Renal cell carcinoma is well-known for its propensity to metastasize to unusual sites. However, metastasis to the gallbladder has been rarely reported in the literature. A 75-year-old Japanese (Asian) woman presented for further evaluation of a gallbladder polyp, 15 years after right radical nephrectomy for renal cell carcinoma. Computed tomography revealed a 12 mm enhancing pedunculated tumor in the gallbladder fundus. Open simple cholecystectomy was performed and the tumor was histologically confirmed as a metastasis of renal cell carcinoma to the gallbladder. Our patient is alive and has been disease-free for 3 years after cholecystectomy. Although metastasis of renal cell carcinoma is a rare differential diagnosis of gallbladder tumors, simple cholecystectomy is likely to offer a chance of long-term survival for patients with gallbladder metastases of renal cell carcinoma.

INTRODUCTION: It is rare for a patient to present with adrenal insufficiency secondary to bilateral adrenal metastases from a malignant colorectal tumor. CASE PRESENTATION: An 82-year-old Japanese man presented to our hospital with high fever and malaise. He was receiving oral chemotherapy for the treatment of rectal cancer with multiple metastases. Computed tomography showed new bilateral adrenal gland metastases. A rapid adrenocorticotropic hormone (ACTH) test showed adrenal insufficiency. Treatment with hydrocortisone provided immediate symptom improvement. DISCUSSION: Adrenal insufficiency secondary to bilateral adrenal metastases from rectal cancer is rare. A rapid ACTH test is useful to diagnose adrenal insufficiency. CONCLUSION: The incidence of adrenal insufficiency may be underestimated in patients with multiple metastasis. Appropriate therapy with adrenal corticosteroid hormone supplementation may lead to a significant improvement in the patient’s symptoms and quality of life. Highlights:

Portal vein tumor thrombosis from colorectal cancer is rare, and this recurrence pattern was mainly reported in patients with renal cell carcinoma and hepatocellular carcinoma. Furthermore, the recurrence pattern of portal vein tumor thrombosis without liver parenchymal invasion from colorectal carcinoma has not been previously reported. Herein, we present a patient with progressive portal vein tumor thrombosis without liver parenchymal invasion following curative resection. A 61-year-old man with a chief complaint of constipation with abdominal pain associated with rectal carcinoma was admitted to our hospital. Computed tomography (CT) showed that the rectosigmoid colon wall was thickened, regional lymph nodes were swollen, and the light space-occupying lesion (SOL) was detected at segment 8 (S8). Neoadjuvant chemotherapy was performed, which was followed by laparoscopic anterior resection. The final diagnosis was stage IIIb (SS, N2, M0). After operation, systemic adjuvant chemotherapy was introduced. At first, tumor marker levels were within the normal range and there were no accumulations on positron emission tomography (PET). Tumor marker levels were elevated, and contrast-enhanced CT demonstrated that the portal vein SOL slowly extended from S8 to S5. Additionally, PET showed that the standardized uptake value was abnormally high at 5.8. Based on the diagnosis of portal vein tumor thrombosis, right hepatectomy was performed. On pathological analysis, tumor thrombosis was associated with rectal carcinoma, and there was no invasion toward the liver parenchyma. Additionally, the surgical cut end was tumor free. Six months after the hepatectomy, the paraaortic lymph nodes showed swelling. The patient is currently undergoing systemic chemotherapy. Aggressive surgical resection should be considered in cases of portal vein tumor thrombosis. A good long-term prognosis could be obtained by a combination of curative resection and systemic chemotherapy.

Usp21, a member of the ubiquitin protease family, plays a vital role in various biological functions. However, the effects of Usp21 dysfunction remain incompletely understood. In this study, we generated Usp21 knockout (KO) mice. Blood tests showed no impairment of liver function but did reveal elevated levels of total cholesterol (T-CHOL) and free fatty acid (FFA) in Usp21 KO mice compared to wild-type (WT) mice. Next, we performed RNA-sequencing (RNA-seq) to identify genes that Usp21 regulates. The results highlighted several candidate genes based on their biological relevance, and their expression levels were validated by RT-qPCR. The Usp21 KO mice exhibited significant elevations in the expression of the genes Fabp7, Nlrc5, and Ppargc1a, which play an important role in lipid metabolism, compared to WT. These data suggest that Usp21 may play roles in lipid metabolism in association with Fabp7, Nlrc5 and Ppargc1a. To clarify the involvement of USP21 in human hypercholesterolemia, we examined single-nucleotide polymorphisms (SNPs) around USP21 in non-hypercholesterolemic and hypercholesterolemic outpatients. We found that the rs11421 SNP downstream of USP21 was significantly associated with hypercholesterolemia. These data suggest that Usp21 plays a role in mice and human lipid metabolism and that its polymorphism may be a diagnostic marker for human hypercholesterolemia.

USP21, a member of the ubiquitin protease family, plays a vital role in various biological functions. However, the effects of USP21 dysfunction have yet to be fully understood. Here, we generated Usp21 knockout (KO) mice and conducted microarray to identify genes that Usp21 regulates. Its results raised several genes based on their biological characteristics, and RT-qPCR confirmed their expression. KO mice exhibited significant elevations in the expression of the genes Fabp7 and Nlrc5, which play a role in lipid metabolisms, compared to wild-type mice. Blood tests showed no impairment of liver function but did reveal elevated levels of total cholesterol and free fatty acids in KO mice compared to wild-type mice. These data suggest that Usp21 may play roles in lipid metabolism associated with Fabp7 and Nlrc5. To clarify the involvement of USP21 in human hypercholesterolemia, we examined single nucleotide polymorphisms (SNPs) around USP21 in non-hypercholesterolemic and hypercholesterolemic outpatients. We found that the rs11421 SNP downstream of USP21 was associated with hypercholesterolemia. These data suggest that USP21 plays a role in mice and human lipid metabolism and that its polymorphism may be a diagnostic marker for human hypercholesterolemia.

Background: Delayed onset of colorectal liver metastasis (CRLM) > 5 years after primary colorectal surgery is rare. Herein, we report a case of delayed-onset CRLM that occurred 10 years after primary surgery, for which laparoscopic hepatectomy was performed. Case presentation: A 68-year-old man was admitted to the hospital. His medical history revealed double colon cancer detected 10 years ago, for which laparoscopic colectomy was performed. The pathological tumor–node–metastasis stages were stages I and II. Thereafter, oral floor cancer occurred 7 years after the primary surgery and was curatively resected. The annual follow-up with positron emission tomography–computed tomography (CT) identified a tumor at segment 7/8 (S7/8) of the liver with an abnormal accumulation of fluorodeoxyglucose. Dynamic CT showed a 23-mm tumor, with ring enhancement in the early phase. Magnetic resonance imaging with gadolinium–ethoxybenzyl-diethylenetriamine penta-acetic acid demonstrated that the tumor had high intensity in T2 weighted sequences and low intensity in the hepatobiliary phase. With a preoperative diagnosis of intrahepatic cholangiocarcinoma or delayed liver metastasis, laparoscopic S7/8 partial resection was performed. The operative time was 324 min, and the intraoperative bleeding volume was 35 mL. The patient was discharged on day 15 without any postoperative complications. Upon histopathological examination, the final diagnosis was CRLM. The patient has survived for 1 year without any recurrence. Conclusions: It is important to pay attention to the occurrence of delayed-metachronous CRLM.