Multicenter phase II clinical study of the efficiency and safety of capecitabine plus intermittent oxaliplatin with bevacizumab as first-line therapy in patients with metastatic colorectal cancer (VOICE trial).

PURPOSE: The aim of this phase II study was to evaluate the efficacy and safety of combination therapy with five-cycle CAPOX (capecitabine plus oxaliplatin) plus bevacizumab, followed by five-cycle maintenance therapy with capecitabine plus bevacizumab and reintroduction of CAPOX plus bevacizumab for five cycles, with a preplanned intermittent oxaliplatin strategy in metastatic colorectal cancer (mCRC). METHODS: Patients with untreated mCRC were administered CAPOX (130 mg/m2 oxaliplatin on day 1, 2000 mg/m2/day capecitabine on days 1-14, every 21 days) + bevacizumab (7.5 mg/kg) every 3 weeks for five cycles, maintenance treatment without oxaliplatin for five cycles, and CAPOX + bevacizumab reintroduction for five cycles or upon tumor progression. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were the time to treatment failure (TTF), overall survival, response rate (RR), and safety. RESULTS: Forty-seven patients who fulfilled the inclusion criteria were enrolled in the evaluation of efficacy and safety. Median PFS was 14.1 months (95% confidence interval [CI], 8.6-19.5), and median TTF was 12.3 months (95% CI, 10.3-14.3). The objective RRs were 51.1% (24/47) during induction therapy, 58.3% (21/36) during maintenance therapy, and 63.6% (14/22) during reintroduction therapy. The frequency of patients with neutropenia, diarrhea, peripheral sensory neuropathy, venous thromboembolism, or grade ≥ 3 allergic reactions was 2.1%. CONCLUSION: CAPOX plus bevacizumab therapy with a preplanned intermittent oxaliplatin strategy consisting of brief five-cycle induction therapy, five-cycle maintenance therapy with capecitabine plus bevacizumab, and five-cycle reintroduction therapy consisting of CAPOX plus bevacizumab is safe and effective for mCRC patients. TRIAL REGISTRATION: UMIN ID: 000,005,732, date of registration: June 7, 2011.  https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000006695.

Outcomes of surgical resection for gastric cancer liver metastases: a retrospective analysis.

BACKGROUND: The indications for the surgical treatment of gastric cancer liver metastases (GCLMs) remain controversial. In addition, the outcome of surgery for the treatment of liver metastases of alpha-fetoprotein-producing gastric cancer (AFP-GC) has not yet been reported. We assessed the clinicopathologic features, including AFP-GC, and the surgical results of these patients. METHODS: This retrospective study analyzed 20 patients who underwent hepatectomy for GCLM at Odawara Municipal Hospital between April 2006 and January 2016. RESULTS: The actuarial 1-, 3-, and 5-year overall survival (OS) rates after primary hepatectomy were 80.0%, 55.5%, and 31.7%, respectively, with a median OS of 42 months. Four patients survived for more than 5 years after their final hepatectomy procedures. A multivariate analysis showed multiple metastases in the liver, the elevated level of carbohydrate antigen 19-9 (CA19-9), and an age of less than 70 years to be independently associated with a poor prognosis in terms of OS. No significant differences were noted between the AFP-GC and AFP-negative GC groups. CONCLUSION: Surgical treatment is therefore considered to be a feasible option for GCLM. The findings of the present study showed the number of metastatic liver tumors, the level of CA19-9, and the patient age to be prognostic indicators for the surgical treatment of GCLM.

[A Case of Primary Breast Cancer and Gastric Cancer Metastasis to the Skin-Usefulness of Immunohistochemistry in Differentiating Primary Breast Cancer from Metastatic Breast Cancer].

