Predictors of renal function deterioration at one year after off-clamp non-renorrhaphy partial nephrectomy.

BACKGROUND: Preservation of renal function is an important goal in renal cell carcinoma-related surgery. Although several case-dependent techniques for renal pedicle clamping and hemostasis have been used, their effects on long-term renal function are controversial. METHODS: The clinical records of 114 patients who underwent off-clamp non-renorrhaphy open partial nephrectomy at our hospital were retrospectively reviewed. Perioperative estimated glomerular filtration rate (eGFR) preservation was calculated, and predictors of eGFR decline 12 months post-surgery and overtime deterioration of renal function were identified using a multivariate regression analysis. RESULTS: The median patient age was 65 years, and the median tumor size was 27 mm. The mean eGFR preservation at 1, 3, and 12 months post-surgery were 90.1%, 89.0%, and 86.9%, respectively. eGFR decline at 1 and 3 months were associated with poor eGFR preservation at 12 months with the odds ratio (95% confidence interval (CI)) of 1.97 and 3.157, respectively. Multivariate regression analyses revealed that tumor size was an independent predictor of eGFR decline at 12 months. Among 65 patients with eGFR preservation over 90% at 1 month post-surgery, eGFR value of 28 patients deteriorated below 90% at 12 months post-surgery compared with preoperative eGFR. Tumor size and eGFR preservation at 1 month were independent predictors of long-term renal function deterioration. CONCLUSION: Tumor size predicted eGFR decline 12 months post-surgery. Only a mild decline in eGFR was observed between 3 and 12 months after open partial nephrectomy. Tumor size and eGFR preservation at 1 month predicted the deterioration of renal function over time.

Integrated enhancer regulatory network by enhancer-promoter looping in gastric cancer.

Enhancer cis-regulatory elements play critical roles in gene regulation at many stages of cell growth. Enhancers in cancer cells also regulate the transcription of oncogenes. In this study, we performed a comprehensive analysis of long-range chromatin interactions, histone modifications, chromatin accessibility and expression in two gastric cancer (GC) cell lines compared to normal gastric epithelial cells. We found that GC-specific enhancers marked by histone modifications can activate a population of genes, including some oncogenes, by interacting with their proximal promoters. In addition, motif analysis of enhancer-promoter interacting enhancers showed that GC-specific transcription factors are enriched. Among them, we found that MYB is crucial for GC cell growth and activated by the enhancer with an enhancer-promoter loop and TCF7 upregulation. Clinical GC samples showed epigenetic activation of enhancers at the MYB locus and significant upregulation of TCF7 and MYB, regardless of molecular GC subtype and clinicopathological factors. Single-cell RNA sequencing of gastric mucosa with intestinal metaplasia showed high expression of TCF7 and MYB in intestinal stem cells. When we inactivated the loop-forming enhancer at the MYB locus using CRISPR interference (dCas9-KRAB), GC cell growth was significantly inhibited. In conclusion, we identified MYB as an oncogene activated by a loop-forming enhancer and contributing to GC cell growth.

Pathologic Complete Response and Long-Term Survival After Preoperative Chemotherapy for Transverse Colon Cancer With Para-Aortic Lymph Node Metastases.

A 52-year-old male patient was diagnosed with transverse colon cancer and synchronous stage IVA para-aortic lymph node (PALN) metastases (cT3N1bM1a of the lymph node). Six courses of mFOLFOX6 plus bevacizumab were administered as neoadjuvant chemotherapy. Computed tomography showed shrinkage of the primary tumor and PALN metastases. Extended right hemicolectomy, D3 lymph node dissection, and PALN dissection were performed. A pathologic examination indicated that the tumor had completely changed and comprised necrotic tissue with no viable cells. Therefore, it was considered that mFOLFOX6 plus bevacizumab resulted in a pathologic complete response. Postoperatively, six courses of mFOLFOX6 were administered. Six years postoperatively, the patient did not exhibit any signs of recurrence. There have been few reports of pathologic complete response after neoadjuvant therapy and resection for colon cancer with synchronous PALN metastases. This report describes a unique case involving a pathologic complete response with long-term survival after mFOLFOX6 plus bevacizumab and radical resection, including PALN dissection. Preoperative mFOLFOX6 plus bevacizumab followed by radical resection and adjuvant mFOLFOX6 therapy was safe and resulted in a good outcome. This regimen should be considered for advanced colon cancer with PALN metastases.

Bilateral fumarate hydratase deficient renal cell carcinoma in a patient with hereditary leiomyomatosis and renal cell cancer syndrome.

