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A 79-year-old man with unresectable advanced gastric cancer due to invasion to the pancreas and positive lavage cytology( T4b, N+, M1, CY1, cStage ⅣB; Japanese classification of gastric carcinoma, 15th edition)received standard chemotherapy, including 6 courses of S-1 plus cisplatin as first-line therapy and 2 courses of paclitaxel plus ramucirumab followed by 6 courses of paclitaxel monotherapy as second-line therapy. The primary lesion became PD with these treatments. Subsequently, nivolumab monotherapy was introduced as third-line therapy. After 9 courses, the primary tumor shrunk, and lavage cytology turned to negative on diagnostic laparoscopy. We judged that the tumor was resectable, and the patient underwent radical total gastrectomy and D2 lymphadenectomy as conversion surgery. The pathological stage was ypT3(SS), N0, M0, CY0, and the therapeutic effect was Grade 1b. R0 resection was accomplished. He has been alive without recurrence for 18 months after resection without adjuvant chemotherapy.

Microsatellite instability(MSI)testing is performed in cancer patients to determine the indication for chemotherapy with immune checkpoint inhibitors. We report on our scheme to ensure that Lynch syndrome patients are offered the opportunity for genetic counseling and genetic testing. Two hundred and eight cancer patients(107 males and 101 females, 20- 87 years, mean 63.3 years)underwent MSI testing at our hospital between February 2019 and November 2021. From February 2019 to December 2020, the MSI testing was performed with a consent document that included a commentary on Lynch syndrome, and the results were explained only by the attending cancer doctors. Eleven(8.6%)of the 136 cases had MSI-high, but none of them led to a visit to the genetic medicine department. The Genome Center in our hospital, which was operational from April 2020, undertook information sharing by multiple professions and established a system to provide appropriate support to cancer doctors. Consecutively, 72 MSI tests were performed between January and November 2021, and 2 patients(2.8%)with MSI-high(1 with endometrial cancer and 1 with colorectal cancer)were referred to the Department of Clinical Genetics for genetic counseling. Through genetic testing, both were diagnosed with Lynch syndrome, and information on future surveillance and health care for blood relatives was provided.

A 52-year-old female with stage Ⅳ, bilateral, HER2-positive, breast cancer as well as bilateral axillary lymph node(LN) metastasis and bilateral pulmonary metastasis was administered trastuzumab plus pertuzumab plus docetaxel as a standard chemotherapy. After this treatment the right breast cancer, right axillary LN metastasis, and bilateral pulmonary metastases contracted, while the left breast cancer and left axillary LN metastasis expanded. Trastuzumab emtansine was then administered, and the left axillary LN metastasis contracted, however, the left breast cancer expanded, resulting in marked breast engorgement. When trastuzumab deruxtecan(T-DXd)was administered, the left breast cancer contracted for the first time during the overall treatment process, and the signs of breast inflammation disappeared. Other lesions showed no recrudescence. T-DXd was administered seven times, and, at the stage of maximum contraction during the treatment period, a total left mastectomy and left axillary LN dissection were performed. Pathological examination then confirmed that tumor cells were no longer present in the left breast and left axillary LN. In this case T-DXd was highly effective for the local treatment of intractable, HER2-positive, breast cancer.

A 71-year-old female was referred to our hospital for abdominal distention and anorexia. Gastrointestinal endoscopy revealed wall thickening of the entire circumference. Abdominal CT scan showed diffuse thickening of the stomach, but there was no obvious metastasis. Scirrhous gastric cancer was strongly suspected, but endoscopic biopsies could not demonstrate malignant features. Staging laparoscopy was performed. There was a small amount of ascites and numerous peritoneal dissemination. She was diagnosed with gastric cancer pStage Ⅳ(pT4a, NX, H0, M1, P1, CY1)without HER2 positivity. We experienced a case of scirrhous gastric cancer in which staging laparoscopy was useful for histological diagnosis and staging.

A 73-year-old man was presented with epigastric pain and indicated high CA19-9 levels, and computed tomography detected a tumor in the uncinate process of the pancreas infiltrated duodenum and superior mesenteric artery. The patient was diagnosed with borderline resectable pancreatic carcinoma and received neoadjuvant chemotherapy with gemcitabine and S-1. During neoadjuvant chemotherapy, the patient also received radiotherapy to control duodenal bleeding. After neoadjuvant chemotherapy, stable disease(SD)was proven on the Response Evaluation Criteria in Solid Tumors(RECIST), and subtotal stomach-preserving pancreaticoduodenectomy was performed. The pathological findings showed pancreatic adenosquamous carcinoma. After 7 days postoperatively, hepatic metastasis was detected, and after 78 days postoperatively, the patient died.

A 78-year-old man who underwent esophagectomy for middle thoracic esophageal squamous cell carcinoma(pT1bN0M0, pStage Ⅰ)was diagnosed with lymph node recurrence 12 months after the initial surgery. He received chemoradiotherapy(5- fluorouracil plus cisplatin); however, the treatment was terminated at the middle of the treatment course because of progressive disease. He received chemotherapy(docetaxel plus 5-fluorouracil plus cisplatin)as a second-line treatment, which was also canceled due to serious adverse events. Partial response was achieved after the second therapy; therefore, surgical excision was performed. Thirteen months after the second surgery, he was diagnosed with second local recurrence with invasion to the trachea. Another course of chemotherapy(docetaxel[2-weekly]plus 5-fluorouracil plus cisplatin)was administered, which also achieved a partial response. Thus, surgical excision with partial tracheal resection and mediastinal tracheostomy was performed. He has been alive without recurrence for 6 months after the final operation. In case of postoperative solitary lymph node recurrence of esophageal cancer, long-term survival can be expected with multidisciplinary treatment.

