A case of pulmonary primary MALT lymphoma with distinctive bronchoscopic findings.

Mucosa-associated lymphoid tissue (MALT) is a low-grade lymphoma, but cases in which it has transformed into a high-grade lymphoma have been reported, necessitating an accurate diagnosis. The patient was a 79-year-old nonsmoking Japanese female with history of ocular sarcoidosis. A computed tomography scan of her chest revealed a 35-mm nodule in the left S1 + 2, contiguous with the lymph nodes. Additional nodules were observed around the left B5 and B10a. Bronchoscopy revealed stenosis caused by a white, glossy, elevated lesion with angiogenesis at the orifice of the left upper lobe bronchus. The biopsy specimen demonstrated the dominance of lymphoid cells and tested positive for CD20, CD79a, Bcl-2, and IRTA-1, which is consistent with the findings in MALT lymphoma. Therefore, in the presence of multiple infiltrative shadows along the bronchi with glossy elevated lesions without necrosis on bronchoscopy, it is important to consider MALT lymphoma as a differential diagnosis.

Non-esterified fatty acid palmitate facilitates oxidative endoplasmic reticulum stress and apoptosis of ß-cells by upregulating ERO-1α expression.

Adipose tissue-derived non-esterified saturated long-chain fatty acid palmitate (PA) decisively contributes to ß-cell demise in type 2 diabetes mellitus in part through the excessive generation of hydrogen peroxide (H2O2). The endoplasmic reticulum (ER) as the primary site of oxidative protein folding could represent a significant source of H2O2. Both ER-oxidoreductin-1 (ERO-1) isoenzymes, ERO-1α and ERO-1ß, catalyse oxidative protein folding within the ER, generating equimolar amounts of H2O2 for every disulphide bond formed. However, whether ERO-1-derived H2O2 constitutes a potential source of cytotoxic luminal H2O2 under lipotoxic conditions is still unknown. Here, we demonstrate that both ERO-1 isoforms are expressed in pancreatic ß-cells, but interestingly, PA only significantly induces ERO-1α. Its specific deletion significantly attenuates PA-mediated oxidative ER stress and subsequent ß-cell death by decreasing PA-mediated ER-luminal and mitochondrial H2O2 accumulation, by counteracting the dysregulation of ER Ca2+ homeostasis, and by mitigating the reduction of mitochondrial membrane potential and lowered ATP content. Moreover, ablation of ERO-1α alleviated PA-induced hyperoxidation of the ER redox milieu. Importantly, ablation of ERO-1α did not affect the insulin secretory capacity, the unfolded protein response, or ER redox homeostasis under steady-state conditions. The involvement of ERO-1α-derived H2O2 in PA-mediated ß-cell lipotoxicity was corroborated by the overexpression of a redox-active ERO-1α underscoring the proapoptotic activity of ERO-1α in pancreatic ß-cells. Overall, our findings highlight the critical role of ERO-1α-derived H2O2 in lipotoxic ER stress and ß-cell failure.

Cytomorphological features of sebaceous carcinoma of the breast.

Sebaceous carcinoma of the breast is an extremely rare histological subtype of breast cancer, with fewer than 30 cases reported to date. Because of its extremely rare histological presentation, there are few case reports that highlight its cytological findings. In this case report, the cytomorphological features of a sebaceous carcinoma of the breast are described in detail. Cytomorphological analysis revealed atypical cells presenting predominantly as loose clusters. No tubular or papillary structures were evident in the clusters and no mucin production was observed. The diagnosis of sebaceous carcinoma of the breast requires prominent sebaceous differentiation of cells. In Papanicolaou-stained smears, the differentiated tumor cells were found within the yellowish clusters. When these yellowish clusters were observed at high magnification and shifted out of focus, the sebaceous differentiation of tumor cells could be recognized. This finding is an advantage of observing Papanicolaou-stained specimens. Like previous reports, some individual cells showing sebaceous differentiation were also observed. In cases where many yellowish clusters appear, close observation of the interior of the clusters can confirm the presence of sebaceous differentiation of tumor cells and serve as a diagnostic clue for the cytological diagnosis of sebaceous carcinoma of the breast.

