A unique autopsy case of ascending aortic dissection caused by giant cell arteritis without drug therapy.

Giant cell arteritis is a granulomatous inflammation of large and medium-sized arteries, occurring predominantly in older women. In this case, a 76-year-old woman was hospitalized for examination because of a high C-reactive protein (CRP) level, but nothing remarkable was found on thoracicoabdominal computed tomography (CT) or head magnetic resonanse imaging (MRI). On the 46th day from the first visit, she died suddenly due to cardiac tamponade. On pathological autopsy, we found the cause of death to be acute aortic dissection (Stanford type A) due to giant cell arteritis occurred in the ascending aorta. Histologically, granulomatous vasculitis with giant cells was recognized in the ascending aorta, thoracic descending aorta and abdominal aorta and their branches. Interestingly, similar granulomatous vasculitis was also found in the medium and small vessels of other plural organs, including the heart, liver, uterine corpus, and its appendages. To our knowledge, giant cell arteritis with multiple-organ granulomatous changes has not been reported before. We herein reported a unique autopsy case of giant cell arteritis in a patient not treated with medication.

Assessment of aggressiveness of rectal cancer using 3-T MRI: correlation between the apparent diffusion coefficient as a potential imaging biomarker and histologic prognostic factors.

BACKGROUND: Diffusion-weighted magnetic resonance imaging (DW-MRI) permits non-invasive assessment of tumor characteristics. PURPOSE: To assess the value of DW-MRI as a potential non-invasive marker of tumor aggressiveness in rectal cancer by analyzing the relationship between tumoral apparent diffusion coefficient (ADC) values of MRI and histopathologic prognostic parameters that are not affected by preoperative chemoradiation therapy. MATERIAL AND METHODS: Forty patients with rectal cancer were assessed with primary staging 3-T MRI, including DWI, before undergoing surgical therapy. In all patients, surgery was performed without neoadjuvant therapy. Mean tumor ADC was measured and compared between subgroups based on pretreatment carcinoembryonic antigen (CEA) levels, MRI parameters (e.g. postoperative local recurrence), and histopathologic parameters, including A (invasive distance: A1, T-stage; A2, mesorectal fascia [MRF] status), B (differentiation grade: B1, poorly differentiated; B2, moderately differentiated; B3, well differentiated), C (others: C1, N-stage; C2, lymphangiovascular invasion). RESULTS: Mean tumor ADCs were different when comparing groups stratified by histologic differentiation grades (P=0.0192). There was no significant difference in mean ADCs when stratifying patients according to CEA levels, T-stage, N-stage, MRF status, presence of lymphangiovascular invasion, or the presence of local recurrence. CONCLUSION: Significant correlations were found between mean ADC values and differentiation grade. ADC may be useful as an imaging biomarker of tumor aggressiveness, but it cannot serve as an independent biomarker of advanced rectal cancer.

Isoniazid- and streptomycin-resistant miliary tuberculosis complicated by intracranial tuberculoma in a Japanese infant.

In Japan, the incidence of severe pediatric tuberculosis (TB) has decreased dramatically in recent years. However, children in Japan can still have considerable opportunities to contract TB infection from adult TB patients living nearby, and infants infected with TB may develop severe disseminated disease. A 3-month-old girl was admitted to our hospital with dyspnea and poor feeding. After admission, miliary TB and multiple brain tuberculomas were diagnosed. Anti-tuberculous therapy was initiated with streptomycin (SM), isoniazid (INH), rifampicin and pyrazinamide. Symptoms persisted after starting the initial treatment and mycobacterial cultures of gastric fluid remained positive. Drug sensitivity testing revealed the TB strain isolated on admission as completely resistant to INH and SM. Treatments with INH and SM were therefore stopped, and treatment with ethambutol and ethionamide was started in addition to rifampicin and pyrazinamide. After this change to the treatment regimen, symptoms and laboratory data gradually improved. The patient was treated with these four drugs for 18 months, and then pyrazinamide was stopped. After another 2 months, ethambutol was stopped. Treatment of tuberculosis was completed in 24 months. No adverse effects of these anti-TB drugs were observed. The patient achieved a full recovery without any sequelae. On the other hand, the infectious source for this patient remained unidentified, despite the extensive contact investigations. The incidence of drug-resistant TB is increasing in many areas of the world. Continuous monitoring for pediatric patients with drug-resistant TB is therefore needed.

