[A Case of Self-Expandable Metallic Stent Placement to Treat Colon Obstruction Due to Metastatic Gastric Cancer].

A66 -year-old woman presented with abdominal pain and nausea. She was diagnosed with wall thickening of the gastric antrum and bowel obstruction caused by tumors of the splenic flexure on computed tomography. Aself -expandable metallic stent(SEMS)was placed in the splenic flexure of the colon 4 days after transanal ileus tube replacement. No complication was observed, and she could ingest a normal diet, permitting her discharge from the hospital 12 days after SEMS placement. She was diagnosed with gastric cancer(Type 4, cT4a[SE], N2, H0, P1, M1[LYM], cStage IV )on upper gastrointestinal endoscopy and computed tomography, and administration of S-1 plus oxaliplatin(SOX)was started. Nab-paclitaxel as the second-line chemotherapy was administered after 8 courses of SOX therapy because of an increase in the amount of ascites. No late complication associated with stent placement was recognized. SEMS placement was suggested to be effective for treating colon obstruction due to metastatic gastric cancer.

[Examination of Patients with Malignant Obstruction Treated with Chemotherapy after Ileo/Coleostomy].

Management for obstructive cancer of the colon diverges into many ways. The aim of this study was to evaluate the treatment course of patients with malignant obstruction after ileo/coleostomy. Thirty-six patients with malignant obstruction who underwent ileo/coleostomy in our hospital from May 2012 to January 2016were enrolled in the study. Clinical outcomes were the period before treatment initiation, chemotherapy, radiotherapy, primary lesion resection, and death, and these were retrospectively analyzed. Although 9 stomal complications occurred, no case experienced a delayed treatment start. However, patients with perioperative complications, sepsis due to the tumor, pneumonia, cerebral infractions, and ileus needed a long recovery period before treatment initiation. Patients who need ileo/coleostomy must be considered for performance status and ways to decrease perioperative complications to prevent stomal complications from chemo/radiotherapy.

[A case of malignant melanoma of the esophagus].

A 56-year-old female with chest pain after a meal was found to have the black mucous membrane of the middle intrathoracic esophagus by esophagogastroduodenoscopy. The lesion was diagnosed as primary malignant esophageal melanoma without lymph nodes and other organ metastasis. We underwent a subtotal esophageal by right thoracotomy and laparotomy. She survives with relapse-free for 3 years after the surgery. There is no standard therapy because primary malignant esophageal melanoma is not common. However, we thought a surgical treatment should be performed for a curatively resectable case.

[A case of luminal B recurrent breast cancer with liver and lymph node metastases successfully treated with combination therapy of S-1 plus trastuzumab].

We experienced a case of Luminal B recurrent breast cancer with liver and lymph node metastases achieving significant improvement by S-1 plus trastuzumab combination therapy. This patient was a 47-year-old woman. Trastuzumab monotherapy was administered after recurrence, but her condition grew worse. Thus, we started combination therapy of trastuzumab plus S-1. S-1 was administered orally at 100 mg/day every day for 4 weeks followed by a 1-week rest period as one course, and trastuzumab was then injected at 2 mg/kg every week. All metastases disappeared after two courses of the treatment, and no new malignant lesions appeared. In conclusion, combination therapy of S-1 plus trastuzumab could be effective treatment for maintaining good QOL in Luminal B recurrent breast cancer with lymph node and liver metastases.

[A case of bleeding tendency due to warfarin in a patient treated with chemotherapy by S-1].