We retrospectively examined 106 cases of tapentadol use in Japan in August 2014 for cancer pain at our hospital.The advantage of the opioid medication tapentadol is that its introduction is suitable in patients undergoing anti-cancer treatment because of the low incidence of gastrointestinal symptoms, with glucuronidation involved in the metabolism, and lack of interactions with other drugs.However, depending on the dosage form and presence of swallowing disorders, the administration should be considered carefully.

A66 -year-old man was diagnosed with chronic myeloid leukemia(CML). Imatinib treatment had been initiated, and a major molecular response(MMR)was achieved. The patient had anemia and was diagnosed with descending colon cancer. The patient was surgically treated, and then received postoperative adjuvant chemotherapy with UFT/LV. However, imatinib was not administered during that period. The patient could undergo postoperative adjuvant chemotherapy for 6 months without acute exacerbation of the CML.

Case: A man in his 60s reported upper abdominal pain; close examination revealed a tumor in the body-tail of the pancreas that was suspected to be infiltrating the stomach. Multiple liver lesions(S3, S4)were also detected. Histological examination by EUS-FNA showed poorly-differentiated carcinoma; thus, this case was diagnosed with unresectable pancreatic cancer with liver metastases(cT3, cN1[No. 7], cM1[P0, H1], cStage Ⅳ: JPS 7th). After 2 kinds of systemic chemotherapy(9 courses of GEM plus nab-PTX and 9 courses of modified FOLFIRINOX), obvious distant metastases or local progression did not appear and conversion surgery was scheduled. Although a metastatic lesion was identified at S5 of the liver just before the surgery, it was assumed that an R0 resection could be achieved; therefore, the operation(distal pancreatectomy with combined proximal gastrectomy, left adrenalectomy, lymph node dissection, partial hepatectomy of S5, and cholecystectomy)was performed. Histopathological examination showed squamous metaplasia of the epithelial tissue combined with glandular formation. This case was, thus, diagnosed as adenosquamous carcinoma of pancreas. This patient was discharged 90 days after the operation. The patient is still alive 2 years and 2 months since the first diagnosis.

Case 1 is a 68-year-old woman with locally recurrent rectal cancer(LRRC)developed 5 years after resection of primary rectal cancer. The tumor seized right lateral side in pelvic. We performed tumor excision after preoperative chemoradiation comprised external beam radiation with oral S-1(tegafur/gimeracil/oteracil). He has been relapse-free for 3 years 3months after surgery. Case 2 is a 74-year-old man with LRRC developed 2 years after resection of primary rectal cancer. The tumor was located dorsal to anastomosis site in pelvic. We performed abdominoperineal resection for LRRC after preoperative chemoradiation with oral S-1. He has been relapse-free for 2 years. It was suggested that preoperative radiotherapy combined with oral FU for local recurrence after rectal cancer may contribute to distant and local control.

A 67-year-oldman underwent lower anterior resection for rectal cancer andresection of liver metastatic tumor 5 years later. Seven years and 2 months after the initial surgery, a soft tissue mass was detected in the left diaphragm. Further retrospective review of CT scan images showedthat the diaphragmatic tumor was present just before the hepatectomy. Partial resection of the left diaphragm was performed, and no relapse has occurred since then for 2 years. Most cases of diaphragmatic metastasis are considered to arise from dissemination, but we considered this case as more likely to be hematogenous. When surgery is chosen to treat metastatic tumors of colorectal cancer, checking for other metastasis via preoperative imaging andperforming curative resection is important.

Regorafenib is an oral multikinase inhibitor; the CORRECTtrial evaluated its efficacy in patients with metastatic colorectal cancer following disease progression with standard therapies. However, regorafenib has toxicities that develop quickly. Few studies have reported the safe dose and usage of regorafenib to avoid these adverse events in Japanese patients. We examined the side effects and safe administration technique of regorafenib in this study. We administered regorafenib to 15 patients with metastatic colorectal cancer following disease progression with standard therapies. Between August 2013 and January 2014, 5 patients received 160 mg oral regorafenib once daily on days 1-21 of a 28 day course(group A). Between February 2014 and July 2015, 10 patients received initiating therapy with 120 mg regorafenib, with the intention of increasing the dose(group B). We retrospectively assessed side effects, number of dose courses, and total dose of regorafenib in both groups. The median dosing course was 5 coureses in group B, which was more than the 1 course in group A. The median total dose was 10,800 mg in group B, which is about 4 times as much as the 2,400 mg in group A. In group B, 7 out of 10 patients (70%)were successful in the dose escalation of regorafenib from 120 to 160 mg daily over 3-5 courses. The disease control rate was 40% in both groups. The rate of adverse events of Grade 3 or higher was 60% in group A, compared to 40% in group B within 2 courses. The overall survival time was 308 days in group B, which was significantly longer than the 168 days in group A. Initiating therapy with 120 mg regorafenib with the intention of increasing the dose improves safety and allows an increase in dosing courses, as well as in the total dose of regorafenib and overall survival time.

Skin metastases from esophageal cancer are comparatively rare but have poor prognosis. Here, we report a case of esophageal cancer metastases to the skin. A 70-year-old man was admitted to our hospital for nodules with ulceration in the nose, and biopsy revealed a metastatic carcinoma. FDG-PET indicated FDG accumulation in the skin, liver, and esophagus, while an endoscopic study of the upper gastrointestinal tract showed a type 3 tumor at the upper mid-thoracic esophagus. We diagnosed the patient with metastatic esophageal cancer and administered chemotherapy. Radiation therapy (40 Gy/20 Fr) was simultaneously administered for the tumor in the nose because the patient's quality of life (QOL) decreased daily owing to pain and bleeding caused by metastatic skin cancer. The radiation therapy reduced the size of the tumor in the nose, but the tumor had remained along with the presence of a scar 3 to 6 months after the start of radiation therapy. Radiation effectively promoted the QOL of our patient with skin metastases.

