Recurrence- and progression-free survival in intermediate-risk non-muscle-invasive bladder cancer: the impact of conditional evaluation and subclassification.

OBJECTIVES: To assess the change in rates of recurrence-free survival (RFS) and progression-free survival (PFS) based on the duration of survival without recurrence or progression among patients with intermediate-risk (IR) non-muscle-invasive bladder cancer (NMIBC), and to examine the predictive factors for recurrence at different time points by assessing conditional RFS and PFS. PARTICIPANTS AND METHODS: A cohort of 602 patients treated with transurethral resection of bladder tumour and histopathologically diagnosed with IR NMIBC was included in this retrospective study. RESULTS: The conditional RFS rate at 1, 2, 3, 4 and 5 years improved with increased duration of RFS; however, the conditional PFS rate did not improve over time. Multivariable analyses showed that recurrent tumour, multiple tumours, tumour size (>3 cm), immediate postoperative instillation of chemotherapy, and administration of BCG were independent predictive factors for recurrence at baseline. The predictive ability of these factors disappeared with increasing recurrence-free survivorship. Subclassification of these patients with IR NMIBC into three groups using clinicopathological factors (recurrent tumour, multiple tumours, tumour size) demonstrated that the high IR group (two factors) had significantly worse RFS than the intermediate (one factor, P < 0.001) and low IR groups (no factor, P = 0.005) at baseline. This subclassification stratified conditional risk of RFS also at 1, 3 and 5 years, which provides the basis for distinct surveillance protocols among patients with IR NMIBC. CONCLUSION: Conditional survival analyses of patients with IR NMIBC demonstrate that RFS changes over time, while PFS does not change. These data support distinct surveillance protocols based on the subclassification of IR NMIBC.

[A Case of Extranodal NK/T-Cell Lymphoma with Perforation of the Small Intestine].

A rare case of extranodal NK/T-cell lymphoma(ENKL)with small intestinal perforation is reported. A 92-year-old man was admitted for a loss of consciousness. Computed tomography(CT)scan revealed the presence of an intraperitoneal abscess that was drained. Two days later, the drained fluid changed to intestinal juice, and intestinal perforation was suspected. The patient underwent surgery which revealed a 1 cm perforation site in the ileum. A high fever continued after surgery, and malignant lymphoma was diagnosed from pathological findings; however, further treatment could not be performed. He died 24 days after the operation. Pathological dissection revealed metastasis of ENKL at the systemic lymph nodes.

The transition of tissue inhibitor of metalloproteinases from -4 to -1 induces aggressive behavior and poor patient survival in dedifferentiated liposarcoma via YAP/TAZ activation.

Liposarcoma (LS) is the most common soft-tissue sarcoma. Dedifferentiated liposarcoma (DDLS) shows more aggressive biological behavior than that of well-differentiated liposarcoma (WDLS), so advanced therapeutic agents based on molecular mechanism are urgently needed. Here we show that tissue inhibitors of metalloproteinases (TIMPs) from TIMP-1 to TIMP-4 are differently expressed and regulate yes-associated protein (YAP)/transcriptional co-activator with PDZ binding motif (TAZ) in LS. Database analysis showed high TIMP-1 expression in DDLS patients correlating with poor prognosis, but high TIMP-4 expression in WDLS patients with better prognosis. Stable TIMP-1 knockdown inactivated YAP/TAZ and inhibited proliferation, colony formation and migration in DDLS cells, which was rescued by a constitutive active YAP. However, stable overexpression of TIMP-1 showed the opposite in WDLS cells. Stable TIMP-4 knockdown activated YAP/TAZ and promoted proliferation and migration in WDLS cells, which was suppressed by YAP/TAZ inhibitor (verteporfin) or knockdown of YAP/TAZ. Recombinant TIMP-4 showed opposite results in DDLS cells. These results indicate that dedifferentiation in LS shifts the expression of TIMPs from type 4 to type 1, inducing more aggressive behavior and poor prognosis through YAP/TAZ activation, which can be prognostic markers and therapeutic targets for LS patients.

