancer. We assessed the actions of LPHNs, including LPHN1, LPHN2, and LPHN3, in human prostate cancer lines via their ligand (e.g., α-LTX, FLRT3) treatment or shRNA infection, as well as in surgical specimens. In androgen receptor (AR)-positive LNCaP/C4-2/22Rv1 cells, dihydrotestosterone considerably increased the expression levels of LPHNs, while chromatin immunoprecipitation assay revealed the binding of endogenous ARs, including AR-V7, to the promoter region of each LPHN. Treatment with α-LTX or FLRT3 resulted in induction in the cell viability and migration of both AR-positive and AR-negative lines. α-LTX and FLRT3 also enhanced the expression of Bcl-2 and phosphorylated forms of JAK2 and STAT3. Meanwhile, the knockdown of each LPHN showed opposite effects on all of those mediated by ligand treatment. Immunohistochemistry in radical prostatectomy specimens further showed the significantly elevated expression of each LPHN in prostate cancer, compared with adjacent normal-appearing prostate, which was associated with a significantly higher risk of postoperative biochemical recurrence in both univariate and multivariable settings. These findings indicate that LPHNs function as downstream effectors of ARs and promote the growth of androgen-sensitive, castration-resistant, or even AR-negative prostate cancer.

Risk Stratification by Quantification of Perineural Cancer Invasion on Prostate Needle Core Biopsy: Should It Be Counted?

PURPOSE: We assessed the prognostic significance of quantification of perineural invasion on prostate biopsy. MATERIALS AND METHODS: We quantified actual perineural invasion foci in the entire prostate biopsy specimens from 724 patients and compared corresponding radical prostatectomy findings and long-term oncologic outcomes. RESULTS: No perineural invasion was detected in 524 (72.4%) prostate biopsies, whereas 1 (n=129; 17.8%), 2 (n=40; 5.5%), 3 (n=18; 2.5%), 4 (n=7; 1.0%), and 5-10 (n=6; 0.8%) perineural invasion foci were present in other cases. We confirmed a higher risk of recurrence after radical prostatectomy in patients with perineural invasion on prostate biopsy than in those with no perineural invasion (P < .001). Remarkably, recurrence-free survival was comparable between those with 0 vs 1 perineural invasion (P = .9) or 2 vs ≥3 perineural invasions (P = .3). Nonetheless, multifocal perineural invasion per prostate biopsy (vs single perineural invasion; P < .001) and >1 perineural invasion per 10-mm tumor (vs ≤1 perineural invasion; P = .008) were associated with worse outcomes. Interestingly, in a subgroup outcome analysis of single vs multifocal perineural invasions per prostate biopsy, there was a significant difference in patients showing perineural invasion involving only 1 of the sextant sites. In multivariable analysis, both multifocal perineural invasion/case (HR=5.48, P < .001) and >1 perineural invasion/10-mm tumor (HR=3.96, P < .001) showed significance for recurrence. Meanwhile, compared with CAPRA (Cancer of the Prostate Risk Assessment) score alone (0.687/0.685), Harrell's C index/AUC for predicting 5-year recurrence-free survival was gradually increased when 1 (0.722/0.740), 2 (0.747/0.773), or 3 (0.760/0.792) point(s) were additionally assigned to multifocal perineural invasion. CONCLUSIONS: Multifocal perineural invasion and >1 perineural invasion per 10-mm tumor on each prostate biopsy were thus found to be associated with poorer prognosis, as independent predictors, in men with prostate cancer undergoing radical prostatectomy.

GABBR2 as a Downstream Effector of the Androgen Receptor Induces Cisplatin Resistance in Bladder Cancer.

