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Introduction: Cisplatin (CDDP)-induced nephrotoxicity is a concern in CDDP-based chemotherapy. The goal of this multicenter retrospective study was to identify potential risk factors for CDDP nephrotoxicity. Methods: Clinical data were reviewed for 762 patients who underwent chemotherapy including CDDP ≥60 mg/m2 per day from Spring 2014 to September 2016. CDDP nephrotoxicity was defined according to the National Cancer Institute Common Terminology Criteria for Adverse Events for acute kidney injury. Univariate and multivariate logistic regression analyses were performed to identify risk factors for CDDP nephrotoxicity. Results: CDDP nephrotoxicity was observed in 165 patients (21.7%). Multivariate analysis showed a significantly higher rate of CDDP nephrotoxicity in patients with cardiac disease (odds ratio [OR]: 2.05, 95% confidence interval [CI]: 1.07–3.93, p = 0.03), hypertension (OR: 1.57, 95% CI: 1.06–2.32, p = 0.02), and high-dose CDDP therapy (OR: 2.15, 95% CI: 1.50–3.07, p < 0.01). Magnesium (Mg) supplementation (OR: 0.65, 95% CI: 0.45–0.93, p = 0.02) and diuretic use (OR: 0.22, 95% CI: 0.08–0.63, p < 0.01) were also independent risk factors for CDDP nephrotoxicity. Conclusions: Our results suggest that high-dose CDDP and comorbidities of cardiac disease and hypertension are independent risk factors for CDDP nephrotoxicity. Therefore, close monitoring of serum creatinine values during CDDP treatment is recommended for patients with these risk factors. In addition, Mg supplementation and administration of diuretics might be effective for prevention of CDDP nephrotoxicity.

Herein, we investigated the pharmacokinetic (PK) profile of nedaplatin (cis-diamine-glycolateplatinum; CDGP) in a hemodialysis (HD) patient with advanced esophageal squamous cell carcinoma (ESCC) by administering the CDGP immediately prior to HD. Our patient was treated with CDGP (45 mg/m2 for a total dose of 60.2 mg) and 5-fluorouracil (560 mg/m2 for a total dose of 750 mg) before initiating HD. The total platinum (Pt) concentration (Pt_total) and free Pt concentration (Pt_free) 2 h after completion of HD were 0.4 μg/mL and 0.3 μg/mL, respectively. The removal rates of Pt_total and Pt_free by the dialyzer were 76.5% and 84.6%, respectively. Twenty-four hours after CDGP administration, the Pt_free was below the detection limit of the method of analysis. Pt_free within the range of the recommended CDGP target AUC0-24 was 8-10 μg/mL•h, the AUC0-24 of Pt_total and Pt_free were 16.5 μg/mL•h and 8.8 μg/mL•h, respectively. We conclude that HD should be performed after the end of CDGP infusion as part of the CDGP chemotherapy regimen for HD patients with ESCC, and suggest that HD is effective for obtaining a PK profile of CDGP similar to patients with normal renal function.

This paper considers a bilateral tele-rehabilitation control system by using an electrical stimulation. The therapist rehabilitates the patient who is far away from the therapist by using the electrical stimulation. The therapist also feels the reaction force which indicates the motion error between the therapist and the patient by utilizing the electrical stimulation. In previous our research, the haptic device has been used to feel the reaction force for the therapist. This paper uses the mechanical device only to constrict the range of motion of the therapist. The reaction force can be felt by means of the electrical stimulation. To detect the force which is provided by the therapist, the force sensor which is set on the haptic device is used in previous our works. This paper proposes to utilize the control input of the therapist and the velocity of the mechanical device to estimate the force provided by the therapist. First, the bilateral tele-rehabilitation control system with the modified force detection is proposed. The scattering matrix method as a stabilizing method for the time delay is applied, the stability condition is indicated. Next, the experimental equipment and the experimental result that the therapist’s arm and the patient’s knee joint are controlled are indicated. The stability and the control performance are verified from the experimental result.