Guidelines for the Management of Respiratory Infectious Diseases in Children in Japan 2022.

The members of the Japanese Society for Pediatric Infectious Diseases and the Japanese Society of Pediatric Pulmonology have developed Guidelines for the Management of Respiratory Infectious Diseases in Children with the objective of facilitating appropriate diagnosis, treatment and prevention of respiratory infections in children. The first edition was published in 2004 and the fifth edition was published in 2022. The Guideline 2022 consists of 2 parts, clinical questions and commentary, and includes general respiratory infections and specific infections in children with underlying diseases and severe infections. This executive summary outlines the clinical questions in the Guidelines 2022, with reference to the Japanese Medical Information Distribution Service Manual. All recommendations are supported by a systematic search for relevant evidence and are followed by the strength of the recommendation and the quality of the evidence statements.

Hepatoid carcinoma of the pancreas penetrating into the gastric cavity: a case report and literature review.

A 79-year-old Japanese woman was admitted to our hospital for treatment of a pancreatic tumor measuring approximately 7 × 5 cm. The tumor had invaded the left adrenal gland and gastric wall and had penetrated into the gastric cavity. Surgical resection was performed. The tumor was composed of a brown to whitish solid area and a zone of hemorrhage, necrosis, and cystic degeneration resembling the gross features of solid pseudopapillary tumor (SPT). Histologically, the tumor showed a heterogeneous growth pattern with a combination of seat-like, trabecular, papillary and hemorrhagic-necrotic areas in various proportions. The differential diagnoses first considered were acinar cell carcinoma, neuroendocrine carcinoma and SPT with malignant transformation. Immunohistochemistry showed tumor cells were negative for pancreatic exocrine enzymes and endocrine markers. Tumor cells diffusely expressed cytokeratin 19, alpha-fetoprotein, carcinoembryonic antigen and glypican-3, but lacked vimentin or ß-catenin expression. Small proportions of tumor cells expressed hepatocyte paraffin-1. Although typical morphological features of well-differentiated hepatocellular carcinoma (HCC) were not distinctly apparent, the tumor morphology partly resembled poorly differentiated HCC. Given these findings and considerations, the tumor was finally diagnosed as poorly differentiated hepatoid carcinoma of the pancreas.

A case of unclassified multicystic biliary tumor with biliary adenofibroma features.

A 40-year-old Japanese man was admitted to our hospital for evaluation of upper abdominal pain. Abdominal computed tomography (CT) revealed a well-circumscribed multicystic mass measuring approximately 7 × 6 cm. The mass contained a solid lesion measuring 3 × 2 cm. Biopsy of a swollen cervical lymph node led to a diagnosis of diffuse large B-cell lymphoma. After initial chemotherapy for lymphoma, the multicystic mass was surgically resected. The tumor was composed of a multicystic lesion and a solid lesion. Histopathologic examination of the multicystic lesion revealed that the locules were lined by biliary epithelium, demonstrating various degrees of cytological atypia. The stroma was fibrous, and the tumor showed marked apocrine snouts. Part of the tumor showed papillary growth with strong cytological atypia. The solid lesion showed tubulocystic proliferation of tumor cells, with prominent apocrine snouts, embedded in dense and partially hyalinized fibrous stroma. The morphology of the solid part was quite similar to that of reported biliary adenofibroma. Despite lengthy discussion, an appropriate pathological diagnosis could not be found among the current classifications of biliary tumor. The tumor was finally diagnosed as unclassified multicystic biliary tumor with adenofibroma features.

Metachronous aortic aneurysms due to sarcoidosis.

A 62-year-old male developed metachronous aortic aneurysms at different locations over an interval of one year and three months. He was diagnosed to have sarcoid aneurysms due to the presence of noncaseating epithelioid granulomas in the aortic wall and lymph nodes. The patient was treated with steroids, but his sarcoidosis progressed gradually and extended into other major organs, and the lungs and heart were clinically determined to have been involved by sarcoidosis. He died of cardiac tamponade four years after the first operation for an aortic aneurysm.

