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The case was a 70-year-old man of highly advanced gastric cancer with 2 liver metastases(S3, S8)and pancreatic invasion. Three courses of S-1 plus L-OHP(SOX therapy)were performed, and total gastrectomy and combined resection of the spleen and body and tail of the pancreas and partial resection of the liver S3 and S8 were performed after reduction of primary tumor and liver metastasis. S-1 therapy was continued for 1 year as postoperative adjuvant chemotherapy. Left adrenal metastasis was detected by CT, 1 year and 6 months after the operation. PET-CT revealed no other areas suspected of recurrence, so left adrenalectomy was performed through the retroperitoneal space. Radical resection was not achieved because adhesions and scarring from the previous surgery were severe. Paclitaxel plus Ramucirumab was started and after 10 courses, the disappearance of the tumor shadow was observed on enhanced CT, and PET-CT. Three years and 3 months after the initial surgery and 1 year and 8 months after resection of adrenal metastasis, the patient is alive without recurrence.

We experienced a case of rapidly progressing transverse colon NEC that was treated with laparoscopic right hemispherectomy. A 72-year-old man underwent a follow-up lower gastrointestinal endoscopy at another hospital after a polyp resection. The examination showed a surrounding mass with stenosis of the intestinal tract of the transverse colon. A biopsy led to a diagnosis of poorly differentiated adenocarcinoma. A laparoscopic right hemicolectomy was performed of the transverse colon tumor. He was discharged on postoperative day 13 without complications, and NEC was diagnosed. We decided to administer postoperative adjuvant chemotherapy, starting with cisplatin plus etoposide. Four courses of postoperative adjuvant chemotherapy were completed. Approximately 1 year has passed since the operation, and progress has been observed in the outpatient department without recurrence.

The patient was a 79-year-old man who underwent robot-assisted gastrectomy for esophagogastric junction cancer. pT4aN1M0, pStage ⅢA. Nine months after surgery, he had emergency visit to the hospital due to abdominal pain and vomiting, and contrast CT scan showed a small intestine with poor contrast effect above the left diaphragm. He was diagnosed as a diaphragmatic hernia with small intestinal strangulation and underwent emergency surgery. Under laparotomy, 2 fb hernia orifice were observed on the ventral side of the esophageal hiatus, and a 50 cm jejunum was incarcerated and became necrotic. A partial jejunectomy was performed, and the esophageal hiatus was closed by suturing the stomach with 3-0 absorbable suture. He was discharged from the hospital with good postoperative course. But one month after the operation, the patient was seen in the hospital again with abdominal pain. Under laparotomy, it was found that one suture was dropped off the esophageal hiatus at the previous surgery, and a 100 cm jejunum was incarcerated, which was not necrotic. The hiatal hernia was closed by suturing the stomach and the hiatal hernia with 3-0 non-absorbable suture. Diaphragmatic hernia is a rare late complication of esophagogastric junction cancer.

Our patient was a 72-year-old man in whom a liver mass was identified on abdominal ultrasonography at the examination for which he was referred to our hospital. Contrast-enhanced CT showed that the liver mass was a hemangioma with a surrounding AP shunt. Gallbladder wall thickening could not be ruled out as gallbladder cancer; however, a high possibility of adenomyomatosis was considered. EOB-MRI determined that the gallbladder wall thickening was adenomyomatosis and liver mass was a metastatic malignant tumor of unknown primary origin. Our policy was to resect gallbladder adenomyomatosis and the liver tumor for diagnostic purposes. Cholecystectomy plus hepatic S4a subsegmental resection and hepatoduodenal mesenteric lymph node dissection were performed. The histopathological diagnosis was neuroendocrine cancer of the gallbladder. A similar histology of the liver mass suggested continuity from the gallbladder tumor and was considered direct infiltration. Fifteen months after the operation, no recurrence was observed.

A man in his 40s underwent a transbronchial lung biopsy and received a diagnosis of adenocarcinoma of the right upper lobe of the lung(cT4N0M0, Stage Ⅲ)with no EGFR gene mutation, no ALK fusion gene, no ROS1 fusion gene, and a tumor proportion score(TPS)of 50-74%. During the postoperative follow-up period, enlarged right supraclavicular lymph nodes and right upper and lower paratracheal lymph nodes were detected, diagnosed as recurrence by positron emission tomography-computed tomography. Although a positive rheumatoid factor test, as the patient had no symptoms of rheumatoid arthritis(RA), treatment with pembrolizumab was initiated. Before the second treatment course, a pharmacist conversing with the patient observed that the patient was experiencing pain in his fingers. After discussing the possibility of treatment continuation and test items with the attending physician, the patient underwent tests and received a diagnosis of RA.

Objective: Cisplatin(CDDP)is a key drug for head and neck cancer therapy, but frequently induces severe adverse events including renal dysfunction. Nedaplatin(CDGP)was developed and is used in Japan; it has certain benefits over CDDP. Unlike CDDP, CDGP treatment does not require hydration. However, CDGP is not used globally and thus safety information is lacking. Therefore, we surveyed safety profiles for CDGP-based chemotherapy., Methods: A survey was conducted at Showa University Hospital. Thirty-eight patients treated for head and neck cancer combined with radiotherapy(RTx)and tegafur- gimeracil-oteracil(S-1)between April 2012 and March 2015 were included. Laboratory-based adverse events(WBC, Hb, platelet[Plt], SCr, Alb)and oral mucositis were assessed according to CTCAE v5.0. Time-onset profiles for adverse events were evaluated after starting chemoradiotherapy., Results: In 38 patients, Plt nadir was observed following 40(30-70)Gy and sustained for 14(7-35)days. WBC patterns followed similar profiles, but for Hb, nadir was observed following 60(40- 70)Gy and was less frequently sustained throughout the RTx. Alb and SCr levels were not correlated with therapy. Oral mucositis was observed following 50(10-70)Gy., Conclusion: In conclusion, at approximately 40 Gy, we observed decreases in WBC and Plt, with an increase in oral mucositis. Based on these results, medical staffs must closely monitor patients, especially at doses within range of 40 Gy.