We report the case of a 70-year-old man with unresectable advanced gastric cancer because of invasion to the pancreas and multiple liver metastases. He could have continued with fourth-line chemotherapy by controlling intermittent bleeding from the cancer by means of 2 rounds of radiotherapy and trans-arterial embolization. The serum hemoglobin level declined to 4.5 g/dL during second-line chemotherapy. As the venous bleeding from the cancer was difficult to control by endoscopic hemostasis, radiotherapy with 40 Gy/20 fractions was applied to the cancer. We were able to restart chemotherapy after the hemostasis, but 6 months later, the serum hemoglobin level declined to 6.1 g/dL. Additional radiotherapy of 20 Gy/10 fractions was delivered to the tumor, and successful hemostasis was achieved; the serum hemoglobin level reached 7.5 g/dL. However, a contrast-enhanced CT, which was performed 3 weeks later, demonstrated extravasation from the cancer into the gastric cavity. We conducted trans-arterial embolization, and the patient no longer required transfusion. We planned to restart chemotherapy soon, but after 1 month, he died of pneumonia.

The safety and feasibility of chemotherapy for super-elderly patients (over 85 years old) has not been clarified yet. We report an extremely aged patient with recurrent rectal cancer that was successfully treated with capecitabine plus bevacizumab chemotherapy. An 85-year-old-woman underwent a Hartmann procedure for rectal cancer. Nine months after surgery, tumor markers were elevated. CT and MRI revealed liver metastases in S5 and S7. We administered capecitabine plus bevacizumab chemotherapy. Tumor makers were normalized after 2 courses, and the liver metastases disappeared after 6 courses. Although Grade 1 hypertension developed, no other adverse event occurred. Chemotherapy has been safely performed for 20 courses. The patient's PS score has been maintained at 0, and she has been under treatment as an outpatient. We suggest that capecitabine plus bevacizumab chemotherapy is an effective regimen for extremely aged patients with recurrent colorectal cancer.

A 67-year-old man had a gastric polyp diagnosed on screening. Atrophic changes in the upper gastric mucosa were seen on upper gastrointestinal endoscopy. In addition, endoscopy revealed in the middle area of the stomach wall a 10 mm polyp that was diagnosed as a carcinoid tumor through biopsy. Blood serum gastrin was elevated at 2,800 pg/mL.We diagnosed a Rindi Type 1 gastric carcinoid. The patient was planned to be treated with surgical laparoscopy assisted distal gastrectomy (LADG); however, the procedure was changed to intraoperative laparoscopy assisted total gastrectomy (LATG). Chromogranin-positive tumor pathological findings in the mucous membrane submucosa and in the muscularis mucosae endocrine cell micronest (ECM) were widespread. There was no obvious vascular invasion. After the surgery, the serum gastrin level normalized and the patient remains alive.

Approximately 20% of patients develop some complications after gastrectomy. These complications should be treated appropriately to achieve a positive outcome. The records of 6 patients with postoperative intra-abdominal abscesses treated with interventional radiology (IVR) were analyzed. The cause of abscess was anastomotic leakage in 4 patients and contaminated surgery after gastric perforation in 2 patients. Intra-abdominal abscesses were detected on postoperative day 12 (median), and an IVR-guided drainage tube was inserted with a median interval of 1 day. The drainage tube was kept in place for 26 days (median), and patients were discharged 6.5 days (median) after drainage tube removal. No patients were converted to open surgery. Early IVR-guided drainage was essential and effective for intra-abdominal abscess treatment after gastrectomy.

A 78 -year-old man with rectal cancer underwent abdominoperineal resection of the rectum. In the postoperative period, the patient experienced wound infection, leading to an abdominal wall hernia. Two years following surgery, a rise in the serum CEA level was seen. A metastatic tumor was detected in the right lung on chest CT. VATS right lung inferior lobe segmental resection was performed. After lobectomy, the serum CEA level continued to increase. Another metastatic tumor was detected in the right lung on chest CT. Chemotherapy with capecitabine, oxaliplatin, and bevacizumab was commenced. The erosive part of the abdominal wall scar hernia extended during the nine weeks of chemotherapy. The chemotherapy was then discontinued. In the follow-up CT scan, a right pleural recurrence, local recurrence in the pelvis, and a liver metastasis were detected. Chemotherapy was re-introduced 3 years after surgery. The erosive part of the abdominal wall hernia again began to spread with chemotherapy recommencement. Four months after restarting chemotherapy, the hernia ruptured, with a loop of the small intestine protruding out of it. The patient covered this with a sheet of vinyl and was taken by the ambulance to our hospital. The erosive part of the abdominal wall hernia had split by 10 cm, and a loop of the small intestine was protruding. As ischemia of the small intestine was not observed, we replaced it into the abdominal cavity, and performed a temporary suture repair of the hernia sac. Following this, bevacizumab was discontinued, and the erosive part reduced. We performed a radical operation for abdominal wall scar hernia repair 11 weeks after the discontinuation of bevacizumab.

The prognosis of esophageal cancer patients who undergo non-curative resection is very poor. Here, we retrospectively analyzed the factors associated with non-curative resection. Thirty-five patients with cT3 or T4 thoracic esophageal cancer treated with neoadjuvant chemotherapy or chemoradiotherapy followed by esophageal resection were included in this study. Among the 35 patients, 27 underwent curative resection (R0 group), while 8 underwent non-curative resection (R1R2 group). A comparison of the clinicopathological factors between groups revealed no significant differences in presurgical factors. The pathological T factor was significantly deeper in the R1R2 group than in the R0 group (p=0.0086). Histopathological response tended to be higher in the R0 group (p=0.055). An accurate preoperative diagnosis of T factor is important.

