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.

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.

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.

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.

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.

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.

Myopericytoma proliferating in an unusual anastomosing multinodular fashion.

We herein describe a case of myopericytoma that proliferated in an unusual fashion. Myopericytoma is described as a group of rare, benign, dermal or subcutaneous tumors that are characterized histologically by a striking, concentric, perivascular proliferation of spindle cells and showing apparent differentiation towards perivascular myoid cells. Myopericytoma forms a morphological continuum with myofibroma/myofibromatosis, glomus tumor and angioleiomyoma. The patient was a 64-year-old woman who demonstrated a recurrent ulcer on an atrophic plaque on her left shin. A histopathological examination of the plaque demonstrated that tumor cells proliferated in an anastomosing multinodular fashion along the vessels in the dermis and subcutaneous tissue. In those nodules, there were numerous, small, concentric proliferations of myoid-appearing spindle cells around small vascular lumina. The present case is an unusual example of myopericytoma, manifesting in a characteristic anastomosing, multinodular, infiltrating fashion.

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.

A case of mucosa-associated lymphoid tissue lymphoma of the gastrointestinal tract showing extensive plasma cell differentiation with prominent Russell bodies.

A 73-year-old Japanese woman was hospitalized for detailed examination of nausea, diarrhea and loss of appetite. Atypical erosion in the ileum was found on endoscopy. Biopsy of this erosion showed proliferation of cells containing numerous Russell bodies. Differential diagnoses considered were Russell body enteritis, crystal-storing histiocytosis, Mott cell tumor, immunoproliferative small intestinal disease (IPSID) and mucosa-associated lymphoid tissue (MALT) lymphoma. The cells containing prominent Russell bodies showed diffuse positivity for CD79a and CD138, but negative results for CD20, CD3, UCHL-1, CD38 and CD68. Russell bodies were diffusely positive for lambda light chain, but negative for kappa light chain, and immunoglobulin (Ig) G, IgA and IgM. Based on these findings, Russell body enteritis, crystal-storing histiocytosis and IPSID were ruled out. As the tumor formed no mass lesions and was restricted to the gastrointestinal tract, MALT lymphoma with extensive plasma cell differentiation was finally diagnosed. The patient showed an unexpectedly aggressive clinical course. The number of atypical lymphocytes in peripheral blood gradually increased and T-prolymphocytic leukemia (T-PLL) emerged. The patient died of T-PLL 7 mo after admission. Autopsy was not permitted.

Actual status of clinical diagnosis in patients with primary gallbladder cancer associated with adenomyomatosis.

AIM: The purpose of this study was to reveal differences in clinical diagnosis of gallbladder cancer among patients with or without adenomyomatosis (ADM) by analyzing demonstrated tumor patterns on imaging and diagnostic opportunities. METHODS: Ninety-seven patients with gallbladder cancer were enrolled. Demonstrated imaging patterns were classified into mass lesion (ML), wall thickening (WT), and papillary lesion (PL). Clinical status during periodic follow up and other diagnostic opportunities were determined from medical records. RESULTS: All adenomyomatosis-associated cases were diagnosed at the T2 or higher stage. The distribution of demonstrated imaging patterns was significantly different between the adenomyomatosis-associated and non-adenomyomatosis-associated groups (p = 0.0002). No adenomyomatosis-associated gallbladder cancer had the PL pattern, which was readily identifiable and characteristic of early-stage cancer. The WT pattern presented difficulties for diagnosis, and the ML pattern was relatively specific, although most of these cases were at advanced stages. Approximately 40% of ADM patients were found to be in advanced stages of gallbladder cancer, in spite of undergoing periodic follow up. CONCLUSIONS: This study revealed the difficulty of early diagnosis of primary gallbladder cancer in the setting of concurrent ADM. Current results suggest the possible utility of preventive cholecystectomy for management of asymptomatic ADM patients.

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.

Pathological features of classical polyarteritis nodosa: analysis of 19 autopsy cases.

Classical polyarteritis nodosa (cPN) is a rare autoimmune disease featuring systemic inflammation of middle- and small-sized arteries. Because most of autopsy cases underwent clinical treatment, arterial fibrinoid necrosis, which is the most specific finding of cPN, is often obscure. The aim of this study was to seek morphological characteristics of the middle-sized arteries in autopsy cases of cPN, and to identify immunohistochemical markers for the diagnosis of cPN. Nineteen patients who had undergone autopsy with a diagnosis of cPN were enrolled. Twenty-one autopsy cases without cPN were examined as control group. Arterial fibrinoid necrosis in medium-sized arteries was observed in 8/19 autopsy cases. Elastica van Gieson staining showed an increased number of elastic fiber layers (P<0.0001) and greater distances between elastic fiber layers (P<0.0001) in the renal middle-sized arteries of the cPN group. These findings probably reflected the post-inflammatory remodeling process after necrotizing vasculitis. On immunohistochemical examination, the cPN group showed high matrix metalloproteinase-1 and tumor necrosis factor-α expressions and decreased smoothelin expression in the vascular wall compared to the control group. When uncertain or atypical autopsy cases of cPN are examined, these findings can help to make the pathological diagnosis of cPN.

