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Patients undergoing outpatient cancer chemotherapy are prescribed"as-needed"medication(antiemetics, laxatives, and antibiotics)as a form of self-care for early response to side effects. We conducted a questionnaire survey to clarify whether prescribed"as-needed"medication contributes to the relief of patients' anxiety about cancer chemotherapy. We obtained responses from 80 breast cancer patients who received neoadjuvant or adjuvant chemotherapy from 2019-2021". As- needed"medication was used by 68(85.0%)of patients. Fifty patients(73.5%)who used"as-needed"medication experienced relief of anxiety associated with chemotherapy. Also, 10 patients(83.3%)who did not use"as-needed"medication experienced relief of anxiety associated with chemotherapy". As-needed"medication may contribute to the relief of anxiety associated with chemotherapy in breast cancer patients.

A 51-year-old male presented with swelling on the left side of his neck. A diagnosis of thoracic esophageal cancer(Lt type 5a, squamous cell carcinoma, T3N4[16LN]M1[skin, bone, retroperitoneum, lung], cStage Ⅳb)was made, and treatment with a combination of 5-FU plus CDDP and pembrolizumab was initiated. After the 1st round of chemotherapy, there was an increase in metastases in the left cervical lymph node and skin, along with the development of back pain because of an L3 lumbar spine metastasis. Palliative radiotherapy(Σ24 Gy/6 Fr)was administered for all lesions. Subsequently, pembrolizumab was administered for the persistent decline in white blood cell and neutrophil counts. After 6 courses of pembrolizumab, computed tomography(CT)revealed an absence of lesions. Positron emission tomography/CT demonstrated no significant accumulation, prompting a diagnosis of complete response(CR). The patient is currently under pembrolizumab therapy and continues to remain in a state of CR.

Immune checkpoint inhibitor(ICI)combination therapy is the first-line of treatment for unresectable or recurrent esophageal cancer. The frequency and mechanism of immune-related adverse events(irAEs)associated with ICI are still unclear and may require differentiation from other diseases. The present study examined a patient with unresectable, advanced esophageal cancer treated with cisplatin plus 5-fluorouracil(CF)plus nivolumab as the first-line treatment. CF therapy was discontinued after 1 course owing to adverse events. Nivolumab was continued, but progressive anemia stemming from pure red cell aplasia(PRCA), an irAE of nivolumab administration, was observed. Nivolumab was discontinued, but later, interstitial pneumonia also developed, and pulse steroid therapy was begun. After steroid tapering, both the PRCA and interstitial pneumonia improved. At present, about 6 months have elapsed since the last nivolumab administration without any PRCA recurrence or evidence of tumor progression.

The patient described herein was diagnosed with left breast, endometrial, and early gastric cancers at 49, 53, and 57 years of age, respectively. Magnetic resonance cholangiopancreatography performed when she was undergoing treatment for cholecystitis at 50 years of age showed local pancreatic duct dilatation in the pancreatic head. She was followed in the Department of Gastroenterology at our hospital for an intraductal papillary mucinous neoplasm(IPMN). An abdominal computed tomography scan obtained at 59 years of age revealed dilation of the main pancreatic duct in the pancreas body and tail, therefore an endoscopic ultrasound-guided fine needle aspiration was performed. She was diagnosed with pancreatic cancer and underwent a laparoscopic distal pancreatectomy. The postoperative course was uneventful; however, the pancreatic cancer recurred and she died approximately 14 months postoperatively. Reports of multiple cancers associated with IPMNs are rare, yet we managed a patient with a pancreatic head IPMN complicated by metachronous quadruple carcinomas( breast, endometrial, gastric, and pancreatic cancers).

We analyzed 4 cases who experienced extravasation of anthracyclines and had dexrazoxane therapy in our hospital. Concerned drugs were 2 adriamycin and 2 amrubicin cases and all cases received steroid ointment therapy, and no cases showed severe condition such as skin ulcer. As dexrazoxane is known to enhance bone marrow suppression of anti-cancer drugs, the nadir of neutropenia and thrombocytopenia was observed from day 10 to 17 in our cases. We made a domestic manual and have used in various professionals. Dexrazoxane would contribute to the reduction of skin damage due to extravasation if we could manage bone marrow suppression successfully.

An-81-year-old man presented to another doctor complaining of epigastric pain. He was referred to us after the laboratory data revealed a high serum CEA and abdominal ultrasonography showed the space occupying lesion in the left liver. Abdominal CT revealed advanced gallbladder cancer infiltrating the liver and colon and found annular pancreas surrounding the descending portion of duodenum. We chose partial hepatectomy(S4a+S5), extrahepatic bile duct resection with hepaticojejunostomy and partial colectomy. Pathological diagnosis of the tumor was pT3N1M0, gallbladder cancer. The patient was discharged on the 21 days after operation. The frequency of malignant tumors in adult annular pancreas are not revealed. But some cases present with adult annular pancreas complicating the biliary tract tumor. We experienced a case of advanced gallbladder cancer with adult annular pancreas and report our case and review the pertinent literature.

The patient was a 42-year-old woman. After 4 courses of capecitabine therapy for right chest wall recurrence of breast cancer, ER(+, 10-15%), PgR(-), HER2(-), she underwent pleurodesis using OK-432 for increased right pleural effusion. On the 12th day after pleurodesis diffuse infiltrative shadows in the right lung, and frosted shadows in both lungs, were observed, and she was diagnosed with drug-induced lung injury. About 3 weeks after administration of prednisolone 1 mg/ kg a tendency for improvement in lung injury was observed, but the patient died of breast cancer progression. Drug- induced lung injury by pleurodesis carries the risk of delaying resumption of chemotherapy. We report this case with a review of the literature.

