Intracardiac Thrombosis and Systemic Embolism in a Patient with Cardiac Amyloidosis in Sinus Rhythm.

Intracardiac thrombosis formation in patients in sinus rhythm is a rare phenomenon. An 84-year-old woman was admitted because of worsening dyspnea on exertion. An electrocardiogram showed sinus rhythm, left atrial overload, marked left axis deviation, low voltage, and poor r-wave progression in leads V1-4. An echocardiogram showed relatively preserved left ventricular ejection fraction with minimal wall thickening. Her serum level of B-type natriuretic peptide (931 pg/mL) was markedly elevated and a diagnosis of worsening heart failure was made. During the course of treatment for heart failure, she was complicated by acute abdominal aortic thromboembolism together with left atrial thrombus. An emergency abdominal aortic thrombectomy was followed by the removal of a left atrial thrombus 2 days later. Left ventricular biopsy performed during the surgery revealed amyloid deposits in the myocardial interstitium. Immunohistochemical study confirmed the diagnosis of transthyretin cardiac amyloidosis. It is postulated that the risk of intracardiac thrombosis and systemic embolism is increased even in sinus rhythm in patients with cardiac amyloidosis.

Paraganglioma of the urinary bladder initially diagnosed as gastrointestinal stromal tumor requiring combined resection of the rectum: a case report.

BACKGROUND: Paraganglioma of the urinary bladder (Pub) is rare and presents with clinical symptoms caused by catecholamine production and release. The typical symptoms of Pub are hypertension, macroscopic hematuria, and a hypertensive crisis during micturition. The average size of detected Pubs is approximately 3 cm. Herein, we report a case of a large Pub in which the symptoms were masked by oral medication, precise preoperative diagnosis was difficult, and intraoperative confirmation of tumoral adhesion to the rectum resulted in hypertensive attacks during surgery. CASE PRESENTATION: A 64-year-old Japanese male with a history of hypertension and arrhythmia controlled with oral medication presented with a large tumor in the pelvic region, detected on examination for weight loss, with no clinical symptoms. Computed tomography and magnetic resonance imaging revealed a tumor measuring 77 mm in diameter in the posterior wall of the urinary bladder. The border with the rectum was unclear, and the tumor showed heterogeneous enhancement in the solid part with an enhancing hypodense lesion. Cystoscopy revealed compression of the bladder trigone by external masses; however, no tumor was visible in the lumen. Endoscopic ultrasonography-guided fine-needle aspiration revealed CD34-positive spindle-shaped cells in the fibrous tissue, suggestive of a mesenchymal neoplasm. The tumor was suspected to be a gastrointestinal stromal tumor, and surgery was performed. After laparotomy, we suspected that the tumor had invaded the rectum, and total cystectomy and anterior resection of the rectum were performed. Histologically, the tumor cells had granular or clear amphophilic cytoplasm with an oval nucleus and nests of cells delimited by connective tissue and vascular septations. Immunohistochemically, the tumor was positive for chromogranin A, CD56, and synaptophysin, and a diagnosis of paraganglioma of the urinary bladder was confirmed. There was no tumor recurrence at the 7-month follow-up. CONCLUSION: This case highlights the importance of careful examination of pelvic tumors, including endocrine testing, for detecting paraganglioma of the urinary bladder in patients with a history of hypertension or arrhythmia.

[Recurrence of Rectal Cancer with Submucosal Invasion in the Bone and Lymph Nodes 89 Months after Surgery--A Case Report].

