Switching to Dupilumab from Other Biologics without a Treatment Interval in Patients with Severe Asthma: A Multi-Center Retrospective Study.

BACKGROUND: Dupilumab is a fully humanized monoclonal antibody that blocks interleukin-4 and interleukin-13 signals. Several large clinical trials have demonstrated the efficacy of dupilumab in patients with severe asthma. However, few studies have examined a switch to dupilumab from other biologics. METHODS: This retrospective, multi-center observational study was conducted by the Okayama Respiratory Disease Study Group. Consecutive patients with severe asthma who were switched to dupilumab from other biologics without a treatment interval between May 2019 and September 2021 were enrolled. Patients with a treatment interval of more than twice the standard dosing interval for the previous biologic prior to dupilumab administration were excluded. RESULTS: The median patient age of the 27 patients enrolled in this study was 57 years (IQR, 45-68 years). Eosinophilic chronic rhinosinusitis (ECRS)/chronic rhinosinusitis with nasal polyp (CRSwNP) was confirmed in 23 patients. Previous biologics consisted of omalizumab (n = 3), mepolizumab (n = 3), and benralizumab (n = 21). Dupilumab significantly improved FEV1 (median improvement: +145 mL) and the asthma control test score (median improvement: +2). The overall response rate in patients receiving dupilumab for asthma as determined using the Global Evaluations of Treatment Effectiveness (GETE) was 77.8%. There were no significant differences in the baseline characteristics of the GETE-improved group vs. the non-GETE-improved group. ECRS/CRSwNP improved in 20 of the 23 patients (87.0%). Overall, 8 of the 27 patients (29.6%) developed transient hypereosinophilia (>1500/µL), but all were asymptomatic and able to continue dupilumab therapy. CONCLUSIONS: Dupilumab was highly effective for the treatment of severe asthma and ECRS/CRSwNP, even in patients switched from other biologics without a treatment interval.

A case of colonic perforation in collagenous colitis without diarrheal symptoms.: A case report.

INTRODUCTION: Collagenous colitis is an inflammatory disease characterized by hyperplasia of the collagen band beneath the colonic mucous membrane. Chronic diarrhea is a characteristic clinical symptom. The disease is often diagnosed accidentally on colonoscopy for chronic diarrhea, and patients without chronic diarrhea have few chances to suspect the disease. PRESENTATION OF CASE: The patient was a 75-year-old woman. The chief complaint was sudden upper abdominal pain and vomiting. There were no important findings regarding the consumed food or bowel habits (no diarrhea). Computed tomography revealed wall thickness and a small amount of free air around the descending colon. An emergency laparotomy was performed with the diagnosis of spontaneous colonic perforation. Intra-operative findings revealed a longitudinal ulcer and micro-perforation to the mesenterial side at the descending colon. Pathological findings revealed subepithelial collagenous band in the submucosal background of the ulcer, and which was diagnosed as collagenous colitis. DISCUSSION: Intestinal perforation in collagenous colitis is extremely rare. It was considered that perforation was caused by a transient increase in intestinal pressure in the background of collagenous colitis. Further, to the best of our knowledge, this is the first report of a critical case which presented without the characteristic symptom of chronic diarrhea. CONCLUSION: We report a rare case of colonic perforation of the collagenous colitis.

Long-term effect of pulmonary rehabilitation in idiopathic pulmonary fibrosis: a randomised controlled trial.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is characterised by worsening dyspnoea and exercise intolerance. RESEARCH QUESTION: Does a long-term pulmonary rehabilitation improve exercise tolerance in patients with IPF treated with standard antifibrotic drugs, which are expected to reduce disease progression? METHODS: This open-label randomised controlled trial was performed at 19 institutions. Stable patients receiving nintedanib were randomised into pulmonary rehabilitation and control groups (1:1). The pulmonary rehabilitation group underwent initial rehabilitation which included twice-weekly sessions of monitored exercise training for 12 weeks, followed by an at-home rehabilitation programme for 40 weeks. The control group received usual care only, without pulmonary rehabilitation. Both groups continued to receive nintedanib. The primary and main secondary outcomes were change in 6 min walking distance (6MWD) and change in endurance time (using cycle ergometry) at week 52. RESULTS: Eighty-eight patients were randomised into pulmonary rehabilitation (n=45) and control (n=43) groups. Changes in 6MWD were -33 m (95% CI -65 to -1) and -53 m (95% CI -86 to -21) in the pulmonary rehabilitation and control groups, respectively, with no statistically significant difference (mean difference, 21 m (95% CI -25 to 66), p=0.38). Changes in endurance time were significantly better in the pulmonary rehabilitation (64 s, 95% CI -42.3 to 171)) than in the control (-123 s (95% CI -232 to -13)) group (mean difference, 187 s (95% CI 34 to 153), p=0.019). INTERPRETATION: Although pulmonary rehabilitation in patients taking nintedanib did not improve 6MWD in the long term, it led to prolonged improvement in endurance time. TRIAL REGISTRATION NUMBER: UMIN000026376.