Metabolic and Epigenetic Reprogramming in a Case of Nuclear Protein in Testis (NUT) Carcinoma of the Retroperitoneum.

Nuclear protein in testis (NUT) carcinoma is a rare but highly aggressive carcinoma, driven by genetic rearrangement of the NUT midline carcinoma family member 1 (NUTM1) gene on chromosome 15q14. Recently, a tight link has been suggested between genetic abnormalities and subsequent metabolic and epigenetic dysregulation to drive the progression of malignant tumors. However, it remains elusive whether such reprogramming could contribute to the pathogenesis of NUT carcinoma. We herein report an autopsy case of NUT carcinoma arising in the retroperitoneum of a 31-year-old male. Notably, reprogramming of glycolytic metabolism and epigenetic histone modifications was observed in this unusual NUT carcinoma case, and this phenomenon was further confirmed by an in vitro cell culture model with bromodomain containing 4 (BRD4)-NUT overexpression. The rationale for documenting the case is based on our findings to reveal that metabolic and epigenetic reprogramming could be one of the contributing factors to the pathogenesis of NUT carcinoma, which could be exploitable as a novel therapeutic target for this rare and aggressive cancer type.

Prenatal exposure to intra-amniotic infection with Ureaplasma species increases the prevalence of bronchopulmonary dysplasia.

OBJECTIVES: The present study investigated the relationship between bronchopulmonary dysplasia (BPD) and intra-amniotic infection with Ureaplasma species. METHODS: This was a single-center, retrospective cohort study. Patients with singleton pregnancies who underwent inpatient management at our department for preterm premature rupture of membranes (PPROM), preterm labor, cervical insufficiency, and asymptomatic cervical shortening at 22-33 gestational weeks were included. Amniocentesis was indicated for patients with PPROM or an elevated maternal C-reactive protein level (≥0.58 mg/dL). Patients with an amniotic fluid IL-6 concentration ≥3.0 ng/mL were diagnosed with intra-amniotic inflammation, while those with positive aerobic, anaerobic, M. hominis, and Ureaplasma spp. cultures were diagnosed with microbial invasion of the amniotic cavity (MIAC). Patients who tested positive for both intra-amniotic inflammation and MIAC were considered to have intra-amniotic infection. An umbilical vein blood IL-6 concentration >11.0 pg/mL indicated fetal inflammatory response syndrome (FIRS). The maternal inflammatory response (MIR) and fetal inflammatory response (FIR) were staged using the Amsterdam Placental Workshop Group Consensus Statement. RESULTS: Intra-amniotic infection with Ureaplasma spp. was diagnosed in 37 patients, intra-amniotic infection without Ureaplasma spp. in 28, intra-amniotic inflammation without MIAC in 58, and preterm birth without MIR/FIR and FIRS in 86 as controls. Following an adjustment for gestational age at birth, the risk of BPD was increased in patients with intra-amniotic infection with Ureaplasma spp. (adjusted odds ratio: 10.5; 95% confidence interval: 1.55-71.2), but not in those with intra-amniotic infection without Ureaplasma spp. or intra-amniotic inflammation without MIAC. CONCLUSION: BPD was only associated with intra-amniotic infection with Ureaplasma species.

Comparison of Endoscopic and Artificial Intelligence Diagnoses for Predicting the Histological Healing of Ulcerative Colitis in a Real-World Clinical Setting.

Background: Artificial intelligence (AI)-assisted colonoscopy systems with contact microscopy capabilities have been reported previously; however, no studies regarding the clinical use of a commercially available system in patients with ulcerative colitis (UC) have been reported. In this study, the diagnostic performance of an AI-assisted ultra-magnifying colonoscopy system for histological healing was compared with that of conventional light non-magnifying endoscopic evaluation in patients with UC. Methods: The data of 52 patients with UC were retrospectively analyzed. The Mayo endoscopic score (MES) was determined by 3 endoscopists. Using the AI system, healing of the same spot assessed via MES was defined as a predicted Geboes score (GS) < 3.1. The GS was then determined using pathology specimens from the same site. Results: A total of 191 sites were evaluated, including 159 with a GS < 3.1. The MES diagnosis identified 130 sites as MES0. A total of 120 sites were determined to have healed based on AI. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of MES0 for the diagnosis of GS < 3.1 were 79.2%, 90.6%, 97.7%, 46.8%, and 81.2%, respectively. The AI system performed similarly to MES for the diagnosis of GS < 3.1: sensitivity, 74.2%; specificity: 93.8%; PPV: 98.3%; NPV: 42.3%; and accuracy: 77.5%. The AI system also significantly identified a GS of < 3.1 in the setting of MES1 (P = .0169). Conclusions: The histological diagnostic yield the MES- and AI-assisted diagnoses was comparable. Healing decisions using AI may avoid the need for histological examinations.

