Pathogenesis of hypokalemia in autosomal dominant hypocalcemia type 1

Background

Autosomal dominant hypocalcemia type 1 (ADH1) is a relatively rare endocrine disorder characterized by hypocalcemia and inadequate parathyroid hormone secretion. ADH is caused by activating mutations in the calcium-sensing receptor (CaSR) gene, CASR. CaSR plays a crucial role in calcium and magnesium homeostasis in the kidney. ADH may be accompanied by hypokalemia and metabolic alkalosis when it is classified as type V Bartter syndrome. However, the mechanism underlying hypokalemia in this disease is unclear.

Methods

We investigated a 33-year-old woman with hypocalcemia and hypoparathyroidism since childhood, whose mother also had hypocalcemia and hypoparathyroidism, but with no clinical symptoms. Blood examinations showed hypokalemia and metabolic alkalosis in the patient, but not her mother. We conducted mutation analysis and diuretic tests to clarify the patient’s and her mother’s diagnosis and to investigate the onset mechanism of hypokalemia in ADH1. We also determined the localization of CaSR in the kidney by immunohistochemistry.

Results

We detected a known gain-of-function mutation in CASR in both the patient and her mother. Diuretic tests revealed a response to furosemide and no reaction to thiazide in the patient, although the mother responded well to both diuretics. CaSR co-localized with the Na⁺–Cl^? cotransporter (NCCT) on distal tubular epithelial cells.

Conclusions

These results indicate that the NCCT in the distal convoluted tubule was secondarily affected in this patient. We conclude that the main pathogenesis of secondary hypokalemia in ADH1 in this patient was secondary NCCT dysfunction.

     

PET/CT Colonography for the Preoperative Evaluation of the Colon Proximal to the Obstructive Colorectal Cancer

Purpose  This study was designed to evaluate the usefulness of 18-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) colonography in preoperative diagnosis of the tumors proximal to obstructive colorectal cancers, which were defined as cancers that cannot be traversed colonoscopically. Methods  A whole-body PET/CT protocol for tumor staging and a protocol for CT colonography were integrated into one examination. No cathartic bowel preparation was used before this examination. Thirteen prospective patients with obstructive cancer were examined. We compared the detection rates for obstructive colorectal cancers and tumors proximal to the obstruction using air-inflated PET/CT colonography to intraoperative examinations, histopathologic outcome, and follow-up colonoscopy. Results  PET/CT colonography correctly identified all 13 primary obstructive colorectal cancers and all 2 synchronous colon cancers proximal to the obstruction. The two synchronous colon cancers detected at PET/CT colonography were confirmed and removed at single-stage surgical procedures. PET/CT colonography was able to localize all colorectal cancers precisely. There were no false-negative or false-positive proximal colorectal cancers by PET/CT colonography. Other preoperative examinations missed the synchronous colon cancers. Conclusions  In patients with obstructive colorectal cancers, preoperative PET/CT colonography provided valuable anatomic and functional information of the entire colon to properly address surgery of colorectal cancer.     

Mucosal dysbiosis in patients with gastrointestinal follicular lymphoma

Because the pathogenesis of gastrointestinal follicular lymphoma (GI-FL) remains unclear, no standardized treatment strategy has been established. Of the gastrointestinal lymphomas, gastric mucosa-associated lymphoid tissue lymphomas are strongly associated with Helicobacter pylori; hence, the microbiota may be involved in GI-FL pathogenesis. However, the association between GI-FL and the microbiota remains uninvestigated. Therefore, we compared the mucosal microbiotas of GI-FL patients with those of controls to identify microbiota changes in GI-FL patients. Mucosal biopsy samples were obtained from the second portion of the duodenum from 20 GI-FL patients with duodenal lesions and 20 controls. Subsequent 16S rRNA gene sequencing was performed on these samples. QIIME pipeline and LEfSe software were used to analyze the microbiota. The GI-FL patients had significantly lower alpha diversity (P = .049) than did the controls, with significant differences in the microbial composition (P = .023) evaluated by the beta diversity metrics between the two groups. Comparing the taxonomic compositions indicated that the genera Sporomusa, Rothia, and Prevotella and the family Gemellaceae were significantly less abundant in the GI-FL patients than in the controls. GI-FL patients presented altered duodenal mucosal microbial compositions, suggesting that the microbiota might be involved in the GI-FL pathogenesis.