Morbidly obese patient with non-alcoholic steatohepatitis-related cirrhosis who died from sepsis caused by dental infection of Porphyromonas gingivalis: A case report.

Non-alcoholic steatohepatitis (NASH) is associated with increased risks of developing lifestyle-related diseases including type 2 diabetes, cardiovascular disease and cerebral vessel disease. While the two-hit hypothesis and, recently, multiple parallel hits hypothesis of NASH pathogenesis were proposed, further details have not emerged. Recently, dental infection of Porphyromonas gingivalis (P. gingivalis) has been reported as a critical risk factor for NASH progression, which acts as multiple parallel hits to induce inflammation and fibrogenic responses in steatosis. We describe here a 54-year-old woman who died from sepsis and was diagnosed with NASH. Briefly, her body mass index (BMI) at the age of 35 years old had been 25.6 kg/m(2) , but she became obese after withdrawing into her home at the age of 45 years. Severe obesity continued over 19 years without diabetes mellitus. She was admitted to our hospital due to a sudden disturbance of consciousness. On admission, her BMI was 48.5 kg/m(2) . Computed tomography revealed cirrhotic liver with massive ascites, and laboratory data indicated increased inflammatory responses, renal failure and C grade Child-Pugh classification, suggesting the diagnosis of sepsis. Also, severe periodontal disease was present, because the patient's front teeth fell out easily during intubation. Although the focus of infection was not specified, the oral flora Parvimonas micra, a periodontal pathogen, was detected in venous blood. In spite of intensive care including artificial respiration management and continuous hemodiafiltration, she died on the 43rd day after admission. Surprisingly, P. gingivalis was detected in her hepatocytes. This case may represent the significance of P. gingivalis in the progress to cirrhosis in NASH patients.

Comparison of visual assessment and image analysis in the evaluation of Ki-67 expression and their prognostic significance in immunohistochemically defined luminal breast carcinoma.

OBJECTIVES: To compare the Ki-67 labeling index value obtained through immunohistochemistry analysis by human examiners to that obtained from computer-assisted image analysis, and to establish a cut-off value for Ki-67 labeling index for each method in luminal B breast carcinoma. METHODS: Immunohistochemistry analysis for Ki-67 was performed on the formalin-fixed, paraffin-embedded tissue samples from 403 patients with primary luminal breast cancers. Whole slide images were obtained using the NanoZoomer (Hamamatsu Photonics, Hamamatsu, Japan) and thoroughly analyzed using the Definiens Tissue Studio version 1.1 (Definiens AG, Munich, Germany) to detect the percentage of positively-stained nuclei of carcinoma cells. RESULTS: Although a significant correlation was found between the Ki-67 labeling index obtained by manual assessment and computer-assisted image analysis (Spearman rank correlation coefficient, P < 0.01), the Ki-67 labeling index value obtained by manual assessment was significantly higher than that obtained by computer-assisted image analysis (Wilcoxon signed rank test, P < 0.0001). Disease-free survival was significantly lower in 403 patients with tumors having high Ki-67 labeling index values determined by automated analysis (cut-off value: 11.5%; P < 0.00001) and visual counting (cut-off value: 28.5%; P < 0.00001). Disease-free survival was also significantly lower in 288 patients who received adjuvant endocrine therapy alone having high Ki-67 labeling index values determined by automated analysis (cut-off value: 11.5%; P < 0.0001) and visual counting (cut-off value: 19.7%, P < 0. 0001). CONCLUSIONS: The Ki-67 labeling index values determined by automated analysis and visual counting could equally predict disease-free survival in patients with luminal B breast carcinoma, including those who received endocrine therapy.

[Long-term survival of a patient with stage IV basaloid squamous carcinoma of the esophagus with lung metastases following combined modality therapy].