A 35-year-old man who had fever and stomachache was referred to our hospital. He underwent surgery and chemoradiotherapy for neuroblastoma as a child and subsequently developed leukemia. Frequent blood transfusions and bone marrow transplants were performed due to anemia. Abdominal contrast CT scan and contrast MRI showed tumorous lesions with a diameter of 60×42 mm in liver S6, and a tendency to increase in a short term. There was also hemochromatosis in the liver. We considered it a malignant tumor and performed a right lobectomy. Pathological examination diagnosed the tumor hepatic angiosarcoma. The postoperative course was fine and he was discharged without complications. But multiple liver metastases appeared 6 months after surgery. We performed chemotherapy but he passed away 10 months after surgery. Hepatic angiosarcoma is a rare disease among liver malignancies and has a very poor prognosis. As for the cause of hepatic angiosarcoma, many of them are unknown, but chronic exposures such as vinyl monomers have been reported in some cases. Hemochromatosis has been reported as a background factor for malignant tumors such as hepatocellular carcinoma. In this case it is possible that it contributed to the development of hepatic angiosarcoma.

We experienced a case of solitary liver tumor that developed after renal cancer surgery. Before the surgery, the tumor was suspected to be hepatocellular carcinoma and was subsequently diagnosed as renal cancer liver metastasis. An 81-year-old man underwent retroperitoneal laparoscopic nephrectomy for left renal cancer in January 2017. After that, the cancer had not recurred, but a follow-up CT examination 1 year after the operation revealed a 42 mm-sized tumor in the liver S6. Liver biopsy was performed for diagnosis, but in histopathological findings, the diagnosis was difficult to make. Eventually, the preoperative final diagnosis was hepatocellular carcinoma. Laparoscopic partial hepatectomy was performed in June 2018, and in the histopathological findings of the resected specimen, the final diagnosis was the liver metastasis from renal cancer. Generally, the prognosis of renal cancer with liver metastasis is poor, but if complete resection is possible, it is recommended in the Clinical Practical Guideline for Renal Cancer. In recent years, the number of minimally invasive laparoscopic surgeries for hepatectomy has increased, and its safety has also improved. Therefore, resection is diagnostic treatment for cases where, like this case, preoperative diagnosis for solitary liver tumor is difficult. Laparoscopic hepatectomy could be one of the effective treatment strategies.

The case is a 59-year-old woman. A medical examination revealed a high CA19-9, she visited a nearby hospital. Abdominal echo showed thickening of the gallbladder wall, and she was referred to our hospital for further examination. EUS-FNA was performed and a biopsy of #12 lymph node revealed undifferentiated cancer, which was diagnosed as gallbladder cancer. FDG-PET showed accumulation of FDG in the gallbladder lumen and swollen lymph nodes around the aorta. Therefore, the cancer was considered unresectable and chemotherapy was performed. FDG-PET was re-examined after 4 courses of gemcitabine plus cisplatin combination chemotherapy. As a result, the lymph node swelling contracted, the accumulation of FDG disappeared, and surgery was scheduled. Extended cholecystectomy and extrahepatic bile duct resection were performed. She was discharged 22 days after the surgery without complications. Histopathological examination showed fibrotic tissue at the gallbladder and lymph nodes, but no residual tumor cells. There are no recurrences 11 months after surgery. Although the prognosis of gallbladder cancer with para-aortic lymph node metastasis is generally poor, it is suggested that conversion surgery with multimodality treatment including preoperative chemotherapy may be a useful therapeutic strategy.

Antiemetic therapy with aprepitant, palonosetron, and dexamethasone is recommended for moderately emetogenic chemotherapy in several guidelines to prevent chemotherapy-induced nausea and vomiting. There is a lack of information about the efficacy and safety of antiemetic therapy with aprepitant, palonosetron, and dexamethasone in patients treated with oxaliplatin in Japan. We recruited patients with untreated colorectal cancer who underwent oxaliplatin-based chemotherapy. All patients were treated with aprepitant, palonosetron, and dexamethasone. The complete response and complete protection rates were analyzed. A total of 52 patients were enrolled in this clinical trial. The complete response rate overall, and in the acute and delayed phases was 92.3%, 98.1%, and 92.3%, respectively. The complete protection rate overall and in the acute and delayed phases was 73.1%, 86.5%, and 73.1%, respectively. Grade 3-4 non-hematological toxicity did not occur. Antiemetic therapy with aprepitant, palonosetron, and dexamethasone is effective and safe in patients treated with oxaliplatin.

A 60's man came to our hospital for jaundice. Contrast-enhanced CT showed irregular thickening of the hilar bile duct, and the lymph nodes(LN)were swollen from the hilar to the abdominal aorta. These LNs showed similar findings in endoscopic ultrasonography(EUS), and fine needle aspiration cytology(FNA)was performed on the enlarged No.13LN to diagnose LN metastasis of hilar cholangiocarcinoma. Since the peri-aortic LN was also markedly enlarged, it was considered to be metastasis, and was diagnosed as unresectable hilar cholangiocarcinoma with distant LN metastasis. When gemcitabine/cisplatin therapy(GC therapy)was started, tumor markers normalized and LN decreased in 4 months. We performed GC therapy for a total of 12 cycles and did not re-exacerbate. Cholangioscopy revealed that bile duct stenosis at the hilar portion had improved. We have determined that curative resection is possible and performed surgery. We confirmed that No.16b1LN was negative by pathological diagnosis during surgery and performed left hepatic caudate lobectomy, extrahepatic cholangectomy, and biliary reconstruction. Diagnosis was pT2aN1(n8a)M0, fStage ⅢB, and pR0. After surgery, adjuvant chemotherapy with S-1 was continued.

The case presented is a 72-year-old male with no history of hepatitis B or C. Dynamic CT revealed a 2 cm mass in the liver (S8), with arterial phase hyperenhancement and delayed phase washout. The patient underwent an open S8 subsegmentectomy. The mass was pathologically diagnosed as well-to-moderately differentiated hepatocellular carcinoma(T2N0M0, Stage Ⅱ). At 2 years 10 months postoperatively, MRI showed a 4 cm mass in contact with the pancreatic head, inferior vena cava, and duodenum. The mass had moderate FDG uptake on PET scan, and early phase hyperenhancement and delayed phase washout on dynamic CT. We performed laparoscopic mass resection, suspecting lymph node metastasis of the hepatocellular carcinoma, which was confirmed by the pathological diagnosis. The patient has survived for 1 year without recurrence. Lymph node metastasis of hepatocellular carcinoma is rare. It is unclear whether surgical resection is feasible in such cases. Here, we report a case of lymph node metastasis of hepatocellular carcinoma resected by laparoscopic surgery.