Pneumococcal infectious aortic aneurysm: A caution for a life-threatening vascular complication caused by non-vaccine-covered serotypes.

The 23-valent pneumococcal polysaccharide vaccine (PPSV23) has contributed to reducing pneumonia caused by Streptococcus pneumoniae. However, in Japan, invasive pneumococcal diseases caused by non-vaccine-covered serotypes have increased over the years. A 73-year-old man with a history of PPSV23 was referred to our hospital due to persistent fever and back pain following pneumococcal pneumonia. Contrast-enhanced computed tomography revealed an infectious aneurysm (IAA) at the distal part of the aortic arch. The patient was surgically treated with in situ aortic reconstruction and administered antibiotics. On pathogenic examination of the resected IAA, atherosclerotic changed aortic wall, neutrophil infiltration, and abscesses were observed. Although multiple blood culture tests were negative, tissue culture tests and 16S ribosomal RNA gene-based polymerase chain reaction identified S. pneumoniae. According to capsular polysaccharide synthesis B gene-based serotyping, the serotype was identified as 23A, which is not covered with PPSV23. Serotype 23 is among the most frequently identified serotypes in recent years and associated with in-hospital mortality. Although several pneumococcal serotypes are responsible for lethal infections, the association between these serotypes and disease is uncertain. Further studies on the association between pneumococcal serotypes and IAA, and the development of a broader-covered vaccine are required. Learning objective: •To be able to make a differential diagnosis of invasive pneumococcal pneumonia in patients with persistent fever and newly emerging back pain following pneumococcal infection.•To understand the importance of combining culture tests and molecular analysis to diagnose invasive pneumococcal diseases accurately.•To understand the threat of non-vaccine-covered serotypes even in patients with vaccination histories because the vaccine is limited to only one-fourth of all pneumococcal serotypes.

Jejunal gastrointestinal stromal tumor that developed in a patient with neurofibromatosis type 1: a case report.

BACKGROUND: Neurofibromatosis type 1 (NF1) is known to be associated with the frequent occurrence of unique gastrointestinal stromal tumors (GISTs), preferably occurring in the small intestine, with no mutations in the c-kit proto-oncogene or platelet-derived growth factor receptor-alpha (PDGFRA), with a high tendency for multifocal development, indolent nature, with low proliferation activity and favorable prognosis. CASE PRESENTATION: A woman in her forties visited her local doctor complaining of menstrual pain; a large mass was detected in her lower abdomen, and she was referred to our hospital. The patient had hundreds of skin warts and café au lait spots. The patient's mother had been diagnosed with type 1 neurofibromatosis. The patient met the diagnostic criteria for NF1 and was diagnosed with NF1. Ultrasonography showed a large heterogeneous cystic mass with various echo patterns, solid compartments and multiple septations. Magnetic resonance imaging showed a multilocular cystic mass with liquid content exhibiting various intensities, including that of blood. A small round solid mass was also observed close to the cystic tumor. Contrast-enhanced computed tomography showed that the round solid mass showed strong enhancement in the early phase, unlike the cystic tumor component. Open laparotomy revealed a multicystic exophytic tumor measuring 11.5 cm originating from the jejunal wall, 20 cm distal to the duodenojejunal flexure. A solid tumor measuring 2.1 cm was also found on the anal side of the large tumor. We resected the short segment of the jejunum, including the two lesions. Microscopic findings revealed that the cystic and solid tumors consisted of spindle-shaped tumor cells showing little atypia with a fascicular or bundle arrangement. Nuclear mitosis was scarce. Immunostaining of the tumor cells showed positive staining for KIT and DOG1 and negative staining for S100 and desmin. The NF1 patient was diagnosed with multiple GISTs accompanied by intratumoral hemorrhagic denaturation arising from the jejunum. The TNM staging was pT4N0M0, stage IIIA. CONCLUSION: We report a case of GISTs associated with NF1 that showed a jejunal origin, multifocal development and few mitotic figures. The recurrence risk, survival prognosis and need for adjuvant chemotherapy, particularly in cases where the initial GIST exhibits a very indolent pathology in NF1-related GISTs, remain to be elucidated.