[A Case of Obstructive Rectal Cancer with Flaccid Constipation Resected One Year and Three Months after SEMS Implantation].

We report a case of rectal cancer that was resected 1 year and 3 months after SEMS implantation. An 89-year-old man was previously diagnosed with sigmoid colon cancer at another hospital but did not undergo surgery. Three years and 7 months after the diagnosis, SEMS was implanted at another hospital. Four years and 10 months after the diagnosis, the patient was diagnosed with intestinal obstruction at our hospital. Since the SEMS was open on colonoscopy, the patient was also suspected of having flaccid constipation. The primary tumor was resected, and a colostomy was constructed in the descending colon. Bridge to surgery for obstructive colorectal cancer was performed within a few weeks after SEMS implantation. At our hospital, resection was performed after a long time. No complications, such as obstruction or perforation, were observed. In addition, although there were concerns regarding increased vascular invasion due to compression and drainage of the cancerous tissue, in our case, the vascular invasion was mild, and no distant metastasis or invasion of other organs was observed. SEMS can be used for long-term implantation and does not necessarily cause cancer progression.

[Surgical Outcomes of Laparoscopic Gastrectomy for Upper Gastric Cancer and Verification of the Validity of Laparoscopic Proximal Gastrectomy].

Laparoscopic proximal gastrectomy(LPG)for upper gastric cancer is still inadequate. We verified the validity of LPG by comparing the surgical outcomes of 15 cases who underwent LPG(PG group)and 14 cases who underwent laparoscopic total gastrectomy(TG group)in 29 cases who underwent laparoscopic surgery for upper gastric cancer at our hospital between January 2014 and December 2022. As a patient background, the PG group was significantly older(p=0.03)than the TG group and tended to have more high-risk cases(p=0.12). As a tumor factor, cancer progression tended to be earlier in the PG group(p=0.05). As a surgical(short-term)outcomes, although the range of lymph nodes dissection was narrow (p<0.01)and the amount of blood loss was significantly lower(p=0.01)in the PG group, there was no difference in operation time or postoperative complications between the 2 groups. Furthermore, there was no difference in the rate of weight loss, the rate of change in nutritional indicators in the medium-term(1 year after surgery), or the long-term prognosis.

[Synchronous Double Primary Non-B, and Non-C Intrahepatic Cholangiocarcinoma and Hepatocellular Carcinoma-A Case Report].

A 78-year-old man without hepatitis virus B or C underwent right hemi-hepatectomy and lymph node dissection for a tumor 5 cm in diameter located in the hepatic hilum of the posterior segment of the liver with portal vein thrombi extending into the main portal trunk and a tumor 1.5 cm in diameter in the peripheral side of segment 5 of the liver. Histopathologically, the former was diagnosed as intrahepatic cholangiocarcinoma and the latter as hepatocellular carcinoma(HCC). Five months after the surgery, intrahepatic and lymph node metastases were diagnosed based on computed tomography(CT); therefore, chemotherapy with S-1 for 3 months and gemcitabine and cisplatin(GC)for 5 months was administered, after which the metastatic lesions were not detected. Nineteen months after the surgery, partial resection of segment 2 of the liver was performed for a tumor 3 cm in diameter, which was diagnosed as HCC histopathologically. Two years after the second surgery, 2 recurrent nodules in the liver in segments 3 and 4 were detected on CT. Platinum-based hepatic arterial infusion chemotherapy(HAIC)and transcatheter arterial chemoembolization(TACE)were performed, and chemotherapy with GC was then administered for 7 months. For a new tumor detected in segment 1 in the liver, TACE was performed 17 months after initial HAIC. Seventy-four months after the initial surgery, 5 new nodules less than 1 cm in diameter were detected, and chemotherapy with sorafenib was administered for 5 months, after which the patient died of coronavirus disease 2019.