The triplet antiemetic regimen is administered to prevent chemotherapy-induced nausea and vomiting (CINV) after moderately emetogenic chemotherapy (MEC). However, the superiority of palonosetron over first-generation 5-hydroxytryptamine-3 receptor antagonists in triplet antiemetic therapy remains unclear. In this study, we evaluated the efficacy of palonosetron (PALO) and granisetron (GRA) in triplet antiemetic therapy for CINV. This study included 267 patients who received MEC at our hospital between April 2017 and September 2020. Patients were pretreated with antiemetic therapy comprising PALO or GRA and dexamethasone on day 1 and aprepitant on days 1-3. We evaluated the rate of complete response (CR) (i.e., no vomiting and no use of rescue medication) in the acute phase (0-24 h), delayed phase (24-120 h), and overall phase (0-120 h) after first-cycle chemotherapy. Furthermore, multivariate analysis was conducted to identify risk factors for non-CR. The rate of CR in the overall and delayed phases was significantly higher in the PALO group (91.9 and 91.9%, respectively) than in the GRA group (74.1 and 75.5%, respectively). In the acute phase, the incidence was not different between the GRA and PALO groups (96.5 and 99.2%, respectively). Multivariate analysis revealed that female sex and the use of GRA were risk factors for non-CR. Subgroup analysis revealed the superiority of PALO over GRA in female patients, but not in male patients. In conclusion, PALO was more effective than GRA in triplet antiemetic therapy in preventing CINV during MEC, especially for female patients.

We administered FOLFOX (oxaliplatin (L-OHP) plus infusional 5-fluorouracil (5-FU) and leucovorin) to an hemodialysis (HD) patient with advanced gastric cancer (AGC), and investigated pharmacokinetics (PKs) and dialyzability of L-OHP. The patient was a 54-year-old Japanese man with a diagnosis of inoperable AGC. FOLFOX was instituted 3 h prior to the start of a 4 h HD period with the L-OHP and 5-FU doses reduced by 50% for the first cycle, and 30% reduced dose was administered for the second cycle. We performed an analysis of the PKs of L-OHP during these two cycles. Volume of distribution and area under the curve of the 30% reduced L-OHP dose were 56.7 L and 30.0 μg·h/mL, respectively. A dose reduction of L-OHP by 30%−50% may be advisable for the initial administration, given the need for careful administration of chemotherapy in HD patients, with particular attention to the development of hematological toxicities and neuropathy.

Background Daikenchuto (TJ-100), a traditional Japanese herbal medicine, is widely used in Japan. Its effects on gastrointestinal motility and microcirculation and its anti-inflammatory effect are known. The purpose of this prospective randomized controlled trial was to investigate the effect of TJ-100 after esophagectomy in esophageal cancer patients. Methods Forty patients for whom subtotal esophageal resection for esophageal cancer was planned at our institute from March 2011 to August 2013 were enrolled and divided into two groups at the point of determination of the operation schedule after informed consent was obtained: a TJ-100 (15 g/day)-treated group (n = 20) and a control group (n = 20). The primary efficacy end-points were maintenance of the nutrition condition and the recovery of gastrointestinal function. The secondary efficacy end-points were the serum C-reactive protein (CRP) level and adrenomedullin level during the postoperative course, the incidence of postoperative complications, and the length of hospital stay after surgery. Results We examined 39 patients because one patient in the TJ-100 group was judged as having unresectable cancer after surgery. The mean age of the TJ-100 group patients was significantly older than that of the control group patients.The rate of body weight decrease at postoperative day 21 was significantly suppressed in the TJ-100 group (3.6% vs. the control group: 7.0%, p = 0.014), but the serum albumin level was not significantly different between the groups. The recovery of gastrointestinal function regarding flatus, defecation, and oral intake showed no significant between-group differences, but postoperative bowel symptoms tended to be rare in the TJ-100 group. There was no significant between-group difference in the length of hospital stay after surgery. The serum CRP level at postoperative day 3 was 4.9 mg/dl in the TJ-100 group and 6.9 mg/dl in the control group, showing a tendency of a suppressed serum CRP level in the TJ-100 group (p = 0.126). The rate of increase in adrenomedullin tended to be high postoperatively, but there was no significant difference between the two groups. Conclusions TJ-100 treatment after esophageal cancer resection has the effects of prompting the recovery of gastrointestinal motility and minimizing body weight loss, and it might suppress the excess inflammatory reaction related to surgery.

Esophageal squamous cell carcinoma (ESCC) is more frequent in male, and female ESCC patients have better prognosis and tend to diagnose at an earlier stage than male. Regarding these female advantages, gender differences of immunological reaction and sex hormone relations were investigated previously. However, the gender differences of clinicopathological features and prognostic factors of ESCC remain well unknown. A total of consecutive 170 Japanese patients, including 28 females with ESCC who newly diagnosed and underwent esophagectomy between January 2004 and March 2013 in our institute, were examined. Clinicopathological features and p53 expression, a potent biomarker reflecting chemoresistance and prognosis, were compared. Prognostic factors were analyzed using a multivariate analysis. The rates of current drinking, flusher, smoking habits, and Brinkman index in female were lower than those in male (p Grade2) was seen much more in female significantly (36.1:66.7 %, p = 0.048). Immunohistostaining revealed positive rates of p53 expression were significantly high in male (50.4:30.5 %, p = 0.007). Postoperative complication occurred more frequently in male than female (52.8:28.6 %, p = 0.024). Estimated 5-year disease-specific survivals by Kaplan–Meier method were worse in male than female at rates of 46.2 and 76.7 %, respectively (p = 0.045). Multivariate analysis by Cox’s proportional hazards model showed that female gender (HR: 0.508, p = 0.023) and tumor depth (HR: 0.572, p = 0.018) were independent prognostic factors of ESCC after resection. Female ESCC showed prefer prognosis to male ESCC. Low p53 imunohistochemical expression in the female ESCC patients might be related with higher sensitivity to neoadjuvant chemotherapy.

