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A man in his 40s visited a facility with the chief complaint of abdominal pain;liver dysfunction was detected, and consequently, he was referred to our hospital for further examinations. His medical history was unremarkable. He used to drink alcohol (beer, 1500mL) every day. Magnetic resonance imaging and computed tomography showed stenosis of the distal bile duct and slight dilation of the upstream bile duct. Common bile duct stones and gallbladder stones were not detected. Malignant tumors in the bile duct biopsy were not discovered. The patient underwent subtotal stomach preserving pancreatoduodenectomy. The pathological diagnosis was chronic pancreatitis with amputation neuroma-like neurogenesis of the bile duct.

A woman in her 60s visited our hospital due to elevation of ALP (1357U/L). The patient had been treated with lamivudine (LAM) in 2005, LAM+adefovir (ADV) in 2009, and ADV+entecavir in 2015 for chronic hepatitis B (CH-B). The ALP isozyme was predominantly bone type. Urinary β-2 microglobulin (MG) and α-1MG increased to 49635μg/L and 64.1mg/L, respectively. Though no fractures were found during bone scintigraphy, the patient was diagnosed with Fanconi syndrome. However, 3 months after switching from ADV to tenofovir alafenamide (TAF), ALP decreased to 856U/L, and urinary β-2MG and α-1MG decreased to 624μg/L and 6.0mg/L, respectively. Fanconi syndrome should be considered when an increase in ALP is observed in patients treated with ADV, and urinary β-2MG and α-1MG assays are useful for establishing a diagnosis. Switching from ADV to TAF was an effective therapeutic option.

Development of immunotherapy, especially checkpoint inhibitors, dramatically improved the prognosis of some malignancies. However, problems on the occurrence of severe adverse effects and limited responses to these checkpoint inhibitors remain. Recently, tumor infiltrating lymphocytes(TILs)are the predictive markers of immunotherapies based on clinical evidence. The proportion of cytotoxic T cells in the tumor has been reported to affect the antitumor effect. TILs in the tumor are thought to be controlled by the interaction between cancer and tumor microenvironment. As a cause of tumor immunosuppression, cancer-associated fibroblasts(CAFs)play the main role in the tumor microenvironment. We considered the strong involvement of tumor microenvironment, particularly the role of CAFs, and reported the interaction between CAFs and proliferation, invasion, angiogenesis, and resistance in the conventional therapy. The correlation between CAFs and tumor immunity and the immunosuppression promoted by CAFs were also evaluated. Their effects will be reported in our future studies.

The esophagorespiratory fistula(ERF)is a fatal complication ofesophageal cancer, because ofadvanced oncological status and poor conditions due to pneumonia and/or malnutrition.We report here a case of patient who was successfully treated for esophageal cancer with ERF with multimodality therapy including three-stage operation. A 65-year-old woman ofesophageal cancer received preoperative chemotherapy, and developed EFR before operation. Prolonged conservative therapies for ERF let her general condition get worse. Therefore, the patient underwent esophagostomy and gastrostomy to recover her condition. She received chemo-radiotherapy followed by esophagectomy. And she was performed the reconstruction next month. She is still alive without recurrence at 20 months after resection. In previous reports, a total of 6 cases have been performed esophagectomy for esophageal cancer with ERF in Japan. Only one case was reported that had survived longer than 12 months. This multimodality therapy can be one ofthe best strategies for the patients ofesophageal cancer with ERF, even ifthey have poor condition.

We report a case of an elderly patient with advanced esophageal cancer who underwent multidisciplinary treatment. An 86-year-old male consulted our hospital with complaints of pharynx discomfort and difficulty in swallowing. He was preoperatively diagnosed with esophageal cancer, T3N2M0, Stage III . We performed 2 courses of cisplatin plus 5-FU therapy as neoadjuvant chemotherapy. The primary tumor and metastatic lymph nodes reduced in size, and thoracoscopic esophagectomy in the prone position was performed. Pathological findings were esophageal cancer, pT3-Ad, INF b, ly2, v1, IM0, pPM0, pDM0, pRM1, pN3, pStage III . As the radical margin was positive, chemoradiotherapy was performed. We continued postoperative chemotherapy for approximately 1 year, and the patient has survived without relapse for 4 years from esophagectomy. Even in patients over 80 years old, long-term prognosis can be expected by performing radical surgery and chemoradiotherapy.