A 82-year-old male patient had suffered from a cancer of the papilla of Vater. After the operation, he received 4 courses of gemcitabine(GEM)adjuvant chemotherapy and warfarin(WF)administration because of thrombosis in the left internal jugular vein. Since the tumors re-grew, GEM was discontinued, and chemotherapy including S-1 and GEM was examined. However, the chemotherapy could not be continued because of edema in both lower legs and tassel midway in the 2nd course. Because of a bleeding tendency(non-measurable INR(international normalized ratio of prothrombin time)), WF administration was discontinued on the 11th day after S-1/GEM combined therapy was suspended. On the following day, although the INR value recovered to 1.7, it gradually worsened and the symptoms of pulmonary embolism developed on the 13th day. Then, INR was controlled by continuous infusion of heparin. Since the INR level decreased after that, in addition to heparin, re-medication of WF was performed. We tried to analyze the genotype of a patient, who had a tendency to bleed by coadministration of WF with S-1, in terms of hepatic cytochrome P-450(CYP)2C9 and vitamin K epoxide reductase complex subunit 1(VKORC1). We also measured the plasma concentration of S-and R-WF by HPLC after obtaining informed consent from the patient. We found that he is homozygous for CYP2C9 1/1 and for A/A of VKORC1(-1639G>A). The obtained data did not show the abnormalities of blood coagulation. Because the genotype of a patient with a tendency to bleed was a major type in a Japanese population, fine monitoring of INR is required in order to prevent side effects of blood coagulation by S-1 and WF coadministration, regardless of patient genotypes.

[A case of advanced gastric cancer treated with chemo-radiotherapy as the fourth-line therapy].

A 69-year-old female patient with type 2 advanced gastric cancer (s-T4N0M0H0Cy0P0, f-Stage IIIA) located from lower corps to antrum underwent a distal gastrectomy with D2 lymphandectomy in May 2006. After surgical treatment, S-1+ docetaxel combined chemotherapy was started for pEM (+) due to direct invasion to pancreas head as the first-line chemotherapy. However, the local recurrence whose diameter was 24 mm at pancreas head was detected with enhanced CT in December 2006. Moreover, nevertheless CPT-11+CDDP combined chemotherapy or paclitaxel monotherapy as the second or the third-line chemotherapy, respectively, the diameter of the local recurrence enlarged to 38 mm in November 2007. Therefore, chemo-radiotherapy using with S-1 and CDDP was started in December 2007 and the diameter of local recurrence was reduced to 25 mm in January 2008. No adverse event of grade 3 or more occurred during chemo-radiotherapy except for grade 3 of neutropenia. Chemo-radiotherapy for this gastric-cancer patient with local recurrence of multiple anti-tumor drug resistance was effective and safe.

[A case of S-1 resistant multiple lung metastases after curative total gastrectomy for gastric cancer successfully treated by S-1 combined with CPT-11 as the third-line chemotherapy].

A 78-year-old female underwent a curative total gastrectomy with D2 lymphandectomy for advanced gastric cancer in March 2003. S-1 mono-therapy (80 mg/m2, day 1-28/42 days) began as the first-line chemotherapy from October 2004 when multiple lung metastases were detected by CT. Paclitaxel mono-therapy (80 mg/m2, days 1, 8, 15/28 days) began as the second-line chemotherapy from April 2005 when prior S-1 mono-therapy judged as progressive disease (PD) by CT. Paclitaxel mono-therapy judged it as partial response (PR) in June, but the final judgement was as PD in September 2005. S-1 + CPT-11 combination therapy (S-1: 80 mg/m2, day 1-21, CPT-11: 80 mg/m2, days 1, 15/35 days) began as the third-line chemotherapy from September 2005. After 10 courses, multiple lung metastases were judged as complete response (CR) in September 2006. During the third-line chemotherapy, any adverse event of grade 2 or more did not occur. After judgment of CR, the patient has been followed without chemotherapy due to patient's desire, and is still alive without any recurrence in July 2007.

[Neoadjuvant therapy with imatinib mesilate for gastrointestinal stromal tumor of the stomach before subsequent successful surgical resection].

A 65-year-old man is presented here with a huge mass of 13 cm in diameter in the left upper abdomen. Histopathologic assessment of endoscopic forceps biopsy revealed a c-kit positive gastrointestinal storomal tumor (GIST) of the stomach. Abdominal computed tomography (CT) showed a direct invasion to the pancreas. Imatinib mesilate was administered as neoadjuvant therapy according to the NCCN Guidelines. Imatinib mesilate therapy was stopped within 2 weeks because of adverse events such as Grade 2 of facial edema and dizziness. However, no hematological adverse event was shown. After three months of treatment (relative dose intensity was 87.5%), CT revealed a reduction in tumor diameter of 35.6% and showed no longer a direct invasion to the pancreas. The radical operation was considered feasible and partial gastrectomy was performed. The tumor was well encapsulated and radical surgery was possible without rupture. Adjuvant therapy was not performed. The patient has now been in good health without a recurrence for three months after the surgery.