We herein report the case of a 76-year-old female patient who had undergone gastrectomy for advanced gastric cancer (histologically tubular adenocarcinoma)before 5 months, presenting with abdominal skin tumor. A skin biopsy revealed tubular adenocarcinoma. Positron emission tomography-computed tomographic scanning detected right breast tumor. A partial mastectomy of the right breast and local resection of abdominal skin tumor were performed and both tumors depicted similar histology of tubular adenocarcinoma in routine pathological examination. Immunohistochemically, positive for CDX2 and MUC5AC in previously resected gastric cancer and skin tumor tissues, whereas negative for both antigens in breast cancer. Thus, the final pathological diagnosis demonstrated skin metastasis originating from gastric cancer and primary breast cancer(invasive ductal carcinoma)histologically mimicking gastric cancer. We emphasize difficulties in diagnosis of this situation and that immunohistochemistry is helpful to distinguish primary breast cancer from gastric cancer metastasizing to the breast.

[Postoperative Recurrence of Pancreatic Cancer Successfully Treated with the Gemcitabine plus Oxaliplatin Regimen Resulting in Long-Term Survival-ACase Report].

A 38-year-old woman who presented with complaints of back pain was diagnosed with cancer of the pancreatic body. Since invasion of the celiac artery/superior mesenteric artery was suspected, she was referred to our department for chemotherapy. She received 4 courses of gemcitabine plus S-1(GS), and she underwent distal pancreatectomy with en bloc celiac axis resection/portal vein resection/reconstruction using a left renal vein graft(OP-CAR). Histopathological examination of the resected specimen revealed a positive margin(R1). She received 11 courses of GS as postoperative adjuvant chemotherapy. She developed marked abdominal distension due to metastatic ovarian enlargement, and bilateral salpingo-oophorectomy was performed. The intraoperative findings revealed multiple peritoneal dissemination. Peritoneocentesis was performed, and the patient was started on gemcitabine plus oxaliplatin(GEMOX)for control of the ascites. This treatment was followed by a rapid decrease in the size of the ascites and resolution of the symptoms of stenosis. The serum tumor marker levels decreased over the following 18months. She received a total of 35 courses of GEMOX. This patient showed long-term survival after the start of treatment: she survived for 5 years and 11 months after the initial examination and for 5 years and 6 months after the surgery. Our experience in this case suggests that GEMOX could be a useful treatment option to improve prognosis.

[Long-Term Survivors after Resection for Primary Pancreatic Carcinoma Stage IV].

We discuss the prognosis of cases of Stage IV pancreatic carcinoma with distant metastases(7th Edition of General Rules for the Study of Pancreatic Cancer, Japan Pancreas Society)for which any treatment was performed at our hospital. Fiftythree patients were radiographically or pathologically diagnosed as having Stage IV pancreatic carcinoma with definite prognosis, and received treatments, includingsurg ery or chemotherapy, at our department. Twenty-two cases showed more metastases, and celiac artery or superior mesenteric artery invasion was suspected in 28 cases. The 5-year survival rate of all 53 cases was 3.8%, and the median survival time(MST)was 6.2 months. The MST in the palliative surgery cases was 6.7 months, and that in the cases given best supportive care(BSC)was only 1.9 months. There were no 2-year survivors in the group given chemotherapy without any other treatments and in the group given BSC alone, while the longest survival time and MST were 66.9 and 31.3 months(p<0.001), respectively, in the 10 patients treated by primary tumor resection. There was only 1 patient who showed relapse-free survival. Primary site resection and chemotherapy over 4 cycles was revealed as an independent prognostic factor by multivariable analysis. Patients with Stage IV pancreatic carcinoma have a poor prognosis. However, the possibility of achievingimproved prognosis was noted with combined-modality therapy, including aggressive resection in limited cases showinga good response to chemotherapy or cases in whom preoperative metastasis assessment was difficult.

[Long-Term Survival in Response to Multimodality Therapy in a Patient with Invasive Pancreatic Cancer with Cyst Formation].