A 50-year-old woman was diagnosed as having pancreatic head cancer with multiple hepatic metastases. FOLFIRINOX therapy was initiated. After completing 18 courses of therapy, partial remission(PR)was achieved based on images, and surgery was then planed. The subtotal stomach-preserving pancreaticoduodenectomy and hepatic S7 partial resection were performed. Macroscopically, complete resection was achieved. Regarding pathological findings of the primary lesion and hepatic metastatic lesions, fibrous formation and hyalinizing condition induced by chemotherapy were noted; moreover, complete disappearance of cancer cells was detected. However, metastasis of poorly differentiated adenocarcinoma was detected in 12b lymph node tissue. One month after the surgery, postoperative adjunctive chemotherapy with S-1 was initiated. However, new hepatic metastasis was detected 3 months after the surgery. Although recurrence treatment was initiated, the disease progressed, and the patient died 11 months after the surgery.

We report a case of conversion surgery for a locally advanced unresectable(UR-LA)pancreatic cancer that was radically resected after S-1 therapy. A 65-year-old man visited a referral physician because of fatigue and liver dysfunction. A CT scan revealed a mass in the pancreatic uncinate process that was suspected to be superior mesenteric artery(SMA)infiltration and was diagnosed as UR-LA pancreatic cancer. GEM nab-PTX therapy was initiated but was discontinued after 2 courses because of adverse events. The treatment was switched to S-1 monochemotherapy. After that, the tumor did not progress for around 1.5 years, and the patient was referred to our hospital for surgical treatment. As the contact between the tumor and the SMA was considered to be less than half-round, we made a diagnosis of borderline resectable(BR-A)pancreatic cancer. Subsequently, we performed a pancreaticoduodenectomy with partial resection of the portal vein and achieved R0 resection. The patient received adjuvant chemotherapy with S-1 and showed no signs of recurrence for 10 months after surgery.

A 56-year-old man underwent distal pancreatectomy due to pancreatic body carcinoma in 2009, at the age of 46. There had been no sign of metastasis and recurrence until levels of tumor markers began to increase in January 2014. PET scan, CT scan, and other examinations showed a possible carcinoma in the pancreas head. The patient underwent total remnant pancreatectomy. The tumor was located in the uncinate process of the pancreas with infiltration of the portal vein. The pathological diagnosis of the tumor was moderately differentiated adenocarcinoma. The ductal lumen structure was relatively maintained and the cytoplasm was comparatively clear. Since its pathological findings were similar to those observed in 2009, the tumor appeared to be a recurrence of the tumor resected at that time. The patient had received postoperative chemotherapy and remains alive in 2019 without recurrence. While there is evidence that surgical resection for the recurrence of other cancers such as colon cancer may improve patient survival, it remains unclear if surgical resection of recurrence in the remnant pancreas after pancreatectomy of pancreatic cancer is feasible. We report a case with long survival after surgical resection of a pancreatic carcinoma recurrence in the remnant pancreas.

In this paper, we report our work in home visit rehabilitation based on the philosophy of community rehabilitation. Our team consists of in physiatrist, physical therapist, occupational therapist, clinical psychologist, public health nurse, and social worker. First, our team visited people with disabilities who lived in the community to determine their various needs and the causes of their potential challenges. Second, we offered support to ensure that people with disabilities realized better living, employing all accessible rehabilitation technologies and social resources. The focus of this paper is the case of a female patient with cervical spinal cord injury who changed her mind regarding living better and actively participating in society, from merely persisting to achieve"meaningless physical recovery." We recommended house renovation for easy movement and the use of assistive devices, which enable people with disabilities to move safely in their living space. We also advised the patient to use" Care lifts, which are equipment for moving the body up and down for transfer and movement,"or independent bathing and changing wheelchairs. After the intervention, she could actively participate in volunteer activities to help persons with disability when they go out.

Kawasaki City has been developing its community rehabilitation system for people with disabilities since 1996. In this system, the home visit rehabilitation project plays a main role. This project involves teams comprising physiatrists, physical and occupational therapists, psychologists, speech therapists, and social workers. They visit a patient at his/her residence to provide rehabilitation of the patient's living model after medical rehabilitation at a medical facility. The teams then perform comprehensive rehabilitation using interdisciplinary procedures to improve the patient's quality of life in their home and social activities. In this paper, we outline the home visit rehabilitation project being implemented in Kawasaki City, including the role of the social worker who manages the overall home visit rehabilitation services.

Patients with amyotrophic lateral sclerosis(ALS)often experience reduced social participation because of their need for constant medical and physical care. In the community, care teams that consist of home care workers, nurses, and other professionals provide support for these patients. However, these care teams may not have sufficient knowledge of ALS. Therefore, these are requests to us from some of these teams when they want to get specific advice on support for patients with ALS. In this study, we report our experience of home visit rehabilitation for an adult with ALS who aimed to continue their Social participation. We carried out comprehensive assessment and provided expert advice on seating systems, communication and transportation aids, and building a relationship with the care team.

Since 1996, Kawasaki City has been constructing community rehabilitation programs for persons with disabilities. In 2000, a comprehensive community rehabilitation plan for Kawasaki City was established, including the activities that would realize it. This community rehabilitation plan aims to provide people with disabilities with comprehensive rehabilitation for improving their quality of life in the community through maintaining or rebuilding lifestyles. Its basic philosophy is represented by the key words "comprehensiveness," "expertise," and "community-based." We entrust it with our own financialresources. Over the last 20 years, the City government and the non government organization have collaborated to develop this plan. The homevisit rehabilitation service is the most important and main program in the comprehensive community rehabilitation system in Kawasaki City.