[Diagnosis and treatment of childhood tuberculosis in Japan].

In recent years, the incidence rate of childhood tuberculosis (TB) in Japan has declined steadily and it reached at a lower level than that in U.S. On the other hand, because the incidence rate in adults has still stayed at a moderately high level, the chance to receive TB infection for children cannot be disregarded. The accurate diagnosis and appropriate application of drug therapy to latent or active TB in children are still very important. Diagnosis of infection should be judged based on not only QuantiFERON TB results, but also careful history taking and tuberculin skin test results. To obtain good treatment outcomes, the application of standardized treatment regimens according to the relevant diagnostic category, with support for the good adherence to treatment, is indispensable.

A Case of Low-Grade Oncocytic Tumor/Chromophobe Renal Cell Carcinoma (Oncocytic Variant) of the Kidney.

The oncocytic variant of chromophobe renal cell carcinoma (oChRCC) and low-grade oncocytic tumor (LOT) is introduced as new renal disease entity. Both of these tumors are low-grade malignancies consisting of cells with eosinophilic cytoplasm. Distinguishing between eosinophilic variant of chromophobe renal cell carcinoma (eCRCC) and oncocytoma is often a diagnostic challenge in routine surgical pathology. However, oChRCC and LOT might be independent disease entities that might not fit completely into any of these categories. Histologically, these tumors have greater morphological similarity with oncocytoma than with ChRCC. However, immunohistochemically, they exhibit diffuse and dense positivity for CK7 and are negative for CD117. In the present case, we initially had difficulty distinguishing among oncocytoma, eCRCC, and type 2 papillary renal cell carcinoma (2-pRCC). However, after learning about new disease entities such as oChRCC and LOT, we were able to diagnose this tumor.

Age-related changes in the hyoepiglottic ligament: functional implications based on histopathologic study.

PURPOSE: The study aimed to identify age-related changes in the hyoepiglottic ligament associated with function of the epiglottis during swallowing and respiration. MATERIALS AND METHODS: Normal postmortem laryngeal tissue samples were obtained at autopsy from 20 individuals with no history of laryngeal disease. The subjects were divided into 2 groups: those aged 81-91 years (elderly group, n = 11) and those aged 31-48 years (non-elderly group, n = 9). Specimens were subjected to Elastica van Gieson and hematoxylin-eosin staining, and characteristics of the hyoepiglottic ligament were compared between groups. RESULTS: The hyoepiglottic ligament extended from the epiglottis to both lingual muscles and the hyoid bone (pars lingualis and pars hyoideus). The numbers of muscle fibers (P < .001), collagenous fibers (P < .01), and elastic fibers (P < .001) were significantly decreased in the elderly group in comparison to those in the non-elderly group. CONCLUSION: Age-related changes in the hyoepiglottic ligament appear to be associated with aspiration, obstructive sleep apnea syndrome, and acquired laryngomalacia in the elderly.

[Case of systemic myositis and subacute sensory neuropathy concomitant with signet-ring cell carcinoma].

A 72-year-old woman referred to our hospital because of slowly progressive (over 2 years) muscle weakness and paresthesias of the lower limbs. On neurological examination, weakness and muscle atrophies were noted in the distal upper limbs as well as the proximal lower limbs. She had also paresthesias of the legs. The level of creatinine phosphokinase (CK) was 126 IU/l. The magnetic resonance imaging demonstrated gadolinium enhancement of the nerve roots at the L4-S2 vertebrate levels. Nerve conduction study showed decreased compound muscle action potential and motor conduction velocity of tibial and peroneal nerves. Biopsy of the left biceps brachii muscle showed variations in fiber size, endomysial mononuclear cell infiltration and the findings like a rimmed vacuole. Although almost of her findings were in accord with clinical features of inclusion body myositis, strong inflammatory cellular influences allowed us to administer corticosteroid therapy. Because her weakness was well responded to steroid therapy, polymyositis was considered as differential diagnosis. Then, further examinations were investigated to search any occult neoplasm, and detected the early gastric cancer. Total gastrectomy was performed later, and the pathological diagnosis was made as a signet-ring cell carcinoma. To our knowledge, this is the first report of systemic myositis and subacute sensory neuropathy concomitant with signet-ring cell carcinoma. These symptoms might be occurred as a result of paraneoplastic syndrome associated with satellite effects of the signet-ring cell carcinoma.