Objective: To retrospectively assess data on immune checkpoint inhibitors(ICIs)in an actual clinical setting, examine the factors that contribute to response and survival using real-world data, and compare the effectiveness of the 3 types of ICIs for patients with non-small cell lung cancer(NSCLC)., Methods: A retrospective analysis of 127 patients with NSCLC treated with ICIs at our hospital was conducted., Results: Nivolumab(56 patients)showed a 3-year survival rate of 21.6% and a disease control rate of 57.1%. These results are consistent with the clinical trials of Nivolumab. Pembrolizumab(36 patients) showed a 2-year survival rate of 60.3%, a response rate of 50.0%, and a disease control rate of 63.9%. Atezolizumab(35 patients)displayed a particularly low response rate with a 1-year survival rate of 58.4%, response rate of 8.6%, and disease control rate of 25.7%. The treatment results for recurrence after surgery for lung cancer were comparable to those for unresectable lung cancer., Conclusion: Anti-PD-1 antibody displayed better therapeutic results than anti-PD-L1 antibody. The efficacy of ICI administration for postoperative recurrent lung cancer was also shown in this study.

Objective: The aim of this study is to assess prophylactic prescriptions for febrile neutropenia(FN)caused by chemotherapy., Investigation: We retrospectively surveyed prophylactic antibiotic prescriptions administered to 930 cancer treatment naive outpatients at Showa University Hospital. Factors associated with prophylactic antibiotic prescriptions were assessed based on patient characteristics, intensity of chemotherapy regimens, laboratory data and diagnoses using logistic regression analysis., Results: The number of patients given prophylactic antibiotic prescriptions was significantly higher in high-risk regimens(n= 349)compared to low-risk regimens(n=288), with an odds ratio of 8.93(6.07-13.14). In logistic regression analysis, significant factors affecting the prophylactic prescription of antibiotics were high-risk regimens(OR: 2.05, p=0.009), age(+ 1 year, OR: 0.98, p=0.002), female sex(OR: 7.10, p<0.001), WBC count(+1.0×10 / 3mL, OR: 1.19, p=0.013)and operation history before and after chemotherapy(OR: 23.19, p<0.001)., Conclusions: Physicians(including pharmacists)should therefore pay attention to the prophylactic prescriptions especially in high-risk female cancer patients with operation history. This prescription pattern provides basic information needed for the proper use of antibiotics in cancer patients.

A 64-year-old man was found to have an irregular region in the stomach by medical examinations. Upper gastrointestinal fiberscopy(GIF)revealed a reddish lesion in the lesser curvature of the upper stomach. Biopsy showed moderately differentiated adenocarcinoma. CT revealed swollen lymph nodes from the lesser curvature of the stomach to the para-aortic region. EUS-FNA was performed twice; however, histology revealed few atypical cells. A definitive diagnosis could not be obtained. Endoscopic findings revealed that the gastric cancer had invaded as far as the mucosa. Moreover, the swollen lymph nodes were considered to have originated from a different disease, such as lymphoma. The lesion of the stomach was an indication for ESD. On April 2016, ESD was performed, and histology revealed the following: Ⅱc, 31×23 mm, tub2, T1a(M), UL-, ly-, v-, VM0, and HM0. Incisional biopsy of the lymph nodes of the para-aorta was performed the followingmonth, and histology revealed poorly differentiated adenocarcinoma, which metastasized from gastric cancer. SOX therapy was performed in 10 courses. The para-aortic lymph nodes disappeared, and the number of lesser curvature lymph nodes decreased. On August 2018, follow-up GIF endoscopy was performed. A depressed mucosa was found in the lesser curvature of the gastric body, which was away from the ESD scar. Biopsy showed moderately differentiated adenocarcinoma. Total gastrectomy with lymph node dissection was performed on November 2018. Metastasis of the lesser curvature lymph nodes was positive; however, curative resection was performed histologically.

The patient was a 68-year-old man who underwent pancreaticoduodenectomy for pancreatic cancer in 2011(T3N1M0, Stage Ⅲ). Fifty-one months after surgery, 2tumors measuring about 8mm in diameter were detected in the right lung. Thus, partial resection of the right lung was performed. Histological examination of both tumors revealed a tubular adenocarcinoma, with positive staining for CA19-9 and cytokeratin 7 and negative staining for cytokeratin 20, TTF-1, and napsin A, which were diagnosed as metastasis of pancreatic cancer. Twenty-nine months after the lung operation, he died because of peritoneal dissemination. Recurrent pancreatic cancer with metastasis has a particularly poor prognosis; however, surgical resection of lung metastasis in pancreatic cancer might result in a better prognosis.

A 74-year-old male had undergone laparoscopic abdominoperineal resection for lower rectal cancer in July 2009. The pathological diagnosis was T2, N0, M0, pStage I (TNM 7th). Because of pathological venous invasion, adjuvant chemotherapy with Tegafur-uracil(UFT)plus Leucovorin for a year was performed. A CT examination revealed slowly growing peripheral right internal iliaclymph node. PET-CT demonstrated a 20mm right lateral lymph node(LLN)metastasis without other distant metastases. On diagnosis of solitary LLN metastasis of rectal cancer, the patient underwent surgical lymph node resection in September 2014. The pathological diagnosis was lymph node metastasis from rectal cancer. Subsequently, the patient received mFOLFOX6 adjuvant chemotherapy for 6 months. The patient remains alive without any recurrence 31 months after the second surgical treatment. lt is important to consider that LLN metastasis of Stage I rectal cancer might still occur a long time after the curative operation.