We report a case of a malignant lymphoma that was treated with laparoscopic resection of the pericardium. A 43-year-old woman was diagnosed with asymptomatic extrahepatic nodule by medical examination. CT, MRI, and PET-CT examination indicated a solitary fibrous tumor(SFT). Therefore, we performed laparoscopic resection for definitive diagnosis and treatment. The tumor was located in the upper abdominal wall and adhered to the liver; hence, we additionally performed partial resection of the liver. Thereafter, we dissected the tumor from the abdominal wall alongwith a part of the diaphragm. Because intraoperative pathological examination revealed more malignancy than was preoperatively expected, we also resected a part of the pericardium. The laparoscopic approach to the pericardium can be performed safely because of its magnification effect, which is an advantage of laparoscopic surgery.

We encountered a case of type 4 gastric cancer with esophageal invasion that responded to neoadjuvant chemotherapy containing S-1 and oxaliplatin(SOX)followed by surgery, which could be curative resection. A 46-year-old man was referred to our hospital because of abnormal upper gastrointestinal series findings. He was diagnosed with type 4 advanced gastric cancer with esophageal invasion, cT4b(diaphragm)N2M0, Stage ⅢC, and 3 courses of neoadjuvant SOX therapy were administered. Adverse events were minor. After NAC, the primary lesion and lymph nodes showed marked reductions on CT; total gastrectomy and subtotal thoracic esophagectomy were performed. The pathological response to NAC was evaluated as Grade 2 in the primary tumor and Grade 3 in the lymph node; overall, NAC showed considerable antitumor effects. The final diagnosis was ypT3N0M0P0CY0H0, StageⅡA, and was judged as curatively resected. Currently, we are continuing to administer adjuvant chemotherapy containing S-1.

A safety evaluation of chemotherapy is performed by CTCAE. It is the evaluation by health care workers, and distress evaluation by patient himself is not included in it. Therefore, a health care worker underestimates patients' distress. This study was carried out to identify the patients' characteristics underlying differences between safety evaluation and distress evaluation. The patients who met the criteria were 72 in number. They were divided into 2 groups. Group A(17 patients)included patients who demonstrated difference between safety evaluation and distress evaluation. Group B(55 patients)included patient who did not show difference between safety evaluation and distress evaluation. The patients who visited a hospital were evaluated for QOL, depression screening, CTCAE(safety evaluation), and PRO-CTCAE(distress evaluation). A meaningful difference was observed between depression screening, QOL-ACD(physical status, psychological status, face scale, and total), and the number of items of side effect by PRO-CTCAE through a univariate analysis. A meaningful difference was observed for QOL-ACD(physical)in logistic regression analysis(odds ratio=1.47, p=0.013). It is suggested that having physical distress reflected by the QOL evaluation before chemotherapy results in the difference between safety evaluation and distress evaluation.

Chemotherapy for unresectable pancreatic cancer has moved from using gemcitabine (GEM) and/or S-1 to using 5- fluorouracil plus Leucovorin plus oxaliplatin plus irinotecan (FOLFIRINOX) or GEM and nano albumin-bound paclitaxel (nab- PTA). We administered weekly PTA 80mg/m2 (days 1, 8, 15 every 4 weeks) in 22 patients with both GEM and S-1 resistance before nab-PTX became available through medical insurance in Japan. This regimen was used as a second-line in 3 cases, as the third-line in 14 cases and as a later line in 5 cases. The mean number of chemotherapy courses was 2.7, and the mean dose intensity was 86.1%. Postponement and dose reduction was made in 15 and 5 cases, respectively. The best overall response was 1 PR, 5 SD, 15 PD and 1 NE. The response rate was 4.5%, and disease control rate was 27.3%. The median progression-free survival was 1.7 months, and the median overall survival was 4.6 months. The main adverse events included anorexia, general malaise, and peripheral neurotoxicity and they were tolerable. This study wherein nab-PTX plus GEM was one of the standard therapies, indicated that the PTX alone was effective in pancreatic cancer patients who were resistant to GEM and S-1.

A 64-year-old man visited his physician complaining of bilateral gynecomastia and left shoulder pain. Chest X-ray showed multiple bilateral masses in the lung, and he was referred to our hospital. Radiographical findings, elevation of serum total hCG, and histological findings of the cervical lymph node revealed multiple pulmonary, nodal, and brain metastases of poorly differentiated carcinoma of an unknown primary site with choriocarcinoma components. He was administered a regimen of reduced bleomycin, cisplatin, etoposide combination(reduced BEP regimen)to reduce the risk of acute respiratory failure with intra-alveolar hemorrhage related to post-chemotherapy early tumor necrosis. After chemotherapy, the tumor marker hCG levels were almost restored to normal levels, and radiography showed he had achieved a clinical partial response.

The patient was a 59-year-old man. He was admitted to our hospital because of increasing anal pain with induration of the perianal region. There were large secondary orifices with mucous discharge on the left side of the perineal resion and buttock. We diagnosed adenocarcinoma on analysis of a biopsy specimen from induration of the perianal region. Pelvic CT and MRI showed that the tumor spreaded within the pelvis, with invasion of the prostate and sacrum. We performed neoadjuvant chemoradiotherapy preoperatively. After chemoradiotherapy, the tumor reduced in size greatly. We performed abdominoperineal resection and massive resection of skin of the perianal region. The defect of the pelvic floor and perianal skin was repaired using skin flap. The surgical margin was tumor free. Neoadjuvant chemoradiotherapy was considered effective for locally advanced carcinoma associated with anal fistula.

An 81-year-oldwoman with advancedgastric cancer was referredto our hospital. Preoperative contrast-enhancedCT revealeda roundcalcification of the splenic hilum with 15mm in diameter as a splenic artery aneurysm. She underwent transcatheter arterial embolization(TAE)for the splenic artery aneurysm. Celiac artery angiography showedcollateral arterial network of the spleen from left gastric artery. Surgery for the gastric cancer was performed1 4 days after TAE. We cut the right gastric andbilateral epigastric arteries. After the left gastric artery clamping, we performedintraoperative indocyanine green(ICG)fluorography. ICG fluorography confirmedthat the bloodflow of the upper thirdof the stomach andspleen were maintained. We safely performed distal gastrectomy, and the postoperative course was uneventful.