Introduction: Patients with hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome have high risks of uterine and cutaneous leiomyomas and renal cell carcinoma (RCC), which are caused by germline mutation of the fumarate hydratase (FH) gene. RCC lesions are mostly high-grade tumors with a poor prognosis. Case presentation: A 37-year-old man who had previously undergone treatment for a left RCC was referred to our hospital with a diagnosis of right RCC. Robot-assisted partial nephrectomy was performed, and the pathological diagnosis revealed fumarate hydratase (FH)-deficient RCC. The left RCC, which was originally diagnosed as mucinous tubular and spindle cell carcinoma, was reviewed and diagnosed as FH-deficient RCC. The patient's father and uncle both died of RCC, and the father's tumor was also immunohistochemically proven to be FH-deficient RCC. Conclusion: HLRCC-related RCC should be considered in a differential diagnosis of young patients with a family history of RCC.

A case of anal canal carcinoma with pagetoid spread that was curatively resected by multiple endoscopic and surgical treatments.

A 57-year-old woman with no significant medical history was referred after a colonoscopy for abdominal distension, which revealed a tumor in the lower rectum. Pre-operative colonoscopy showed the tumor was 12 mm in size, located from the anorectal junction to beyond the dentate line, and was diagnosed as high-grade intramucosal neoplasia or shallow submucosal invasive cancer. Endoscopic submucosal dissection was performed, and the lesion was resected en bloc. Pathological examination revealed moderately differentiated tubular adenocarcinoma with tubulovillous adenoma. The stratified squamous epithelium adjacent to the anal side of the lesion showed pagetoid spread of atypical cells with positive horizontal margins. We referred her to a surgeon for radical treatment. The mucosa surrounding the endoscopic submucosal dissection scar was normal on narrow-band imaging magnification. We marked its oral side endoscopically as the resected boundary. Transanal local excision was performed. The horizontal margins were positive because atypical cells had spread into the stratified squamous epithelium of the anorectal side of the lesion. The patient was followed on an outpatient basis. Sixty days postoperatively, residual tumor growth was observed. The second local resection was performed after mapping biopsy. All resection margins were negative, there was no lymphovascular invasion. One year after surgery, no recurrence was observed. Regarding endoscopic findings, there are no reports of endoscopic findings of the rectal mucosa, or the squamous epithelium of the anus of pagetoid spread. Here, we report a review of perianal Paget's Disease that resulted in difficulties in borderline diagnosis of pagetoid spread, resulting in multiple therapeutic interventions.

A case of small bowel aneurysm hemorrhage with submucosal tumor-like findings.

A 51-year-old woman visited our hospital with the chief complaint of tarry stools. Contrast-enhanced abdominal computed tomography revealed leakage of contrast medium into the lumen of the small intestine. Subsequently, a double-balloon endoscopy was performed, which revealed a submucosal mass-like lesion in the jejunum. Although hemostasis was attempted with clips, complete hemostasis was difficult to achieve, and angiographic embolization was performed. Nevertheless, the anemia progressed, and a small bowel resection was performed. Histopathological examination led to a diagnosis of a ruptured submucosal aneurysm of the small intestine. Endoscopic hemostasis is often difficult to achieve for submucosal aneurysms in the intestine. The submucosal tumor-like finding observed on endoscopy in submucosal aneurysms is termed an "SMT-like sign" and is considered an important finding to diagnose aneurysms.

Endoscopic management of gastric ectopic pancreas with repeated ulcerations and bleeding: A case report.

A 25-year-old man was referred to our center for investigation of a gastric submucosal tumor and an ulcer that had developed on its oral side. Endoscopic ultrasonography findings suggested the presence of an ectopic pancreas, and treatment with an oral proton pump inhibitor was planned for the ulcer. Over the subsequent 3 years, the patient endured recurring epigastric pain and episodes of passing black stools. Emergency endoscopy revealed that the morphology of the gastric submucosal tumor had transformed into a pedunculated polyp-like morphology with a bleeding ulcer at the apex of the lesion. Endoscopic hemostasis using hemostatic forceps was performed. However, the patient continued to pass black stools. In light of the persistent symptoms and unique morphology of the lesion, endoscopic resection was attempted as a curative approach. The lesion was excised by hot snare polypectomy. Post-treatment, the patient exhibited no signs of recurrence, marking a successful resolution. Three months later, a gastroduodenal endoscopy showed that the excised site had undergone scar formation without recurrence of the lesion. This case holds significant clinical value as it demonstrates the efficacy of a minimally invasive treatment strategy in managing repeated bleeding ulcerations of an ectopic pancreas, ultimately achieving a complete cure.