Mitotic count reflects prognosis of gallbladder cancer particularly among patients with T3 tumor.

The surgical strategy for gallbladder cancer (GBC) depends on the extent of the disease. Thus, the identification of useful prognostic markers exerting strong prognostic impact for each T stage would be beneficial in the development of rational therapeutic strategies. The purpose of this study was to identify useful prognostic markers of GBC for each T stage. CD8+ tumor-infiltrating lymphocytes (TIL), Ki-67 labeling index (LI), p53 nuclear expression and mitotic count (MC) were investigated as candidate prognostic markers. In total, 86 patients with invasive GBC were included. Of the prognostic markers examined, only MC showed a correlation with reduced survival (P=0.0383) in the univariate analysis of overall T stage. In the univariate analysis of T2 stage (n=31), only high p53 expression correlated with survival showing a positive correlation (P=0.0154). In the univariate analysis of T3 stage (n=40), the only factor showing a significant correlation with survival was MC (P=0.0113). Multivariate analysis, including N and M as factors, identified only MC as an independent prognostic factor in T3 stage GBC (P=0.0419). In conclusion, this study demonstrated the strong prognostic impact of MC in GBC, particularly in patients with T3 tumor.

Analysis of Extrahepatic Multiple Primary Malignancies in Patients with Hepatocellular Carcinoma according to Viral Infection Status.

Previous studies have investigated extrahepatic multiple primary malignancy (EHPM) associated with hepatocellular carcinoma (HCC). However, its correlation with viral infection, such as hepatitis B virus (HBV) or hepatitis C virus (HCV), has not been examined. The aim of this study is to investigate the association between EHPM and hepatitis infection in HCC patients. A total of 412 patients who underwent surgical resection for primary HCC were enrolled. Viral infection was evaluated by serum HBV surface antigen (HBs Ag) and HCV antibody (HCV Ab). Sixty-eight (16.5%) patients had one or more EHPM. The most frequent EHPM was gastric cancer (n = 32) in this cohort. No statistical significance was observed in the distribution of viral infection and incidence of entire EHPM. However, HCV Ab, HBs Ag, and negative status for both were correlated with the frequency of gastric (P = 0.0194), urinary tract (P = 0.0067), and breast cancer (P = 0.0036), respectively. Infection of Helicobacter pylori was investigated by immunohistochemistry in gastric EHPM and resulted that 20 out of 21 analyzed cases were negative for Helicobacter pylori. Although it should be verified by well-designed large cohort studies, the current results suggested correlation between HCV infection and gastric cancer, HBV infection and urinary tract cancer and viral hepatitis-free status and breast cancer in HCC patients.

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.

Clinicopathologic features of advanced gallbladder cancer associated with adenomyomatosis.

Adenomyomatosis of the gallbladder has not been considered to have malignant potential, but gross features of adenomyomatosis are sometimes encountered in gallbladders resected under a diagnosis of gallbladder carcinoma. The purpose of this study was to determine the clinicopathologic features and survival rates in cases of gallbladder cancer with gross features of adenomyomatosis. The study subjects were 97 surgically treated gallbladder carcinoma patients. Only gallbladder showing typical gross features of adenomyomatosis was judged as adenomyomatosis-positive gallbladder cancer. In terms of gross findings, 25 cases (25.8%) were classified as adenomyomatosis-positive. The status of adenomyomatosis was significantly associated with the T stage (P=0.0004), lymph node (LN) metastasis (P<0.0001), distant metastasis (P=0.008), and stage (P=0.0005). In the adenomyomatosis-positive group, 16 of the 25 cases (64.0%) were classified as segmental type and 9 cases (36.0%) were classified as fundal type. No diffuse-type cases were present in this series. The status of adenomyomatosis correlated significantly with survival (P=0.0007). However, the multivariate analysis of significant variables identified from the univariate analysis identified only T stage (P=0.0178) and LN metastasis (P=0.0048) as independent prognostic factors. Subset analysis with T stage according to the status of adenomyomatosis showed no significant impact on survival. These results indicate that adenomyomatosis-positive gallbladder cancer is more often diagnosed clinically in the advanced stages. Since preceding adenomyomatosis may prevent the early detection of gallbladder cancer, the usefulness of preventive cholecystectomy in cases of asymptomatic adenomyomatosis should be considered.