A woman in her 60s showed positive results on a fecal occult blood test and consulted her doctor. Early-stage cancer of the lower rectum was diagnosed, and a transanal local excision was performed. Histopathological examination revealed that the depth of submucosal invasion was ≧1,000 mm, and the submucosal invasive part of the tumor was a poorly differentiated adenocarcinoma. Therefore, she was referred to our hospital for additional resection. Intersphincteric resection was performed 11 months after the initial operation. The cancer stage was T1N0M0, Stage Ⅰ(UICC 7th edition), and the cancer did not recur. The patient visited our hospital again, 78 months after the additional resection, because of left hip-joint pain. Positron-emission tomography revealed fluorodeoxyglucose uptake in the left acetabulum, para-aortic lymph nodes, and left external iliac lymph nodes; these findings indicated recurrence of the rectal cancer. The patient received radiation therapy (57 Gy) and FOLFIRI; bevacizumab was added from the third course onward. The therapy reduced the size of the tumor recurrence in the bone. This was a rare case of rectal cancer with submucosal invasion that showed recurrence in the bone and lymph nodes 78 months after the additional resection.

[A case of adenosquamous carcinoma of the ascending colon].

A 6 8-year-old man was admitted to our hospital with lower abdominal pain. Lower gastrointestinal endoscopy showed type 2 advanced cancer in the ascending colon. Histopathological examination after endoscopical biopsy revealed both moderately differentiated adenocarcinoma and well-differentiated squamous carcinoma. Subsequently, right hemicolectomy was performed. The tumor was 55 × 40 mm in size and was diagnosed as an adenosquamous carcinoma A, type 2, pSS, pN0, sH0, sP0, sM0, fStageII. Adenosquamous carcinoma is extremely rare, represents about 0.1% of all colorectal cancer, and usually has a poor prognosis. Thirty-one months after surgery, the patient is still in good health and displays no signs of recurrence.

[Transurethral resection of a intravesical recurrence of a tumor after resection of sigmoid colon cancer].

A 66-year-old man presented to the urology clinic with hematuria. Cystoscopy with biopsy was performed for suspected bladder cancer, and a pathological diagnosis of adenocarcinoma was made. Colonoscopy revealed sigmoid colon cancer, and he was referred to our hospital. Computed tomography (CT) and magnetic resonance imaging (MRI) showed sigmoid colon cancer with urinary bladder invasion. Sigmoidectomy with lymph node dissection and partial cystectomy were performed under laparotomy. The pathological diagnosis was moderately differentiated adenocarcinoma: T4b (bladder), N1, M0, and the bladder margin was negative. Four months after surgery, CT revealed a small mass in the bladder. Cystoscopy showed a papillary pedunculated tumor at the bladder trigone, and a transurethral resection was performed. Pathological examination revealed a moderately differentiated adenocarcinoma, similar to the prior sigmoid colon cancer, which was diagnosed as an intravesical recurrence of the tumor. More than 8 years after the transurethral resection, the patient has shown no signs of recurrence.

Central amygdala is related to the reduction of aggressive behavior by monosodium glutamate ingestion during the period of development in an ADHD model rat.

Introduction: Monosodium glutamate (MSG), an umami substance, stimulates the gut-brain axis communication via gut umami receptors and the subsequent vagus nerves. However, the brain mechanism underlying the effect of MSG ingestion during the developmental period on aggression has not yet been clarified. We first tried to establish new experimental conditions to be more appropriate for detailed analysis of the brain, and then investigated the effects of MSG ingestion on aggressive behavior during the developmental stage of an ADHD rat model. Methods: Long-Evans, WKY/Izm, SHR/Izm, and SHR-SP/Ezo were individually housed from postnatal day 25 for 5 weeks. Post-weaning social isolation (PWSI) was given to escalate aggressive behavior. The resident-intruder test, that is conducted during the subjective night, was used for a detailed analysis of aggression, including the frequency, duration, and latency of anogenital sniffing, aggressive grooming, and attack behavior. Immunohistochemistry of c-Fos expression was conducted in all strains to predict potential aggression-related brain areas. Finally, the most aggressive strain, SHR/Izm, a known model of attention-deficit hyperactivity disorder (ADHD), was used to investigate the effect of MSG ingestion (60 mM solution) on aggression, followed by c-Fos immunostaining in aggression-related areas. Bilateral subdiaphragmatic vagotomy was performed to verify the importance of gut-brain interactions in the effect of MSG. Results: The resident intruder test revealed that SHR/Izm rats were the most aggressive among the four strains for all aggression parameters tested. SHR/Izm rats also showed the highest number of c-Fos + cells in aggression-related brain areas, including the central amygdala (CeA). MSG ingestion significantly decreased the frequency and duration of aggressive grooming and attack behavior and increased the latency of attack behavior. Furthermore, MSG administration successfully increased c-Fos positive cell number in the intermediate nucleus of the solitary tract (iNTS), a terminal of the gastrointestinal sensory afferent fiber of the vagus nerve, and modulated c-Fos positive cells in the CeA. Interestingly, vagotomy diminished the MSG effects on aggression and c-Fos expression in the iNTS and CeA. Conclusion: MSG ingestion decreased PWSI-induced aggression in SHR/Izm, which was mediated by the vagus nerve related to the stimulation of iNTS and modulation of CeA activity.