A case of condyloma acuminatum of the bladder concurrently diagnosed with urothelial carcinoma.

Introduction: Condyloma acuminatum usually occurs in the external genitalia and rarely in the bladder mucosa. Here, we report a case of condyloma acuminatum of the bladder that was detected concurrently with urothelial carcinoma. Case presentation: A 42-year-old man was referred to our urology department with positive urine cytology for urothelial carcinoma. Cystoscopy revealed a broad-base nonpapillary bladder tumor. The patient underwent a transurethral resection of the bladder tumor. Pathological examination revealed urothelial carcinoma, high-grade pT1, and concurrent resection of condyloma acuminatum. DNA was extracted from the paraffin-embedded transurethral resection of the bladder tumor tissue specimens. HPV11 was detected in condylomas by PCR and in situ hybridization, whereas HPV was not detected in urothelial carcinomas. Conclusion: We report a rare case of condyloma acuminatum of the bladder that was concurrently diagnosed with urothelial carcinoma from the same site.

Asymptomatic renal granuloma diagnosed 3 years after Bacillus Calmette-Guérin intravesical injection: A case report and a literature review.

Introduction: Intravesical Bacillus Calmette-Guérin immunotherapy is an effective treatment for non-muscle-invasive bladder cancer, which is occasionally associated with side effects and complications. The incidence of significant renal complications after intravesical Bacillus Calmette-Guérin immunotherapy is less than 2%. We report a case of renal granuloma after intravesical Bacillus Calmette-Guérin immunotherapy for bladder cancer, which radiologically resembled a papillary renal cell carcinoma. Case presentation: A 65-year-old man, who had a medical history of urothelial carcinoma and received intravesical Bacillus Calmette-Guérin therapy, was referred to our Urology Department with a right renal tumor. Imaging findings suggested papillary renal cell carcinoma. Robot-assisted partial nephrectomy was performed, and the histopathological examination revealed epithelioid cell granuloma, which were considered to be Bacillus Calmette-Guérin-related renal granuloma. Conclusion: Bacillus Calmette-Guérin-related renal granuloma mimicking papillary renal cell carcinoma have been reported. We should consider the possibility of renal granulomas when encountering image abnormalities for patients treated with intravesical Bacillus Calmette-Guérin therapy.

Advantages of enhanced recovery after surgery program in robot-assisted radical cystectomy.

Radical cystectomy is a gold-standard treatment for muscle-invasive bladder cancer. We recently introduced robot-assisted radical cystectomy (RARC) with perioperative enhanced recovery after surgery (ERAS). The medical records of patients with bladder cancer who underwent open radical cystectomy (ORC) or RARC/ERAS at NTT Medical Center Tokyo were retrospectively reviewed to compare the surgical outcomes, hospital stay, and medical costs between groups. Multidisciplinary full ERAS items were provided for the RARC/ERAS group. The median estimated blood losses in the ORC and RARC/ERAS groups were 650 and 100 mL, and the median operative times were 312 and 445 min, respectively. In addition, the median times to liquid food intake in these groups were 6 and 0 days, the median times to first flatus and first defecation were 2 and 1 day, and 3 and 1.5 days, respectively. The rates of postoperative ileus in the ORC and RARC/ERAS groups were 27.5% and 4.5%, and the median postoperative hospital stays was 26.5 and 12 days, respectively. Medical costs excluding surgery were significantly lower in the RARC/ERAS group. In conclusion, RARC/ERAS represents a safe treatment option for muscle-invasive bladder cancer with decreased perioperative complications and lower medical costs.

Inter- and intra-tumor heterogeneity of genetic and immune profiles in inherited renal cell carcinoma.

Patients with von Hippel-Lindau disease (vHL) are at risk of developing spatially and temporally multiple clear cell renal cell carcinomas (ccRCCs), which offers a valuable opportunity to analyze inter- and intra-tumor heterogeneity of genetic and immune profiles within the same patient. Here, we perform whole-exome and RNA sequencing, digital gene expression, and immunohistochemical analyses for 81 samples from 51 ccRCCs of 10 patients with vHL. Inherited ccRCCs are clonally independent and have less genomic alterations than sporadic ccRCCs. Hierarchical clustering of transcriptome profiles shows two clusters with distinct immune signatures: immune hot and cold clusters. Interestingly, not only samples from the same tumors but also different tumors from the same patients tend to show a similar immune signature, whereas samples from different patients frequently exhibit different signatures. Our findings reveal the genetic and immune landscape of inherited ccRCCs, demonstrating the relevance of host factors in shaping anti-tumor immunity.