We report the cases of 2 patients with advanced rectal cancer who achieved pathological complete response to treatment with preoperative therapy. Case 1 was a 72-year-old man diagnosed with cT3N1M0 advanced rectal cancer. Neoadjuvant chemoradiotherapy with S-1 (120 mg/day) and radiation (50 Gy/25 Fr) was administered. Eight weeks after the last chemoradiation therapy, we performed laparoscopic Hartmann's operation. Case 2 was a 59-year-old man diagnosed with cT4aN0M0 advanced rectal cancer. He was treated with XELOX plus bevacizumab as neoadjuvant chemotherapy. Four weeks after 4 courses of treatment, he underwent laparoscopic Mile's operation. Neoadjuvant therapy was performed without any complications, and a pathological complete response was achieved in both patients. These cases demonstrated that neoadjuvant therapy can be a promising option for locally advanced rectal cancer.

It is sometimes difficult to differentiate between metastatic and primary liver tumors, when the liver tumor occurs simultaneously with a gastric cancer. We encountered a case of resected gastric cancer, which occurred concomitantly with intrahepatic cholangiocarcinoma after S-1 plus cisplatin chemotherapy, in a patient who was previously diagnosed with metastatic liver tumor before treatment. An 80-year-old man was admitted to our hospital because of epigastralgia. Endoscopic study of the upper gastrointestinal tract showed a type 3 tumor at the upper body of the stomach. A plain CT scan showed an irregular, low-density area, which was enhanced by contrast medium in the lateral segment of the liver. We performed an ultrasound- guided needle biopsy, because it was impossible to make a definitive diagnosis by dynamic CT, contrast-enhanced ultrasonography, and MRI. Immunohistochemical analysis for cytokeratin 7/20 resulted in 7 (+)/20 (-) for both the gastric cancer and the liver tumor. Therefore, we diagnosed the patient with gastric cancer, which occurred concomitantly with the metastatic liver tumor, and administered chemotherapy with S-1 plus cisplatin. After 3 courses of the regimen, a reduction in the size of mass was observed in the stomach and the liver. We subsequently performed left hepatectomy and total gastrectomy with lymph node dissection. Microscopic examination revealed the gastric cancer, which occurred simultaneously with the intrahepatic cholangiocarcinoma. The postoperative course was uneventful, and the patient remains well without recurrences.

The diagnosis of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas includes radiographic (CT, MRI) and endoscopic evaluation (ERCP, EUS). The treatment strategy is outlined in the 2012 International Consensus Guidelines (ICG). Herein, we report a case initially not indicated for surgery. Four months after the initial diagnosis, the cystic lesion transformed into a solid mass-like lesion visible on CT. FDG-PET showed abnormal FDG uptake at the same location. Surgical resection was performed immediately, and the tumor was diagnosed as IPMN with inflammation. FDG-PET showed a false-positive diagnosis for the malignancy in this case of IPMN.

Purpose: Here, we investigated the efficacy of chemotherapy with trastuzumab for patients with advanced or recurrent gastric cancer., Materials and Methods: We investigated the progression free survival (PFS) and overall survival (OS) of advanced gastric cancer patients who received first-line chemotherapy with trastuzumab in our hospital., Result: After first-line chemotherapy, the median PFS and median OS of patients who received trastuzumab combined with capecitabine/cisplatin chemotherapy was not significantly longer than those of patients who received trastuzumab combined with S-1/cisplatin chemotherapy (PFS, 138 [95%CI: 118-187] vs 169 [95%CI: 83-251] days, p=0.9684; OS, 393 [95%CI: 240-469] vs 466 [95%CI: 256-482] days, p=0.4703). After second-line chemotherapy, the median PFS of patients who received trastuzumab plus irinotecan chemotherapy was not significantly longer than that of patients who received trastuzumab plus paclitaxel chemotherapy (PFS, 63 [95%CI: 52-266] vs 58 [95%CI: 26-184] days, p=0.5447).

A 64 -year-old woman was referred to our hospital with a diagnosis of advanced rectal cancer with metastases to the left supraclavicular lymph nodes and paraaortic lymph nodes. Alow anterior resection was performed because of the symptoms of ileus. Subsequently, chemotherapy consisting of XELOX with bevacizumab was initiated as the first-line regimen, over 6 courses. Asecond -line regimen of FOLFIRI with bevacizumab was selected due to multiple lung metastases and the progression to both left supraclavicular and paraaortic lymph nodes. During the first 3 courses, the patient had no harmful side effects. Although the patient received adequate prophylactic antiemetic therapy and supportive treatment, grade 4 delayed emesis induced by irinotecan (CPT-11) occurred at 7 days after the fourth course of FOLFIRI chemotherapy. The patient was given total parenteral nutrition, after which she recovered substantially from the emesis. Delayed emesis is occasionally seen with irinotecan therapy and can be efficiently managed with adequate prophylactic antiemetic therapy. However, delayed emesis occurring one week after administration is rarely observed. Delayed emesis and subsequent therapy affect the quality of life (QOL) of the patient and subsequent therapy therefore, adequate attention and prompt management are required for delayed emesis.

We investigated the clinicopathological findings of 13 patients with perforated colorectal cancer. In 6 patients, the primary region affected by the cancer was the sigmoid or rectosigmoid colon, and 9 out of 13 patients had perforations at the location of the tumor itself. The Hartmann operation was performed in 5 patients, and D2 or D3 lymph node dissection was performed in 6 patients. The final stages of the 13 patients were as follows: 1 patient with stage II cancer, 5 patients with stage III cancer, and 7 patients with stage IV cancer. Postoperative death occurred in 1 patient. Five out of 7 patients with curative operations had recurrences; 2 patients had peritoneal disseminations, 2 patients had lung metastases, and 1 patient had paraaortic lymph node metastases. Even if patients underwent a curative operation, a high frequency of recurrence, especially of peritoneal dissemination, was observed. Therefore, we conclude that a careful follow-up is required.