Withdrawal of chemotherapy because of side effects may be due to"problems with toxicity"or"patient refusal"."Problems with toxicity"is intended to secure patient safety and decisions about it are primarily made by the oncologist. On the other hand,"patient refusal"is influenced by the degree of distress the patient is experiencing and the patient's preference. Providing sufficient medical information is essential in decision making, because it is a decision made by the patient. In addition, the perception of side effects has changed owing to progress in supportive therapy in recent years. In particular, cancer patients are concerned about changes in appearance. In our study(4/2015 to 3/2016), chemotherapy was withdrawn because of side effects during treatment for solid carcinomas in 8%(4/51)of the patients. Two of these patients experienced liver function disorders, and 2 developed interstitial pneumonitis. Patient refusal was observed in 2%(1/51)of the patients.

Regional lymph node recurrence without distant metastasis after the initial treatment of breast cancer is a relatively rare event. The optimal management for regional lymph node recurrence is poorly understood. We retrospectively evaluated 21 patients who developed regional lymph node recurrence between January 1, 2003 and December 31, 2014. The median interval between regional lymph node recurrence and distant metastasis was 1.0 years(range, 0.4 to 2.5 years). On followup, 15 cases(71.4%)were found to eventually develop distant metastases. Median follow-up time after lymph node recurrence was 1.8 years(range, 0.4 to 20.3 years). The 2-year survival rate after regional lymph node recurrence was 65.5%. The mean distant-disease-free interval was 2.2 years in patients with estrogen receptor(ER)-positive tumor(n=10)and 0.7 years in patients with ER-negative tumor(n=11). The distant-disease-free interval after regional lymph node recurrence was significantly shorter in patients with ER-negative tumor than in patients with ER-positive tumor(p=0.008). The 2-year survival rate after regional lymph node recurrence was significantly lower in patients with ER-negative tumor(33.3%)than in patients with ER-positive tumor(100%, p=0.016). This study revealed that regional lymph node recurrence after initial treatment is associated with an increased risk of distant metastasis and death and ER-negative tumors are indicative of a poor prognosis.

Many investigators have attempted to reach a consensus, though with limited evidence available, on second-line chemotherapy for advanced pancreatic cancer. Specifically, treatment consists of gemcitabine-based regimens and 5-FU-based regimens. The regimen that is not used for first-line chemotherapy will be used as second-line chemotherapy. In Japan, S-1 is frequently used in 5-FU-based regimens. When the FOLFIRINOX regimen is used as first-line chemotherapy, gemcitabine is recommended as second-line chemotherapy. On the other hand, when nab-PTX/gemcitabine is used as first-line chemotherapy, S-1 is recommended as second-line chemotherapy.

We enrolled 62 elderly patients( ≥70 years of age) with colorectal cancer who had undergone surgery and postoperative adjuvant chemotherapy at our department and analyzed the overall surviva(l OS) and disease-free surviva(l DFS) to identify the patients who responded to treatment. Postoperative adjuvant chemotherapy was performed with oral anticancer agents, including doxifluridine( 5'-DFUR), uracil/tegafur( UFT), and UFT/Leucovorin( LV); all patients also received polysaccharide K( PSK), an immunomodulator, in combination with chemotherapy. The 3-year OS and DFS rates for all patients were 83.4% and 78.6%, respectively, with no significant differences in these rates based on the chemotherapeutic agents used. The patients were assigned to low and high groups on the basis of the median cut-off values of each clinical laboratory parameter and the data obtained were subjected to univariate analysis. The results of the univariate analysis suggested that carcinoembryonic antigen (CEA) and cancer antigen 125 (CA125) levels were significant prognostic factors. Further multivariate analysis using Cox regression analysis identified the preoperative CEA level alone as an independent factor. When stratification analysis was performed using a preoperative CEA level of 4.0 ng/mL as the cut-off value, the results indicated that the outcome of patients with a high preoperative CEA level may be 8-fold worse than that of patients with a low preoperative CEA level. For these patients, the use of chemotherapeutic drugs that elicit a more potent antitumor effect should be considered.

A 52-year-old woman had a primary neuroendocrine tumor, Grade 2(NET G2)with multiple liver metastases and a mesenteric tumor. Since no drugs were approved for NET at that time in Japan, we treated her with sunitinib after approval by the Ethics Committee of Mie University Hospital and obtaining informed consent. Sunitinib was administered at a daily dose of 37.5mg/day, but the dose was reduced to 12.5mg/day because of thrombocytopenia(G3)and neutropenia(G3). CT revealed stable disease after 3 months of treatment, but disease progression was observed after 11 months. The non-hematological toxicity was hypertension(G3), which was controlled with antihypertensive agents. Although there are no previous reports of the treatment of well-differentiated NET with sunitinib in Japan, sunitinib may be effective against this disease.

The protein human endoplasmic reticulum oxidoreductin 1-like α(hERO1-L α) is a hypoxia-inducible endoplasmic reticulum resident oxidase that regulates the redox state of various proteins via protein disulfide isomerase. The major histocompatibility complex(MHC) class I molecule contains intramolecular disulfide bonds. hERO1-L α is expressed within normoxic cells at very low levels, but may be induced in hypoxic cells such as tumor cells in response to low oxygen availability. We therefore examined whether hERO1-L α affects the oxidation state and expression level of MHC class I in the colon cancer cell line SW480. We generated SW480 cells in which hERO1-L α was overexpressed or knocked down. The surface expression of MHC class I molecule was upregulated in the hERO1-L α-overexpressing SW480 cells and downregulated in the hERO1-L α-knockdown SW480 cells. Moreover, the oxidized form of MHC class I was increased in the hERO1-L α-overexpressing SW480 cells, and the hERO1-L α-knockdown SW480 cells exhibited an impaired response to cytotoxic T lymphocytes. These data suggest that hERO1-L α regulates immune response via modulation of MHC class I expression and oxidation, and that hERO1-L α may act as a new predictive factor for cancer immunotherapy.