Appendiceal cancer showing a submucosal tumor-like morphology in the ascending colon on colonoscopy: a case report.

Few reports have described a submucosal tumor (SMT)-like colon tumor together with appendiceal cancer. Moreover, some appendiceal tumors may exhibit a cecal protuberance. Here, we report an uncommon case of appendiceal cancer with an SMT-like tumor, which was a protuberant lesion in the ascending colon. To our knowledge, this is the first report in Japan. Our case was a 50-year-old man with an ascending colon tumor presented at our hospital for further evaluation of this lesion. This was discovered as a cystic lesion near the ascending colon on colonoscopy. Our initial diagnosis was an ascending colon SMT-like tumor, and our treatment strategy was laparoscopic resection. The differential diagnosis was appendiceal cancer or mucocele. Postoperative pathological findings led to a diagnosis of adenocarcinoma of the appendix. The postoperative course was uneventful, and the patient was followed up with computed tomography and blood sampling on an outpatient basis.

Histological transformation to signet-ring cell carcinoma in a patient with clinically aggressive poorly differentiated adenocarcinoma of the ascending colon after response to chemotherapy plus cetuximab: a case report.

BACKGROUND: Alteration of chemosensitivity or tumor aggressiveness in response to chemotherapy has been reported, and liquid biopsy assessment during chemotherapy for colorectal cancers has confirmed the acquisition of mutations in various oncogenes. However, the occurrence of histological transformation seems to be extremely rare in colorectal cancers, and the few existing case reports of this transformation are from lung cancer and breast cancer. In this report, we describe the histological transformation of clinically aggressive scirrhous-type poorly differentiated adenocarcinoma of the ascending colon to signet-ring cell carcinoma in almost all recurrent tumors that were confirmed by autopsy after response to chemotherapy plus cetuximab. CASE PRESENTATION: A 59-year-old woman visited our hospital with whole abdominal pain and body weight loss and was diagnosed with scirrhous-type poorly differentiated adenocarcinoma of the ascending colon with aggressive lymph node metastases. The intrinsic chemosensitivity of the tumors was evident upon initiation of mFOLFOX6 plus cetuximab therapy, and right hemicolectomy was performed, and the tumor obviously remained in the peripancreatic area, paraaortic region, or other retroperitoneal areas. The ascending colon tumors mainly consisted of poorly differentiated adenocarcinoma and were not associated with signet-ring cell components except for minute clusters in a few lymphatic emboli in the main tumor. Chemotherapy was continued, and metastases were eliminated at 8 months after the operation; this response was maintained for an additional 4 months. Discontinuation of chemotherapy plus cetuximab resulted in immediate tumor recurrence and rapid expansion, and the patient died of the recurrent tumor 1 year and 2 months after the operation. Autopsy specimens revealed that almost all of the recurrent tumors exhibited transformation and consisted of signet-ring cell histology. CONCLUSION: This case might suggest that various oncogene mutations or epigenetic changes resulting from chemotherapy, especially regimens that include cetuximab, contribute to the transformation of non-signet-ring cell colorectal carcinoma to signet-ring cell carcinoma histology and can promote the aggressive clinical progression characteristic of signet-ring cell carcinoma.

Effects of COVID-19 pandemic on hospital visit of head and neck cancer patients.

