BackgroundRegorafenib is an oral multikinase inhibitor that has been demonstrated as clinically effective in patients with metastatic colorectal cancer in phase III studies. Although disease control was achieved in 40% of the pretreated patients with metastatic colorectal cancer in the pivotal studies, radiological response has rarely been reported. Severe adverse events associated with regorafenib are known to occur during the first and second courses of treatment. We present a case of a 62-year-old Japanese patient whose metastatic colorectal cancer has been responding to treatment with regorafenib for 2 years.Case presentationA 54-year-old Japanese man visited our institute exhibiting general malaise, and he was diagnosed with ascending colon cancer in April 2006. He underwent right hemicolectomy, and the final staging was T3N0M0, stage II. After 19 months, pulmonary metastasis and anastomotic recurrences were detected, and a series of operations were performed to resect both metastatic lesions. After that, liver metastasis, a duodenal metastasis with right renal invasion, right adrenal metastasis, and para-aortic lymph node metastases were observed during follow-up, and chemotherapy and resection were performed. The patient had metastatic para-aortic lymph nodes after the fifth tumor resection and underwent multiple lines of chemotherapy in April 2014. Regorafenib monotherapy was started at 80 mg/day. Then, regorafenib was increased to 120 mg/day in the second cycle. Regorafenib monotherapy led to 60% tumor shrinkage within the initial 2 months, and the tumor further decreased in size over 4 months until it became unrecognizable on imaging studies. The clinical effects of regorafenib monotherapy have shown a partial response according to Response Evaluation Criteria in Solid Tumors criteria. No severe adverse events were observed, except for mild fatigue and hand-foot syndrome. The patient has received 24 courses of regorafenib over 2 years without exhibiting tumor progression.ConclusionsTo the best of our knowledge, this is the longest treatment with regorafenib without tumor progression ever reported. A reduced dosage of regorafenib at induction may ameliorate the cutaneous and hepatic toxicity associated with its use.

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Background Hemobilia refers to bleeding into the biliary tract. Hepatic artery pseudoaneurysm (HAP) rupture is an uncommon cause of hemobilia, and cases of HAP associated with Mirizzi syndrome are extremely rare. Although transarterial embolization is recommended as the first-line treatment for hemobilia, surgery is sometimes required. Case presentation A 76-year-old woman was referred to our hospital with epigastric pain. She was febrile and had conjunctival icterus and epigastric tenderness. Laboratory tests revealed abnormal white blood cell count and liver function. An abdominal computed tomography (CT) revealed multiple calculi in the gallbladder, an incarcerated calculus in the cystic duct, and a slightly dilated common hepatic duct. Based on examination findings, she was diagnosed with Mirizzi syndrome type I, complicated by cholangitis. Intravenous antibiotics were administered, and we performed endoscopic retrograde cholangiopancreatography (ERCP) to place a drainage tube. The fever persisted; therefore, contrast-enhanced CT (CECT) was performed. This revealed portal vein thrombosis and hepatic abscesses; therefore, heparin infusion was administered. The following day, she complained of melena, and laboratory tests showed that she was anemic. ERCP was performed to change the drainage tube in the bile duct; however, bleeding from the papilla of Vater was observed. CECT demonstrated a right HAP with high-density fluid in the gallbladder and gallbladder perforation. Finally, she was diagnosed with hemobilia caused by HAP rupture, and emergency surgery was performed to secure hemostasis and control the infection. During laparotomy, we found that a right HAP had ruptured into the gallbladder. The gallbladder made a cholecystobiliary fistula, which indicated Mirizzi syndrome type II. Although we tried to repair the right hepatic artery, we later ligated it due to arterial wall vulnerability. Then, we performed subtotal cholecystectomy and inserted a T-tube into the common bile duct. There were no postoperative complications except for minor leakage from the T-tube insertion site. The patient was discharged after a total hospital stay of 7 weeks. Conclusions We experienced an extremely rare case of emergency definitive surgery for hemobilia due to HAP rupture complicated by Mirizzi syndrome type II. Surgery might be indicated when controlling underlying infections was required.

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