A 72-year-old man visited our hospital because of dysphagia and weight loss. He was diagnosed by endoscopy with advanced (stage IV) basaloid squamous carcinoma of the thoracic esophagus. CT and CT-guided tumor biopsy revealed two lung metastases in the right upper and lower lobes, with diameters of 8 and 5 mm, respectively. The primary lesion disappeared after concurrent chemoradiotherapy consisting of 5-FU, cisplatin, and 60-Gy irradiation, which was administered for palliation of obstructive and hemorrhagic symptoms. Subsequently, eight cycles of chemotherapy were administered, resulting in a reduction in size of the metastases. However, multiple cycles of chemotherapy caused prolonged toxicity, and the metastases slightly enlarged during chemotherapy-free periods. Since the number of metastases did not change, stereotactic body radiotherapy was performed, which resulted in disappearance of the lung metastases. Five years following initial diagnosis, the patient has been doing well, with no signs of disease recurrence.

[A case of triple-negative breast cancer responding to multidisciplinary treatment containing bevacizumab].

We report a case of a 64-year-old woman with Stage IV breast cancer who responded well to chemotherapy containing bevacizumab. She noticed a left breast tumor with acute progression and was diagnosed as having Stage IV, estrogen receptor( ER)(-), progesterone receptor(PgR)(-), human epidermal growth factor receptor 2(HER2)(-)breast cancer (T4cN3cM1[lymph nodes]). She received 5 courses of adriamycin(60mg/m / 2)plus cyclophosphamide(600mg/m2)(AC therapy)and 4 courses of weekly paclitaxel(PTX 90mg/m / 2)plus bevacizumab(AVA 10 mg/m2)as systemic therapy. Computed tomography(CT)and magnetic resonance imaging(MRI)revealed a complete response(CR). After local resection of the breast tumor and radiation to the breast and regional lymph nodes, capecitabine therapy was initiated. Currently, at 5 months after surgery, no new lesion has been detected.

Pseudomesotheliomatous Carcinoma of the Lung with Morphological Characteristics of Signet Ring Cell Carcinoma: An Autopsy Case Report.

A 50-year-old woman presented with left pleural effusion. A pleural fluid cell-block specimen and longitudinal lymph node needle biopsy suggested signet ring cell carcinoma (SRCC). Although computed tomography showed a consolidation shadow in the left lower lobe, a left lung biopsy could not be performed. Upper gastrointestinal endoscopy revealed no malignancies. We administered carboplatin, pemetrexed, ipilimumab, and nivolumab for lung cancer; however, she died due to progressive respiratory failure. Pathological autopsy revealed that the left pleura was thickened as in mesothelioma, based on which pseudomesotheliomatous carcinoma of the lung (PMCL) was diagnosed. PMCLs exhibiting an SRCC morphology are rare.

Peritoneal dissemination of appendiceal goblet cell adenocarcinoma mimicking white pus caused by peritonitis following appendicitis: an instructive case report.

BACKGROUND: Goblet cell adenocarcinoma is an extremely rare tumor in which the same cells exhibit both mucinous and neuroendocrine differentiation. It is considered more aggressive compared to conventional carcinoids and more likely to cause metastasis. CASE PRESENTATION: We report a case of goblet cell adenocarcinoma with peritoneal metastases. A 62-year-old man underwent appendectomy for acute appendicitis. Intraoperatively, inflammatory white pus and a small amount of dirty ascites were observed in the lower abdomen with severely inflamed appendix. Histopathological examination of the specimen collected during appendectomy revealed goblet cell adenocarcinoma with a positive surgical margin. One month later, additional ileal resection was planned. Laparoscopic examination revealed disseminated nodules throughout the abdominal cavity. Therefore, the patient underwent resection of the peritoneal nodules. The peritoneal specimens confirmed the histopathological findings. Thus we diagnosed the patient with peritoneal dissemination of appendiceal goblet cell adenocarcinoma. CONCLUSIONS: In cases wherein white pus is observed during surgery for acute appendicitis, considering the possibility of dissemination, collecting samples for histopathological examination, and initiating early treatment are crucial.

Preoperative diagnosis and safe surgical approach in gallbladder amyloidosis: a case report.