[Analysis of Koch's phenomenon by BCg vaccination with the multi-puncture method in Japan].

PURPOSES: In Japan, BCG vaccination without a prior tuberculin skin test was started in 2005. Koch's phenomenon is well known as a skin reaction that appears within a few days at the BCG vaccination site if the vaccination is given to a person infected with tuberculosis. However, little has been known regarding Koch's phenomenon in cases where BCG is administered by the multi-puncture method. All doctors who observe Koch's phenomenon are requested to provide a report to the local government, which then transfers the report to the Ministry of Health, Labour, and Welfare. The purpose of the present study was to clarify the issues and challenges regarding Koch's phenomenon in Japan. METHODS: We analyzed a total of 814 reports of Koch's phenomenon submitted between April 2005 and March 2009. The results were redefined in this study as follows. Non-specific reaction: Cases that we judged to not be infected with M. tuberculosis (not true Koch's phenomenon). This category includes cases classified as "follow up" on the report with a negative PPD result. Follow-up with positive tuberculin test: Cases that were highly suspected to be infected from a positive tuberculin test but that were followed up without treatment. This category includes cases in which treatment was recommended but was refused by the guardians. Koch's phenomenon: Cases that were treated as latent tuberculosis infection or disease. Referred to other hospital: Cases that were referred to another hospital and their final outcomes are not known. Unknown: Cases for which the final outcomes are not known due to a lack of information. RESULTS: The age at vaccination from 3 to 6 months in most cases, with an average age of 4 months (124 days). Skin reactions were noticed within 3 days in most (95.6%) of the cases. No serious reactions due to Koch's phenomenon were reported. The numbers of reported cases and the rates by the number of births were quite diverse among prefectures. The results for the reports were as follows: non-specific reaction: 578 (71.1%); follow-up with positive tuberculin test: 34 (4.2%); Koch's phenomenon: 106 (13.0%); referred to other hospital: 54 (6.6 %); unknown: 44 (5.4%). DISCUSSION: The differences in the number of reports by prefecture may partially be explained by differences in the risk of infection, but mostly by human factors such as: 1) explanation of Koch's phenomenon to guardian at the time of vaccination; 2) reaction to notification from guardian; 3) report system from doctor in charge to MHWL etc. The results showed a trend toward a steady decrease in the non-specific reaction over the 4-year period. When BCG direct vaccination was started in 2005, health professionals were not aware that a mild skin reaction at the vaccinated site could appear and then fade out within a few days without any special reason. Almost all the noted skin reactions in the first year were reported. It is now known, however, that such non-specific reactions can appear together with a negative tuberculin skin test and then fade out within a few days. The incidence of a "true" Koch's phenomenon (cases treated as LTBI or disease as well as cases diagnosed as LTBI but for which treatment was refused by guardians) was less than estimated based on the annual risk of infection. This result is probably due to the following: 1) some cases with a risk of infection do not receive the BCG; 2) a final result was not obtained in 12.0% of the cases, which must include a certain number of cases with a "true" Koch's phenomenon; 3) skin reactions were sometimes missed by guardians; 4) a proper diagnosis was not made for a suspected case; 5) the actual risk of infection in infants aged less than 4 months is less than estimated. CONCLUSION: Accurate information regarding Koch's phenomenon should be provided to guardians as well as doctors and/or health workers in charge of BCG vaccinations.

A MELAS Patient Developing Fatal Acute Renal Failure with Lactic Acidosis and Rhabdomyolysis.