OBJECTIVE: Head and neck cancer (HNC) often causes respiratory symptoms, so diagnostic delays due to COVID-19 are anticipated. Especially, our institute is a designated medical institute for Class 1 specified infectious diseases, and most of the severe COVID-19 patients in this region were preferentially admitted or transferred. Hereby, we evaluated the trends of the numbers, primary sites and clinical stages of HNC patients before and after COVID-19 pandemic. METHODS: A retrospective analysis of all patients diagnosed and treated for HNC from 2015 to 2021 was performed. Especially, 309 cases between 2018 and 2021 were extracted in order to examine a direct impact of COVID-19 pandemic, which were dichotomized into "Pre" group in 2018-2019 and "COVID" group in 2020-2021. They were compared about the distribution of clinical stage, the period between onset of symptom and hospital visit. RESULTS: HNC patients decreased by 38% in 2020 and by 18% in 2021 compared to average number of patients from 2015 to 2019. Patients of stage 0 and 1 in "COVID" group significantly decreased compared to that in "Pre" group. Cases performed emergent tracheostomy in hypopharyngeal cancer and laryngeal cancer increased in "COVID" group (10.5% vs 1.3%). CONCLUSION: Patients with slight symptoms would hesitated to visit hospital after COVID-19, and only a few delays of HNC diagnosis could have increased tumor burden and caused narrowed airway, especially in advanced HPC and LC.

Adenocarcinoma with mediastinal lymph node involvement developed from a pure ground grass nodule during 14 years.

A 69-year-old female Japanese patient presented with an abnormal shadow on chest computed tomography (CT). She had received a mastectomy 14 years prior. Under the diagnosis of primary lung cancer, left upper lobectomy was conducted. Pathology showed a lepidic adenocarcinoma with mediastinal lymph node metastases with pT2aN2M0. Upon retrospective analysis, the chest CT at the time of mastectomy depicted a ground-glass nodule (GGN) of less than 20 mm. Over the previous 10.5 years, the concentration of the central part of the GGN increased. Conclusively, a pure GGN developed into lung adenocarcinoma with mediastinal lymph node involvement over 14 years. She had bone metastases 4 years after the lobectomy but has survived for five and a half years after surgery with treatment with osimertinib. Comparison readings of films should be performed throughout the patient's clinical history to detect subtle shadow alterations indicative of tumour progression.

Pituicytoma with pleomorphism: A case report with cytological findings.

Pituicytoma is a rare neoplasm, arising in the posterior pituitary or in the hypophyseal stalk, and its cytological findings have not yet been well-described. We have experienced a case of pituicytoma, which was difficult to diagnose intraoperatively, because of its cellular pleomorphism. A tumor measuring 18 mm in maximum diameter was found at the sella turcica in a Japanese woman in her forties. Both intraoperative crush cytology and histology of the resected tumor showed pleomorphic spindle or round cells, including multinucleated cells. Tumor cells were positive for TTF-1, S-100 protein, and vimentin, partially positive for glial fibrillary acidic protein and epithelial membrane antigen, and negative for synaptophysin, hormones of the anterior pituitary gland, CD34, Olig2, PAX8, and napsin A. Ki-67 labeling index was 2.0%. Tumors included in the differential diagnosis in general are pituitary adenoma, craniopharyngioma, germinoma, and metastatic tumor on the radiological standpoint, and pilocytic astrocytoma and meningioma on the cytological standpoint. However, our case was difficult to differentiate especially from high-grade glioma only by morphology, and immunohistochemistry including TTF-1 was helpful.

Reproductive Isolation and a Change in the Development Mode of the Tideland Snail Batillaria flectosiphonata (Gastropoda: Batillariidae).

Microsatellite analyses of sympatric populations of a tideland snail endemic to the Nansei Islands, Japan, Batillaria flectosiphonata, and its sister species, Batillaria multiformis, from a tideland on Amami-Oshima Island, indicated that the two species are reproductively isolated from each other, confirming the validity of B. flectosiphonata, whose monophyly was supported only by a low bootstrap probability in the previous molecular phylogenetic analysis. Egg capsules of B. flectosiphonata from Tokunoshima Island of the Amami insular group and Okinawajima Island of the Okinawa insular group were examined, which revealed that this species is a direct developer. Thus, the direct development has evolved twice within batillariids in Japanese waters. The lower genetic diversity of B. flectosiphonata than that of B. multiformis in the sympatric habitat might be attributed to its long-term isolation within the Amami insular group.

IgG4-related brain pseudotumor mimicking CNS lymphoma. A case report.