A 61-year-old man was referred to our hospital because of gastric pain and weight loss.Upper gastrointestinal endoscopy revealed a superficial depressed (Type 3) tumor with pyloric stenosis.The tumor was diagnosed as tubular adenocarcinoma by pathological examination.Abdominal computed tomography showed enlarged paraaortic and No. 8a lymph nodes.The patient underwent distal gastrectomy (D0)and Roux-en-Y reconstruction.After surgery, chemotherapy combined with molecular targeted therapy (S-1+cisplatin[CDDP]+trastuzumab), based on overexpression of the HER2 protein in the primary tumor as assessed by immunostaining, was administered.After the molecular targeted chemotherapy, the carcinoembryonic antigen (CEA )levels decreased to the normal range and the enlarged lymph nodes were remarkably decreased in size. The patient is currently alive without progressive disease.

Purpose: The efficacy of chemotherapy for advanced or recurrent gastric cancer in patients who were aged over 75 years was investigated., Materials and Methods: Progression free survival (PFS) and overall survival (OS) of advanced gastric cancer patients who received first-line chemotherapy with TS-1 plus cisplatin or TS-1 in our hospital from 2009 to 2013 were determined. The patients were divided into two groups: H and L. H group patients were aged over 75 years, and L group patients were aged less than 75 years., Results: Median PFS and median OS of patients in the H and L groups who received TS-1 plus cisplatin chemotherapy were not significantly different. PFS was 77[range, 13-211] days and 139[range, 53-211]days for the H and L groups, respectively(p=0.141), while OS was 523[range, 22-1,030] days and 402 [range, 322-623] days, respectively (p=0.620). Similarly, median PFS and median OS of patients who received TS-1 chemotherapy were not significantly different between the H and L groups. PFS was 103[range, 51-156]days and 152.5[range, 85-278]days for the H and L groups, respectively (p=0.230), while OS was 414 [range, 224-714]days and 605[range, 452-1,077] days, respectively ( p=0.1337)., Conclusion: PFS and OS were not significantly different in younger patients with advanced gastric cancer who received TS-1 plus cisplatin or TS-1 chemotherapy compared to that in similarly treated elderly patients with advanced gastric cancer.

A regimen of capecitabine plus oxaliplatin(XELOX)has become one of the standard postoperative adjuvant chemotherapies for colon cancer. However, few tolerability studies have been conducted in Japan. In this study, we retrospectively examined treatment continuation and the adverse events that occurred during 8 courses of postoperative adjuvant chemotherapy with XELOX in 21 patients with colorectal cancer who had undergone curative resection. The completion rate for 8 courses of treatment with XELOX was 71.4%, while the median relative dose intensities of capecitabine and oxaliplatin were 85.0% and 75.0%, respectively. Although the incidence of subsequent Grade 3 or higher hand-foot syndrome was 14.3%, the rate of peripheral neuropathy was 0%. Our hospital had a high rate of XELOX treatment continuation, suggesting that XELOX adjuvant chemotherapy would be well tolerated in clinical practice as well.

Background: In our hospital, the starting dose of S-1 for patients over 75 years of age with advanced gastric cancer was determined by body surface of area, creatinine clearance, performance status(PS)and the presence of complications. The objective of this retrospective study was to investigate the proper administration of S-1 in elderly patients by comparing patients given a standard dose of S-1 to those given a reduced dose., Methods: Twenty patients participated. Six patients were administered S-1 at a standard dose(standard group)and fourteen patients with at a reduced dose(reduced group). Safety, feasibility and anti-tumor effects were assessed., Results: Three cases of grade 3 adverse events were found in the standard group, and one case was found in the reduced group. Time to treatment failure was 4. 4 months for the standard group and 8. 2 months for the reduced group. The overall response rate was 25% in the standard group and 30% in the reduced group., Conclusions: It is important to reduce S-1 administration to patients over 75 years of age with caution, and take into account the patient's renal function, PS and Ccr complications.

In this review, we discuss recent issues about cancer stem cells, especially in solid tumors. Cancer stem cells show the ability to self-renew; and they possess multi-potential differentiation and tumorigenic potential. Cancer stem cells are reported to show resistance to anticancer drugs and radiotherapy, and therefore, they are involved in progression, recurrence, and metastasis in cancer. The existence of cancer stem cells in leukemia has long been known, since early times. In recent years cancer stem cells have been identified in solid tumors of breast, prostate, lung, brain, colon, and pancreas, owing to the development of identification techniques using cell surface markers. Although many features remain to be addressed, it is expected that cancer stem cells could be a main target for cancer therapy in the near future.

The patient was a 75-year-old male, who was diagnosed with type 3 advanced gastric cancer and bulky lymph node metastasis. Two courses of neoadjuvant chemotherapy (S-1, CDDP) which showed a partial remission and distal gastrectomy were performed. Although he received S-1 medication as adjuvant chemotherapy, lymph node recurrence appeared 6 months after the operation. Radiation therapy at a total dose of 65 Gy (10MV X ray, 2.5 Gy/day × 26 Fr) selectively targeting for recurrent lymph node metastasis with S-1 medication were applied. There were no adverse effects during chemoradiation therapy and the metastatic node showed regression (30 mm to 15 mm). Sixteen months passed from chemoradiation, and the patient remains alive with no signs of relapse without any treatment after the chemoradiation. Therefore, our case suggests that chemoradiation therapy could be an effective treatment for recurrent lymph nodes metastasis in gastric cancer.