The synchronous existence of lung cancer and gastrointestinal stromal tumors (GIST) is considered to be extremely rare. To the best of our knowledge, this is the first report about the treatment of lung cancer and GIST with two kinds of molecular targeting drugs. An 83-year-old woman with a rectal GIST, which carried a c-kit mutation, and pulmonary adenocarcinoma, which exhibited an epidermal growth factor receptor (EGFR) mutation, was treated alternately with imatinib and erlotinib. Good control over both diseases was achieved for two years. The present case is not only of interest due to the rare co-occurrence of GIST and lung cancer, but also because it involved two tumors carrying different gene mutations, and both tumors were brought under control using different molecular targeting drugs.

BARLEYmax® is a unique barley rich in dietary fiber and resistant starch, which are considered to decrease the risk of developing type II diabetes mellitus. In this study, we evaluated the postprandial glycemic response for boiled BARLEYmax and determined its glycemic index in a Japanese population. Eleven healthy subjects were administered a 50 g/150 mL glucose drink twice and boiled BARLEYmax containing 50 g available carbohydrate after a wash-out period. Postprandial blood glucose, its change from baseline over 90 min, and the incremental area under the curve for BARLEYmax were statistically lower than those for the glucose drink. The glycemic index of the BARLEYmax was 24.3 (standard error of the mean, 3.5). These results suggest that in Japanese individuals, boiled BARLEYmax contributes to improving the postprandial glycemic response, which is one of the possible risk factors for the development of type II diabetes mellitus.

We report the case of a 50-year-old female Jehovah's Witness with advanced esophageal cancer who underwent esophagectomy following induction chemotherapy. She visited our hospital complaining of dysphagia and was diagnosed of advanced esophageal cancer by upper endoscopy. She refused allogeneic transfusion. Induction chemotherapy was performed. Severe anemia occurred as an adverse event. A subtotal esophagectomy was performed after her anemia improved. During the surgery, a large volume of replacement fluid was injected, the blood was diluted, and intraoperative bleeding was relatively reduced. Intraoperative blood salvage was made using Cell Saver. The postoperative course were stable by using autologous blood and albumin infusion. The patient was discharged on postoperative day 27. Jehovah's Witnesses with gastrointestinal malignancies can be treated safely by performing surgical therapy based on blood replacement therapy and autologous blood transfusion.

We reported four consecutive advanced esophageal cancer patients with esophago-bronchial fistula (EBF) who were managed well and achieved long-term survival with timely multimodality therapy including bypass operation. Eighty-four patients with esophageal cancer located in the upper or middle esophagus who were treated in our institute from 2005 to 2013 were diagnosed with cT4 at the time of admission. Eight (9.5 %) of those 84 cT4 patients developed the esophago-bronchial/tracheal fistula. Out of eight patients, four (50 %) who responded to prior chemotherapy or chemoradiotherapy received esophageal bypass operations to manage their QOL and continue the following therapy. Not only nutrition and quality of life but also fighting spirit were maintained by allowing oral intake and resulted in completion of postoperative chemoradiotherapy in all 4 patients. Multimodality treatment including a bypass operation provided high QOL and long-term survival even in advanced esophageal cancer patients with EBFs.

The incidence of and the risk factors for nausea and vomiting in patients undergoing low emetic risk chemotherapy (LEC) are unclear. The aim of the study was to provide information on these topics by performing a multicenter, observational, prospective study. The study consisted of patients who were administered first-time LEC that was consistent or inconsistent with current guidelines. Using the visual analog scale, patients recorded their daily food intake and the occurrence and severity of nausea over a 5-day treatment period. The overall incidence of chemotherapy-induced nausea and vomiting did not differ significantly between patients undergoing guideline-consistent (n = 89) or guideline-inconsistent (n = 121) prophylaxis (30.3 vs. 22.3%, respectively; P = 0.19). Logistic regression analysis identified a history of nausea and LEC other than taxanes as independent risk factors associated with nausea and vomiting in patients undergoing LEC. The mean daily visual analog scale scores for nausea severity and a decrease in food intake were