Dementia has become a priority worldwide in terms of both public health and social care due to its rapidly increasing burden in communities. Therefore, the early identification of possible risk factors and the establishment of preventive and treatment strategies for dementia have become increasingly important. The Japan Prospective Studies Collaboration for Aging and Dementia (JPSC-AD) is a collaborative prospective cohort study of approximately 10,000 elderly people from 8 newly established community-based dementia cohort studies in Japan. In this study, the data are prospectively collected using a pre-specified standardized protocol. The purpose of this study is to quantitatively evaluate the environmental and genomic risk factors for dementia in Japan and to establish effective preventive strategies to promote a healthy aging society.

Stroke was the leading cause of death in Japan until 1980s. The results from the Hisayama study, which is a population-based study in Japan, showed that incidence and mortality of stroke decreased with time owing to the improved management of hypertension. Although the incidence of hemorrhagic stroke decreased markedly, the proportion of hemorrhagic stroke among the incident cases of stroke in Japan is higher than in European countries. Among the incident cases of ischemic stroke, the proportion of lacunar infarction decreased significantly, whereas the proportion of atherothrombotic and cardioembolic stroke increased. These changes may be caused by elevating prevalence of metabolic disorders-namely, diabetes and hypercholesterolemia. Effective prevention and management of the metabolic disorder are necessary for further prevention of stroke.

Advances in molecular and cellular biochemistry, such as the development of targeted cancer therapy, have dramatically improved the prognosis of cancer patients. Emerging data have suggested that bevacizumab treatment may act by controlling the cancer microenvironment. Many reports have examined the interaction of cancer cells with the tumor microenvironment, and cancer-associated fibroblasts (CAFs) are thought to play a central role in this process. We speculated that the cancer microenvironment and in particular, CAFs, strongly influence the development of esophageal cancer. We have analyzed the signaling pathways of molecular targets. However, inhibition of a single signaling pathway is insufficient to treat cancer effectively. Photoimmunotherapy is a molecular-targeted specific cancer therapy using near-infrared radiation, which was introduced by Mitsunaga et al. in 2011. We are using its specific method of killing cells to target CAFs. We will report the results of its effect on cancer cells in the future.

Severe oral mucositis induced by cancer chemotherapy can cause intolerable pain and increase the risk of systemic infections, necessitating dose reduction and discontinuation of antineoplastic agents. Moreover, this adverse effect may have an impact on patient nutrition and quality of life. An effective and prophylactic intervention should be useful for alleviating this complication. Because Nagoya Memorial Hospital has neither a dentistry nor an oral surgery department, we collaborated with dental associations near the hospital. First, we performed a questionnaire survey on the present status of the members of the local dental associations. The survey showed that 86% of the community dentists were interested in communicating with our hospital. In addition, they agreed to provide us with information on their specialty and status of amenities. In discussion with the community dentists, we decided on fax-based communication for collaboration to improve the quality of oral management in cancer patients. Three seminar series were conducted to share updated information on cancer treatment and enhance communication between the medical doctors and the dentists. Our hospital has registered 129 community dentists and enrolled 81 cancer patients in this medical and dental cooperation initiative.

Lynch syndrome is an inherited syndrome associated with the development of colorectal, endometrial, stomach, and other cancers; it is caused by defects in the mismatch repair genes. Such patients are at risk of developing multiple abdominal cancers after colectomy, and the presence of adhesions may render future abdominal surgeries difficult. We recommend that patients with Lynch syndrome should be considered good candidates for laparoscopic surgery. A 43-year-old Japanese man was admitted following a positive fecal occult blood test result. The patient was diagnosed with multiple colon cancers in the right colon. He had undergone endoscopic mucosal resection for a colon polyp when he was 24 years of age. Two people among his father's second-degree relatives had colorectal cancer, and he fulfilled the revised Bethesda guidelines. He underwent laparoscopic-assisted right hemicolectomy and D3 lymph node dissection. Microsatellite instability testing indicated the presence of MSI-H, and genetic testing demonstrated a pathogenic mutation of MLH-1.

We report a case of advanced colon cancer with multiple liver metastases treated by two-stage laparoscopic surgery. An 82-year-old woman, whose main complaint was constipation, was diagnosed with stage IV sigmoid colon cancer. With the aim of decompressing the colon, a transanal decompression tube was inserted. She underwent laparoscopic-assisted sigmoidectomy and D3 lymph node dissection, and an ileostomy was created. Systemic chemotherapy was administered immediately after the operation. After 4 courses of chemotherapy, she underwent the second operation, i.e., laparoscopic- assisted partial hepatectomy and radiofrequency ablation of liver metastases. Cases of obstructive colon cancer are more advanced than cases of non-obstructive colon cancer. Systemic treatments are required after the resection of primary tumors. We aim to improve the prognosis of patients with obstructive colon cancer by the use of laparoscopic surgery.