The precise molecular mechanisms responsible for resistance to cisplatin-based chemotherapy in patients with bladder cancer remain elusive, while we have indicated that androgen receptor (AR) activity in urothelial cancer is associated with its sensitivity. Our DNA microarray analysis in control vs. AR-knockdown bladder cancer sublines suggested that the expression of a GABA B receptor GABBR2 and AR was correlated. The present study aimed to determine the functional role of GABBR2 in modulating cisplatin sensitivity in bladder cancer. AR knockdown and dihydrotestosterone treatment considerably reduced and induced, respectively, GABBR2 expression, and the effect of dihydrotestosterone was at least partially restored by an antiandrogen hydroxyflutamide. A chromatin immunoprecipitation assay further revealed the binding of AR to the promoter region of GABBR2 in bladder cancer cells. Meanwhile, GABBR2 expression was significantly elevated in a cisplatin-resistant bladder cancer subline, compared with control cells. In AR-positive bladder cancer cells, knockdown of GABBR2 or treatment with a selective GABA B receptor antagonist, CGP46381, considerably enhanced the cytotoxic activity of cisplatin. However, no additional effect of CGP46381 on cisplatin-induced growth suppression was seen in GABBR2-knockdown cells. Moreover, in the absence of cisplatin, CGP46381 treatment and GABBR2 knockdown showed no significant changes in cell proliferation or migration. These findings suggest that GABBR2 represents a key downstream effector of AR signaling in inducing resistance to cisplatin treatment. Accordingly, inhibition of GABBR2 has the potential of being a means of chemosensitization, especially in patients with AR/GABBR2-positive bladder cancer.

Trp53 Mutation in Keratin 5 (Krt5)-Expressing Basal Cells Facilitates the Development of Basal Squamous-Like Invasive Bladder Cancer in the Chemical Carcinogenesis of Mouse Bladder.

The biological processes of urothelial carcinogenesis are not fully understood, particularly regarding the relationship between specific genetic events, cell of origin, and molecular subtypes of subsequent tumors. N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-induced mouse bladder cancer is widely accepted as a useful model that recapitulates the pathway of human bladder tumorigenesis from dysplasia to invasive cancer via carcinoma in situ. However, the long and variable time of tumorigenesis often hinders efficient preclinical or translational research. We hypothesized that Trp53 mutation in specific types of urothelial cells facilitates efficient development of clinically relevant bladder cancer. Using lineage tracing, we showed that Trp53 mutation in Krt5-expressing cells resulted in more efficient tumorigenesis of mouse muscle-invasive bladder cancer (MIBC) with squamous differentiation compared with Trp53 mutation in Upk2-expressing cells, or wild-type or hemizygous Trp53 in the entire urothelium. Mouse MIBC that developed at 24 weeks of BBN treatment showed morphologic and genetic similarities to the basal squamous subtypes of human MIBC, irrespective of pre-induction of Trp53 mutation or whether the cell of origin was Krt5- or Upk2-expressing cells. Our findings suggest that intermediate cells as well as basal cells also can give rise to basal-like MIBC, with pre-induction of Trp53 mutation accelerating MIBC. Thus, in BBN chemical carcinogenesis, pre-induction of Trp53 mutation in basal cells facilitates efficient modeling of the basal squamous subtype of human MIBC.

Androgen Receptor Signaling Induces Cisplatin Resistance via Down-Regulating GULP1 Expression in Bladder Cancer.

The underlying molecular mechanisms of resistance to cisplatin-based systemic chemotherapy in bladder cancer patients remain to be elucidated, while the link between androgen receptor (AR) activity and chemosensitivity in urothelial cancer has been implicated. Our DNA microarray analysis in control vs. AR knockdown bladder cancer lines identified GULP1 as a potential target of AR signaling. We herein determined the relationship between AR activity and GULP1 expression in bladder cancer cells and then assessed the functional role of GULP1 in cisplatin sensitivity. Androgen treatment in AR-positive cells or AR overexpression in AR-negative cells considerably reduced the levels of GULP1 expression. Chromatin immunoprecipitation further showed direct interaction of AR with the promoter region of GULP1. Meanwhile, GULP1 knockdown sublines were significantly more resistant to cisplatin treatment compared with respective controls. GULP1 knockdown also resulted in a significant decrease in apoptosis, as well as a significant increase in G2/M phases, when treated with cisplatin. In addition, GULP1 was immunoreactive in 74% of muscle-invasive bladder cancers from patients who had subsequently undergone neoadjuvant chemotherapy, including 53% of responders showing moderate (2+)/strong (3+) expression vs. 23% of non-responders showing 2+/3+ expression (P = 0.044). These findings indicate that GULP1 represents a key downstream effector of AR signaling in enhancing sensitivity to cisplatin treatment.