A 64-year-old man was admitted to our hospital because of epigastralgia. Gastrointestinal endoscopyrevealed a submucosal tumor with ulceration in the upper bodyof the stomach. The tumor was histologicallydiagnosed as a neuroendocrine carcinoma. CT showed that the tumor had directlyinfiltrated the pancreas and splenic vessels. The patient underwent onlyan exploratorylaparotomybecause the tumor seemed to involve the celiac artery. Chemotherapywas conducted using CPT-11/ CDDP. After 15 courses of chemotherapy, a significant tumor reduction was obtained. We performed total gastrectomy with D2 lymphadenectomy, distal pancreatectomy and splenectomy. Histopathological examination of surgical specimens showed that onlyfew carcinoma cells remained in the stomach and pancreas. Neoadjuvant chemotherapycan be a useful treatment for unresectable locallyadvanced neuroendocrine carcinoma of the stomach.

S-1 is an oral antineoplastic agent containing tegafur, gimeracil, and oteracil potassium. Recently, ophthalmic disorders, particularly epiphora, have been reported. We retrospectively investigated the incidence of ophthalmic disorders in patients treated with a regimen containing S-1 at our institution. Ophthalmic disorders were noted in 28 of 261 patients(10.7%). These included epiphora(17 cases), eye discharge(10 cases), conjunctivitis(6cases ), blurred vision(3 cases), and eye discomfort(2 cases), as well as eye pain, pruritus, dry eye, hordeolum, and visual loss(1 case each). The median time from starting treatment to appearance of the condition was 3.0(interquartile range 1.5-4.5)months and the median cumulative S-1 dose was 4.2(interquartile range 2.2-9.5)g. More men than women developed ophthalmic disorders on S-1. The median total dose and duration of treatment were higher in those developed ophthalmic disorders than in those who did not (12.4 g vs 6.3g and 8.6 months vs 4.4 months). Epiphora was the most common of a number of ophthalmic disorders seen in our patients treated with S-1. Patients and physicians should be fully informed of the potential association between S-1 and ophthalmic disorders, and patients receiving this treatment need to be carefully monitored.

A 72-year-old man was diagnosed with acute myeloid leukemia and advanced esophageal cancer(cT3N3M1, clinical Stage IV, high-moderately differentiated squamous cell carcinoma). He was started on remission induction chemotherapy and postremission therapy provided according to the Japan Adult Leukemia Study Group's AML201 protocols. His acute myeloid leukemia showed a complete response. After that, he was administered radiotherapy for esophageal cancer and showed a partial response. One year after treatment, he developed a local recurrence of esophageal cancer. A salvage operation was performed at another hospital, and his postoperative course was uneventful. A case of acute myeloid leukemia with advanced esophageal cancer is rare and has a poor prognosis, but we could improve the prognosis and quality of life.

We describe a case of liver metastasis of colorectal cancer that became resectable after bevacizumab (Bmab), CPT-11, and S-1 ie Bmab+IRIS combination chemotherapy. A 65-year-old man experienced repeated constipation and diarrhea in August of 2013. Colonoscopy was conducted by a local doctor, and a tumor(diagnosed as adenocarcinoma tub1 by biopsy)was found in the upper rectum. Computed tomography performed at our institution detected synchronous liver metastasis. On September 9, laparoscopic rectal anterior resection was performed to prevent metastasis to the ileus, and on October 9, the patient began receiving Bmab+IRIS combination chemotherapy. Before chemotherapy, 3 metastases with a maximum diameter of 7 cm diameter)were observed in the right lobe of the liver. After 4 courses of chemotherapy, their maximum diameter was 3 cm, which allowed resection. Ultimately, the metastases were completely resected. Conversion of non optimal resection cases of liver metastases to optimal cases by using Bmab+IRIS chemotherapy is extremely rare. We suggest that Bmab+IRIS chemotherapy could be an option for conversion of non optimal liver resection cases to optimal cases. We report this rare case and discuss the implications of adjuvant chemotherapy for this patient.

The importance of home care medicine has been well recognized by the National and Prefectural policy. We have conducted several meetings on home care medicine and discussed various problems and barriers that need to be overcome. These meetings were held with various professionals. The meetings, however, were conducted with little communication between professionals, especially regarding cancer and non-cancerous lesions. The members who perform the home care medicine are the same persons regardless of the regions they are from. We are, therefore, trying to improve the communication between these professionals in order to consolidate these meetings. We have recognized and understand the present status of home care medicine through these meetings and are willing to make efforts to improve the home medical practice and care.

Since the launch of pure oxycodone injections in May 2012, it has been possible to use oxycodone without opioid rotation. Although an extremely important step showing progress, very few studies regarding the use of pure oxycodone injections have been performed. In this study, we evaluated the safety and efficacy of pure oxycodone injections in 31 terminally ill cancer patients receiving home care. The difficulty in oral oxycodone intake was the main reason for changing to pure oxycodone injections. The mean administered period of subcutaneous pure oxycodone was 5.6 ± 6.7 days. One out of 5 patients receiving pure oxycodone injections complained of worsening sleepiness. However, other symptoms improved. In addition, in cases wherein pure oxycodone injection was the initiating opioid, 1 out of 6 patients showed no improvement of respiratory discomfort, while other symptoms improved. It was difficult to evaluate more patients because of the short period for administration. Although 5 patients experienced skin problems, they were successfully managed by changing the injection site. Of these 5 patients, 2 patients had sensitive skin, with a previous history of alcohol rash. In conclusion, our study suggests that pure oxycodone injections are beneficial over oral oxycodone treatment for terminally ill cancer patients. However, further evaluation of skin problems associated with pure oxycodone injections is required by performing larger studies.