The association between hypertension and dementia has received much attention in epidemiological research. However, the results from observational longitudinal studies and randomized control trials addressing the effects of hypertension on the risks of dementia and its subtypes are still inconclusive. The Hisayama Study, which is a prospective cohort study conducted in a Japanese community, demonstrated that people with midlife hypertension were at an increasing risk of late-life onset of vascular dementia, regardless of late-life blood pressure levels, whereas such associations were not observed for Alzheimer's disease. These findings suggest the clinical value of the early management of midlife hypertension to reduce the risk of late-life dementia. Further investigation would be needed to elucidate these issues.

After 1990's, the development of new generation anti-cancer agents produced encouraging improvement of prognosis in inoperable or relapsed stomach cancer and colorectal cancer. However, non-hematological toxicity, such as peripheral neuropathies, become a new dose-limiting toxicity. In several new generation drugs, measures for controlling peripheral neuropathy had not been established besides dose modification or schedule modification. We tried to control the peripheral neuropathy induced by anti-cancer agents with the assistance of an adjuvant analgesics ladder. A total of 18 digestive cancer patients who presented with peripheral neuropathy of grade 1 or more(NCI-CTCAE ver 3.0), in the chemotherapy including Taxol or Oxaliplatin, were enrolled. The first stage of the adjuvant analgesics ladder was set as the antidepressant(amoxapin), the second stage was anticonvulsive drugs(valproic acid or clonazepam) and the third stage was antiarrhythmic drug(mexiletine). In each stage, if the drug turned out to be ineffective after two / weeks follow-up, it shifted to the next stage. The response rate of each step was 61.1%(11/18)of the first stage, 50.0%(5/10)of the 2nd stage, 50.0%(2/4)of the 3rd stage, and the overall response rate was 77.8%. The discontinuance of cancer treatment by peripheral neuropathy was observed only in 1 patient 5.5%(1/18)in the Taxol administered group. The toxicity profile was skin eruption and drowsiness, but the skin eruption was observed only in 1 patient at the 3rd stage and the drowsiness in 2 patients at the 2nd stage. It appears that the method to control the peripheral neuropathy induced by anti-cancer agents with the assistance of adjuvant analgesics ladder was effective and safe, but a large-scale clinical trial was warranted.

The first acute case of methylmercury (MeHg) poisoning by the consumption of fish arose in Minamata, Japan, in 1953. It was officially recognized and called Minamata disease (MD) in 1956. There are still arguments about the definition of MD in terms of its associated clinical symptoms and lesions even 50 years after the initial recognition of MD. Studies on this MD epidemic are reviewed along with its historical background. Since MeHg dispersed from Minamata to the Shiranui Sea, residents living around the sea had been exposed to low-dose MeHg through fish consumption for about 20 years (at least from 1950 to 1968). These chronic MeHg poisoning patients complained of paresthesia at the distal parts of their extremities and around the lips even 30 years after the cessation of exposure to MeHg of anthropogenic origin. The persisting somatosensory disorders after the discontinuation of exposure to MeHg were induced by diffuse damage to the somatosensory cortex, but not by damage to the peripheral nervous system, as previously believed. Based on these findings, symptoms and lesions in MeHg poisoning are reappraised.

An 80-year-old woman was admitted to our hospital because of chest oppression and general malaise. On admission, auscultation of the heart revealed friction rub, so-called water-wheel like murmur. Chest X-ray film and computed tomography showed cardiomegaly and free air in the pericardium. Electrocardiogram showed low voltage with ST elevation in II, III, aVF and V1-V4. These findings suggested that the patient had pneumopericardium with pericarditis. Wenchebach type A-V block and atrial bradycardia appeared. Thus, the ventricular pacing was performed. However, patient died of multiple organ failure. The postmortempericardiography showed the gastro-pericardial fistula with hiatus hernia.

One hundred and eighty eight children with acute lymphoblastic leukemia (ALL) were treated in a Children's Cancer and Leukemia Study Group high-risk ALL 874 study from April, 1987 to September, 1991. These patients received a four-drug induction regimen followed by the early consolidation regimen, cranial irradiation at 6 months of remission and three years of continuation therapy with rotational administration of four drugs. The patients were randomized into two regimens. In regimen A, the consolidation chemotherapy consisted of the intermediate dose cytosine arabinoside (Ara-C), cyclophosphamide (CPM) plus 6MP, and in regimen B, it consisted of high-dose Ara-C plus CPM. Regimen A was given to 106 patients and 82 patients received regimen B. The complete remission induction rate for regimen A and B was 89.4% (93/104) and 98.7% (78/79), respectively. The 3-year event-free-survival (EFS) rate was 70.6% for regimen A, which was higher than the 56.7% for regimen B. The 3-year EFS rate was 44.4% for the 53 patients with an initial leukocyte count > or = 10 x 10(4)/microliters and 72.2% for 132 patients with a leukocyte count < 10 x 10(4)/microliter. We considered that Ara-C plus L-asp, added to the conventional high-risk ALL 811 protocol, improved the prognosis of the high risk ALL patients. However, further intensive chemotherapy was required for improvement of the outcome of the patients with hyperleukocytosis (> or = 10 x 10(4)/microliters).