Remission Induction of IgG4-related Membranous Nephropathy with Multitarget Therapy.

IgG4-related membranous nephropathy (MN) is often refractory to glucocorticoid (GC) therapy, and treatment remains unclear. We herein report a 67-year-old Japanese man with IgG4-related MN and tubulointerstitial nephritis. A post-gastroscopy antibody test revealed Helicobacter pylori infection. After eradication, his proteinuria decreased indefinitely. We started prednisolone (30 mg/day), long-term GCs, and immunosuppressant therapy. However, remission proved challenging to achieve, with persistent proteinuria present at 1.0-2.0 g/gCr. We performed multitarget therapy for refractory IgG4-related MN, achieving proteinuria remission (<0.3 g/gCr). Multitarget therapy with low-dose GCs can resolve refractory IgG4-related MN through remission induction of proteinuria and minimize the risks associated with GC therapy.

Primary Pleural Angiosarcoma Treated with Nivolumab and Ipilimumab: A Case Report.

Primary pleural angiosarcoma (PPA) is a rare and clinically fatal pleural tumor originating from vascular endothelial cells. Herein, we presented the case of a 73-year-old man who was referred to our emergency room with complaints of right chest and back pain for a few days. Chest computed tomography revealed massive pleural effusion and a large mass in the right chest cavity. Thoracoscopic examination demonstrated a large hemorrhagic tumor on the parietal pleura whose pathological analysis indicated PPA. The patient received immunotherapy combined with nivolumab and ipilimumab. A cycle of nivolumab and ipilimumab improved his hemorrhagic anemia and reduced the pleural effusion and tumor size. This treatment outcome suggests that nivolumab and ipilimumab comprise a vital treatment option for PPA.

Can EUS-FNA cytology reliably classify gastric submucosal spindle cell tumors?

BACKGROUND: Cytological diagnosis using endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for gastric submucosal spindle cell tumors, such as gastrointestinal stromal tumors (GISTs), leiomyomas, and schwannomas, is challenging because of their similar morphological characteristics. OBJECTIVE AND MATERIALS: To clarify the cytological differential points, we reviewed the EUS-FNA cytology specimens of GISTs (37 cases), leiomyomas (11 cases), and schwannomas (4 cases). METHOD: Twelve cytomorphological features were evaluated: lymphocytes, crushed nuclei, naked spindle nuclei, mast cell, length of the streaming arrangement, cellularity, nuclei at the cluster margin (nuclei located at the periphery of the cell cluster), peripheral feathering (loosely aggregated cells at the margin of a cell cluster tended to taper like feathers), metachromasia, wavy nuclei, fishhook-type nuclei, and anisonucleosis. RESULTS: Among these features, lymphocytes, naked spindle nuclei, length of the streaming arrangement, cellularity, nuclei at the cluster margins, peripheral feathering, and anisonucleosis were statistically significant for differentiation. Based on these findings, we developed an algorithm for cytodiagnosis. The algorithm was taught to four cytologists, and the interobserver agreement and correct diagnosis rates were compared before and after education, which showed a significant improvement. DISCUSSION: The histological types of gastric submucosal spindle cell tumors can be estimated using this algorithm for EUS-FNA cytology. Furthermore, this algorithm can be applied for cytological diagnosis at bedside during rapid on-site evaluation.

Gastric-type duodenal neoplasms with rapid growth: A report of two cases.

While duodenal neoplasms of the gastric phenotype are uncommon and their natural history is unknown, gastric neoplasms of gastric phenotype reportedly grow rapidly and can invade the submucosa. Several studies suggest that duodenal neoplasms of gastric phenotype might have a high risk of deep invasion and lymph node metastasis. Duodenal neoplasms of gastric phenotype might also have a high biological malignancy and likely require early treatment if detected. Here, we report two cases of intramucosal duodenal carcinoma with a gastric phenotype that grew rapidly but was successfully resected endoscopically.

Microsatellite instability in the high-grade dysplasia component of duodenal adenoma is associated with progression to adenocarcinoma.