The patient was a 61-year-old man. Computed tomography(CT)in April 2007 revealed a pancreatic cyst in the tail of the pancreas. Rapid enlargement was noted in November 2007, and the patient was referred to the surgery department. CT showed a cystic lesion containing a nodular shadow in the pancreatic tail. Tumor marker measurements yielded normal carcinoembryonic antigen(CEA)and carbohydrate antigen 19-9(CA19-9)levels, but the duke pancreatic monoclonal antigen type 2(DUPAN-2)level was elevated. A diagnosis of mucinous cystic neoplasm(MCN)of the pancreas was made in December 2007, and distal pancreatectomy and partial colectomy were performed. The pathological diagnosis was a mucinous pancreatic cyst in the pancreatic tail and a moderately differentiated tubular adenocarcinoma that had invaded the spleen and serosal adipose tissue of the transverse colon. No clear ovarian-type stroma was detected, and there was no definitive evidence of MCN. The postoperative course was favorable and complication-free, and gemcitabine postoperative adjuvant therapy was administered. A metastasis was detected in the left lung in April 2011, and was excised. Chemotherapy was administered to the fifth-line, but the patient died of his cancer in August 2015, 7 years and 8 months after the initial surgery, and 4 years and 8 months after the detection of the lung metastasis. MCN and intraductal papillary mucinous neoplasm(IPMN)are typical mucus-producing pancreatic tumors, and they have a relatively good prognosis. Our patient had an invasive cancer associated with a mucinous pancreatic cyst, but no definitive diagnosis was made, and it was considered IPMN. The long-term survival appeared to have been achieved because of subsequent multimodality therapy.

[R0 Resection of Locally Advanced Pancreatic Cancer after Combination Chemotherapy with Gemcitabine and S-1].

A 68-year-old female was referred to our institution in October 2014 for additional therapy for cancer of the head of the pancreas. Utilizing a computed tomography scan, he was initially diagnosed with locally advanced unresectable cancer because of massive invasion to the superior mesenteric artery (SMA). Combination chemotherapy consisting of gemcitabine and S-1 was administrated for 10 months. Since the tumor was remarkably reduced after chemotherapy, pancreaticoduodenectomy combined with portal vein resection was performed. Since the histopathological findings indicated few residual cancer tissues, our chemotherapy was considered dramatically effective. The postoperative course was uneventful and the patient remains well and without any recurrences 14 months after the surgery. We therefore report a case of locally unresectable pancreatic cancer, which achieved R0 resection after combination chemotherapy with gemcitabine and S-1.

[R0 Resection by Distal Pancreatectomy with En Bloc Celiac Axis Resection after Down-Staging by FOLFIRINOX Therapy in a Case of Pancreas Cancer--Report of a Case].

The patient, a 55-year-old man, was diagnosed elsewhere as having cancer of the tail of the pancreas and was referred to our hospital. Abdominal computed tomography (CT) revealed a remarkably large tumor, 90 mm in diameter, in the tail of the pancreas, with invasion of the adjacent spleen, stomach, left adrenal gland, diaphragm, and celiac artery; metastasis to the liver; and peritoneal dissemination. The serum levels of the tumor markers CEA and CA19-9 were elevated (21.2 ng/mL and 9,530 U/mL, respectively). Since surgery was not considered to be feasible in this condition, the patient was started on FOLFIRINOX therapy. Adverse events, including Grade 3 decreased neutrophil count, anorexia, diarrhea, and hyperkalemia occurred; however, the patient was able to receive 10 cycles of therapy with downward adjustments of the dosage. In response to the therapy, the tumor marker levels fell rapidly, and on CT, the tumor shrank to 40 mm in diameter; however, resection was still scheduled because positron emission tomography (PET)-CT revealed suspected remnants of the disease in the pancreatic tail. After preoperative transcatheter embolization of the common hepatic artery and the left gastric artery, distal pancreatectomy with en bloc celiac axis resection (DP-CAR) was performed. Intraoperative ultrasonography revealed no metastatic lesions in the liver. Histopathologically, the resected sites were found to be almost totally replaced with fibrous scar tissue, and only trace evidence of moderately differentiated tubular adenocarcinoma components were seen in the pancreatic tail, gastric submucosa, and left adrenal gland. Therefore, R0 resection had been achieved. The patient remains alive, showing no signs of recurrence at 18 months after the initial treatment and 11 months after the tumor resection. The results in this case suggest that FOLFIRINOX therapy can increase the radical curability of pancreatic cancer via down-staging and eventually improve the prognosis.