We report a case of liver metastasis from gastric cancer that was effectively controlled with stereotactic radiation therapy (SRT). A 77-year-old man underwent total gastrectomy, splenectomy, cholecystectomy and D2 dissection in February 2007 for type 3 gastric cancer in the upper third area that was diagnosed well to moderately differentiated adenocarcinoma and Stage II (T3 (SE) N0 H0 P0 CY0 M0). He suffered from the liver and peritoneal metastases with ascites in December 2007, so S-1 was administered. Ascites was disappeared, but liver metastasis was enlarged. Therefore, SRT (total of 52.8 Gy per 4 fractions) was performed for the liver metastasis. A clear reduction in tumor size was noted and he was presently alive with no sign of recurrence after 2 years. Immediately after SRT, grade 3 neutropenia and grade 2 AST/ALT elevation were occurred. Grade 2 pneumothorax and pleural effusion were recognized in August 2009 as tardive adverse event. It is thought that SRT is one of effective treatments for liver metastasis from gastric cancer.

We have recently experienced a case in which S-1/CDDP combination therapy proved remarkably efficacious for a rapid, extensive lymph node recurrence with metastasis into a Virchow node that had developed after resection of advanced gastric carcinoma accompanied with a marked invasion of the esophagus. The patient, a woman aged 73, underwent a total gastrectomy upon left thoracolaparotomy for a gastric carcinoma at the cardia with a 5-cm involvement of the esophagus. On day 65 post-operation, a diagnosis of Virchow node and para-aortic lymph node recurrence was made on the basis of CT scan findings. Of tumor markers checked, CEA and CA19-9 were noted to be increased to as high as 37.55 ng/mL and 3,235 U/mL, respectively. The patient received three courses of S-1/CDDP combination therapy, with a consequent noticeable contraction of the Virchow node and enlarged para-aortic lymph node. Further, she was given two courses of S-1 therapy, which resulted in normalization of tumor markers. The patient has since been on continued chemotherapy without any sign of recurrence.

An 88-year-old woman, who had undergone distal gastrectomy for Stage IIIA gastric cancer, was diagnosed with recurrent abdominal lymph node metastasis 11 months after surgery. Creatinine clearance of this patient calculated by Cockcroft-Gault method was 44 mL/min and renal function was impaired, so we reduced the administration dosage to 50 mg/day. S-1 was administered for two weeks followed by one week rest. This schedule induced grade 2 anorexia and fatigue after one week administration, so it was converted to one week administration followed by one week rest. By this dosage and administration schedule, a partial response(PR)was continued for about four years without any adverse reaction. This successful case might indicate that it was important for older adult patients with gastric cancer to consider not only appropriate reduction of the dosage but also shortening of S-1 administration.

A 71-year-old woman with peri-anal pain and anal bleeding was found to have a tumor in lower rectum in colonoscopic examination, which was histologically diagnosed as poorly differentiated adenocarcinoma. Computed tomography and magnetic resonance imaging showed a tumor 5 cm in diameter deeply infiltrating mesorectum, and swelling of intra-pelvic lymph nodes. At the first operation, infiltration of the tumor was so deep that a complete surgical resection was considered to be difficult, and only a sigmoid colostomy construction was done. After chemo-radiation therapy of 50.4 Gy and 5-FU plus levofolinate calcium (Isovorin) infusion, the tumor was reduced in size and lymph nodes were extremely decreased. The patient underwent an abdominoperinial resection 6 weeks after the end of chemo-radiation, and pathological examination revealed a complete replacement of tumor with necrosed tissue, and no viable tumor cell was found. Poorly differentiated adenocarcinoma of the colon is reported to be highly malignant and associated with poor prognosis. Preoperative chemo-radiation therapy can be a promising candidate for adjuvant treatment of locally-advanced poorly differentiated adenocarcinoma of the rectum.

Orbital metastasis from breast cancer is relatively rare. We report a case of successfully treated orbital metastasis from breast cancer by radiation therapy. This 50-year-old female patient underwent a mastectomy (Bt+Ax) of her left breast in October 2000. The diagnosis was invasive lobular carcinoma, Stage IIB (T2N1M0). Retroperitoneal and bladder metastases were found five years after the operation, and chemohormonal therapy was done. Right orbital swelling appeared 8 months after chemohormonal therapy, and orbital metastasis from breast cancer was diagnosed by MRI. Radiation therapy (a total 30 Gy) was administrated, and the swelling disappeared. An MRI was performed 16 months after radiation therapy and did not detect any metastases. A complete response (CR) was achieved. No sign of recurrence was found, and a sufficient local control has remained for 2 years after radiation therapy.

The authors analyzed the 25-patient who underwent a removal of W-spiral (WS) catheter after cessation of hepatic arterial infusion (HAI) chemotherapy. The catheter was easily removed in all cases, which resulted in improved patients' quality of life as well as preserved patency of hepatic arteries. However, arterial bleeding was occurred postoperatively in one case, which needed a surgical treatment. Although HAI using WS catheter and subsequent removal of the catheter is a reasonable strategy, a careful management of some complications should be considered.

Multiple regional metastases due to colon cancer usually show poor prognosis. Various treatments such as chemotherapy and radiation therapy are not sufficient, and the outcome is generally poor in many cases. We report here on a patient with multiple regional metastases who was successfully treated with several therapies and remains still alive. A 69-year-old man presented with fever and epigastralgia. A colonoscopy revealed primary sigmoid colon cancer. A computed tomography showed multiple hepatic metastases, and metastases to supraclavicular, mediastinal and para-aortic regional lymph nodes. The bone metastases were detected by scintigram. He was treated with combination chemotherapy of 5-FU via hepatic artery and CPT-11 by systemic administration. The primary tumor had completely disappeared (complete response), and metastases to liver and lymph nodes showed a remarkable shrinkage (partial response) after the chemotherapy. In contrast, bone metastases showed progressive growth (progressive disease). Radiation therapy and bisphosphonate infusion for bone metastases were achieved, and the treatments have controlled the growth of the metastases. Primary tumors and metastases are still controlled well for 3 years after the initial chemotherapy.