Preventive effects of hemorrhagic cystitis by the use of sodium 2-mercaptoethane sulfonate (MESNA) was evaluated in 40 children undergoing peripheral blood stem cell autografts (PBSCT) after marrow-ablative chemotherapy which included high-dose cyclophosphamide (CY, 50mg/kg x 2). Fifteen patients received MESNA (group A) and 25 did not (group B), and all received concomitant hyperhydration (3,000ml/m2/day). No renal dysfunction or toxicity attributed to the use of MESNA was observed in either group of patients. Transient hemorrhagic cystitis developed in one of the 15 group A (6.7%) and 3 of 25 (12.0%) group B patients but there was no statistical significance. Although the results may suggest that MESNA is a controversial agent in preventing hemorrhagic cystitis caused by CY when hyperhydration protocol is used, further observation with a larger number of patients is required to establish a firm conclusion.

Thirty children (1-16 y.o.; median, 10 y.o.) with acute leukemia or non-Hodgkin's lymphoma (NHL) associated with high-risk features underwent high-dose chemotherapy without total body irradiation and peripheral blood stem cell autografts (PBSCT). Eighteen patients had acute lymphoblastic leukemia (ALL), 6 had acute non-lymphoblastic leukemia (ANLL), 2 had mixed-lineage leukemia and 4 had NHL. Twelve patients with two or more high-risk features (WBC greater than 10 x 10(4)/microliter, T- or B-phenotypes, infancy, massive organ infiltration, or induction failure) underwent PBSCT in 1st CR. Twelve patients underwent PBSCT in 2nd CR, and 4 in the subsequent remission greater than or equal to 3rd CR). Two patients were treated at refractory relapse. After PBSCT the number of days required to achieve a granulocyte count of 0.5 x 10(9)/l and a platelet count of 50 x 10(9)/l was 6.39 (median, 13) and 9-427 (median, 16), respectively. The disease-free survival rate was 6/12 in 1st CR group (6-41 mo) and 6/16 in the patients who underwent PBSCT in 2nd or subsequent remission (2-35 mo). The data justify the incorporation of PBSCT in the design of salvage protocol for children with leukemias or NHL. However, the application of the procedure as part of initial therapy in patients still remaining in 1st CR should be regarded as highly experimental and deserve further clarification.

We experienced general anesthesia of two patients with cerebral palsy presupposed to have difficulties in tracheal intubation by reason of scoliosis. Case 1 is a 26-year-old woman. Chest X-ray photography and respiratory sounds in both pulmonary areas indicated neither airway stricture nor respiratory distress, but severe scoliosis presupposed difficult tracheal intubation. However, under the impression of possible intubation obtained by preoperative laryngoscopy, orotracheal intubation was tried with rapid induction. Epiglottis deviation to the left noted upon developing larynx made the glottis direct invisible, but some compression of cricoid from outside barely succeeded in intubation. The fixation of the endotracheal tube found much difficulties in its proper positioning so as to make stethoscopy uniform in both pulmonary areas, but trial rotations of the tube both in various directions and at various depths barely managed to find a position of uniform stethoscopy in both pulmonary areas, in which position the tube was fixed as proper positioning. Anesthesia was performed by nitrous oxide.oxygen.halothane; peroperative hemodynamics remained stable and arterial blood gas analysis presented no problems. Case II is a 16-year-old man. Resting respiration presented stridor and chest X-ray photography indicated scoliosis and laryngeal stricture. Patient's lack in the degree of cooperation made laryngoscopy impossible. Thus, in view of a high possibility of difficult tracheal intubation, orotracheal intubation was tried under the control of spontaneous respiration. While the intubation was being carried out by means of a stylet without developing larynx, severe bronchostriction was palpable at the point when the tube barely passed through the glottis, making the intubation impossible. However, the tube barely managed to be inserted while rotating with the stylet being extracted. Anesthesia was carried out by nitrous oxide.oxygen.halothane; peroperative hemodynamics underwent no remarkable change and arterial blood gas analysis presented no problems.