BACKGROUND: Preoperative diagnosis of gallbladder amyloidosis is usually difficult. In our case, the patient exhibited gallbladder dyskinesia, which led us to suspect cholecystic amyloidosis. We were able to safely perform surgery before cholecystitis onset. CASE PRESENTATION: A 59-year-old male patient with a history of multiple myeloma and cardiac amyloidosis presented to our hospital with a chief complaint of epicardial pain. Abdominal ultrasonography and computed tomography revealed an enlarged gallbladder and biliary sludge without any specific imaging findings of cholecystitis. After percutaneous transhepatic gallbladder aspiration (PTGBA), the patient experienced recurrent bile retention and right upper quadrant pain. Flopropione was effective in relieving these symptoms. Based on his symptoms and laboratory findings, we diagnosed the patient with dyskinesia of the gallbladder. Considering his medical history, we suspected that it was caused by amyloidosis of the gallbladder. A laparoscopic cholecystectomy was performed. The histopathological examination showed amyloid deposits in the gallbladder mucosa, from the intrinsic layer to the submucosa, and in the peripheral nerves of the gallbladder neck. The patient was discharged on postoperative day 5 and has had no recurrence of abdominal pain since then. CONCLUSION: In our case, gallbladder dyskinesia symptoms led us to suspect gallbladder amyloidosis. We safely surgically treated the patient before cholecystitis onset.

Comparison of Ultra-Magnifying Endocytoscopic and Hematoxylin-Eosin-Stained Images of Lung Specimens.

Endocytoscopy enables real-time observation of lesions at ultra-magnification. In the gastrointestinal and respiratory fields, endocytoscopic images are similar to hematoxylin-eosin-stained images. This study aimed to compare the nuclear features of pulmonary lesions in endocytoscopic and hematoxylin-eosin-stained images. We performed an endocytoscopy to observe resected specimens of normal lung tissue and lesions. Nuclear features were extracted using ImageJ. We analyzed five nuclear features: nuclear number per area, mean nucleus area, median circularity, coefficient of variation of roundness, and median Voronoi area. We conducted dimensionality reduction analyses for these features, followed by assessments of the inter-observer agreement among two pathologists and two pulmonologists to evaluate endocytoscopic videos. We analyzed the nuclear features of hematoxylin-eosin-stained and endocytoscopic images from 40 and 33 cases, respectively. Endocytoscopic and hematoxylin-eosin-stained images displayed a similar tendency for each feature, despite there being no correlation. Conversely, the dimensionality reduction analyses demonstrated similar distributions of normal lung and malignant clusters in both images, thus differentiating between the clusters. The diagnostic accuracy of the pathologists was 58.3% and 52.8% (κ-value 0.38, fair), and that of the pulmonologists was 50% and 47.2% (κ-value 0.33, fair). The five nuclear features of pulmonary lesions were similar in the endocytoscopic and hematoxylin-eosin-stained images.

Comprehensive genomic profiling of Japanese patients with thoracic malignancies: A single-center retrospective study.

BACKGROUND: Few studies have been conducted on comprehensive genomic profiling (CGP) panels in Japanese patients with thoracic malignancies after completing standard treatment. Consequently, its value in clinical practice remains unclear. METHODS: We conducted a retrospective study of Japanese patients with thoracic malignancies who underwent CGP between June 2019 and November 2022 at our hospital. We evaluated the detection rate of actionable genetic alterations and percentage of patients who received genomically-matched therapy. Furthermore, we examined the value of the CGP panel in patients who underwent multiplex gene-panel testing prior to their initial treatment. This study was performed in accordance with the principles of the Declaration of Helsinki. RESULTS: The study included 56 patients, of whom 47 (83.9%) had actionable genetic alterations and 8 (14.3%) received genomically-matched therapy. Of these, four patients were treated with approved drugs and three patients were treated with investigational agents. In addition, one patient was treated with approved drugs using the patient-directed care system. Of the 17 patients who had multiplex gene-panel testing performed at the start of their initial therapy, two (11.8%) were newly identified by the CGP panel and subsequently received genomically-matched therapy. EGFR L718Q and MET amplification were observed in two of the seven patients with epidermal growth factor receptor-tyrosine kinase inhibitor resistance. CONCLUSIONS: The CGP panel could identify genetic alterations, thereby facilitating genomically-matched therapy, even in patients with thoracic malignancies who could not be identified using multiplex gene-panel testing.

