Kidney Biopsy Proven Thrombotic Microangiopathy Induced by Methamphetamine: A Case Report.

A 47-year-old man was admitted to our hospital with acute kidney injury, severe hypertension, heart failure, thrombocytopenia, and elevated lactate dehydrogenase. Renal biopsy revealed fibrin thrombi within the glomerular capillaries and moderate fibrotic intimal thickening in the interlobular arteries. The histological diagnosis was thrombotic microangiopathy (TMA). Regarding cardiac involvement, we found marked stenosis in the left anterior descending artery on coronary angiography and cardiomyopathy on myocardial biopsy. Blood concentrations of amphetamine and methamphetamine were high (14.1 ng/mL and 333 ng/mL, respectively). It is important to consider methamphetamine as a cause of renal TMA and multi-organ dysfunction.

Standardized Classification of Lung Adenocarcinoma Subtypes and Improvement of Grading Assessment Through Deep Learning.

The histopathologic distinction of lung adenocarcinoma (LADC) subtypes is subject to high interobserver variability, which can compromise the optimal assessment of patient prognosis. Therefore, this study developed convolutional neural networks capable of distinguishing LADC subtypes and predicting disease-specific survival, according to the recently established LADC tumor grades. Consensus LADC histopathologic images were obtained from 17 expert pulmonary pathologists and one pathologist in training. Two deep learning models (AI-1 and AI-2) were trained to predict eight different LADC classes. Furthermore, the trained models were tested on an independent cohort of 133 patients. The models achieved high precision, recall, and F1 scores exceeding 0.90 for most of the LADC classes. Clear stratification of the three LADC grades was reached in predicting the disease-specific survival by the two models, with both Kaplan-Meier curves showing significance (P = 0.0017 and 0.0003). Moreover, both trained models showed high stability in the segmentation of each pair of predicted grades with low variation in the hazard ratio across 200 bootstrapped samples. These findings indicate that the trained convolutional neural networks improve the diagnostic accuracy of the pathologist and refine LADC grade assessment. Thus, the trained models are promising tools that may assist in the routine evaluation of LADC subtypes and grades in clinical practice.

Long-term survival with nivolumab followed by irinotecan after total gastrectomy in alpha-fetoprotein-producing gastric cancer: a case report and review of the literature.

BACKGROUND: Alpha-fetoprotein-producing gastric cancer (AFPGC) is a rare type of aggressive gastric cancer (GC) with a dismal prognosis. We present a patient with AFPGC who achieved long-term survival through a multidisciplinary approach. CASE PRESENTATION: A 67-year-old man with advanced GC was referred to our hospital for systemic chemotherapy. He was diagnosed with cStage IVB AFPGC. During 2nd-line treatment, we could not control bleeding from the GC itself. After complete resection, during chemotherapy, portal venous tumor thrombi (PVTTs) and liver metastases were identified. With nivolumab followed by irinotecan, the PVTTs and liver metastases disappeared. Without immunotherapy and chemotherapy for 23 months, the patient has survived for 48 months so far with no recurrence of GC. CONCLUSION: Long-term survival with AFPGC can be accomplished by using several different approaches, such as surgery, immunotherapy, and chemotherapy.

Use of Immunosuppressive Therapy in the Treatment of IgA-dominant Infection-related Glomerulonephritis.

A 51-year-old Japanese man who experienced colon cancer recurrence following primary and metastatic lesion resection was hospitalized due to facial cellulitis with febrile neutropenia and purpura on his lower extremities after chemotherapy. It was complicated by rapidly progressive glomerulonephritis. He was diagnosed with immunoglobulin A (IgA)-dominant endocapillary proliferative glomerulonephritis based on kidney histology. His glomeruli were positive for the nephritis-associated plasmin receptor, plasmin activity and galactose-deficient IgA1 (Gd-IgA1). A skin biopsy immunofluorescence study revealed IgA deposition within perivascular regions but no Gd-IgA1 deposition. The final diagnosis was IgA-dominant infection-related glomerulonephritis (IRGN). The patient's renal function returned to normal after receiving immunosuppressive therapy that consisted of a glucocorticoid and a cyclophosphamide. Immunosuppressive therapy should be considered in cases of IRGN if the patient's infection is completely under control.

Molecular Pathology of Pulmonary Large Cell Neuroendocrine Carcinoma: Novel Concepts and Treatments.

Pulmonary large cell neuroendocrine carcinoma (LCNEC) is an aggressive neoplasm with poor prognosis. Histologic diagnosis of LCNEC is not always straightforward. In particular, it is challenging to distinguish small cell lung carcinoma (SCLC) or poorly differentiated carcinoma from LCNEC. However, histological classification for LCNEC as well as their therapeutic management has not changed much for decades. Recently, genomic and transcriptomic analyses have revealed different molecular subtypes raising hopes for more personalized treatment. Two main molecular subtypes of LCNEC have been identified by studies using next generation sequencing, namely type I with TP53 and STK11/KEAP1 alterations, alternatively called as non-SCLC type, and type II with TP53 and RB1 alterations, alternatively called as SCLC type. However, there is still no easy way to classify LCNEC subtypes at the actual clinical level. In this review, we have discussed histological diagnosis along with the genomic studies and molecular-based treatment for LCNEC.