[A Greater Than Four-Year Survival of a Patient with Inoperable Hilar Cholangiocarcinoma following Portal Vein Embolization and Administration of S-1].

We report a patient with inoperable hilar cholangiocarcinoma due to invasion at the umbilical portion who survived more than 4 years after right portal vein embolization and administration of S-1(50 mg/day). A 64-year-old male patient was immediately hospitalized for liver dysfunction and a high level of HbA1c. The disease was diagnosed as hilar cholangiocarcinoma mainly extending along the right hepatic duct. We made a request for operation to Nagoya University. He received right portal vein embolization in order to grow the residual liver but was deemed inoperable because of invasion at the umbilical portion. He refused chemotherapy but accepted administration of S-1(50 mg/day). Approximately 3 months after starting S-1, his ALP level normalized and about 9 months later stenting tube was lost. Subsequently, he returned to his job. Approximately 2 years and 2 months later, administration of S-1 was interrupted due to a harmful side effect. After approximately 13 months without S-1, the levels of CA19-9 and ALP again became elevated and administration of S-1 was restarted. He was temporarily hospitalized for abdominal pain and fever, but quickly recovered. Although CA19-9 and ALP levels re-normalized, he died after returning home. We emphasize the possibility of maintaining long-term health by minimal- dose S-1 therapy for inoperable hilar cholangiocarcinoma.

[Clinical Characteristics, Surgical Outcomes, and Optimal Approach Methods for Transverse Colon Cancers].

Surgery for transverse colon cancer is very difficult because of small number of patients, variations in the vascular system, and complexity of the mobilize hepatic and splenic flexure of colon. We analyzed the clinical characteristics and surgical outcomes in 51 cases who underwent surgery for transverse colon cancer at our hospital between January 2014 and December 2021, and examined the optimal laparoscopic approach method. The surgical procedure was right hemicolectomy in 24 cases, transverse colectomy in 22 cases, and left hemicolectomy in 5 cases, of which 37 cases had laparoscopic surgery. In laparoscopic surgery, when comparing the cranial first approach group in 21 cases and the caudal approach group in 16 cases, the operative time was almost the same between the 2 groups. In the cranial first approach group the amount of bleeding tended to be small, the number of MCA lymph node dissections tended to be large and the hospital stay tended to be short, though there was no statistically significant difference. The results suggest that the cranial first approach tends to be safer and more accurate than the caudal approach.

[Penrose Method Independent of the Rib Arch for Retraction of the Liver in Laparoscopic Gastrectomy y-Shape+1 Method].

We report the y-shape+1 method, which is a retraction of the liver method, independent of the position of the costal arch. Additionally, we report changes in liver enzymes induced by different methods of liver retraction. Three Penrose No. 6 drains were cut into 6 cm pieces. Penrose 1 was fixed with a thread attached to the end and Penrose 2 in a y-shape. A knitting thread with needles was prepared, and a loop was made at the end of the thread. The needle thread was passed over the abdominal wall and through the Penrose 2. The needle thread was passed over the diaphragmatic leg and through the Penrose 3. The thread was pulled over the abdominal wall and diaphragmatic leg and fixed to the end of Penrose 1 out of the body, and the liver was drained. The rate of change in liver enzymes from the preoperative to postoperative stages was examined separately in the Penrose and Nathanson groups. In the y-shape+1 technique, retraction of the liver can be performed regardless of the position of the rib arch; however, intracorporeal suture ligation is necessary. This method is useful when the conventional Penrose method is inappropriate because of the position of the rib arch.

[Surgical Outcomes and Clinicopathological Analysis of Non-Ampullary Duodenal Tumors].