A 60-year-old female was diagnosed as advanced gastric cancer with multiple bone, neck and mediastinal lymph node metastases. As a primary chemotherapy, she was treated with S-1(50 m g/body, twice daily for 4 weeks, followed by a 2- week rest). After 3 courses of S-1, she developed a disease progression with pulmonary lymphangitic carcinomatosis and disseminated intravascular coagulation(DIC). Therefore, she received second-line chemotherapy of irinotecan(CPT-11 150 mg/m2, biweekly). Within 3 weeks of starting the treatment, the clinical and laboratory signs of DIC were dramatically resolved. There have been no previous reports of irinotecan alone showing such remarkable effectiveness in a patient with 5- FU-resistant gastric cancer with DIC.

SN-38, an active metabolite of irinotecan (CPT-11), is glucuronidated into SN-38G mainly by UGT1A1, during detoxification. However, significant interindividual pharmacokinetic variability in SN-38 is caused by factors, including inherited predispositions that may affect the function and expression of UGT1A1. Moreover, these individual differences can contribute to the development of clinical conditions, such as severe leucopenia and diarrhea. Similar to SN-38, bilirubin is excreted into bile after being glucuronidated by UGT1A1. Thus, bilirubin is metabolized by a mechanism similar to that of SN-38. This suggests that the bilirubin level may be an indicator of the adverse effects caused by CPT- 11. On the other hand, the ratio between the AUC of SN-38 and the AUC of SN-38G (AUCSN-38/AUCSN-38G) indicates the ability of SN-38 to be glucuronidated, and is known to correlate with leucopenia and diarrhea. However, many blood sampling points are required to calculate these AUCs. Therefore, the daily estimation of the AUCSN-38/AUCSN-38G values of individual patients is not practical at the clinical level. Thus, the objectives of this study were as follows: (1) to establish whether or not the total bilirubin level is a useful indicator in predicting the development of CPT-11 toxicity. (2) to investigate the correlation of SN-38/SN-38G (the ratio of the serum concentrations of SN-38 and SN-38G) with AUCSN-38/AUCSN-38G. Based on the result of this investigation, it will be discussed whether or not SN-38/SN-38G may be used as an alternative to AUCSN-38/AUCSN-38G. This study included 14 patients with small cell lung cancer or non-small-cell lung cancer, in whom serum concentrations of CPT-11, SN-38, and SN-38G were measured by HPLC. The results demonstrated a significant correlation between the total bilirubin levels prior to chemotherapy and the logarithmic values for AUCSN-38/AUCSN-38G (r2=0.852). Among the cases with high values for both the total bilirubin level and the AUCSN-38/AUCSN-38G ratio, none of the patients had grade-3 diarrhea, while many cases tended to have grade-3 to -4 neutropenia. Additionally, the results of regression analysis suggest that SN-38/SN-38G (2 hr) and SN-38/SN-38G (4 hr) might be preferable as a predictive index for AUCSN-38/AUCSN-38G. These findings suggest that the total bilirubin level and SN-38/SN-38G, 2 to 4 hours after administration might be used as indicators to predict CPT-11-induced neutropenia. These indicators are likely to contribute to the pharmacogenetic analysis of UGT1A1 genes, as well as individualized therapy, in future, and further studies on this subject are expected.

Objective: We evaluated retrospectively single-agent S-1 chemotherapy in non-small cell lung cancer patients in clinical practice., Methods: Sixteen consecutive patients treated with single-agent S-1 for NSCLC between July 2005 and June 2007 at the Department of Thoracic Surgery, Tsuchiura Kyodo General Hospital. The treatment schedule comprised oral administration of S-1 at 80-120 mg/day. One cycle of S-1 consisted of consecutive administration to 14 (10 cases)or 28(6 cases)days followed by a 14-day rest., Results: Patients profiles were: M/F: 11/5, median age 68 years old(range 51-83), PS 0/1/2/3: 2/6/5/3, adeno/squamous/large: 13/2/1, clinical stage 3A/3B/4: 3/4/9, prior chemotherapy regimens 0/1/2/3/4: 2/3/4/5/2, prior surgery/radiation: 12/5 were performed. Median number of delivered cycles was 5 cycles(range 1-13). Grade 3 hematological toxicities were anemia(6%)and thrombocytopenia(6%). Grade 3 non-hematological toxicities were nausea(6%)and vomiting(6%). Response of 13 patients could be evaluated after 2-4 cycles of S-1. Four partial responses were observed, for a response rate of 31%. The survival time was 67-852 days(average 14.0 months), 1-year survival rate was 74.0%, median time to progression was 4.6 m, and 1- year progression free survival was 25.0%., Conclusion: Single-agent S-1 chemotherapy has modest activity and is the one of the important regimens and tolerable for elderly, poor-PS, recurrent patients with NSCLC in clinical practice.