In order to establish a reasonable prophylactic hepatic arterial infusion (HAI) chemotherapy following curative resection of colorectal liver metastases, the authors performed a randomized control study comparing two regimen. A weekly 5 hour-administration of 5-FU (1500 mg) which was repeated for 8 weeks showed a comparable effect to a continuous infusion group with an identical total dosage of 5-FU. Furthermore, adverse events were observed in only several patients of each group with low grade severity, suggesting that this simple regimen with a weekly HAI is promising. We also analyzed the clinical course of patients receiving HAI using a W spiral catheter which has a shape memory alloy in its tip. The catheter was implanted angiographycally without coil fixation to the vascular wall, which allowed us to remove the catheter after cessation of the scheduled chemotherapy. In all of the patients, the catheters were easily removed without any complications. A 3D-CT angiograph revealed that the hepatic arteries were well patent in all of the patients with a 3.3 Fr type catheter. HAI chemotherapy is basically an invasive treatment. In consideration of its efficacies as well as limitations, a reasonable approach is needed from the viewpoint of patients' quality of life.

A 67-year-old woman was diagnosed by a series of examinations as having ascending colon cancer with synchronous multiple liver metastasis. She underwent an operation after the PTPE (percutaneous transhepatic portal vein embolization) to the right lobe of the liver, as we considered that the metastatic liver tumors were all resectable. In the surgery, we identified seven peritoneal tumors and a lymph node swelling. We then pathologically diagnosed them as being peritoneal dissemination (p3) and lymph node metastasis (n2(+)). Therefore, hepatectomy was not performed, but the right hemicolectomy (D2) and insertion of an arterial infusion catheter into the hepatic artery were performed. In addition, all seven peritoneal tumors were resected. After being discharged from hospital, she was treated as an outpatient with the combination chemotherapy of systemic intravenous administration (5-fluorouracil or 5-FU, 2,500 mg/month) and hepatic arterial infusion (5-FU, 1,500 mg/week) for 16 months. Then, she continued to take tegafur uracil (300 mg/day) by mouth for 39 months. The metastatic liver tumors were gradually reduced and resulted in complete response (CR) for 20 months after the operation. She has been in remission for the past 5 years without recurrence. During the treatment, we noticed a complete atrophy that was sustained in the right lobe of the liver to which PTPE was performed. As far as hepatic arterial infusion chemotherapy is concerned, our case study was interesting and effective.

Analysis of thymidine phosphorylase (TP), thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) or their mRNA are now being applied before-the start of chemotherapy to predict the therapeutic efficacy. Although these key enzymes were reported to be basically independent, we found the differences in TS between cancer and adjacent mucosa was reversely correlated with the difference in DPD. We found a significant relationship between TP and DPD in 52 patients with colon cancer. TP and DPD were measured by EIA. Statistical analysis was made non-parametrically using Statview 5.0. TP was significantly higher in cancer (78 +/- 58 U/mg protein) than in the adjacent mucosa (43 +/- 24 U/mg protein). Conversely, DPD was significantly lower in cancer(43 +/- 32 U/mg protein) than in the adjacent mucosa (55 +/- 18 U/mg protein). The amount of TP and DPD in cancer were not correlated with the clinicopathological parameters. TP was significantly (r = 0.70) correlated with DPD in cancer but not in adjacent mucosa. The difference in TP between cancer and adjacent mucosa was significantly (r = 0.69) correlated with the difference in DPD as well. In the colon cancer with low TP, DPD in cancer is lower than in the adjacent mucosa, however, the more TP in cancer increased, the higher the DPD in cancer increased over that in the adjacent mucosa. Modulation of DPD as well as TP may be necessary when high levels of TP or DPD are measured in the cancer tissue. The understanding of the basic relationship among these key enzymes will improve the 5-FU-based chemotherapeutic prediction.

The aim of this study was to evaluate the effect of the local therapy for colorectal liver metastases on overall survival. Seventy-two patients who had resected liver metastases from colorectal cancer during the period from 1982 to 2001 were evaluated for survival. There was no significant difference in overall survival by either surgical method for colorectal liver metastases or postoperative arterial infusion chemotherapy. However, the 5-year survival rate of resected metachronous liver metastases with postoperative arterial infusion chemotherapy was 44.9%, and that for patients with no extra hepatic metastases was 57.4%. Patients who have metachronous liver metastases from colorectal cancer should therefore be considered for postoperative arterial infusion chemotherapy. It is necessary to improve the outcome for cases that have extra hepatic metastases.

Dihydropyrimidine dehydrogenase (DPD) and thymidylate synthase (TS) in cancer are considered to play key roles in the sensitivity to 5-FU-based chemotherapy. We measured DPD activities and TS content in cancer and normal mucosa obtained from 59 patients with colorectal carcinomas and examined their relationship and clinicipathological relevance. DPD activity was significantly decreased in cancer compared to that in adjacent mucosa, irrespective of the clinicopathological parameters (p < 0.0001), while TS content was significantly increased in cancer (p < 0.0001). DPD activity in cancer correlated with that of the normal mucosa (r = 0.57, p < 0.001), but no correlation was found between TS content of normal mucosa and cancer. The DPD activity difference between cancer and normal mucosa was significantly correlated with difference in TS content (r = 0.70, p < 0.0001). These results suggest that the reduction of DPD activity is associated with the elevation of TS content, which may be connected with the development of 5-FU resistance and the effectiveness of biochemical modulation through the stabilization of TS inhibition with folic acid in colon carcinoma.