We investigated the trend in admission to new a palliative care unit (PCU) over 9 months. We observed a significant difference in the length of PCU stay depending on whether patients had access to a house call doctor. These findings suggest that house call doctors play an important role in ensuring a smooth admission to the PCU. In addition, our study suggests that review of the operational management in the PCU is required.

Background: In July 2008, cetuximab treatment for unresectable advanced or recurrent colorectal cancer was approved in Japan, but there have been few reports on this therapy in Japan., Purpose: We retrospectively analyzed the efficacy and safety of cetuximab(Cmab)+irinotecan(CPT-11)for unresectable advanced or recurrent colorectal cancer from October 2008 to April 2010 at 5 centers in the Kanagawa region., Patients and Methods: The number of patients enrolled was 38, all of whom were treated after second-line therapy., Results: The RR was 24%. DCR was 68%. TTF was 105 days and OS was 242 days., Conclusion: At 5 centers, Cmab+CPT-11 was an effective and safe treatment after second-line therapy.

A screening CT of a 78-year-old man suffering from a laryngeal foreign body revealed multiple lymph nodes swelling at the left subclavicular, mediastinal, perigastric, and paraaortic space. He was diagnosed as advanced gastric cancer. After five courses of S-1/docetaxel therapy, the primary tumor became flat and lymph nodes became undetectable. After seven courses, he received operation(total gastrectomy and D2 lymph nodes dissection)because of tumor bleeding and severe adverse effects. The pathological chemotherapeutic effect was Grade 1b for the primary tumor and Grade 3 for lymph nodes. He received S-1 maintenance therapy for three years afterward, and is now still in good condition without recurrence 53 months after the first administration. S-1/docetaxel therapy was thought to be a useful optional regimen for highly advanced gastric cancer.

A40 -year-old woman visited our hospital with adenocaricinoma of the sigmoid colon with multiple liver metastases and ovarian metastasis. Because of a stenosis of the primary tumor, she underwent a colostomy before chemotherapy. 5-fluorouracil and irinotecan and leucovorin(FOLFIRI)was selected as first-line chemotherapy. At the start of chemotherapy, just after the end of irinotecan and leucovorin administration, the patient developed dysarthria. There were no neurological abnormalities or hematological abnormalities. The treatment was temporarily discontinued, and the dysarthria completely disappeared within 90 minutes. 5-fluorouracil was administered after the disappearance of dysarthria. Within 60 minutes of the administration of irinotecan and leucovorin at the second chemotherapy treatment, the patient developed dysarthria again. The patient had no neurological or hematological abnormalities. Magnetic resonance imaging(MRI)showed no abnormalities. The treatment was stopped and dysarthria disappeared within 60 minutes as it did the first time. At each time, no treatment for dysarthria was performed. This patient refused to continue irinotecan because of dysarthria. Therefore, chemotherapy without irinotecan was continued for the third time onward. In the previous literature, 8 cases of dysarthria caused by irinotecan were reported as a rare toxicity. In all cases, dysarthria was temporary and reversible. Because the mechanism of dysarthria is unclear, specific treatment and precaution for dysarthria is not recommended. Since dysarthria is reversible, however, irinotecan might be continued until progression.

In patients with carcinomatous peritonitis caused by the invasion and peritoneal dissemination of gastrointestinal cancer, disease progression can trigger complications such as ileus, ascites, and hydronephrosis.Anorexia, impaired oral intake, nausea, vomiting, abdominal pain, abdominal bloating, anuria, and other symptoms can develop, negatively affecting patients' general condition and quality of life.The treatment of carcinomatous peritonitis is an important determinant of outcomes, but the guidelines for its diagnosis, the evaluation of its response to chemotherapy, and the question of which standard therapy to apply remain unestablished.In recent years, however, clinical trials have attempted to evaluate the benefits of systemic chemotherapy and the intraperitoneal administration of drugs such as cisplatin and paclitaxel in patients with advanced or recurrent gastric cancer who have peritoneal dissemination.In the field of palliative therapy, octreotide has been approved in Japan for the amelioration of symptoms associated with gastrointestinal obstruction.Such treatment is expected to contribute substantially to improving patients' quality of life.

IgG4-related sclerosing disease is a systemic disease histologically characterized by extensive T lymphocytes and IgG4-positive plasma cell infiltration of various organs. Major clinical manifestations are apparent in the pancreas (autoimmune pancreatitis), bile duct (sclerosing cholangitis), gallbladder (sclerosing cholecystitis), salivary gland (sclerosing sialadenitis), and retroperitoneum (retroperitoneal fibrosis), in which tissue fibrosis with obliterative phlebitis is pathologically induced. Autoimmune pancreatitis is a pancreatic lesion and its extrapancreatic lesions are organs reflecting an IgG4-related sclerosing disease. In some cases, only one or two organs are clinically involved, while in others three or four organs are affected. The disease occurs predominantly in elderly males, is frequently associated with lymphadenopathy, and responds well to steroid therapy. Since malignant tumors are frequently suspected on initial presentation, IgG4-related sclerosing disease should be considered in the differential diagnosis to avoid unnecessary surgery. Some cases of autoimmune pancreatitis were reportedly associated with pancreatic cancer. Although no relationship between the two diseases is known, we showed frequent and significant K-ras mutations in the pancreas, the bile duct, and the gallbladder in autoimmune pancreatitis.