We herein present a patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), who developed serious acute renal failure with lactic acidosis, followed by rhabdomyolysis. Despite receiving intensive care, he suffered multiple cardiopulmonary arrests and died 10 days after presentation due to a sudden deterioration of his symptoms. Renal pathology revealed diffuse tubular necrosis with interstitial edema and tubular dilatation on light microscopy, and a severe degeneration of intracellular organelles on electron microscopy. These pathological findings could have resulted from multiple cardiopulmonary arrests; however, we must be aware of the extremely rare but sudden occurrence of these fatal conditions in MELAS patients.

Fumagillin inhibits colorectal cancer growth and metastasis in mice: in vivo and in vitro study of anti-angiogenesis.

Fumagillin is an inhibitor of type 2 methionine aminopeptidase that can block blood vessel formation, but its molecular mechanism and therapeutic value in colon cancer still remain to be elucidated. In this study, male severe combined immunodeficiency (SCID) mice were injected with colon cancer cells in the subcutis and then treated with Fumagillin and Cyclo (Arg-Gly-Asp-D-Phe-Val), an integrin alphavbeta(3) antagonist. The tumor weight, microvessel density (MVD), and number of pulmonary metastatic foci were examined. Gene expression profiles were examined by microarray analysis of human umbilical endothelial cells (HUVEC). The Fumagillin-treated mice had smaller tumor mass, fewer pulmonary metastases, and lower MVD-CD105 levels than control animals. In vitro proliferation and tube formation of HUVEC was also significantly decreased by Fumagillin. Microarray analysis of Fumagillin-treated HUVEC showed upregulation of 71 genes and downregulation of 143 genes. Expression changes were involved in cell proliferation, migration, adhesion, and gene transcription. Quantitative real-time-polymerase chain reaction and western blotting showed decreased expression of cyclin E2, activated leukocyte cell adhesion molecule (ALCAM), and intercellular adhesion molecule-1 (ICAM-1) genes in the presence of Fumagillin. This downregulation by Fumagillin may be involved in the anti-angiogenesis by Fumagillin. In conclusion, Fumagillin was found to suppress colorectal cancer growth and metastasis by suppressing angiogenesis.

Fibroadenoma of the gallbladder with borderline malignancy: a poorly recognized gallbladder tumor.

Fibroadenoma of the gallbladder is extremely rare tumor, with only two cases reported in the world. It is characterized by abundant loose edematous connective tissue, glandular structure, polypoid structure covered by epithelia, and a filamentous pedicle. We report a case of 78-year-old woman histopathologically diagnosed after surgery. Macroscopically, the tumor was a dark-greenish solid mass with a short stalk, filling the gallbladder cavity, and it measured 11.5 x 4.0 x 3.5 cm in diameter. Microscopically, the tumor was composed of abundant loose stroma and a glandular component. Some of the glandular cells had hyperchromatic nuclei with disturbed polarity and were positively stained by p53 (30%) and Ki-67 (30-40%). Part of the stromal component revealed hypercellularity with an irregular nucleus, mitosis (2-3 cells/10 high-power fields), and positivity for Ki-67 (20%) and p53 (50%). We diagnosed this peculiar tumor as "fibroadenoma of the gallbladder with borderline malignancy". We present the details of this extremely rare case and discuss the pathological findings, comparing them to those in the two previously reported cases and to carcinosarcoma of gallbladder.

An Open-Label Uncontrolled Trial of the Efficacy and Safety of a Hug with Singing and Rocking for Promotion of Relaxation in Pediatric Patients with Severe Motor and Intellectual Disabilities: Study Protocol.

Children with severe motor and intellectual disabilities (SMID) are continually exposed to stress due to their need to receive daily care. In particular, chronic physical and acute mental stress derived from daily medical care due to unstable health status are issues specific to SMID children. Therefore, it is important to approach these issues for the maintenance of their lives and quality of life. Seventeen children with a SMIDmedical care dependent group (SMID-MCDG) score of 25 or more will be enrolled in this study. Intervention by a hug while singing and rocking will be performed once a week for 24 weeks. The practitioner will sing, and slowly rock the child back and forth. Primary endpoint is high-frequency component of heart rate variability by frequency analysis. Secondary endpoints are low-frequency/high-frequency components of heart rate variability by frequency analysis, activity of salivary amylase, the incidence of adverse events, and changes in appearance. Frequency analysis of heart beat changes and salivary amylase activity are used as physiological indexes for assessing response to being held while singing and rocking. In this study, we will examine the efficacy and safety of hugging while singing and rocking as a practice of Ryouiku to promote relaxation in SMID-MCDG children.