[A Case of Intrahepatic Cholangiocarcinoma with Invasion to the Transverse Colon and Gallbladder, Forming an Intra-Tumor Abscess].

An 81-year-old man was referred to our institution for evaluation of high fever and a liver tumor that had been detected by ultrasonography. Computed tomography revealed a low-density mass with peripheral ring-like enhancement in S5 of the liver. The liver mass was in contact with the gallbladder, and the boundary between the mass and the gallbladder was unclear. On the suspicion of liver abscess, percutaneous transhepatic drainage was performed. The cavity of the abscess communicated with the gallbladder. Because the cavity had no tendency to reduce in size, we performed surgical resection under a preoperative diagnosis of liver abscess or primary liver carcinoma invading to the gallbladder. Intraoperative findings revealed a liver tumor invading the transverse colon and gallbladder. Subsegmentectomy of S4a and S5 of the liver combined with gallbladder and transverse colon resection was performed. Histopathological findings indicated the growth of a mass forming type intrahepatic cholangiocarcinoma with invasion to the transverse colon and gallbladder, and the pathological stage of the tumor was pT3N0M0, fStage Ⅲ. Thus far, the patient is alive without recurrence 9 months after surgery. Here, we report an extremely rare case of intrahepatic cholangiocarcinoma that invaded other organs and was associated with an intra-tumor abscess.

[A Case of Anal Canal Cancer Treated by Abdominoperineal Resection in a 100-Year-Old Woman].

A 100-year-old woman visited our hospital because of erosion and bleeding in her anal region in January 2014. Computed tomography scans revealed the presence of a tumor in the anal canal, which caused a considerable amount of pain and bleeding over the next 4 months. Accordingly, immediate surgical intervention was considered necessary to provide local control. Therefore, we decided to perform abdominoperitoneal resection after consultation with her family. The operation was successfully completed, and histopathological examination indicated a diagnosis of adenocarcinoma of the anal canal. The postoperative course was almost uneventful, and the patient was discharged on the 23rd post-operative day. There are some cases reported in Japan where laparotomy was performed for patients over 100 years of age, but none of them were treated surgically for anal canal cancer. We suggest that elective surgical intervention can be an effective option for the treatment of abdominal and pelvic malignancies even in patients of an extremely advanced age.

[Pancreaticoduodenectomy performed in a patient with transverse colon cancer associated with a duodenal fistula - a case report].

A 71-year-old man with a positive fecal occult blood test was diagnosed with transverse colon cancer and referred to our hospital. Colonoscopy revealed type II transverse colon cancer with circumferential involvement. Contrast-enhanced computed tomography (CT)revealed a tumor with an unclear boundary in the pancreas. No metastases to the liver or lungs were detected, and there were no significantly enlarged regional lymph nodes. During open surgery, the tumor of the transverse colon was found to have formed a mass in the pancreatoduodenum, and it was difficult to separate them. As curative resection was considered possible, resections of both the pancreatoduodenum and transverse colon cancer were performed. Laboratory findings revealed fistula formation between the transverse colon cancer and the duodenum. The cancer was diagnosed as stageII, T4bN0M0, and R0 surgery was successfully performed. The patient was alive without recurrence 14- months after the surgery. Colorectal cancer is more likely to advance locally and directly invade the surrounding organs. However, fistula formation with the duodenum has rarely been reported, occurring at an estimated incidence of 0.1%. Such tumors are typically large; however, metastases rates to the lymph nodes are low. Histopathological examination of the resected specimen revealed a severe inflammatory adhesion, and fistula formation between the traverse colon and the duodenum. There was no evidence of invasion of the lymphatic system or blood vessels, which enabled us to perform a high curative surgery. We propose that it is important to consider high curative resection with positive lymph node dissection for cases of colorectal cancer associated with duodenal fistula formation.

