[IgG4-related sclerosing disease, including its relation to carcinogenesis].

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.

Differentiation of autoimmune pancreatitis from pancreatic cancer by diffusion-weighted MRI.

OBJECTIVES: We sought to clarify the clinical utility of diffusion-weighted magnetic resonance imaging (DWI) for differentiating autoimmune pancreatitis (AIP) from pancreatic cancer. METHODS: Thirteen AIP patients underwent DWI before therapy, and six of them underwent DWI after steroid therapy. The extent and shape of high-intensity areas were compared with those of 40 pancreatic cancer patients. Apparent diffusion coefficient (ADC) values were calculated in the AIP area before and after steroid therapy in pancreatic cancer patients and in a normal pancreatic body. RESULTS: On DWI, AIP and pancreatic cancer were detected as high-signal intensity areas. The high-intensity areas were diffuse (n=4), solitary (n=6), and multiple (n=3) in AIP patients, but all pancreatic cancer patients showed solitary areas (P<0.001). A nodular shape was significantly more frequent in pancreatic cancer, and a longitudinal shape was more frequently found in AIP (P=0.005). ADC values were significantly lower in AIP (1.012+/-0.112 x 10(-3) mm(2)/s) than in pancreatic cancer (1.249+/-0.113 x 10(-3) mm(2)/s) and normal pancreas (1.491+/-0.162 x 10(-3) mm(2)/s) (P<0.001). Receiver operating characteristic analysis yielded an optimal ADC cutoff value of 1.075 x 10(-3) mm(2)/s to distinguish AIP from pancreatic cancer. After steroid therapy, high-intensity areas on DWI disappeared or were markedly decreased, and the ADC values of the reduced pancreatic lesions increased almost to the values of normal pancreas. CONCLUSIONS: DWI is useful for detecting AIP and for evaluating the effect of steroid therapy. ADC values were significantly lower in AIP than in pancreatic cancer. An ADC cutoff value may be useful for distinguishing AIP from pancreatic cancer.

A new embryological theory of the pancreatic duct system.

BACKGROUND/AIMS: To clarify the anatomy of the pancreatic duct system and to investigate its embryology. METHODS: We reviewed pancreatograms of 256 patients with a normal pancreatic head and 36 cases of complete pancreas divisum. RESULTS: Accessory pancreatograms were divided into two patterns. The long-type accessory pancreatic duct (APD) forms a straight line and joins the main pancreatic duct (MPD) at the neck portion of the pancreas. The short-type APD joins the MPD near its first inferior branch. The short-type APD is less likely to have a long inferior branch arising from the APD. The length of the APD from the orifice to the first long inferior branch was similar in the short- and long-type APD. The first long inferior branch from the long-type APD passes through the MPD near the origin of the inferior branch from the MPD. Immunohistochemically, in the short-type APD, the MPD between the junction of the short-type APD and the neck portion originated from the ventral pancreas. CONCLUSION: The long-type APD represents a continuation of the main duct of the dorsal pancreatic bud. The short-type APD is very likely formed by the proximal main duct of the dorsal pancreatic bud and its long inferior branch, with the main duct of the dorsal pancreatic bud at the point of connection with the main duct of the ventral pancreatic bud being obliterated and replaced by this additional communication.

[A case of small cell carcinoma arising in submandibular gland].

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.

Safety and efficacy of rasburicase (SR29142) in a Japanese phase II study.