Takotsubo Syndrome in Older Men　- Clinical Characteristics Differ by Sex and Age.

Background: Takotsubo syndrome (TTS) in male patients is under-studied, particularly in the older population. Methods and Results: From 226 patients with TTS, 44 older male patients (prevalence rate: 19.5%, age: median 77 years) were compared with 182 older female patients (prevalence rate: 80.5%, age: median 80 years). Emotional triggers of TTS were less frequent (2% vs. 19%; P=0.007), whereas physical triggers were more frequent (75% vs. 58%; P=0.040) in older men than in women. Among physical triggers, serious respiratory infection was more common in older men than in women. As initial clues to the diagnosis, ECG T-wave inversion was more frequent (48% vs. 29%; P=0.018) and chest pain and/or dyspnea were less common (23% vs. 38%; P=0.050) in older men than in women. In total, 14 patients (6%) had cardiogenic shock and 41 (18%) had severe heart failure as complications, although there were no significant differences in the frequency of these complications between older men and women. Although cardiac death occurred in 3 female patients (1%) and noncardiac death in 3 male and 5 female patients (4%), there were no significant differences in death rate between older men and women. Conclusions: Emotional triggers of TTS were extremely infrequent whereas physical triggers were common in older men. Although severe heart failure was common, there were no significant differences in the frequency of complications and in-hospital deaths between older men and women.

Phototoxicity avoidance is a potential therapeutic approach for retinal dystrophy caused by EYS dysfunction.

Inherited retinal dystrophies (IRDs) are progressive diseases leading to vision loss. Mutation in the eyes shut homolog (EYS) gene is one of the most frequent causes of IRD. However, the mechanism of photoreceptor cell degeneration by mutant EYS has not been fully elucidated. Here, we generated retinal organoids from induced pluripotent stem cells (iPSCs) derived from patients with EYS-associated retinal dystrophy (EYS-RD). In photoreceptor cells of RD organoids, both EYS and G protein-coupled receptor kinase 7 (GRK7), one of the proteins handling phototoxicity, were not in the outer segment, where they are physiologically present. Furthermore, photoreceptor cells in RD organoids were vulnerable to light stimuli, and especially to blue light. Mislocalization of GRK7, which was also observed in eys-knockout zebrafish, was reversed by delivering control EYS into photoreceptor cells of RD organoids. These findings suggest that avoiding phototoxicity would be a potential therapeutic approach for EYS-RD.

Human iPSC-derived renal collecting duct organoid model cystogenesis in ADPKD.