[An assessment of liver metastasis resection in gastric cancer].

We assessed cases of gastric cancer in which liver metastases had been resected in our hospital. Liver resection was performed in 359 cases of metastatic cancer beginning in April 2003 when we initiated aggressive liver resection in conjunction with standard therapy. Of the 359 cases, 137 included metastatic liver cancer. The most common primary lesion was colorectal cancer, accounting for 101 cases, followed by gastric cancer with 21 cases. Here, we report on 14 cases of gastric cancer following exclusion of a single case of gastric endocrine tumor. The mean overall recurrence-free survival time after the initial liver resection was 8 months. However, mean survival time was prolonged to 45 months by subsequent chemotherapy and repeat hepatectomy. The 3-year survival rate was 64.2%, and the 5-year survival rate was 34.4%. Multivariate analysis identified total gastrectomy and multiple lesions as significant unfavorable prognostic factors. At our hospital, we consider a primary lesion that has been curatively resected, the absence of distant metastasis, and all liver metastases capable of being safely resected to be the indications for surgery. We have performed standard surgery and D2 lymph node dissection to treat primary gastric cancer lesions and have not observed any local lymph node recurrences. However, recurrence in the remnant liver occurred in more than 70% of the cases. We conclude that performing aggressive resection and postoperative chemotherapy according to the regimen for unresectable gastric cancer contributes to prolonging the survival time.

[A case of locoregional recurrence of gastric carcinoma that was treated using pancreaticoduodenectomy].

A 71-year-old man underwent distal gastrectomy for gastric cancer in November 2011. The corresponding pathological diagnosis was of well differentiated adenocarcinoma, pT4a(SE), N1(2/15), H0, P0,M0, pStage IIIA. TS-1 was administered as an adjuvant therapy for one year from the second month after the operation. During the 16th month after the operation, we found an elevated tumor marker level and locoregional recurrence near the pancreas head and the abdominal wall upon computed tomography. We could not find any other suspected tumor recurrence using positron-emission tomography and computed tomography. We performed a pancreaticoduodenectomy and transverse colon merger resection in June 2013. Although the tumor marker was again found to be elevated during the second month after the metastasectomy, chemotherapy was continued because obstructive jaundice and gastrointestinal obstruction were prevented by the operation.

[A case of synchronous triple cancer treated with multidisciplinary therapy - cancers in the middle part of the extrahepatic bile duct, the pancreas head, and the supraglottis].

An 83-year-old man was admitted to our institution for the purpose of investigation of hoarseness in January 2014. He was diagnosed with cancer in the supraglottis via biopsy while undergoing laryngeal microsurgery. Positron emission tomography (PET)evaluation for tumor staging revealed two hot spots, 1 in the hepatoduodenal ligament and 1 in the pancreas head. Accordingly, the patient was diagnosed with synchronous double cancer in the middle bile duct and the pancreas head. The treatment of the bile duct cancer and pancreatic cancer was performed prior to that of the supraglottic cancer. Curative pancreatoduodenectomy was performed, and the postoperative course was uneventful. Three weeks after the surgery, chemoradiotherapy for the supraglottic lesion was initiated. The tumor almost disappeared 2 months after the start of chemoradiotherapy, as observed by using a laryngoscope. Multidisciplinary therapy based on the therapeutic guidelines for each of the cancers was beneficial for the patient.

[Resection of a synchronous liver metastasis from gastric cancer associated with portal vein tumor thrombosis - a case report].