This paper reports a clinical and laboratory experience of peripheral blood stem cell (PBSC) autografts at a single institute. Twenty-eight children with various types of cancer underwent a total of 90 leukaphereses to collect PBSC and 17 of them subsequently received marrow-ablative therapy and PBSC autografts. We found that frozen-thawed progenitor dose is important in determining the rate of hematopoietic recovery after transplantation; in 11 patients who received more than 1 x 10(5) CFU-GM/kg, the granulocyte count reached to 0.5 x 10(9)/L in two weeks. With conditioning chemotherapy without total body irradiation, 6 of 14 patients with high-risk acute leukemia or non-Hodgkin's lymphoma have survived disease-free 3 to 25 months posttransplant. This approach may have a potential to induce prolonged remission-interval and ultimate cure.

Conditioned media (CM) of phyto-hemagglutinin-stimulated lymphocytes from chronic uremic patients were studied for burst promoting activity (BPA), using methylcellulose cultures with cord blood cells as a target population. Renal transplantation procedure was followed by a prompt rise of BPA, as well as the number of blood burst-forming unit erythroid (BFU-E) and hemoglobin levels, while no change in BPA and blood BFU-E number was observed in patients receiving rEpo and recovering from anemia. Thus, low BPA secretion from blood cells may have a role in the development of anemia in uremic patients.

Methylcellulose culture study revealed that the potency of recombinant granulocyte-colony stimulating factor (G-CSF) or granulocyte/macrophage (GM)-CSF to support the growth of purified target cell populations from peripheral blood of patients undergoing peripheral blood stem cell (PBSC) autotransplantation was inferior to that of PHA-stimulated lymphocyte conditioned medium (PHA-LCM) or interleukin-3 (IL-3). In liquid-suspension limiting dilution assay the cells responded directly to IL-3 by proliferation with single-hit kinetics. Hence, optimal culture for PBSC should include the use of PHA-LCM or IL-3. Further study disclosed a linear relationship between the number of CFU-GM infused into the patients and days required to achieve a granulocyte count above 0.5 x 10(9)/l.

The clinical efficacy and safety of acetylspiramycin for Mycoplasma pneumonia in children were studied at a dose level of 50 mg/kg/day q.i.d. and the following results were obtained. Acetylspiramycin showed effect in 24 patients out of 25 (96.0%). The level of transminase was increased in 3 cases on admission. One of them was an uneffective case, and eruption was seen after administrating the drug. Diarrhea and poor appetite were observed in one case as side effects, and they were controlled easily. It may be concluded from these results acetylspiramycin was relatively free from side effects and considered to be useful for Mycoplasma pneumonia.

Rapid and complete hematopoietic reconstitution was achieved in a child with T cell acute lymphoblastic leukemia who was autografted with peripheral blood stem cells (PBSC). A large number of PBSC was collected by two courses of 3-4 hour-lasting lymphopheresis during early remission induced by the second-line chemotherapy and then cryopreserved in liquid nitrogen. A myeloid progenitor cell dose of 203 X 10(4) CFU-GM/kg body weight was reinfused to the patient following marrow-ablative chemotherapy (MCNU 600 mg/m2, cytosine arabinoside 6 g/m2, etoposide 300 mg/m2, cyclophosphamide 160 mg/kg). Neutrophil count reached 0.5 X 10(9)/l by day + 7 and platelet count reached 20 X 10(9)/l by day + 9. Thereafter, white blood cell count continued to increase and reached a maximum of 38 X 10(9)/l on day + 14. Thus, the rapid recovery of hematopoiesis minimised marrow aplasia-related risks. This approach of stem cell rescue operation can be applied to the treatment of children with cancer, who otherwise have no hope to be cured, as an alternative to bone marrow transplantation.

Circulating hematopoietic stem cells were collected by three consecutive leukaphereses during post-chemotherapy expansion of the stem cell pool in a 3-year-old boy with advanced and therapy-resistant neuroblastoma. The cells were fractionated by discontinuous Percoll gradient centrifugation, frozen in a programmed freezer and then stored in liquid nitrogen. Following high-dose chemotherapy, the cells were thawed rapidly and re-infused into the patient. Early evidence of marrow recovery was first noted at day 13 and the times required to achieve a granulocyte count of greater than 0.5 x 10(9)/L and a platelet count of greater than 50 x 10(9)/L were 21 days and 30 days, respectively. This new marrow-rescue operation may have potential in cancer therapy as an alternative to bone marrow transplantation and further clinical investigation is warranted.