Non-ampullary duodenal tumors are relatively rare; however, in recent years, they have been encountered more frequently. We analyzed the surgical outcomes and clinicopathological findings in 20 patients who underwent surgery based on preoperative diagnoses of non-ampullary duodenal tumors at our hospital between January 2011 and April 2021. We performed surgery for 3 cases of GIST, 4 cases of adenoma, and 13 cases of adenocarcinoma. The average age of the patients was 64.3 years and the male-to-female ratio was 17:3. The location of the tumor was the blub in 5 cases, the superior duodenal angle in 2 cases, the descending portion in 9 cases, the horizontal portion in 3 cases, and the ascending portion in 1 case. The histological type of adenocarcinoma was tub1 in all cases of early cancer, whereas in advanced cancer, there were many cases with histological types other than tub1. Various surgical procedures from duodenal local resection to pancreatoduodenectomy can be performed for treating non-ampullary duodenal tumors depending on the tumor location and the necessity of lymph node dissection. It is important to establish a treatment policy that considers both curability and invasiveness.

Laparoscopic Frey's Procedure for Chronic Pancreatitis in a Japanese Patient.

BACKGROUND Chronic pancreatitis is a slowly progressive inflammatory disease, affecting patients' quality of life due to chronic pain as well as endocrine and exocrine pancreatic insufficiency. Patients often choose surgery if medical and endoscopic interventions fail. Surgical approaches for chronic pancreatitis can be categorized as follows: resection of the diseased gland, diversion and drainage of the dilated pancreatic duct, or a combination of these approaches. Frey's procedure, which involves resection and drainage by longitudinal pancreaticojejunostomy and coring out of the pancreatic head, is reserved for patients with debilitating pain. Although laparoscopic surgery is gaining popularity in recent years due to its noninvasiveness and cosmetic benefit, few reports describe performing Frey's procedure laparoscopically. CASE REPORT A 36-year-old Japanese female with chronic pancreatitis complained of back pain and pain in the left upper quadrant abdomen. Plain computed tomography of her abdomen revealed a dilated main pancreatic duct containing diffuse calculi extending to the pancreatic parenchyma. Laboratory findings, including amylase level, were within normal ranges. She was diagnosed with chronic pancreatitis, and subsequently underwent a laparoscopic Frey's procedure. To our knowledge, we are the first to improve operative field visibility by using a Penrose drain to move the stomach from the line of sight. Postoperatively, the patient did well and was discharged 10 days after surgery. She remained symptom-free without medications for 80 months. CONCLUSIONS Due to its noninvasive nature and cosmetic advantages, laparoscopic Frey's procedure may be an attractive therapeutic option for chronic pancreatitis.

[A Case of Malignant Lymphoma Undergoing HAI Treatment for Multiple Liver Metastases of Carcinoid That Appeared about Nine Years after Resection of Rectal Carcinoid with Liver Metastases].

The present case pertained to a 70-year-old woman. The fecal occult blood test was positive. Colonoscopyrevealed rectal cancer. She underwent the first operation of low anterior resection. Pathological diagnosis was carcinoid, se, ly2, v0, n1. Approximately2 months later, multiple liver metastases were found. Because of strong enhancement at angiography, transarterial chemoembolization(TACE)was selected. After 3 rounds of TACE, we operated the residual liver metastasis approximately1 year and 7 months after the first operation. However, approximately8 years and 9 months after the first operation, multiple liver metastases were found again. Hepatic arterial infusion(HAI)was chosen because tumors showed weak en- hancement on CT. First, we tried high-dose HAI(5-FU 1 g/dayat 1-3 and 5-7, amount: 6 g/week), and liver metastases was almost in CR. However, extrahepatic metastasis was found on PET-CT. Because of rapid growth, we operated the growing lymph node. Pathological diagnosis was diffuse large-cell type B-cell malignant lymphoma. Thus, we extended the interval of HAI(weekly, biweekly, and monthly)and simultaneously4 courses of R-THP-COP(R: rituximab, THP: pirarubicin, C: cyclophosphamide, O: vincristine, P: prednisolone)therapyfor malignant lymphoma was administered. She is now an outpatient. Liver metastases continue to be in CR at approximately1 year and the IL-2R value is almost within normal range.

[Endoscopy Guided Single-Incision Laparoscopic Partial Duodenectomy of Duodenal Tumor].

The use of endoscopic submucosal dissection(ESD)for the treatment of duodenal tumors has increased recently. ESD is less invasive than surgical resection of duodenal tumors. However, a high rate of complication, including perforation and bleeding, has been reported to be associated with ESD. Here, we report the minimally invasive surgical procedure called "endoscopy guided single-incision laparoscopic partial duodenectomy" for the treatment of duodenal tumors, along with its and safety and treatment outcomes. Five patients were included in this study. We mounted the LAP PROTECTORTM and EZ access®in the umbilical incision. Single-incision laparoscopic surgery was performed using 3 trocars(5mm)that were placed into the EZ access®. First, we mobilized the duodenum and pancreatic head from the retroperitoneum using the laparoscopic "Kocher maneuver". Next, the peritumoral site was marked by an endoscopic procedure using a clip and electric needle knife. Using an endoscope, we performed laparoscopic full-thickness resection of the duodenal wall including the tumor. The defect in the duodenal wall was then closed by suturing.