An autopsy case of obstructive jaundice due to hepatic multiple peribiliary cysts accompanying hepatolithiasis.

A 73-year-old Japanese male, who had a history of alcoholic cirrhosis, was admitted to Saga University Hospital to receive treatment for hepatocellular carcinoma. The patient was treated to maintain his liver function, however, the total bilirubin level continued to increase gradually. Endoscopic retrograde cholangiography demonstrated an obstruction of the bilateral intrahepatic ducts. Although endoscopic nasobiliary drainage was performed, the patient died two months after admission. At the autopsy, multiple peribiliary cysts were found to almost completely obstruct the bilateral intrahepatic bile ducts. In addition, hepatolithiasis was found in the right hepatic duct. To date, only a few such cases of multipleperibiliary cysts with obstructive jaundice have been reported, and no such case accompanied by hepatolithiasis. It is also important to note that all the reported cases resulted in a poor prognosis. We herein report a very rare autopsy case with obstructive jaundice due to multiple peribiliary cysts accompanying hepatolithiasis. Generally, multiple peribiliary cysts are considered to be clinically harmless, but once they cause obstructive jaundice, their presence suggests the occurrence of end-stage cirrhosis and a poor prognosis.

Intrahepatic multicystic biliary hamartoma: report of a case.

Multicystic biliary hamartoma is a very rare hamartomatous nodule in the liver, which has recently been described as a new category of hepatic nodular lesion. We herein report the case of a 55-year-old man histopathologically diagnosed with this entity following surgery. A solitary multilocular lesion in the liver was pointed out by ultrasonography during a systemic examination for a positive HBs antigen. This nodule could not be definitively diagnosed by radiologic modalities, including computed tomography, magnetic resonance imaging and arteriography. The patient underwent a partial resection of the posterior segment of the liver. The nodule was a localized lesion which measured 5 x 3 cm at the widest point and displayed a honeycomb appearance. Histologically, it consisted of ductal structures, periductal glands, fibrous connective tissues containing blood vessels, and bile-like materials and xanthogranulomatous inflammation within some ducts. Liver parenchyma was not present in the nodule and the bile ducts were not dilated in the background liver. The ductal epithelium expressed biliary type cytokeratins (CK7 and 19) in immunohistochemical studies. These histopathological features were consistent with multicystic biliary hamartoma, and we discuss this rare case in detail in this report.

Gastric adenocarcinoma of fundic gland type with signet-ring cell carcinoma component: A case report and review of the literature.

A depressed lesion was found at a gastric angle of 76-year-old Japanese woman by esophagogastroduodenoscopy. Four years prior, she was diagnosed with a Helicobacter pylori infection but no eradication was performed. The pathological diagnosis of biopsy specimens was signet-ring cell carcinoma. Endoscopic submucosal dissection (ESD) was performed. Histopathological examination of the ESD specimen revealed proliferation of well-differentiated tubular adenocarcinoma mimicking fundic gland cells at the deep layer of the lamina propria mucosae. These tumor cells expressed focally pepsinogen-I, diffusely MUC6, and scattered H+/K+ ATPase according to immunohistochemistry. Therefore, we diagnosed this tumor as gastric adenocarcinoma of fundic gland type (GA-FG). Adjacent to the GA-FG, proliferation of signet-ring cell carcinoma which diffusely expressed MUC 2 and MUC 5AC was observed. Intestinal metaplasia was focally observed in the surrounding mucosa of the signet-ring cell carcinoma. To the best of our knowledge, this is the first case report of GA-FG with a signet-ring cell carcinoma component. The origin of signet-ring cell carcinoma, i.e., whether it accidentally arose from a non-neoplastic mucosa and coexisted with the GA-FG or dedifferentiated from the GA-FG is unclear at present. We expect the accumulation of similar cases and further analysis to clarify this issue.