The patient was a 71-year-old woman who was referred to our hospital with a diagnosis of gastric cancer. Computed tomography( CT) scans revealed a liver tumor, which we diagnosed as liver metastasis from the gastric cancer. A type 2 tumor was observed in the lesser curvature side of the gastric angle, and a huge tumor measuring 75 mm was seen in the lateral segment of the liver. A tumor thrombus from the metastatic lesion in the liver jutting out into the umbilical portion of the portal vein was observed. Measurement of tumor marker levels showed that the α-fetoprotein (AFP) level was slightly elevated at 20.7 ng/mL. Distal gastrectomy and resection of the left lobe of the liver were performed at surgery. The results of the pathological examination indicated a tub2, T3 (ss), N1, M1 (HEP), ly0, v2, stage IV gastric cancer with liver metastasis, and without AFP expression. The postoperative course was favorable, and the patient was treated in the outpatient clinic with postoperative adjuvant chemotherapy consisting of 80 mg of S-1. No adverse events were noted, and it was possible to complete 10 courses of chemotherapy. Because there was no evidence of recurrence, treatment was completed in 1 year and 2 months. No recurrence was observed until the third year after surgery. Consistent with a slight elevation in the tumor marker levels at 3 years and 6 months, recurrence was observed in the remnant liver. The patient died of her disease at 3 years and 10 months. Gastric cancers that give rise to portal vein tumor thrombosis are rare. Their outcome is generally poor, and early recurrence in the remnant liver is common. In the present case, R0 resection was possible because the liver metastasis was solitary and the tumor thrombosis was mild. To a certain extent, an improvement in the outcome was observed. However, the recurrence progressed rapidly, making it impossible to perform adequate treatment. More diligent examinations and continuation of long-term treatment might have been required to improve the patient's prognosis.

[A case of locally advanced gastric cancer in which pathological complete response( PCR) was obtained after combination chemotherapy with S-1/cisplatin].

A 72-year-old man with advanced gastric cancer was referred to our hospital. Upper gastrointestinal endoscopy revealed a type 3 tumor in the gastric antrum and pyloric stenosis. Computed tomography( CT) demonstrated that the tumor had directly infiltrated the pancreatic parenchyma and that the paraaortic lymph nodes were enlarged. We judged the tumor to be unresectable and performed gastrojejunostomy. Postoperatively, the patient was treated with 9 courses of combination chemotherapy comprising S-1 and cisplatin( CDDP), and significant tumor reduction was obtained. Therefore, we performed radical distal gastrectomy with D2 lymphadenectomy. Histological examination revealed a complete absence of cancer cells in the stomach and all of the lymph nodes( pathological complete response: pCR). Seven months after surgery, the patient is in good health with no recurrence. This case suggests that aggressive chemotherapy can be a useful treatment to enable radical surgery for unresectable locally advanced gastric cancer.

[A case of hepatocellular carcinoma with biliary tumor thrombi treated by extended hepatectomy].

A 61-year-old male patient visited our hospital because of liver dysfunction. Computed tomography (CT) scan revealed a diffuse tumor in the right lobe of the liver with biliary tumor thrombi extending into the common bile duct. Percutaneous transhepatic biliary drainage(PTBD) was performed for obstructive jaundice. After improvement in the liver function, the patient underwent surgical intervention. Right trisectionectomy with removal of tumor thrombi was selected. Although the postoperative course was uneventful, CT scan demonstrated recurrent nodules in the remnant liver 4 months after surgery. Transcatheter arterial chemoembolization(TACE) was successfully performed for the recurrent lesions. The patient survived without any occurrence of viable lesions in the remnant liver. This case indicates that aggressive and curative surgery may improve the prognosis of patients with hepatocellular carcinoma and biliary tumor thrombi.

[A case of hepatocellular carcinoma treated by resection of metachronous rib metastasis after primary hepatectomy].