[The Efficacy of Endoscopic Esophageal Stent Placement for Malignant Esophageal Stenosis].

Malignant esophageal stenosis adversely affects the quality of life(QOL)on account of poor oral intake. Endoscopic esophageal stenting is one of palliative therapy for improve QOL because of minimally invasive and simple procedure. We investigated the outcomes of esophageal stenting in our institution. Twenty patients with malignant esophageal stenosis who underwent esophageal stenting in our institution between April 2014 and December 2019 were included in this study. Six(30%)out of 20 patients showed fistula. Dysphagia score was improved significantly before and after stenting(3.3± 0.6 vs 1.8±0.9, p<0.01). Complications associated with stenting occurred in 6(30%)cases. Thirteen(65%)patients were able to be discharged from the hospital, but 7(35%)patients including 4 with fistula were outcomes of death in the hospital. Esophageal stenting for malignant esophageal stenosis improved food ingestion and QOL. The prognosis in the case of malignant esophageal stenosis with fistula is extremely poor.

[Application of Sugar to the Edematous Stoma for Obstructive Rectal Cancer-A Case Report].

We herein report a case of application of sugar to the edematous stoma for obstructive rectal cancer. A 70-year-old male patient was diagnosed with rectal cancer, bowel obstruction and multiple lung metastases. Colostomy was performed. Seven days after operation, severe edema and congestion of stoma continued. We started spraying of sugar to stoma, and a few days later, edema and congestion of stoma improved. Before discharge, stoma size markedly reduced. Steady state of stoma and achievement the ability to self-care their stoma is important for introduction of chemotherapy. Application of sugar to reduce edema of rectal prolapse and prolapsed stoma have reported. Although the number of reported cases is still small, effectiveness of sugar to reduce edema of stoma have reported. In our case, application of sugar to the stoma is effective in reduction of edema. Application of sugar might be effective in reduction edema of stoma.

[More than Four-Year Survival of Appendiceal Adenocarcinoma Due to Goblet Cell Carcinoid and Manifesting as an Abdominal Tumor and Hydronephrosis].

An 89-year-old woman with complete blindness presented with a right lower abdominal tumor and weight loss. The CT scan showed a huge mass approximately 9 cm in diameter in the ileocecum, invading the right urinary tract and right iliac artery and vein. Findings of the TCS biopsy led to the suspicion of ileocecal carcinoid. Another punch biopsy specimen acquired under general anesthesia indicated mucinous cell carcinoma. When she suffered from right leg pain approximately 3 months later, we provided radiation therapy(50 Gy)because of intolerance to UFT. Consequently, pain disappeared, and the tumor size decreased significantly. We administered TS-1 but discontinued it because of intolerance. Further, 2.8 years after the first medical examination, the tumor recurred, and she developed ileus. We performed ileocolectomy, and pathological findings indicated that the adenocarcinoma in the appendix had progressed from goblet cell carcinoid(sig, si[right ovary], ly1b, v1a, n0). Four years after the first medical examination, CEA had elevated rapidly, and lung metastases were found. She died approximately 4.2 years after the first medical examination. The last measured CEA level had been 596.7 ng/mL. Starting from the lowest level at the first examination, the CEA level had slowly elevated until before the operation and rapidly elevated postoperatively. Immunopathological findings showed that the operated specimen stained diffusely for CEA, without any mucinous component. We suspected that radiation therapy modified goblet cell carcinoid to adenocarcinoma.

[Small Intestinal Metastasis from Lung Cancer with Infiltration into Other Organs-Review of the Literature].