Here, we report a case of IgG4-related brain pseudotumor (IgG4-BP) in a 39-year-old woman, mimicking central nervous system (CNS) lymphoma. She presented with headache, fever, and fatigue. Her medical history was notable for appearance of a tumefactive brain lesion seven years before. Brain biopsy performed at the age of 32 revealed nonspecific inflammatory changes, and her condition improved with oral low-dose steroid therapy. Magnetic resonance imaging performed at the age of 39 identified a hyperintensity lesion with edema located at the medial temporal lobe region adjacent to the inferior horn of the left lateral ventricle on fluid-attenuated inversion recovery images, which showed gadolinium-contrast enhancement on T1-weighted images and a slightly hyperintensity signal on diffusion-weighted images. Methionine-positron emission tomography (PET) depicted a high methionine uptake in the lesion. Additionally, soluble levels of interleukin (IL)-2 receptor (sIL-2R) and IL-10 were increased in cerebrospinal fluid (CSF). Based on these findings, we suspected CNS lymphoma and performed partial resection of the brain lesion. Pathological examination revealed prominent lymphocytic infiltration associated with plasma cell infiltration. Most of the plasma cells were immunoreactive for IgG4. Storiform fibrosis and partially obliterative phlebitis were concomitantly observed. Thus, the patient was diagnosed as having IgG4-BP. To the best of our knowledge, this is the first case report of IgG4-BP with detailed findings obtained by CSF testing, methionine-PET, and pathological examination. Because IgG4-related diseases can present as a pseudotumor that mimics CNS lymphoma, it is essential to carefully differentiate IgG4-BP from CNS lymphoma.

Differential diagnoses of calcified nodules in pulmonary amyloidosis: A case report.

Pulmonary amyloidosis should be included in the differential diagnosis of calcified lung nodules, and more careful preparation for bleeding should be taken when performing bronchoscopy. While management does not require aggressive treatment, follow-up is necessary to monitor for multiple myeloma and malignant lymphoma.

Aluminum potassium sulfate and tannic acid (ALTA) sclerotherapy complicating laparoscopic low anterior resection of rectal cancer: Case report.

INTRODUCTION: Aluminum potassium sulfate and tannic acid (ALTA) sclerotherapy is increasingly popular for treating internal hemorrhoids. This injectable compound incites inflammation to dampen hemorrhoidal blood flow and inflict secondary fibrosis. Herein, we detail the implications of ALTA treatment for laparoscopic low anterior resection of rectal cancer. PATIENT PRESENTATION: A 72-year-old man receiving ALTA sclerotherapy for internal hemorrhoids thereafter required laparoscopic low anterior resection for newly discovered early rectal cancer. Observed changes of anal canal resembled those of radiochemotherapy and proved problematic. There was mural thickening and sclerosis at the planned resection site. To ensure proper removal, the bowel was compressed and stapled slowly. A two-shot resection took place (without straining), anastomosis was performed, and a covering stoma was constructed. Recovery was uneventful, allowing discharge on postoperative Day 10. The ileostomy was closed at a later time. DISCUSSION: Although little information is available on long-term rectal pathology after ALTA therapy, existing data suggest that sclerosis persists well beyond injection timeframes. Hence, caution is required in dissecting and debriding sclerotic remnants. We have identified only four earlier reports in this setting, the present case providing added perspective. CONCLUSION: Colonoscopy is highly advisable prior to ALTA therapy. A thorough work-up before rectal surgery is also essential, documenting any past treatments for anorectal disease, especially ALTA.

Ovarian serous carcinoma in which mediastinal recurrence of the cancer was resected 16 years after surgery: A case report.

We report a rare case of ovarian carcinoma in which a mediastinal recurrence was resected 16 years after the initial operation. A 72-year-old woman underwent hysterectomy with adnexectomy for stage IIIC ovarian serous carcinoma after neoadjuvant chemotherapy. Six courses of adjuvant chemotherapy were administered. Three years after surgery, left supraclavicular lymph node metastasis occurred, and radiotherapy and two courses of chemotherapy were administered. Six years before presentation, a metastasis at the right cardiophrenic lymph node was resected, and six courses of chemotherapy were administered. During follow-up, a retrosternal tumour was found. The metastatic lesion in contact with the diaphragm was thought to result from pleuroperitoneal communication, and it increased in size. Although high-grade serous carcinoma is aggressive, its sensitivity to chemotherapy may suppress early recurrence, contributing to good outcomes, but with late recurrence. Multidisciplinary therapy including surgery is required for improved long-term prognosis for mediastinal metastasis of ovarian serous carcinoma.