In autosomal dominant polycystic kidney disease (ADPKD), renal cyst lesions predominantly arise from collecting ducts (CDs). However, relevant CD cyst models using human cells are lacking. Although previous reports have generated in vitro renal tubule cyst models from human induced pluripotent stem cells (hiPSCs), therapeutic drug candidates for ADPKD have not been identified. Here, by establishing expansion cultures of hiPSC-derived ureteric bud tip cells, an embryonic precursor that gives rise to CDs, we succeed in advancing the developmental stage of CD organoids and show that all CD organoids derived from PKD1-/- hiPSCs spontaneously develop multiple cysts, clarifying the initiation mechanisms of cystogenesis. Moreover, we identify retinoic acid receptor (RAR) agonists as candidate drugs that suppress in vitro cystogenesis and confirm the therapeutic effects on an ADPKD mouse model in vivo. Therefore, our in vitro CD cyst model contributes to understanding disease mechanisms and drug discovery for ADPKD.

[A case report of surgical treatment for axillary lymph node metastasis from descending colon cancer].

We report a rare case of a 78-year-old woman with metachronous axillary lymph node metastasis originating from descending colon cancer. Her past medical history included right mastectomy for breast cancer at age 53 and distal gastrectomy for gastric cancer at age 70. She underwent a left hemicolectomy for descending colon adenocarcinoma in April 2011. Four months after that operation, 3 enlarging nodules in the left lung and a swollen left axillary lymph node were detected by computed tomography. No tumor was detected in the left breast by ultrasonography and mammography. The lung tumors were resected thoracoscopically, and the left axillary lymph node was excised. These specimens were histologically diagnosed as moderately differentiated adenocarcinoma, which had metastasized from colon cancer, not from the previous breast or gastric cancer. She received adjuvant chemotherapy with uracil and tegafur (UFT) plus Leucovorin for 6 months and is still alive after 12 months without recurrence.

Unilateral Pulmonary Edema in Patients With Acute Mitral Regurgitation Caused by Chordal Rupture.

Background: Cardiogenic unilateral pulmonary edema (UPE) has been reported as an unusual condition and to occur in association with severe mitral regurgitation (MR). However, the prevalence of UPE in patients with severe MR remains unknown. Methods and Results: Among 143 consecutive patients with chordal rupture and significant MR, 38 patients with acute severe MR were studied. The prevalence of UPE was 50% (19 patients); all these patients had right-sided UPE. Eight (21%) patients had bilateral pulmonary edema (BPE). All 8 patients with BPE and 18 of 19 patients with UPE had chordal rupture of the posterior leaflet. All patients with UPE and BPE had severe MR with similar left atrial size. Chest radiographs taken ≤48 h from symptom onset diagnosed UPE in 15 of 19 (79%) patients and BPE in 3 of 8 (38%) patients (P=0.037). Chest radiographs taken >48 h from symptom onset diagnosed UPE in 4 (21%) patients and BPE in 5 (62%) patients (P=0.037). Conclusions: The prevalence of UPE was estimated as 50%; it was most frequently right sided and almost always associated with chordal rupture of the posterior leaflet. UPE is not rare, but common, particularly shortly after the development of acute severe MR caused by chordal rupture.

Acute Left Circumflex Coronary Artery Occlusion　- Diagnostic Problems of Initial Electrocardiographic Changes.

Background: Acute coronary syndrome (ACS) with occlusion of the left circumflex coronary artery (LCX) poses diagnostic problems that may lead to a delay in reperfusion. Methods and Results: From a group of 1,269 consecutive patients with ACS, 138 patients with ACS due to LCX occlusion were analyzed for clinical, electrocardiographic, and angiographic presentations, as well as door-to-balloon (DTB) time. Electrocardiographic changes were classified into 4 patterns: ST-segment elevation in inferior/lateral leads (ST-E); ST-segment depression in V1-V4 (ST-D); no significant ST changes (No-ST); and others. The No-ST group was associated with a longer DTB time (P<0.0001) compared with the ST-E and ST-D groups. Compared with the No-ST and ST-E groups, the ST-D group presented with a more advanced Killip class (P=0.003), greater peak creatine phosphokinase (P=0.007) and peak creatine kinase-MB (P=0.006), more frequent proximal LCX occlusion (P=0.007), and worse 1-year outcomes (P=0.0034). Conclusions: One-third of ACS patients with LCX occlusion showed no ST-segment changes, resulting in significantly longer DTB time. Improving diagnostic accuracy is challenging but critical to avoid delayed reperfusion in these patients without electrocardiographic changes.