FOXO1 inactivation induces cisplatin resistance in bladder cancer.

We found that FOXO1-shRNA sublines or FOXO1-positive cells co-treated with a FOXO1 inhibitor were significantly more resistant to cisplatin treatment at pharmacological concentrations, compared with respective control sublines or those with mock treatment. Western blot demonstrated considerable increases in the expression levels of a phosphorylated inactive form of FOXO1 (p-FOXO1) in cisplatin-resistant sublines established by long-term culture with low/increasing doses of cisplatin, compared with respective controls. Immunohistochemistry in surgical specimens from patients with muscle-invasive bladder cancer undergoing cisplatin-based neoadjuvant therapy further showed a strong trend to associate between p-FOXO1 positivity and unfavorable response to chemotherapy.

Discohesive growth pattern (Disco-p) as an unfavorable prognostic factor in lung adenocarcinoma: an analysis of 1062 Japanese patients with resected lung adenocarcinoma.

Discohesive growth pattern (Disco-p) is often observed in lung adenocarcinoma (ADC) and mimics tumor budding (TB), stromal invasive-type micropapillary pattern (SMPP), and complex glandular pattern. However, the clinical impact of Disco-p in lung ADC has not been well studied. To investigate the prognostic significance of Disco-p, we analyzed 1062 Japanese patients with resected lung ADC. Disco-p was defined as an invasive growth pattern composed of single tumor cells, or trabeculae or small nests of tumor cells associated with desmoplastic fibrous stroma. We recorded the percentage of Disco-p in 5% increments independent of the major histologic pattern and investigated its correlation with different clinicopathological factors. We also analyzed the overall survival (OS) and disease-free survival (DFS). Disco-p was observed in 203 tumors (19.1%). Disco-p was significantly associated with male sex, smoking, lymph node metastasis, large tumor size, high TNM stage, lymphovascular and pleural invasion, spread through air spaces, and TB (all, p < 0.001). Of the total cases, only eight cases exhibited a dubious pattern between SMPP and Disco-p. Disco-p was also associated with wild-type EGFR (p < 0.001) and ALK fusion (p = 0.008). Patients harboring tumors with Disco-p had significantly worse prognoses (OS and DFS (both, p < 0.001)) compared with those without Disco-p. On multivariate analysis, Disco-p was an independent prognostic factor of worse OS (hazard ratio (HR), 2.572; 95% confidence interval (CI), 1.789-3.680; p < 0.001), and DFS (HR, 3.413; 95% CI, 2.482-4.683; p < 0.001), whereas TB was not an independent unfavorable prognostic factor. Disco-p was an independent unfavorable prognostic factor in patients with resected lung ADC, although a careful evaluation is necessary to distinguish it from similar patterns. We proposed that Disco-p should be recognized as a new invasive pattern and accurately recorded for the better management of patients with lung ADCs.

Detectability of prostate cancer in different parts of the gland with 3-Tesla multiparametric magnetic resonance imaging: correlation with whole-mount histopathology.