The purpose of this study was to investigate the safety profile of SR29142 when administered as a single agent both prior to chemotherapy and during treatment, and to compare the efficacy of SR29142 administered at two dose levels in adult Japanese patients with leukemia or lymphoma. During this open-label, multicenter, phase II study, patients received SR29142 for 5 days, administered at either 0.15 or 0.20 mg/kg per day. Chemotherapy was started 4­24 h after the first infusion of SR29142. The primary end-point was overall response rate, defined as the normalization of plasma uric acid to 7.5 mg/dL or less, from 48 h after the first infusion to 24 h after the last infusion of SR29142. SR29142-related adverse events including hypersensitivity (allergic) reactions were assessed. Overall, 50 patients received SR29142 at either 0.15 mg/kg per day (n = 25) or 0.20 mg/kg per day (n = 25) followed by chemotherapy. The overall response rate was 100.0% (95% confidence interval, 86.3­100.0%) with 0.15 mg/kg and 96.0% (95% confidence interval, 79.6­99.9%) with 0.20 mg/kg. Both dose levels of SR29142 were equally effective at reducing plasma uric acid levels. In six patients, seven drug-related adverse events of grade 1/2 occurred before chemotherapy. SR29142-related, hypersensitivity-associated reactions occurred in three patients, and rash, anorexia, application site pain and pyrexia occurred in one patient each; only five patients (10%) showed anti-SR29142 antibodies by day 29. In conclusion, SR29142 is effective at reducing plasma uric acid levels with a tolerable safety profile as a single agent both prior to chemotherapy and during treatment.

Pancreaticobiliary maljunction.

Pancreaticobiliary maljunction (PBM) is a congenital anomaly defined as a junction of the pancreatic and bile ducts located outside the duodenal wall, usually forming a markedly long common channel. In PBM patients, this anomaly allows regurgitation between the pancreatobiliary and biliopancreatic tract. Since hydrostatic pressure within the pancreatic duct is usually higher than that in the common bile duct, pancreatic juice frequently refluxes into the bile duct. As a result, pancreatic enzyme levels are generally very high in the bile and there is a related high incidence of biliary cancer. PBM can be divided into PBM with biliary dilatation (congenital choledochal cyst [CCC]) and PBM without biliary dilatation (maximal diameter of the bile duct

[Case of higher efficacy by chemoradiotherapy for anal canal cancer from left cervix metastases to lymph nodes].

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.

[Importance of the primary physician for pain management in patients with recurrent advanced cancer--a questionnaire survey].

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.

[A case of colon cancer with reversible posterior leukoencephalopathy syndrome following 5-FU and oxaliplatin (FOLFOX regime)].

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.

[Two cases of stomach primary diffuse large B cell lymphoma remitted by Helicobacter pylori eradication therapy].

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.

[Genomic and post-genomic approaches to cancer biomarker discovery - microarray standards at last].

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.

[Discussion of the treatment of esophageal carcinoma,especially in the point of non-surgical treatments, from the viewpoint of medical oncology].

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.

[Comparison the standard therapies of gastric cancer in Japan with those in the West].

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.

[Management of chemotherapy-induced mucositis and diarrhea].

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.

[The present state and future of home care for gastric cancer patients].

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.

[Clinicopathological characteristics of gastric cancer in elderly patients].

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.

Thermo-chemo-radiotherapy for advanced gallbladder carcinoma.

BACKGROUND/AIMS: Many gallbladder carcinomas are detected at an advanced stage, and the outcome of the patients with these tumors is dismal despite aggressive tumor removal. We have treated advanced gallbladder carcinoma with chemoradiotherapy combined with hyperthermia. In this study, clinical effectiveness of thermo-chemo-radiotherapy (TCRT) for advanced gallbladder carcinoma was evaluated in comparison with other treatment modalities. METHODOLOGY: Two hundred and seventy patients with advanced gallbladder carcinoma (Stage VI) were treated. According to treatments received, they were divided into five groups as follows: group 1; 30 patients treated with TCRT, group 2; 19 patients underwent R0-resection, group 3; 39 patients underwent R1,2-resection, group 4; 57 patients treated with chemo- and/or radiotherapy, group 5; 125 patients with only supportive therapy. RESULTS: In group 1, there were 19 objective responses (5 complete response and 14 partial response) in respect to tumor regression, and 15 (6 complete response and 9 partial response) of 20 patients with obstructed bile duct showed resolution of the bile duct. The survival rate was best in group 2. A significant improvement of long-term survival was exhibited in group 1 and 3 compared to group 4 and 5, and there was no significant difference between group 1 and 3 (p<0.01). CONCLUSIONS: TCRT can produce significant response and improvement of survival time in patients with advanced gallbladder carcinoma, and may be a favorable alternative to aggressive surgical approaches.