Purpose: The purpose of this study was to evaluate the efficacy of the combination of hepatic arterial infusion therapy and FOLFOX for colorectal cancer with multiple unresectable liver metastases causing severe liver dysfunction., Subjects and Methods: The subjects were 13 colorectal cancer patients who had undergone resection of the primary tumor, and showed multiple, unresectable liver metastases and severe liver dysfunction. They consisted of 8 men and 5 women, with a median age of 63(29-77)years. Of these patients, 7 and 6 had colon and rectum cancers, respectively. They had an average of 8(3-22)liver metastases of 4.6(1.5-14.5)cm in diameter. During surgery, extrahepatic lesions were found in 3 patients(P in 2, and CY in 1). The preoperative serum LDH and ALP levels were high, at 1,099 (322-1,418)and 1,011(644-2,384), respectively. The follow-up period was approximately 500(248-928)days. Only 5-FU in FOLFOX4 or 6 m therapy was infused into the hepatic artery, and LV and L-OHP were injected into the central venous port about every two weeks. Response rates and adverse events were evaluated according to the RECIST criteria and CTCAE ver 3.0, respectively., Results: The therapy was performed 14(6-22)times, with a response rate of 84.6% for liver metastases, facilitating hepatectomy in 1 patient. The overall response rate was 61.5%, with 1 patient dying of the primary cancer on the 265th day. Grade 3 adverse events were neutropenia and anorexia in only 1 patient each, and no adverse events were specific to hepatic arterial infusion., Conclusion: Since the follow-up period after this therapy was still short, only 13 patients have received the therapy. However, it appears that it can be performed relatively safely, and is effective for the control of extrahepatic lesions as well. Therefore, this therapy provides good control, and can be a treatment option.

A 77-year-old man was admitted to our hospital complaining of general malaise, loss of appetite and hemoptysis. Chest X-ray film and computed tomography (CT) scan showed right-sided pleural effusion with lung tumor. Succeeding upper gastro-intestinal fiberscopy and cystoscopy revealed poorly-differentiated adenocarcinoma of the stomach and urothelial carcinoma of the bladder. Repeated treatment with 100 mg/body of S-1 on day 1 followed by 60 mg/m(2) of cisplatin on day 8 was effective in this patient.

Combined chemotherapy is considered essential for further improvement of the cure rate of head and neck carcinoma. Chemotherapy in cases of head and neck carcinoma is administered with one of two objectives: as adjuvant therapy to increase the survival rate after radical treatment in the early stage of the disease, and to prolong the survival rate in cases with advanced or recurrent carcinoma. There is, however, no clear answer to the question of how these objectives can be accomplished. In our department, we use S-1 chemotherapy to achieve these goals. Our modified S-1 administration method until 2005 consists of a 3-week drug administration period followed by a 2-week drug-free period (3w-2w), or a 2-week administration period followed by a 2-week drug-free period (2w-2w). We determined the usefulness of the optimum administration method by examining the rate of completion of the treatment, and its safety and therapeutic efficacy. S-1 administration was used in 68 cases of head and neck carcinoma until 2005. As a result, the rate of completion of the treatment and its safety were high. Further randomized controlled trials with a high degree of accuracy are needed to confirm whether or not our treatment method would improve the survival rate/ prolong the duration of survival in these patients.

The oral alkylating agent, temozolomide (Temodal: TMZ), is the only anticancer drug that has been shown in a phase III study to improve survival in glioblastoma (GBM) when administered with concomitant radiotherapy. Pharmacokinetic studies have documented relatively high concentrations of TMZ in brain tumors and cerebrospinal fluid (20-40% of the area under the plasma concentration curve), and other studies have demonstrated that TMZ is effective for treatment of various brain tumors, including recurrent and newly diagnosed glioma, primary CNS lymphoma, metastatic melanoma, and neuroblastoma. Molecular markers that predict a favorable response to TMZ plus concomitant radiotherapy include methylguanine methyltransferase (MGMT) promoter methylation patients with GBM and chromosome 1p/19q deletion in patients with anaplastic oligodendroglioma or low-grade glioma. Myelosuppression, nausea and constipation are relatively frequent in patients undergoing treatment with TMZ, and prophylaxis against Pneumocystis carinii pneumonia should be instituted. This article will summarize and discuss these issues as well as review ongoing and anticipated studies of TMZ in combination with other anti-cancer therapies.

A 78-year-old woman was admitted to our hospital because for pancytopenia and splenomegaly. The bone marrow examination revealed hairy cells in 11.6% of all nucleated bone marrow cells. Hairy cells were positive for tartaricresistance acid phosphatase (TRAP) staining, CD2, CD11c, CD19, CD20, sIgD, CD25, CD103 and k chain. In addition, abdominal enhanced computed tomography (CT) demonstrated splenomegaly and multiple nodular early stains in the spleen. She was diagnosed as having typical hairy cell leukemia (HCL). The patient was treated with cladribine infused continuously for 7 days at a dose of 0.09 mg/kg/day, which induced partial remission without severe adverse effects. Purine analogs such as cladribine and pentostatine are considered first-line agents for patients with HCL. Treatment with cladribine achieved a high overall response rate for patients with HCL and was safe even in elderly patients like ours. It is necessary to observe carefully the complications of severe infections, second malignancies and relapse of HCL after treatment with cladribine.

The toxicity of platinum-based chemotherapies is a common problem for patients with advanced urothelial carcinoma. We performed a prospective study to assess the efficacy and safety of the combination chemotherapy of methotrexate, epirubicin and nedaplatin (MEN) as first-line treatment in patients with advanced urothelial carcinoma. Eligible patients had pathologically proven measurable unresectable or metastatic urothelial carcinoma. Between February 2003 and February 2006, 11 patients with a mean age of 70 years were treated every 3 weeks with methotrexate (30 mg/m(2) on day 1) and epirubicin (50 mg/m(2) on day 1) and nedaplatin (80 mg/m(2) on day 2). A median of 2.6 cycles were administered. None of the 11 patients achieved a complete response (CR), but 6 patients (55%) achieved a partial response (PR) with a median duration of response of 10 months, and no responses occurred in 4 patients. The median survival time was 11 months. Grade 4 hematological toxicities included neutropenia in 1 case (9%), thrombocytopenia in 2 cases (19%) and anemia in 1 case (9%). None of the 11 patients had febrile neutropenic episodes, and no toxic death was observed. Our results suggest that the combination chemotherapy of methotrexate, epirubicin and nedaplatin (MEN) was effective and acceptable treatment in patients with advanced urothelial carcinoma.

A 73-year-old man was admitted to our hospital complaining of general malaise, loss of appetite and body weight loss. Chest X-ray film showed left-sided pleural effusion. Computed tomographic (CT) scan of the chest also demonstrated left-sided pleural effusion with lung tumor and lymphnode swelling. Repeated treatment with 60 mg/m(2) of cisplatin on day 1 followed by 80 mg/m(2) of irinotecan on days 1 and 8 were effective in this patient.