Single-incision port robot-assisted surgery for thymic carcinoid tumor resection.

BACKGROUND: Multiple endocrine neoplasia (MEN) is divided into MEN type 1 (MEN-1) and MEN type 2 (MEN-2). MEN-1 may be associated with thymic carcinoid tumors. We present a case of the surgical removal of a thymic carcinoid associated with MEN-1 via a single-incision port RATS. CASE PRESENTATION: A 39-year-old male patient with multiple endocrine neoplasia type 1 (MEN-1) who had an anterior mediastinal mass was referred to our hospital. The patient had undergone total parathyroidectomy and auto-transplantation of a partial parathyroid for hyperparathyroidism 6 years ago. Chest computed tomography revealed an isolated anterior mediastinal mass on the thymic gland with a maximum diameter measuring 22 mm. Thymic carcinoid tumor is classified as MEN-1 and has a poor prognosis, so we decided to remove the tumor. Single-incision port RATS was performed, and thymic carcinoid was confirmed in pathology. CONCLUSIONS: This report demonstrates that thymic carcinoid tumor removal is feasible and easy to perform via single-incision port RATS.

Fukutin regulates tau phosphorylation and synaptic function: Novel properties of fukutin in neurons.

Fukutin, a product of the causative gene of Fukuyama congenital muscular dystrophy (FCMD), is known to be responsible for basement membrane formation. Patients with FCMD exhibit not only muscular dystrophy but also central nervous system abnormalities, including polymicrogyria and neurofibrillary tangles (NFTs) in the cerebral cortex. The formation of NFTs cannot be explained by basement membrane disorganization. To determine the involvement of fukutin in the NFT formation, we performed molecular pathological investigations using autopsied human brains and cultured neurons of a cell line (SH-SY5Y). In human brains, NFTs, identified with an antibody against phosphorylated tau (p-tau), were observed in FCMD patients but not age-matched control subjects and were localized in cortical neurons lacking somatic immunoreactivity for glutamic acid decarboxylase (GAD), a marker of inhibitory neurons. In FCMD brains, NFTs were mainly distributed in lesions of polymicrogyria. Immunofluorescence staining revealed the colocalization of immunoreactivities for p-tau and phosphorylated glycogen synthase kinase-3ß (GSK-3ß), a potential tau kinase, in the somatic cytoplasm of SH-SY5Y cells; both the immunoreactivities were increased by fukutin knockdown and reduced by fukutin overexpression. Western blot analysis using SH-SY5Y cells revealed consistent results. Enzyme-linked immunosorbent assay (ELISA) confirmed the binding affinity of fukutin to tau and GSK-3ß in SH-SY5Y cells. In the human brains, the density of GAD-immunoreactive neurons in the frontal cortex was significantly higher in the FCMD group than in the control group. GAD immunoreactivity on Western blots of SH-SY5Y cells was significantly increased by fukutin knockdown. On immunofluorescence staining, immunoreactivities for fukutin and GAD were colocalized in the somatic cytoplasm of the human brains and SH-SY5Y cells, whereas those for fukutin and synaptophysin were colocalized in the neuropil of the human brains and the cytoplasm of SH-SY5Y cells. ELISA confirmed the binding affinity of fukutin to GAD and synaptophysin in SH-SY5Y cells. The present results provide in vivo and in vitro evidence for novel properties of fukutin as follows: (i) there is an inverse relationship between fukutin expression and GSK-3ß/tau phosphorylation in neurons; (ii) fukutin binds to GSK-3ß and tau; (iii) tau phosphorylation occurs in non-GAD-immunoreactive neurons in FCMD brains; (iv) neuronal GAD expression is upregulated in the absence of fukutin; and (v) fukutin binds to GAD and synaptophysin in presynaptic vesicles of neurons.