[A case of small intestinal cancer in the efferent loop of roux-en Y reconstruction after total gastrectomy and liver metastases].

A 61-year-old woman, who had undergone total gastrectomy and distal splenopancreatectomy with Roux-en Y reconstruction for a gastric cancer 16 years earlier, was found primary small intestinal cancer located in intestinal loop of Roux- en Y in gastrointestinal endoscopy for abdominal pain. Computed tomography showed liver metastases which were 8 cm in diameter at lateral segment and 1 cm in diameter at segment 8 of the liver. In the operation, the small intestinal cancer was located in the ρ-anastomosis in the loop of Roux-en Y with the other jejunum fistula. We performed lateral segment hepatectomy, partial hepatectomy of segment 8, partial resection of small intestine including loop of ρ-Roux-en Y, partial resection of transverse colon, and restoration Roux-en Y again. We succeeded in preserving double tract anastomosis at duodenum. Histological examination revealed a moderately differentiated adenocarcinoma of the small intestine and segment 8 of the liver, and angiomyolipoma of lateral segment of the liver. It is extremely rare for small intestinal cancer to arise in a loop of Roux-en Y reconstruction caused by total gastrectomy.

Clinicopathological Analysis of 17 Surgically Resected Pulmonary Pleomorphic Carcinoma Cases.

OBJECTIVES: To determine the outcomes and prognostic factors associated with pulmonary resection of pulmonary pleomorphic carcinoma (PPC). METHODS: During 2008-2017, 17 patients underwent pulmonary resection for primary PPC at the Saitama Cancer Center, Japan. We investigated clinicopathological characteristics and outcomes of these cases. Overall survival (OS) and disease-free survival (DFS) rates were determined using Kaplan-Meier method and compared using log-rank test. Univariate analysis was performed to identify prognostic factors. RESULTS: The 5-year OS and DFS rates were 27.2% and 51.0%, respectively. The median follow-up period was 30.8±24.9 (3.6-92.8) months after pulmonary resections. Patients with disease-free interval (DFI) <1 year of resection had poorer prognosis than those without (p = 0.001). Patients with N2 status and adenocarcinoma components had significantly poorer disease-free prognosis than their counterparts (p = 0.021 and p = 0.019, respectively). Univariate analysis revealed that DFI <1 year was an unfavorable prognostic factor for OS (p = 0.005); N2 pathological status and presence of adenocarcinoma components were unfavorable prognostic factors for DFS (p = 0.038 and p = 0.036, respectively). CONCLUSION: PPC patients with an adenocarcinoma component and N2 pathological status may have an earlier relapse and poorer prognosis than their counterparts. Further assessment of cases may help clarify the predictors of PPC.

Takotsubo Syndrome in Octogenarians and Nonagenarians.

Background: Takotsubo syndrome (TTS) in the very elderly is poorly understood. We sought to clarify the characteristics of octogenarians and nonagenarians with TTS. Methods and Results: From 148 patients with TTS who underwent coronary angiography, 68 very elderly patients aged ≥80 years (octogenarians/nonagenarians) were compared with 80 younger patients aged ≤79 years. Emotional triggers of TTS were less frequent (7% vs. 19%; P=0.043), whereas physical triggers were more frequent (69% vs. 46%; P=0.005), in octogenarians/nonagenarians than in patients aged ≤79 years. As initial clues to the diagnosis, electrocardiogram changes were more frequent (71% vs. 46%; P=0.003) and chest pain and/or dyspnea were less common (25% vs. 51%; P=0.001) in octogenarians/nonagenarians than in patients aged ≤79 years. Twenty-nine patients had acute heart failure (AHF) as a complication. AHF was more frequently found in octogenarians/nonagenarians than in patients aged ≤79 years (29% vs. 11%, respectively; P=0.006). Cardiac death occurred in 2 octogenarians/nonagenarians; non-cardiac death occurred in 3 octogenarians/nonagenarians and in 2 patients aged ≤79 years. Conclusions: Emotional triggers of TTS were infrequent in octogenarians/nonagenarians with TTS. AHF was common and there was significant in-hospital all-cause mortality among octogenarians/nonagenarians.