The application of radiofrequency ablation (RFA) for liver metastasis of colorectal cancer has not yet acquired an established status in clinical cancer therapy research. Removing as much tumor tissue as possible is desirable, but some cases do not allow optimal surgical ablation due to general condition of the patient and tumor status. We introduced endoscopic RFA for liver cancer in 2003, and have applied the procedure to 6 cases with H1 or H2 liver metastases of colorectal cancer to which surgical ablation could not be applied due to the poor general health of patients. Mean tumor diameter was 22.9 mm, and mean number of tumors per patient was 1.2. Tumor location was: S4, n = 2; S5, n = 1; S4, n = 1; S7, n = 2; and S8, n = 1. Mean frequency of session was 3.0. No complications occurred in any cases, and no reoperations were required. Although no recurrence of tumors in the vicinity of ablation was observed, 2 cases of each lung metastasis and intrahepatic recurrence were identified. Intrahepatic recurrence underwent hepatic arterial infusion (HAI) chemotherapy for simultaneous metastatic hepatic tumors (H2) prior to RFA, and relapses occurred in the metastatic focus where the efficacy of HAI was observed. At this point, 2 deaths were reported, 1 each from cancer and other diseases, and mean duration of survival after the procedure was 451.2 days. These results indicate that endoscopic RFA with good local control should be an available treatment for cases involving colorectal cancer with metastasis to the liver in which surgical ablation is difficult to apply.

The patient was a 72-year-old female with gastric carcinoma. A liver metastatic recurrence was detected 27 months after operation. Although temporary partial responses were obtained by each effective chemotherapy, which was a combination chemotherapy with 5'-DFUR and TXT, TS-1 and TXL, the metastatic lesion proved refractory to all of them. Then we tried combination chemotherapy consisting of CDDP 30 mg/m2 and CPT-11 60 mg/m2, respectively (day 1 and 15, every 4 weeks). A partial response was achieved and continued for 8.5 months, and her complaints abated and quality of life improved. Although gastro-intestinal symptoms and bone marrow suppression were observed as side effects, they were within a tolerable range and did not interfere with the combination therapy. This regimen appears to be feasible and effective for recurrent gastric carcinoma refractory to other regimens.

The authors have been devising novel dosage forms with a sustained release of aqueous cis-platinum (CDDP), following the concept of a drug delivery system. First, we prepared biodegradable vehicles with clinically available fibrin and gelatin materials that were used with the ultraviolet (UV)-cross linking technique. Then, each carrier was loaded with CDDP to form new drugs. We basically studied degradability of the carrier, a release profile of the CDDP, and antineoplastic activities with the system. The new drugs gradually disintegrated to dissolve completely within 10-15 days, and 80-90% of the loaded CDDP was delivered in the same period. The released CDDP showed antineoplastic activities, both in vitro and in vivo, while the CDDP directly reacted with human plasma revealed little evidence of anticancer function. The scanning electron microscopic studies suggested that the release profile of the CDDP was closely related with the degradability of the carrier. We presume that UV-modification techniques play important roles in preparation of the new drug carriers. Our newly devised CDDP releasing system is promising as novel cancer chemotherapy.

A 57-year-old male underwent a total gastrectomy with D1 lymph node dissection for gastric carcinoma. The main tumor was located in area UM, measuring 15 x 6 cm and was classified as type 5. Histopathologically, the cancer cells invaded the subserosal layer with a moderately differentiated tubular pattern. Lymph node metastases (No. 1, 3, 7 and 9) were detected. Lymphatic involvement was revealed (ly 2). Three years after the first surgery, a liver metastasis (area S4) with a diameter of 30 mm was detected by abdominal ultrasonography. Percutaneous ethanol injection therapies (PEIT) were performed twice for the lesion. After PEIT, a TS-1 intake program (80 mg/day, for 4 weeks) was started for the metastatic lesion. Both treatments were effective. The patient has survived without recurrence for over 5 years after the total gastrectomy.

In order to evaluate the utility of combination chemotherapy with intra-peritoneal infusion of CDDP and continuous intravenous infusion of 5-FU, we performed this therapy in 23 primary gastric cancer patients with peritoneal metastasis. CDDP was administered intraperitoneally at a dose of 70 mg/m2 over 2 hours on day 1, and 5-FU was continuously administered intravenously at a dose of 700 mg/m2 for 5 consecutive days from day 1, respectively. This treatment was given twice. Median survival time with this treatment was 343 days, and the depth of invasion was selected as an independent prognostic factor according to multivariate analysis. Five patients (21.7%) have survived more than 3 years. Major toxicities were less than Grade 2 except for two patients with each anemia (Grade 3) and venous thrombosis (Grade 3), respectively. This regimen appears to be feasible and effective for gastric cancer patients with peritoneal metastases. Long term survival may be obtained in patients without adjacent organ invasion.

We report a case of gastrointestinal stromal tumor (GIST) with multiple hepatic metastases that responded to tyrosine kinase inhibitor STI571. A 30-year-old woman underwent total gastrectomy on July 10, 1998, with a diagnosis of submucosal tumor of the stomach. Pathological analysis of the primary lesion revealed strong expression of c-kit, and it was diagnosed as GIST. The patient underwent tumor excision due to peritoneal recurrence on May 1, 2000 and November 13, 2000. On August 8, 2001, multiple liver metastases were detected by abdominal CAT scan. Treatment with STI571 at a dose of 400 mg/day for 28 days was initiated on September 14, 2000. CAT scan showed rapid tumor shrinkage after 3 weeks of treatment (reduction rate of 56%) and the response continued after 7 weeks of treatment (reduction rate of 71%). Thus, we evaluated the response as PR. Leukocytopenia, edema, diarrhea and nausea were observed; however, all toxicities were mild and tolerable. This case suggests the efficacy of STI571 for metastatic GIST.