Mixed neuroendocrine non-neuroendocrine neoplasm: a case report and review.

Mixed neuroendocrine non-neuroendocrine neoplasm (MiNEN) of the pancreas is a rare entity, and obtaining a preoperative diagnosis is difficult. We present a 70-year-old man in whom the possibility of MiNEN was successfully discovered preoperatively by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). Immunostaining revealed positive results for the neuroendocrine markers chromogranin A and synaptophysin. We considered the possibility for MiNEN before surgery. He underwent distal pancreatectomy with splenectomy. Immunohistochemical examination of the tumor cells showed a wide range of positivity for trypsin as well as for chromogranin A and synaptophysin. Considering that ≥ 30% tumors ware positive for both acinar and neuroendocrine markers, the patient was diagnosed with MiNEN. MiNEN is a malignant tumor that requires early detection and treatment but is a rare disease for which no method has been established. We found that EUS-FNA and immunostaining are effective diagnostic methods for MiNEN.

Retroperitoneal Bronchogenic Cyst Resected by Single-Incision Laparoscopic Surgery in an Adolescent Female: A Case Report.

A 16-y-old Japanese female was referred to our hospital with a suspicion of infected retroperitoneal cyst. Abdominal CT MRI revealed a 38-mm diameter retroperitoneal cyst under the left diaphragm. Because a retroperitoneal bronchogenic cyst was suspected, total resection was planned. In addition, preoperative 3D reconstruction using multidetector CT provided a detailed location of the lesion. Based on the anatomical position, we decided that single-incision laparoscopic surgery with an anterior approach through the umbilicus would be the optimal choice. The lesion was completely resected without intraoperative complications. Histopathological examination confirmed the diagnosis of bronchogenic cyst. Postoperatively, the surgical wound became completely unnoticeable, and there was no incisional hernia or cyst recurrence at the 2-y follow-up.

Intussusception caused by small intestine metastasis of malignant pleural mesothelioma: a case report.

Malignant pleural mesothelioma (MPM) is an aggressive form of malignant tumor that originates in the pleural mesothelioma and presents as a local disease in the affected hemithorax. Small intestine metastasis is a rare complication. Herein, the case of a patient with jejunal intussusception caused by small intestine metastasis of MPM has been reported. A 72-year-old man with MPM was admitted to our hospital for abdominal pain. Computed tomography revealed small intestine intussusception. An emergency surgery was performed, and the tumor and intussusception were located in the upper jejunum. Histopathological examination of the resected jejunum revealed that the tumor was a small intestinal metastasis of the MPM from the chest wall. This case showed that MPM may metastasize to the small intestine, and metastatic tumors may cause intussusception.

A lymphoepithelial cyst in the pancreatic accessory spleen: A case report.

We present the first report of a lymphoepithelial cyst. As additional cases will likely be encountered in the future, our study sets the precedent for future research.

Chronic kidney disease caused by maternally inherited diabetes and deafness: a case report.

Maternally inherited diabetes and deafness (MIDD) is a mitochondrial genetic disorder with variable clinical presentations, which can delay its diagnosis. Herein, we report the case of a 57-year-old Japanese man with MIDD who developed chronic kidney disease. He developed proteinuria long before his diabetes and deafness; at the age of 36 years, a renal biopsy showed minor glomerular abnormality and electron microscopy showed mild mitochondrial degeneration in the distal tubular epithelial cells. Twenty years later, a second renal biopsy showed nephrosclerosis with interstitial fibrosis and arteriolar hyaline thickening, despite the absence of hypertension and relatively good glycemic control. Granular swollen epithelial cells were found in the medullary collecting duct epithelium. Electron microscopy showed accumulating mitochondria in podocytes and tubular cells, leading to the diagnosis of MIDD. A muscle biopsy also showed ragged-red fibers, despite the absence of muscle weakness. Mitochondrial DNA analysis revealed an m.3243A > G mutation, and taurine supplementation was initiated. Our findings suggest that mitochondrial dysfunction is mainly associated with progressive renal damage.