BACKGROUND: We investigated whether the detectability of prostate cancer with 3-Tesla (3T) multiparametric magnetic resonance imaging (mpMRI) differs by tumor location. METHODS: We identified 136 patients with prostate cancer who underwent 3-T mpMRI before prostatectomy at a single academic center. Two uroradiologists scored all MRIs with Prostate Imaging-Reporting and Data System version 2 (PI-RADS v2). A genitourinary pathologist mapped tumor foci from serial whole-mount radical prostatectomy sections. We assessed concordance of images with cancer sites. Tumor foci with Gleason score ≥  3 + 4 or volume ≥ 0.5 mL were considered significant. RESULTS: A total of 122 foci in 106 cases were identified with mpMRI. Twenty-four were PI-RADS 3, 52 were 4, and 46 were 5. A total of 274 tumor foci were identified with whole-mount pathology. The sensitivity stratified by location to detect significant cancer with a PI-RADS cutoff value of 3 was 56.0% overall, 50.0% in the peripheral zone (PZ), 71.2% in the transitional zone (TZ), 62.4% anterior, 49.5% posterior, 42.0% apical, 63.6% in the midgland, and 43.8% in the gland base. In multivariate analysis, tumor location was not a significant predictor of identification by mpMRI. Tumor volume, Gleason score, and index tumor status were significantly associated with identification by mpMRI. CONCLUSIONS: mpMRI detected the majority of high-grade and large cancers, but had low sensitivity in the PZ, posterior, and apex and base of the gland. The high prevalence of low-volume, low-Gleason score index tumors, as well as satellite tumors in those areas, accounted for the difference.

Diameter of the dilated main pulmonary artery in patients with pulmonary hypertension decreases after lung transplantation.

PURPOSE: The pulmonary artery (PA) in patients with pulmonary hypertension (PH) becomes dilated. We analyzed the postoperative changes of the main PA after lung transplantation (LuTx). METHODS: The subjects of this retrospective study were 68 LuTx recipients, divided into a PH group (n = 36) and a non-PH group (n = 32), based on preoperative right heart catheterization findings. The PA diameter was measured on chest computed tomography. We evaluated the correlation between the mean pulmonary arterial pressure (mPAP) and the main PA diameter and compared the main PA diameters before and 3 months after LuTx. RESULTS: The main PA diameter was significantly correlated with the mPAP (r = 0.423, P < 0.001). Preoperatively, the mean main PA diameter in the PH group was significantly greater than that in the non-PH group. However, by 3 months after LuTx, the main PA diameter in the PH group had decreased significantly from 32.4 ± 6.7 to 26.9 ± 4.8 mm (P < 0.001), while that in the non-PH group had decreased minimally from 28.3 ± 4.9 to 26.4 ± 4.6 mm (P < 0.001), resulting in no significant difference in postoperative main PA diameters between the two groups. CONCLUSIONS: The main PA diameter in recipients with PH was enlarged and correlated with the mPAP. The dilated main PA diameter in PH patients decreased shortly after LuTx.

Downregulation of RalGTPase-activating protein promotes invasion of prostatic epithelial cells and progression from intraepithelial neoplasia to cancer during prostate carcinogenesis.

RalGTPase-activating protein (RalGAP) is an important negative regulator of small GTPases RalA/B that mediates various oncogenic signaling pathways in various cancers. Although the Ral pathway has been implicated in prostate cancer (PCa) development and progression, the significance of RalGAP in PCa has been largely unknown. We examined RalGAPα2 expression using immunohistochemistry on two independent tissue microarray sets. Both datasets demonstrated that the expression of RalGAPα2 was significantly downregulated in PCa tissues compared to adjacent benign prostatic epithelia. Silencing of RalGAPα2 by short hairpin RNA enhanced migration and invasion abilities of benign and malignant prostate epithelial cell lines without affecting cell proliferation. Exogenous expression of wild-type RalGAP, but not the GTPase-activating protein activity-deficient mutant of RalGAP, suppressed migration and invasion of multiple PCa cell lines and was phenocopied by pharmacological inhibition of RalA/B. Loss of Ralgapa2 promoted local microscopic invasion of prostatic intraepithelial neoplasia without affecting tumor growth in a Pten-deficient mouse model for prostate tumorigenesis. Our findings demonstrate the functional significance of RalGAP downregulation to promote invasion ability, which is a property necessary for prostate carcinogenesis. Thus, loss of RalGAP function has a distinct role in promoting progression from prostatic intraepithelial neoplasia to invasive adenocarcinoma.