PURPOSE: We examined the microsatellite instability of duodenal tumors to evaluate their molecular features associated with the adenoma-carcinoma sequence. METHODS: Fifty-two non-ampullary duodenal epithelial tumors collected by endoscopic mucosal resection or surgical resection were studied. When a tumor had two or more dysplasia grades, the highest grade was considered. Representative areas were macro-dissected and subjected to a microsatellite instability analysis and immunohistochemical staining. RESULTS: The 52 tumors were classified as either adenoma with low-grade dysplasia (n = 18), adenoma with high-grade dysplasia (n = 20), or adenocarcinomas (n = 14). Among these, 3 adenocarcinoma cases showed microsatellite instability and the remaining 49 tumors showed microsatellite stability. Of the 14 adenocarcinoma cases, 3 contained both high-grade dysplasia and adenocarcinoma components, and 11 contained only the adenocarcinoma component. Interestingly, all three adenocarcinoma + high-grade dysplasia cases were microsatellite instability-high in both the adenocarcinoma and high-grade dysplasia components. Immunohistochemical staining of mismatch repair proteins showed mismatch repair deficiency in three microsatellite instability-high adenocarcinoma + high-grade dysplasia cases. CONCLUSIONS: Only adenocarcinoma cases with high-grade dysplasia components were microsatellite instability-high (in both the adenocarcinoma and high-grade dysplasia components). This suggests that microsatellite instability in the high-grade dysplasia component of duodenal adenoma is associated with progression to adenocarcinoma.

Association of tumors having Epstein-Barr virus in surrounding lymphocytes with poor prognosis.

Infection with certain viruses is an important cause of cancer. The Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium recently analyzed the whole-genome sequencing (WGS) data from 2656 cases across 21 cancer types, and indicated that Epstein-Barr virus (EBV) is detected in many different cancer cases at a higher frequency than previously reported. However, whether EBV-positive cancer cases detected by WGS-based screening correspond to those detected by conventional histopathological techniques is still unclear. In this study, to elucidate the involvement of EBV in various cancers, we reanalyzed the WGS data of the PCAWG cohort combined with the analysis of clinical samples of gastric and pancreatic cancer in our cohort. Based on EBV copy number in each case, we classified tumors into three subgroups: EBV-High, EBV-Low, and EBV-Negative. The EBV-High subgroup was found to be EBV-positive in the cancer cells themselves, whereas the EBV-Low subgroup was EBV-positive in the surrounding lymphocytes. Further, the EBV-Low subgroup showed a significantly worse prognosis for both gastric cancer and across cancer types. In summary, we classified tumors based on EBV copy number and found a unique cancer subgroup, EBV-positive in the surrounding lymphocytes, which was associated with a poor prognosis.

Impact of Neoadjuvant Chemotherapy on SATB2 Expression in Colorectal Carcinomas: SATB2 Positivity is Preserved in Most Cases, but Down-Expressed in Effective Cases of Chemotherapy.

Special AT-rich sequence-binding protein 2 (SATB2) is a novel, diagnostically useful, and highly sensitive immunohistochemical marker for both primary and metastatic colorectal or appendiceal tumors. In the present study, we aimed to assess the impact of neoadjuvant chemotherapy on SATB2 expression in primary colorectal carcinomas and their corresponding liver metastases. Forty-four patients with colorectal carcinomas who received neoadjuvant chemotherapy were included. SATB2 expression in specimens of biopsy, resected primary colorectal carcinomas, and resected metastatic foci were examined by immunohistochemistry and compared to caudal-type homeobox transcription factor 2 (CDX2). Using a modified H-score, expressions were scored semiquantitatively for both staining intensity and tumor cell proportion with nuclear staining. SATB2 was positive in 43/44 cases (98%) in biopsy specimens, 42/44 cases (96%) in resected colorectal carcinomas with neoadjuvant chemotherapy, and 9/9 cases (100%) with liver metastases. However, these expressions were variably decreased, and the H-score was lower in resected colorectal carcinomas (158 ± 69) than in biopsy specimens (174 ± 60) (p < 0.01). The proportion of SATB2-positive area of colorectal carcinoma was 93% in metastatic foci, while the CDX2-positive area was 78%. When categorized by histopathological tumor regression, the most effective tumors of chemotherapy showed the lowest H-score in resected colorectal carcinomas among the three groups (p < 0.01). SATB2 is a useful marker for both primary colorectal carcinoma and corresponding liver metastases, even with neoadjuvant chemotherapy. However, caution should be exercised when performing needle biopsy for metastatic foci with neoadjuvant therapy because expressions could be decreased, especially in chemotherapy-effective cases, and show immunohistochemically negative results.