A 76-year-old man underwent right hemihepatectomy and partial hepatectomy of segment II for hepatocellular carcinoma (HCC) at our institution. Four months after the primary hepatectomy, the patient complained of severe back pain on the right side, and computed tomography and bone scintigraphy indicated metastasis of the eighth rib on the right side. Because no metastatic lesions were observed in any organ, the patient underwent surgical intervention for the rib metastasis in December 2011. Histopathological findings confirmed that the metastatic tumor originated from the HCC and that cancer tissues were absent from the surgical margins. Postoperative radiotherapy was additionally performed for preventing local recurrence. The sharp cancerous pain disappeared completely, and the patient was lived without recurrence 6 months after the second surgery. In cases where intrahepatic or other metastatic lesions are controllable and only a solitary bone metastatic lesion is evident, surgical resection is effective in HCC patients with bone metastasis.

[A case of diffuse hepatocellular carcinoma(Vp4) treated by right hepatic trisegmentectomy and multidisciplinary therapy regimens].

A 59-year-old woman was admitted to our hospital for treatment of a right humerus fracture. The patient was diagnosed with hepatocellular carcinoma during work-up for hepatic dysfunction. A diffusely spreading tumor was observed from the right lobe to the medial segment of the liver, and a portal vein tumor thrombus filled the right branch of the portal vein and extended into the main trunk, accompanied by cavernous transformation (Vp4). A multidisciplinary treatment regimen including surgical intervention was planned because the patient desired aggressive treatment. Surgical intervention included a right hepatic trisegmentectomy and excision of the portal vein tumor thrombus. The patient experienced an uneventful postoperative course with no signs of hepatic failure and received transcatheter arterial chemoembolization for residual tumor in the hepatic S1 and S2 regions on post-operative day 15. Beginning at 2 months after the operation, the patient was given 3 courses of intraarterial 5-fluorouracil combined with subcutaneous interferon-α therapy. She tested negative for tumor markers at 3 months post-operatively and was noted to have no viable tumors on computed tomography scans at 5 months post-operatively. However, there was a rapid recurrence with deterioration of her general condition at 8 months after the operation, and she died of recurrence the following month. Hepatocellular carcinoma complicated by portal vein tumor thrombus has an unfavorable prognosis, but it was considered feasible to improve this patient's outcome by giving priority to active surgical resection of the tumors including the tumor thrombus, and by undertaking multidisciplinary therapeutic measures.

[A case of long-term survival of a patient with intrahepatic bile duct cancer and early nodal recurrence who responded to S-1 therapy].

A 71-year-old man was referred to our hospital for further evaluation of hepatic dysfunction. A diagnostic workup revealed an intrahepatic bile duct cancer, and a right hepatic lobectomy was performed. Postoperative adjuvant chemotherapy with gemcitabine (1,000 mg/m², given for 3 weeks, followed by a 1 week rest) was begun. Because grade 3 anorexia developed, the dose of gemcitabine was decreased to 800 mg/m² from the third cycle of chemotherapy. Computed tomography showed nodal recurrence 6 months after surgery. One year after surgery, computed tomography revealed an extensive periaortic nodal recurrence, as well as recurrence in the remnant liver. Treatment was switched to S-1 (100 mg/ day, given for 3 weeks, followed by a 1 week rest). Grade 3 thrombocytopenia was developed during the tenth cycle of therapy. The treatment schedule was therefore changed to 3 weeks of therapy, followed by a 2 week rest. From the 36th cycle, the dose of S-1 was lowered to 80 mg/day (given for 2 weeks, followed by a 2 week rest). Nodal recurrence was resolved in 2 years after the start of treatment with S-1, and recurrence in the remnant liver nearly resolved in 4 years after starting the treatment, indicating a partial response. The carcinoembryonic antigen level fell to the normal range and the CA19-9 level remains at about 100 U/mL. Although the patient had grade 2 thrombocytopenia, he is now receiving the 43rd cycle of S-1 and remains alive for 5 years and 1 month after surgery. We believe that the continuation of chemotherapy while monitoring the patient's general condition led to an improved outcome.