[A case of anal metastasis from sigmoid colon cancer in a long-term survivor who had repeated local excisions].

A 72-year-old man underwent sigmoidectomy for sigmoid colon cancer in January 1999. Histopathological examination revealed a moderately differentiated adenocarcinoma, tub 2, SS, ly2, v2, N1, H0, P0, M0, Stage IIIa, cur A. In March 2001, he complained of an anal bleeding and underwent colonoscopy. It showed a submucosal tumor 15 mm in diameter at the anal canal and the biopsy indicated a moderately differentiated adenocarcinoma. This tumor was suspected of metastasis from sigmoid colon cancer and transanal resection was performed in May 2001. Histopathological examination revealed a moderately differentiated adenocarcinoma, which was the same histological type as primary sigmoid colon cancer, tub 2, A, ly2, v2, RM0. The diagnosis of anal metastasis was made on the basis of three points. First, tumor was covered with anal epithelium. Secondly, there were severe lymphatic and venous involvements. Thirdly, there were no findings of other primary anal cancer. By removing anal canal metastases twice, inguinal lymph node metastases three times and lung metastases in each time, he survived for 11 years after a primary surgery. We reported here because it was a very interesting and rare case that the patient was cancer-free after surgeries as many as seven times.

[Intramucosal colorectal carcinomas treated by surgical resection].

Stage 0 colorectal cancer was found only in the innermost lining of the colon and rectum. Treatments for an early stage colorectal cancer were available including endoscopic polypectomy, endoscopic mucosal resection (EMR) and trans-anal or -sacral local excision, laparoscopy-assisted colectomy and open colectomy. Our study indicated that endoscopic therapy for the early stage colorectal cancer was more advantageous than the conventional operative treatment. Although EMR should be applied for intramucosal carcinomas, 11 intramucosal carcinomas were treated by a surgical resection due to several limitations at our institution.

Mixed squamous cell and glandular papilloma of the lung-A case report and literature review in Japan.

INTRODUCTION: Mixed squamous cell and glandular papilloma (MSGP) of the lung is rare neoplasm, only 19 cases previously reported in Japan. MSGP is one of three separate categories of solitary endobronchial papillomas, which account for less than 0.5 % of all lung tumors. MSGP is rarest of the three. We present a rare case of MSGP and review the literature in Japan. PRESENTATION OF CASE: A 49-year-old man presented with a nodulous shadow in the right lower lung field identified on a chest X-ray performed for back pain. Computed tomography demonstrated a well-circumscribed, 9-mm mass in the S8 segment of the right lower lung lobe. Positron emission tomography showed accumulation of 18F-fluorodeoxyglucose in the tumor with a standardized uptake value of 2.29. Following thoracoscopic partial resection, adenocarcinoma was diagnosed by frozen section, and radical segmentectomy of S8 was performed. The final diagnosis was mixed squamous cell and glandular papilloma. The patient had an uncomplicated postoperative course and remains asymptomatic 3 years after the procedure. DISCUSSION: The etiology and pathological characteristics of MSGP remain unclear. There has been no report of recurrence in MSGP cases treated with complete resection; thus, limited resection that preserves pulmonary function is desirable. Further data including new cases are required. CONCLUSION: We present a rare case of mixed squamous cell and glandular papilloma (MSGP) of the lung and review the literature in Japan. Limited resection that preserves pulmonary function, while ensuring complete resection, is desirable. Further investigations with new cases are required.