Sternal Metastasis of Brain Meningioma - A Case Report.

BACKGROUND: Metastases of meningiomas are infrequent and the site of extracranial metastasis such as the bone is extremely rare. CASE REPORT: A 75-year-old male had a history of five sessions of surgery and gamma-knife treatment for brain meningioma over a period of 29 years. He visited our hospital because he noticed a swelling in his anterior chest 2 years and 6 months after the final treatment. After an open biopsy, histopathological analysis revealed the mass to be a metastatic grade II meningioma. We resected the tumor along with the sternum, ribs, pleura, and pericardium. The patient had recurrences in the thoracic cavity and pericardium postoperatively and received radiation therapy. He also had metastasis in the abdominal cavity, which spread rapidly. CONCLUSION: We report on a rare instance of metastasis to the sternum in a case of atypical meningioma, showing rapid growth and invasion after long-term treatment.

Prognostic significance of expression patterns of EGFR family, p21 and p27 in high-grade astrocytoma.

The goal of this study was to investigate the relationship among immunohistochemical expression of epithelial growth factor receptor (EGFR) family proteins, p21, p27 and prognosis in patients with high-grade astrocytoma. Expression of EGFR family proteins (c-erbB-1, c-erbB-2, c-erbB-3, c-erbB-4), p21 and p27 and Ki-67 labeling index (LI) were studied in 59 samples of high-grade astrocytoma. Expression of protein levels was analyzed by immunohistochemical staining of formalin-fixed and paraffin-embedded sections. Results were analyzed in relation to age, gender and survival. Overexpression of c-erbB-1, c-erbB-2, c-erbB-3 and c-erbB-4 was found in 40 (67.8%), 17 (28.8%), 3 (5.1%) and 42 (75.0%) samples, respectively. Similarly, low expression of p21 and p27 was observed in 50 (84.8%) and 27 (45.8%) samples. Mean Ki-67 LI was 17.3 +/- 1.1. Cox multiple regression analysis showed that c-erbB-1 (Hazard rate(HR) 1.57, 95% Confidence interval (CI) 1.08-2.36; p = 0.017), c-erbB-4 (HR 1.79, 95% CI 1.20-2.74; p = 0.004) and p27 (HR 0.50, 95% CI 0.30-0.82; p = 0.006) were significantly associated with survival. High expression of c-erbB-1 and c-erbB-4 and low expression of p27 were associated with poor prognosis in these patients.

A case of a diverticulum-like giant jejunal gastrointestinal stromal tumour presenting with intraperitoneal peritonitis due to rupture.

INTRODUCTION: Early diagnosis of small intestinal gastrointestinal stromal tumours (GISTs) is difficult. These tumours often present with peritonitis and intraperitoneal bleeding due to rupture. We experienced a case of a tumor that grows to 12 cm asymptomatic. PRESENTATION OF CASE: A 46-year-old man presented with sudden abdominal pain. Computed tomography revealed free air in the abdominal cavity, a 12-cm sized dilatation in the small intestine, and pooled residues. He was diagnosed with perforation of the gastrointestinal tract, and emergency surgery was performed. Inside the abdominal cavity, approximately 500 mL of bloody ascites was observed. A diverticulum-like mass measuring approximately 12-cm long was observed on the jejunum approximately 30 cm from the Treitz ligament. There was a large hematoma inside the mass, and perforation was recognised at the neck of the diverticulum. Partial resection of the jejunum and intraperitoneal drainage were performed. Immunohistochemistry revealed that the tumour was positive for KIT and CD34, and GIST was diagnosed. The patient was discharged on postoperative day 10 without significant complications. The patient did not relapse while taking imatinib as an adjuvant chemotherapy. DISCUSSION: Gastrointestinal stromal tumours are the most common mesenchymal tumours of the gastrointestinal tract and may undergo increased diverticulum-like growth, as seen in this case. Local resection and proper chemotherapy increase long-term survival, suppress tumour growth, and reduce the risk of relapse. CONCLUSION: Diagnosing GIST can be difficult due to the absence of clinical symptoms. It is necessary to ensure local resection and careful long-term follow-up.