We report the frequency of lacrimal passage disorder and the outcomes of treatment. This retrospective study was performed on 55 cases that were treated with S-1 for at least 1 month. We asked patients about ocular symptoms. An ophthalmic surgeon examined all patients and diagnosed lacrimal passage disorder in 6 of 55 patients (12. 5%). The mean dose of S- 1 was 10, 300 mg, and the average period to onset of lacrimal passage disorder was 5. 7 months. The causes of epiphora included occlusion/stenosis of lacrimal canaliculus, occlusion of lacrimal puncta and stenosis of nasolacrimal duct. Lacrimal surgery was performed in all 6 patients and epiphora improved. Lacrimal passage disorder may result from systemic treatment of patients with S-1. Symptoms of lacrimal passage disorder improved with early detection and treatment by insertion of a silicone tube.

The patient was a 53-year-old male. He presented with swelling of the left submandibular region. Histopathological examination of a biopsy specimen showed small cell carcinoma. Computed tomography (CT) and bone scintigraphy revealed multiple liver, bone and lymph node metastases. He was diagnosed with small cell carcinoma of the submandibular gland with multiple metastases, Stage IV. Systemic chemotherapy consisting of CPT -11 plus CDDP as first-line and amrubicin as second-line therapy was given. Once CT showed a partial response of the tumors, but he passed away after about 10 months. Small cell carcinoma arising in the submandibular gland is extremely rare, and there are few clinical reports.

A 51-year-old man was referred to our hospital with adenocarcinoma of sigmoid colon with multiple lymph node metastasis. At the time of admission, he had dyspnea, and computed tomography (CT) showed typical signs of lymphangitis carcinomatosa of the lung. Combination of mFOLFOX6 and bevacizumab was started. After start of the therapy, CT revealed an improvement in lymphangitis carcinomatosa. 8 months later, the tumor assessment became progressive disease. FOLFIRI was started as the second-line chemotherapy, but the patient did not respond. Then, dyspnea emerged again, and CT indicated the lymphangitis carcinomatosa had become worse. So as the third-line chemotherapy, combination of irinotecan and cetuximab was started. Dyspnea immediately disappeared, and CT showed an improvement of lymphangitis carcinomatosa. In the previous literature, malignant tumor cases which accompany lymphangitis carcinomatosa might always have a poor course. Our case dramatically responded to the chemotherapy including molecular targeting drug and showed a long survival. So we conclude that aggressive chemotherapy including a molecular targeting drug may be recommended in a case of colorectal cancer which accompanies lymphangitis carcinomatosa of the lung.

We examined the clinical features of bisphosphonate(BP)-related osteonecrosis of the jaws(BRONJ), a serious complication resulting from intravenous BP treatment for multiple myeloma and malignant tumors with bone metastasis. We retrospectively reviewed the medical records of 36 patients who received intravenous BP therapy for the above-mentioned conditions, at Sapporo Medical University Hospital between July 2006 and October 2008. BP therapy caused BRONJ in 7 of 24 patients, but did not affect the bones of the other 17 patients. The other 12 of the 36 patients involved in the study were prescribed BP only after they had undergone an oral examination and treatment for dental inflammation. Of these patients, 7 developed BRONJ with BP treatment, after tooth extraction or acute dental inflammation. Treating dental inflammation before prescribing BP prevented the development of BRONJ. BRONJ is highly intractable and does not resolve with the standard treatment for osteomyelitis. Therefore, preventive therapy, which can be achieved by cooperation between medical doctors and dentists, is currently the most effective strategy for BRONJ. Conservative treatment with antibiotics may also be useful for maintaining or improving the quality of life of BRONJ patients.

We report a rare case of reversible posterior leukoencephalopathy syndrome (RPLS) induced by 5-FU and oxaliplatin (FOLFOX regime). A 35-year-old woman with ileus was diagnosed with sigmoid cancer Stage IV (T4N4M0P2H0), and excision of the sigmoid colon, and left ureteroureteral anastomosis was performed. Postoperative chemotherapy with FOLFOX4 was performed. Complications of hypertension were seen on day 6, and convulsions on day 11 after chemotherapy. Headache and visual disturbance were also complications. MRI of the brain revealed bilateral high signal intensities of posterior lobes on T2 weighted and FLAIR images without enhancement. The patient was treated with antihypertensive therapy and anticonvulsive therapy. Her symptoms entirely disappeared, including the bilateral posterior lesions on MRI after two weeks. This report would suggest that medical oncologists should be aware that multidrug chemotherapies may increase the risk of fatal neurological complications like RPLS.

With the objective of clarifying points that needed improvement to provide earlier and better treatment of pain by assessing the current state of cancer pain management in Japan, we conducted a questionnaire survey about pain management in patients with advanced/recurrent cancer who were suffering from pain. The results of the survey revealed that it is important for primary physician to place greater emphasis on pain management when treating cancer patients, to inform patients that the doctor should always be told if the patient has pain, and provide appropriate information about medical narcotics to their patients. The team approach to management of cancer has been increasing in importance recently. This survey suggested it is important for primary physicians, who play a central role in such teams, to listen to their patients' complaints about symptoms including pain. Furthermore, it should be remembered that patients are eager to establish a good, trusting relationship with their primary physician.