Systematic chemical screening identifies disulfiram as a repurposed drug that enhances sensitivity to cisplatin in bladder cancer: a summary of preclinical studies.

BACKGROUND: Since the standard gemcitabine and cisplatin (GC) chemotherapy for advanced bladder cancer yields limited therapeutic effect due to chemoresistance, it is a clinical challenge to enhance sensitivity to GC. METHODS: We performed high-throughput screening by using a library of known chemicals and repositionable drugs. A total of 2098 compounds were administered alone or with GC to human bladder cancer cells, and chemicals that enhanced GC effects were screened. RESULTS: Disulfiram (DSF), an anti-alcoholism drug, was identified as a candidate showing synergistic effects with cisplatin but not with gemcitabine in multiple cell lines. Co-administration of DSF with GC affected cellular localisation of a cisplatin efflux transporter ATP7A, increased DNA-platinum adducts and promoted apoptosis. Micellar DSF nanoparticles (DSF-NP) that stabilised DSF in vivo, enhanced the inhibitory effect of cisplatin in patient-derived and cell-based xenograft models without severe adverse effects. A drug susceptibility evaluation system by using cancer tissue-originated spheroid culture showed promise in identifying cases who would benefit from DSF with cisplatin. CONCLUSIONS: The present study highlighted the advantage of drug repurposing to enhance the efficacy of anticancer chemotherapy. Repurposing of DSF to a chemotherapy sensitiser may provide additional efficacy with less expense by using an available drug with a well-characterised safety profile.

[Kidney Auto-Transplantation for Intraoperative Right Renal Artery Injury in a Single Kidney Patient : A Case Report].

A man in his 70's who had undergone left radical nephrectomy for kidney cancer had the right renal artery ablated unexpectedly during pancreatoduodenectomy for a huge duodenal tumor. For this intraoperative emergency, an autologous kidney transplantation was performed with the right kidney being removed, perfused, and transplanted into the right iliac fossa. Warm ischemic time was over 2 hours. The patient developed postoperative hemorrhagic infarction of a renal artery branch, which was successfully treated with intravascular intervention. The patient was weaned off hemodialysis and was discharged in 16 weeks postoperatively.

[A Case of Late Onset Nivolumab-Induced Interstitial Nephritis in a Patient with Metastatic Renal Cell Carcinoma].

A 43-year-old man underwent nephrectomy for right renal cell carcinoma (cT3aN0M1 (PUL), clear cell carcinoma). Thereafter, he was treated with sunitinib for lung metastases as the first-line therapy for three months. Because lung metastases progressed and new bone metastases appeared, nivolumab was started for the second-line treatment. Although the cancer progression was suppressed by multidisciplinary treatment combined with systemic immunotherapy and local radiation therapy, he developed severe acute kidney injury with cortical swelling after eighteen months of nivolumab treatment. A diagnosis of acute interstitial nephritis induced by nivolumab was made based on biopsy findings. Treatment with prednisolone (1.0 mg/kg daily) led to a rapid improvement in renal function. We must consider the possibility of immunerelated adverse events, especially nivolumab-induced acute kidney injury, even after long-term treatment.

[Two Cases of Metastatic and Recurrent Non-Clear Cell Renal Cell Carcinoma Re-Diagnosed as Renal Mucinous Tubular and Spindle Cell Carcinoma during Long-Term Follow-Up].