We studied dihydropyrimidine dehydrogenase (DPD) and thymidylate synthase (TS), key enzymes in regulating the pharmacokinetics and chemosensitivity to 5-FU, in 36 breast cancer patients as a control group and 18 patients as a 5-FU group, in which 5-FU was given orally for 2 weeks before surgery at a dose of 200 mg/day. Cancer tissues with adjacent normal tissue were sampled and stored until the assay. The DPD activity and TS amount were determined according to the radio-enzymatic assay and radiobinding assay, respectively. The DPD activity was significantly higher in breast cancer than in the adjacent breast tissue. This finding was observed in T1 and T2, node negative and ER positive breast cancers in the control group as well as in the 5-FU group. The DPD activity in T3 was significantly lower than in T1, and that of the adjacent breast tissue in T3 was significantly higher than in T1; therefore, the tumoral/non-tumoral ratio of DPD activity was significantly lower in T3 than T1. TS was significantly elevated in both groups, without significant differences. The clinical implication of elevated DPD activity in T1, T2, node negative or ER positive breast cancer compared to the respective normal breast tissue activity remains to be studied, because it is still unclear whether or not the tumoral DPD activity regulates the local concentration of 5-FU within the tumor. The amount of TS and DPD activity was not influenced by the oral administration of 5-FU for 2 weeks at the dose of 200 mg/day.

We report a case of pelvic recurrence of advanced rectal carcinoma, presenting a favorable response with a low dose (25 mg/m2) of CPT-11 (Irinotecan) combined with topical hyperthermia for relapse after treatment with 4 cycles of high-dose (100 mg/m2) CPT-11 chemotherapy alone. This combination therapy was safely carried out on an outpatient basis. The degrees of recovery of the left lower limb pain and edema, and of serum CEA reduction were comparable to those in high-dose chemotherapy alone. No significant adverse effects were encountered in the thermo-chemotherapy attempted. Since hyperthermic treatment enhances the cytotoxic effects of CPT-11 in vitro, topical hyperthermia with low-dose CPT-11 therapy may produce a response comparable to that in high-dose CPT-11 chemotherapy alone. However, an optimal dose and comparative study with other chemotherapeutic agents would be needed. This regimen may be advantageous in the maintenance of quality of life for the palliation of postoperative pelvic recurrence since this treatment can be performed on an outpatient basis.

Three rectal cancer patients were treated with arterial infusion chemotherapy through the internal iliac artery. Two patients with pelvic recurrences unresectable after APRA were treated with intensive chemotherapy and the other patient with neoadjuvant chemotherapy. In all cases, 5-FU (500 mg/ body/day) was administered continuously for 5 days or 14 days. We attempted three methods for this procedure which were a bilateral catheterization to the internal iliac artery, a single catheterization with an embolization to the other internal iliac artery and a single catheterization without the embolization. As the result of this treatment, in the resected specimen with neoadjuvant case, histological necrosis was found in 50% in the main tumor and the metastatic lymph nodes. One patient with pelvic recurrence showed a partial response in CT imaging, but died one year later of the recurrence around the external iliac artery. The other patient with pelvic recurrence treated with the bilateral catheterization had no efficacy on CT imaging, but his CEA level has decreased at present. It was concluded that arterial infusion chemotherapy was effective for advanced rectal cancer and the pelvic recurrences. However, the efficacy of this treatment is limited to the area to which the drugs are delivered. Thus, it is important that the method and the location of the catheterization are determined adequately for each case.

A 77-year-old female with left hemiplegia caused by cerebral infarction and with mild senile dementia was admitted for further examination of hematological abnormalities. She was diagnosed as acute myelogenous leukemia (AML-M5a) according to French-American-British classification. Since intensive combination chemotherapy seemed difficult, she was treated with oral administration of cytarabine ocfosfate (200 mg/day, for 14 days), a cytidine deaminase-resistant derivative of Ara-C, resulting in complete remission. Major side effects were nausea, vomiting and appetite loss, but their incidences were reduced tolerably when cytarabine ocfosfate was given just before sleeping. Cytarabine ocfosfate might be useful to treat AML in elderly patients having certain complications such as cerebrovascular disease.

The property of pluronic F127 (PLF) as a base for an anticancer agent, mitomycin C (MMC) was evaluated. A weighed amount of PLF and MMC were slowly added to cold water and mixed completely. The solution was warmed to 37 degrees C and MMC containing PLF gel was formed. The cumulative amount of MMC which was released from the gel during a 3-hour period was calculated. 5.5 percent of MMC was released from PLF-MMC gel which contained 20 or 25% PLF and 3.8% MMC from PLF-MMC gel containing 30% PLF. Intraperitoneal (i.p.) administration of large amount of PLF gel alone in rabbits or mouse revealed severe hepatorenal toxicity, and acute i.p. administered LD50 of PLF was supposed to be between 1.7 g and 5.0 g/kg body weight in mouse. Further evaluation of gradual releasing property of PLF is needed.

Patients with unresectable liver cancer (primary and metastatic) were treated with a newly-devised arterial infusion chemotherapy using Cis-DDP and its antidote Sodium thiosulfate (STS). The patients consisted of 4 with primary hepatoma and 1 with metastatic liver cancer originated from intestinal cancer. For the purpose of reducing unfavourable side effects without changing anticancer effect, Cis-DDP was infused into hepatic artery through the catheter while STS being administered systemically. According to Koyama and Saito's criteria, 2 of 5 patients showed partial response (PR) and the others showed no change (NC). The median survival time after onset of therapy was 6.6 months ranging from 2 to 11 months in all the patients. The myelosuppression and renal toxicity, which were considered to be the most serious side effects of Cis-DDP, were not found and liver function was not affected in all the patients. However, all the patients complained of nausea and vomiting. Thus, our experience has indicated that this newly devised infusion chemotherapy is a promising method for treating unresectable liver cancer, although further efforts are necessary for reducing the gastrointestinal toxicity.