Case. 61-year-old woman. She noticed a left neck tumor and had a checkup by a nearby doctor. Biopsy showed a squamous cell carcinoma. She was searched from head to foot, but the primary carcinoma could not be identified. It was referred to our hospital as a primary unidentified carcinoma. In examination, the anal region had phyma in a rectal examination, and biopsy revealed it to be a squamous cell carcinoma. For anal canal cancer cStage IV, we performed chemotherapies of S-1+CDDP and local radiotherapy. There was a contraction of a lymph gland, and CT four months later lower endoscopy did not show the apparent phyma. We have continued chemotherapies in an outpatient department sequentially, but the image shows no increase of lymph gland nor increase of the primary tumor for 20 months with no decrease in QOL of the patient. Chemoradiotherapy including S-1 was effective for this case of anal canal cancer distant metastasis for which no apparent cause has been established thus far.

CASE 1: The patient was a 71-year-old woman who came to our hospital for epigastric checkup. Upper gastrointestinal endoscopy showed an ulcerative lesion. Because Helicobacter pylori was positive, eradication therapy was given. As a result of biopsy, a diagnosis of diffuse large B cell lymphoma was made and she was introduced to our department. The lesion showed improvement with upper gastrointestinal endoscopy after eradication therapy, and no lymphoma cells were confirmed. She has been doing well without a recurrence. CASE 2: The patient was a 49-year-old man who had an anomaly noted with upper gastrointestinal endoscope. Then he was introduced to our hospital. Helicobacter pylori eradication therapy was performed because MALT lymphoma was suspected by a previous hospital. The only evidence of chronic gastritis was revealed with upper gastrointestinal endoscope at our hospital, but no lymphoma cells. As we reviewed a specimen again before Helicobacter pylori eradication therapy, the diagnosis was diffuse large B cell lymphoma because lymphoma cells were large, the MIB1 index was high, and Bcl-6 was positive. He has been doing well without a recurrence. As for a treatment of localized diffuse large B cell lymphoma, chemo-radiotherapy has generally been performed. However, we reported here two cases of gastric diffuse large B cell lymphoma regression that were confirmed after Helicobacter pylori eradication therapy, and CR was maintained without a recurrence.

A 64-year-old man was admitted to general practitioner because of dyschezia. He was diagnosed with lower rectal cancer by colonoscopy and referred to our hospital for therapy. At first, in spite of multiple liver metastases, we tried a resection of primary lesion in order to control of breeding, dyschezia and pain. However, we had to give up the resection, so we made sigmoid colostomy only. One month after the operation, a combination chemo-radiotherapy using S-1 was performed for controlling of local symptom. S-1 (120 mg/day) was administered on days 1-14, and 21-35. Radiation (2 Gy) was administered on days 1-5, 7-12, 14-19, 21-26, 28-33, and 35-40, a total of 60 Gy. One month after this therapy, the tumor was remarkably reduced and the reduction was judged as partial response. Moreover after 6 courses of FOLFIRI, the reduction was judged as complete response. Local control therapy (S-1+chemo-radiation) plus systemic therapy (FOLFIRI) is one of the promising effective therapies for advanced rectal cancer.

The advent of microarray technology has enabled oncologists to investigate the expression of thousands of genes on the genetic basis of cancer. Gene-expression profiling studies have provided a molecular classification of cancer into clinically relevant subtypes, new tools to predict disease recurrence and response to different treatments. Analyzing these data can often be a quagmire, with endless discussion as to what the appropriate statistical analyses for any given experiment might be, while raising questions about the role of these techniques in clinical practice and patient management. For the analysis of data, many different methods and new computational algorithms have evolved. Here we describe state-of-the-art of gene-expression studies in clinical cancer, and consider both their current limitations and future promise.

Type 4 gastric cancer has a poor prognosis compared with other types of advanced gastric cancer because of the high incidence of peritoneal metastasis which causes intestinal obstruction, hydronephrosis, or obstructive jaundice. Surgical treatment is often only palliative, and systematic chemotherapy is considered to be important for long survival. S-1 showed a higher response rate for undifferentiated-type adenocarcinoma, and S-1 alone or its combination regimens demonstrated greater anti-tumor effects and longer survival time for gastric linitis plastica compared with conventional 5-FU regimens in our historical control study (response rate: S-1/non S-1 57.9%/27.9%, p<0.01; MST: S-1/non S-1 402 days/213 days, p<0.01). S-1 regimens may also improve the survival in patients with type 4 gastric cancer in neoadjuvant or adjuvant settings, but further prospective studies are warranted to prove its significance. Paclitaxel also has a high response rate for undifferentiated-type adenocarcinoma, and can be expected to show high efficacy for peritoneal dissemination. Irinotecan should not be administered in case of intestinal obstruction because its toxicity may be increased. However,survival of patients with type 4 gastric cancer may improve with the availability of active agents like S-1, taxanes, irinotecan as reported in colorectal cancer. Therefore,irinotecan should be administered carefully before intestinal obstruction occurs.

Recently,remarkable advances of non-surgical treatments such as endoscopic treatment and chemoradiotherapy (CRT) are made in the treatment of esophageal carcinoma. Endoscopic treatment is recognized a standard for m 1, m 2 esophageal carcinoma, and it's indication is being extended for sm esophageal carcinoma in combination with chemoradiotherapy. In stage I and stage II, treatment result of CRT is comparative with that of surgical resection. In patients with T 4 esophageal carcinoma, it is already accepted that CRT is a standard therapy. This progress of non-surgical treatments contributes to preservation of esophagus in the treatment of esophageal carcinoma. But various problems such as technical problems, complication of CRT and salvage surgery for non-CR or recurrent case also remain. To improve results in treatment of esophageal carcinoma,it is necessary that we make an effort to cooperate with surgeons and radiation oncologists, further.