[A case of an elderly patient with gastric cancer successfully treated with TS-1 considering impaired renal function caused by aging].

A 75-year-old female patient with impaired renal function caused by aging was treated with TS 1 for gastric cancer with extensive multiple liver metastases. TS-1 contains CDHP, which inhibits DPD activity and maintains a high blood concentration of 5-FU. Because CDHP is excreted from the kidney, a careful TS-1 administration is necessary for patients with impaired renal function considering an occurrence of severe adverse events. Based on the result previously reported by us about pharmacokinetic study and recommended administration dosage of TS-1 for patients with impaired renal function, we administered 50 mg/day of TS-1 for four weeks followed by two weeks rest per one course for this patient. The patient's creatinine clearance calculated by the Cockcroft-Gault method was 38 ml/min, and we reduced the administration dosage in consideration of her impaired renal function, although normal dosage of TS-1 calculated from body surface area for this patient was 100 mg/day. As this patient underwent TS-1 treatment, sizes of multiple liver metastases and the blood concentration level of CEA were gradually reduced, and the reductive rate of the former was more than 90% and the level of the latter fell to a normal range after 12 courses of TS 1 treatment. Through all the treatment courses, relative drug intensity was 100% and the performance status of this patient was kept 0 without any grade 3 or more adverse events under ambulatory treatment. A successful treatment for this patient might indicate that it was important to consider the appropriate reduction of the dosage of TS-1 administration for elderly patients with gastric cancer, because there is a reverse correlation between aging and renal function. To clarify this problem, a multicenter prospective phase II study about TS-1 reductive administration depending on the renal function for elderly patients with gastric cancer (OGSG0404) is ongoing in our clinical study group (OGSG; Osaka Gastrointestinal Chemotherapy Study Group).

[A case of complete remission of carcinomatous ascites refractory for TS-1 monotherapy treated with TS-1 plus paclitaxel combined therapy for gastric cancer].

A 38-year-old female patient with gastric cancer, of which histological type was a poorly differenciated adenocarcinoma and a clinical finding was T3N1MO (Stage IIIA), underwent total gastrectomy with D2 lymphadenectomy as the surgical treatment. However, CY1 was detected during the operation and the final finding was T3N1MOHOPOCY1 (Stage IV). Because this surgical treatment ended in curative C, we administered 80 mg/m2/day of TS-1 for four weeks followed by two weeks rest per one course for CY1 after the surgical treatment. After two courses of TS-1 monotherapy, extensive carcinomatous ascites appeared and blood concentration level of CA19-9 increased. We next treated this patient with TS-1+paclitaxel as a second line chemotherapy, because both of them have been reported to migrate to peritoneal very well and to be effective for peritoneal dissemination. The regimen of this combined therapy consisted of four weeks administration of TS-1 (80 mg/m2/day) followed by two weeks rest and injections of paclitaxel (50 mg/m2) at day 1 and 8 for 21 days as one course. When this patient underwent TS-1+paclitaxel combined treatment, the amount of carcinomatous ascites and blood concentration level of CA19-9 were gradually reduced and the former completely disappeared, and the latter fell to a normal range after five courses. Through all treatment courses, a performance status of this patient was kept 0 without a severe adverse event under ambulatory treatment. After 29 courses, the blood concentration level of CA19-9 rose again and local recurrence was detected at the lesion of esophagoenterostomy, though carcinomatous ascites had been kept in complete remission. We treated surgically for this local recurrence because of CY0 at the operation. At the present, 3 years and 8 months have passed since the first treatment started. This patient is still alive without cancer in ambulatory.