We report a case of metastasis to the small intestine from squamous cell carcinoma of the lung with fistula formation in the adjacent small intestine as well as an analysis of reported cases in Japan of small intestinal metastasis from lung cancer invading other organs. A 63-year-old man was diagnosed with squamous cell carcinoma of the lung as a result of pneumonia. Chemoradiotherapy was administered and sequential chemotherapy was performed, but a single brain metastasis of right parietal lobe was detected 6 months later. Tumor resection was performed. Twelve months after the lung cancer diagnosis, metastasis of the small intestine was detected. Single-incision laparoscopic surgery with partial resection of the small intestine was performed. The tumor had invaded the abdominal wall and 2 parts of the small intestine and had formed a fistula with part of the small intestine. Subsequently, peritoneal dissemination recurred and the patient received the best supportive care. There are 10 reported cases in Japan of small intestinal metastasis from lung cancer invading other organs. Analysis of the reported cases indicates a poor prognosis for patients with fistula. Resection can improve prognosis in patients with primary lung cancer and without distant metastasis. Surgical resection should be considered even if metastasis in the small intestine from lung cancer has invaded other organs.

[Skin Ulcer Caused by Bevacizumab-A Case Report].

A case of a skin ulcer caused by bevacizumab(Bmab)is reported here, which recurred with re-administration of bevacizumab. A 69-year-old male patient was diagnosed with cecal cancer, multiple liver metastases, multiple lung metastases, and bone metastasis. Resection of the cecal cancer was performed, and the patient was post-operatively treated with XELOX and Bmabchemotherapy. After the second cycle of chemotherapy, a skin ulcer developed. The ulcer improved after cessation of chemotherapy, debridement, and treatment with antibiotic medication. In spite of re-administration of XELOX chemotherapy, the skin ulcer healed completely, however, the dermatopathy recurred after re-administration of Bmab. Bmab chemotherapy is associated with various risks, including dermatopathy and protracted wound healing, and some cases of skin ulcers caused by Bmab have been reported. Because the skin ulcer was suspected to be cutaneous actinomycosis, Bmab chemotherapy was reintroduced while the patient was treated using antibiotic agent feeding, but the skin ulcer reoccurred. Reported cases of skin ulcers caused by Bmab in Japan show that skin ulcers often recur after re-administration of Bmab. Therefore, if skin ulcers caused by Bmab develop, re-administration of Bmabshould be considered carefully.

[Laparoscopic Transverse Colectomy by Cranial Approach Preceding Medial Approach after Stenting for Obstructive Transverse Colon Cancer].

Surgery for obstructive colon cancer was highly invasive due to poor nutritional status of patients, risk of emergency surgery, and unavoidable colostomy formerly. However, recently, we have been able to perform laparoscopic elective surgery safely without colostomy, by using self-expanding metallic stents(SEMS). Laparoscopic colectomy for transverse colon cancer is inherently very difficult because of variations in the vascular system, small number of patients, and absence of large, randomized trials. Laparoscopic complete mesocolic excision(CME)for colectomy has been shown to be technically feasible and effective. We report the treatment strategy for obstructive transverse colon cancer which involves laparoscopic transverse colectomy by cranialapproach preceding medialapproach after successfuldecompression by stenting, along with a review of relevant literature. We consider it a s minimally invasive treatment for obstructive transverse colon cancer.

[A Very Elderly Patient Successfully Treated by Multimodality Treatment for Pancreas Cancer with Synchronous Multiple Liver Metastases and Liver Dysfunction].

We report an 86-year-old patient successfully treated by multimodality treatment for advanced pancreatic cancer with synchronous multiple liver metastases and liver dysfunction. Systemic chemotherapy(SC)(gemcitabine[GEM]1 g and 5-FU 1 g biweekly)was initiated. Two weeks after, the radiation therapy(55 Gy/25 days)was added. Three weeks after, the short period's high dose hepatic artery infusion(SPHDHAI)(5-FU[1 g]×3 days: 1 day rest: 5-FU[1 g]×3 days)was started. By these treatments, liver dysfunction was completely improved and abdominal pain was disappeared. After 2 times of weekly high dose hepatic artery infusion(WHDHAI)(5-FU 1,500mg), the mixed chemotherapy(MC)(GEM 800 mg[systemic] and 5-FU 1,500 mg hepatic artery infusion:[HAI]biweekly)were started. She could live without admission for about 1 year. About 13 months after lung metastases was appeared and she died about 19 months after first chemotherapy. Our multimodality treatment(systemic and HAI therapy and radiation)was effective for keeping patient quality of life and for improving the survival even if the patient was a very old age and showed liver dysfunction.