We compare Japanese practice guidelines for gastric cancer with those published from National Comprehensive Cancer Network (NCCN). In surgery, D1 dissection is referred as standard in NCCN, because mortality of D2 dissection was higher than that of D1 (10% vs 4%). However, Japanese investigators show lower mortality rate (0.8%) of D2 dissection, so D2 dissection is referred as standard for stage II/III disease in Japan. Chemoradiotherapy is chosen for residual disease or unresectable disease (M0) in NCCN, but these categories are required D2 dissection or extensive resection in Japan. Because Japanese D2 dissection has better optimized survival rate than chemoradiotherapy,chemoradiotherapy will not be introduced to Japan. In chemotherapy, ECF or taxanes (e.g., DCF) is referred as a prior therapy in NCCN, but 5-FU contain regimen (e.g., FP, LV/5-FU, S-1, or S-1/CDDP) as a prior therapy in Japan. Both ECF and DCF are too toxic regimen for Japanese patient to use. Difference of race seem to be relevant to difference of mortality or toxicities. From the results of ACTS-GC, we think that adjuvant chemotherapy is referred as standard in Japan. Future, results of JCOG 9912 and many other trials will be coming soon, so the guidelines will be changed.

A 77-year-old male patient who had been receiving doxifluridine (5'-DFUR) for about a year after surgery for rectal cancer, was newly prescribed TS-1, because tumor markers were elevated and abdominal ultrasonography documented liver metastasis. However, the patient took TS-1 concomitantly with 5'-DFUR, which is contraindicated to TS-1, and experienced a severe drug interaction. This inadvertent drug interaction was caused by a combination of the newly prescribed drug and the unused drug remaining at the patient's home. This type of medication error has not been reported previously. Health professionals should be aware of such drug interactions which may be caused by newly prescribed drugs plus unused drugs remaining in the patient's home. Furthermore, health professionals should instruct patients on the nature of drug interactions as well as explaining their diagnosis and treatment. Although the severity of such drug interaction may vary, health professionals must be alerted to such incidents, which could happen frequently.

A 41-year-old woman presented to the Department of Obstetrics and Gynecology of our hospital because of abdominal distension and irregular genital bleeding. Computed tomography and ultrasonography of the abdomen revealed bilateral ovarian tumors, massive ascites, and bilateral pleural effusion. Type IV advanced gastric cancer was diagnosed on upper gastrointestinal endoscopy. The patient was admitted to our department. She received 3 courses of combination chemotherapy with methotrexate, 5-fluorouracil, and low-dose cisplatin. Pleural effusion and ascites disappeared. Surgery (total gastrectomy, resection of the tail of the pancreas, lymph-node dissection, total hysterectomy, and adnexectomy) was performed, and the patient was discharged. Chemotherapy was repeated after surgery. Lymph-node metastasis recurred 1 year 8 months after the start of chemotherapy. Treatment was switched to irinotecan plus cisplatin, and the lymph nodes shrank. After 9 months, 3 courses of TS-1 were administered. Two years 10 months after starting chemotherapy, abdominal and low back pain developed. Bone scintigraphy revealed bone metastasis. Lymph node swelling was present. The patient responded to radiotherapy with chemotherapy (cisplatin plus 5-fluorouracil). Subsequently, abdominal computed tomography showed lymph-node swelling, multiple metastases to the liver, ascites, and a right pleural effusion. She was readmitted to the hospital and received intraperitoneal chemotherapy with cisplatin. Her condition deteriorated, and she died. The patient survived for about 3 years 4 months after the start of treatment. Chemotherapy with methotrexate, 5-fluorouracil, and low-dose cisplatin may thus be an effective therapeutic option in patients who have advanced gastric cancer with peritoneal dissemination.

Careful consideration must be given to the efficacy of treatment for elderly patients with advanced gastric cancer. Thirty-two elderly patients, 75 years of age or older with gastric cancer, were treated in Tokyo Metropolitan Komagome Hospital,Department of Chemotherapy, between January, 1993 to December, 2002. We analyzed the data of these patients retrospectively. The male/female ratio was 13:3, and 90.6% of the patients developed complications. Some 29 patients were treated with 5-FU regimen. The response rate was 17.2%, median survival time was 201 days, and 5 PR pts had 421 days' survival time. Patients with good PS had long survival times. A comparative study was conducted between 15 cases treated with cisplatin (CDDP) regimen and 14 cases without CDDP. Among them, 13 pts were given a low dose and 16 pts a full dose of chemotherapy (5-FU+/-CDDP). No differences were found between the two groups in overall survival time. No patients showed a severe adverse effect and some exhibited improvement by the chemotherapy. Therefore, the choice of chemotherapy for an elderly gastric cancer patient mostly depends on the patient' s general condition. Elderly patients can develop many complications, so the organ function test should be carefully evaluated. Development of an oral anticancer drug for gastric cancer is in progress and promises to show good results in the near future. Chemotherapy appears able to preserve good "Quality of Life" and will play an important role in the treatment of gastric cancer in elderly patients.

A 78-year-old woman was admitted to our hospital because of tarry stools. A gastric stromal tumor with liver metastasis was diagnosed. Treatment with imatinib mesilate was begun in a dose of 400 mg daily. After 1 month, the primary tumor showed a partial response; the response of the liver metastasis was stable disease. However, grade 2 edema, leukocytopenia, and anemia developed, and the dose of imatinib mesilate was reduced to 200 mg daily. The adverse reactions resolved promptly, and a partial response of both the primary tumor and liver metastasis to imatinib mesilate has been maintained for 28 months. Strategies for lowering the dose of imatinib mesilate are reviewed.