Renal mucinous tubular and spindle cell carcinoma (MTSCC) is a rare, low-grade renal epithelial neoplasm. MTSCC has a lower malignant potential and shows relatively good prognosis, but can be difficult to distinguish from other renal cell carcinoma (RCC) subtypes. Here, we report two cases of metastatic and recurrent renal MTSCC diagnosed after long-term follow-up. Case 1 was a 79-year-old man with a history of macroscopic hematuria in whom a right kidney mass was detected and diagnosed as RCC (cT3bN0M0). After a radical nephrectomy, microscopic findings showed that the tumor consisted of spindle cells arranged in tubular patterns embedded in sarcomatoid tissues ; we diagnosed it as unclassified RCC with sarcomatoid differentiations (pT3aN0M0). Thereafter, metastases were twice detected and resected completely. The patient had no evidence of disease at his most recent follow-up, 10 years 1 month after the initial surgery. Case 2 was in a 72-year-old man in whom a right kidney mass, swollen lymph nodes, and a lung node were incidentally detected. This tumor was diagnosed as RCC (cT4N2M1), and radical nephrectomy and lymph node dissections were carried out. From the microscopic findings, we diagnosed papillary RCC type-2 (pT3aN2M1). After the surgery, pleural and bone metastases was detected. Despite sequential treatments with IFN-α and sunitinib, the patient suffered indolent-growing metastases and died at 5 years 6 months after operation. As these patients had relatively good prognoses despite assumed aggressive RCC subtypes, we reviewed their pathological findings. In both cases, tumor samples showed tubules lined by short cuboidal cells that were set within myxoid stromata and spindle cells ; we finally diagnosed these cases as renal MTSCC.

[A Case of Thyroid-Like Follicular Carcinoma of the Kidney].

A 51-year-oldwoman with a right renal mass was referredto our hospital. Computedtomographic (CT) scan demonstrated a 30 mm-diameter renal mass with delayed enhancement. She underwent a robotassistedlaparoscopic right partial nephrectomy. The pathological examination showedthat tumor cells with eosinophilic, clear cytoplasm formedtubules of various sizes containing colloid-like material, which resembled the findings of thyroidfollicular carcinoma. The tumor was immunoreactive for vimentin andcytokeratin (CK) 7, whereas it lackedreactivity for thyroidtranscription factor-1 (TTF-1) or thyroglobulin. No tumors were detectedin the thyroidglandor other organs of the patient. Subsequently, the diagnosis of thyroidlike follicular carcinoma of the kidney (TLFCK) was determined. At 4 months postoperatively, the patient is alive with no evidence of disease recurrence. TLFCK is an extremely rare subtype of renal cancer, and only 26 cases have been reportedpreviously. We provide a brief literature review on this cancer.

[Simultaneous Hepatorenal Transplantation from a Brain-Dead Donor for Graft Dysfunction and Renal Insufficiency in a Liver Transplant Recipient : A Case Report].

We report a case of lethal hepatorenal insufficiency in a 52-year-old man who received successful simultaneous hepatorenal transplantation from a deceased donor. The patient had undergone live-donor liver transplantation for type-C hepatitis and liver cirrhosis 11 years before he developed graft liver dysfunction due to recurrent viral hepatitis and cirrhosis. At that instance, he also developed end-stage renal dysfunction due to calcineurin inhibitor nephropathy and hepatorenal syndrome. Although he needed three open hemostases and abundant blood transfusion, he was withdrawn from continuous hemodiafiltration on the 55th day and discharged from the hospital on the 272nd day postoperatively. Simultaneous hepatorenal transplantation was reported to be associated with more favorable outcomes of graft function, lower rejection rates, but higher perioperative complication rates compared with liver transplantation alone in patients on hemodialysis. Particularly, close attention should be paid for hemostasis since patients have a hemorrhagic tendency until the recovery of graft liver function.

[Laparoscopic resection of a retroperitoneal müllerian cyst: a case report].

A 51-year-old woman had a cystic mass in the retroperitoneal space, below the left kidney, which was incidentally detected at a medical check-up. The size of the mass was 6 cm in diameter, which was similar to that obtained by magnetic resonance imaging 4 years ago. We followed the case and found that the mass was slightly enlarged a year later. Because malignancy could not be ruled out, we performed a laparoscopic tumor excision. Histologically, the cyst was diagnosed as a Müllerian cyst, and there was no evidence of malignancy. Retroperitoneal Müllerian cyst is a rare tumor. Sixteen cases have been reported previously and this is the fourth case of a laparoscopic excision.