The 5-FU plus cisplatin containing regimen like FP, ECF and DCF, is considered to be the most effective treatment for advanced gastric cancer in the United States, Europe, and Korea. In Japan, oral fluoropyrimidine S-1 (TS-1) is currently considered to be the first candidate as the standard drug for advanced gastric cancer. S-1 based combination therapies with other promising drugs like cisplatin, irinotecan and taxanes, are expected to yield good results. Above all, S-1+CDDP therapy showed a high efficacy and expected to be a standard therapy for advanced gastric cancer. Two large phase III studies, JCOG 9912 5-FU vs S-1 vs CPT-11 +CDDP and S-1 vs S-1+CDDP, are now on going to establish an acceptable frontline standard for patients with AGC. We therefore need to develop new agents and combination chemotherapy regimens to achieve a greater survival benefit in AGC.

Recently, cancer treatment has been shift from inpatient chemotherapy to outpatient chemotherapy, because of various medical circumstances. In chemotherapy of gastric cancer, outpatient chemotherapy was not spread in the last decade, because the chemotherapy protocol of gastric cancer was not fit for outpatient chemotherapy. But the development of new drugs as TS-1 make outpatient chemotherapy more frequent. So home care of patients has been important for management of gastric cancer. Various symptoms due to obstruction at primary lesion or other lesion prevent patients from living at home in gastric cancer. But recently, technical development and spread of home parenteral nutrition make a possible home care of patients with gastric cancer. It is necessary to make a system that supports patient life at home.

Mucositis is a common complication of cytoreductive cancer chemotherapy. Stomatitis is associated with a higher risk of bacterial infection and treatment-related death. Basic oral care is recommended to reduce the incidence and severity of stomatitis. Recently, new effective prophylaxis against stomatitis has been developed such as human keratinocyte growth factor and AES-14. Gastritis can sometimes cause severe bleeding,and it may be life-threatening. It has been shown that prophylactic H2 blockers or proton pump inhibitors can reduce the incidence and severity of gastric mucosal injury. The risk for chemotherapy-induced diarrhea is significantly greater for chemotherapeutic regimens that contain irinotecan. Intestinal alkalization and Hangeshasin-to a Chinese herbal product are applied in clinical practice in Japan to prevent or reduce irinotecan-induced diarrhea,but careful monitoring,early detection and rapid cure are most important to prevent treatment-related death.

Hospice ward at Matsuyama Bethel Hospital opened in April 2000. The hospice care has been provided for inpatients and outpatients. We considered a system that should be established to allow patients and their families to choose from in-hospital care, outpatient care and home care. The hospice consultation for outpatients opened in April 2004. The terminal cancer patients who are within 6 months of remaining days were hospitalized to the hospice ward. After making the hospice consultation for outpatients, hospice care services have been provided for terminal cancer patients including those with more than 6 months of remaining days under the coordination of palliative care for outpatients and inpatients.

In vitro chemosensitivity test using a collagen-gel method was done on 165 primary gastric cancers. All of 5-FU, CBDCA, CDDP and docetaxel showed a high sensitivity. The effects of per oral (po) administration of TS-1, a combination of po TS-1 and intraperitoneal (ip) administration of CDDP, ip 5-FU and ip docetaxel, were evaluated in athymic mice bearing peritoneal dissemination of a gastric cancer cell line (MKN-45-P that shows a high rate of metastasis to the peritoneal cavity of nude mice). Nude mice were inoculated by ip with 10(7) MKN-45-P cells. No survival benefit was obtained after po administration of TS-1 (12 mg/kg) alone or ip CDDP alone. However, a combination of po TS-1 (8 mg/kg x 10 days, from day 3) and ip CDDP (3.5 mg/kg, day 6 and 13) showed a significant survival improvement than that of po TS-1 or ip CDDP treatment alone. ip administration of 30 mg/kg (3 times/week x 3 weeks) or 15 mg/kg (6 times/week x 3 weeks) of 5-FU significantly improved the survival of mice bearing MKN-45-P. 5-FU concentration of ascites after ip administration of 30 mg/kg of 5-FU was 600-fold higher than po administration of 12 mg/kg of TS-1 at peak level. ip injections of docetaxel of 8 mg/kg, and 2 mg/kg improved the survival of 4 and 1 mice, respectively, and they were tumor-free on day 90. Survival of mice treated with ip injection of CBDCA (100 mg/kg, on day 3, or 50 mg/ kg on day 3 and 10) was significantly better than the control group. These results suggest the potential of po TS-1 + ip CDDP, ip 5-FU, ip docetaxel and ip CBDCA administration for the treatment of peritoneal dissemination of gastric cancer.

The side effect of anticancer agents such as nausea and vomiting frequently interrupt chemotherapy. To reduce these side effects, 5-hydroxytryptamine (5-HT3) receptor antagonist or metoclopramide is administered combined with steroid. In this study, we examined the effect of 5-HT3 receptor antagonist on the frequency of nausea and vomiting in a male cancer patient treated with/without steroid. This patient in his sixties had esophageal cancer (stage IV). He was administered nedaplatin 100 mg/day for 1 day and then 5-fluorouracil (5-FU) 750 mg/day for 5 days combined with radiotherapy (60 Gy) as one cycle of this chemotherapy. In the first cycle, 5-HT3 receptor antagonist was administered, and in the second, the antagonist was administered after treatment with steroid. The blood levels of total bilirubin, GOT, GPT, BUN, Cre, Na, K and Cl were stable normally during both cycles of the chemotherapy, indicating that the hepatopathy and nephropathy which cause nausea and vomiting did not occur in these periods. The frequency and period of the nausea and vomiting were one-third decreased, respectively, by the combination of 5-HT3 receptor antagonist and steroid.