Cisplatin (CDDP) combination chemotherapy is widely administered to patients with advanced lung cancer. The dose depends on multiple factors, including whether the tumor is non-small-cell lung cancer (NSCLC) or small-cell lung cancer (SCLC). Although efficacy is limited by cisplatin-induced nephrotoxicity (CIN), little is known about the risk factors for this complication. The aim of this study was to identify the risk factors for CIN in patients with advanced lung cancer, both NSCLC and SCLC. We retrospectively reviewed clinical data for 148 patients who underwent initial chemotherapy including CDDP ≥50 mg/m2 per patient per day for the first course at Kyushu Medical Center between October 2010 and September 2013. All data were collected from the electronic medical record system. Nephrotoxicity was defined as an increase in serum creatinine concentration of at least grade 2 during the first course of CDDP chemotherapy, as described by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. CIN was observed in nine patients. Univariate analysis revealed that cardiac disease and lower baseline serum albumin (Alb) values conferred a higher risk of nephrotoxicity (p

Central nervous system diseases cause the gait disorder. Early rehabilitation of a patient with central nervous system disease is shown to be benefit. However, early gait training is difficult because of muscular weakness and those elderly patients who lose of leg muscular power. In the patient's walking training, therapists assist the movement of patient's lower limbs and control the movement of patient's lower limbs. However the assistance for the movement of the lower limbs is a serious hard labor for therapists. Therefore, research into and development of various gait rehabilitation devices is currently underway to identify methods to alleviate the physical burden on therapists. In this paper, we introduced the about gait rehabilitation devices in central nervous system disease.

Background Docetaxel is a powerful anticancer agent for esophageal cancer. Preoperative combined chemotherapy with weekly docetaxel plus low-dose cisplatin and 5-fluorouracil (DFP) followed by surgery is expected to improve the survival of patients with resectable esophageal squamous cell carcinoma.

The antineoplastic effects of combinations of anticancer drugs (5-fluorouracil, irinotecan and cisplatin) and triterpenes (ursolic acid, betulinic acid, oleanolic acid and a Japanese apricot extract (JAE) containing triterpenes) on esophageal squamous carcinoma cells were examined by the WST-8 (2-(2-methoxy- 4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt) assay in vitro and by an animal model in vivo. Triterpenes and JAE showed additive and synergistic cytotoxic effects, respectively, on esophageal squamous carcinoma cells (YES-2 cells) by combinational use of 5-fluorouracil. JAE and 5-fluorouracil induced cell cycle arrest at G2/M phase and at S phase, respectively, and caused apoptosis in YES-2 cells. A new animal model of esophageal cancer causing tumor colonization of the peritoneal cavity and producing bloody ascites was made by injecting YES-2 cells into the peritoneal cavity of a severe combined immunodeficiency mouse. In this model, 5-fluorouracil inhibited colonization of tumor cells in the peritoneum. The addition of JAE to 5-fluorouracil augmented the suppression of experimental metastasis of the peritoneum. The numbers of peritoneal nodules of more than 2 mm in diameter in mice treated with 5-fluorouracil and JAE were less than those in mice treated with 5-fluorouracil alone or JAE alone. These results suggest that triterpenes, especially JAE, are effective supplements for enhancing the chemotherapeutic effect of 5-fluorouracil on esophageal cancer.

This article proposes a new muscle strength estimation method for upper limbs. It uses an inverse model of a musculo-skeletal model based on the muscle force applied on joints as well as the arrangement of the muscles. We did basic analyses of the parameters of the shape of a living body from magnetic resonance imaging (MRI) images and electromyography (EMG) in order to express isometric motion using the musculo-skeletal model. The model shows high reproducibility of a living body's isometric motion. We propose two easy methods of estimating muscle strength without optimization calculations and using a model which is the inverse of the musculo-skeletal model: a method based on output force distribution and a method based on joint torque distribution. We have validated them via experiments.

肝細胞癌の孤立性大動脈周囲リンパ節転移に対し, 切除を行い良好な経過を得た症例を経験したので報告する. 症例は60歳代の男性で, C型肝炎を経過観察中の2005年に腹部超音波検査で肝内腫瘤を指摘され当院紹介となった. CTで肝内に4cmと4.5cmの肝細胞癌を2個認め, 大動脈周囲に2.8cmの孤立性腫瘤を認めた. 大動脈周囲の孤立性腫瘤はリンパ節転移を疑ったが, 鑑別診断に難渋したため, 肝内病変の治療を先行し, 経皮的局所療法を施行した. 2月の経過観察中に大動脈周囲の腫瘤は著明に増大傾向を示した. リンパ節転移としても孤立性であり, また, 下大静脈と接することより, 今後増大すれば予後因子と成りうると判断し, 切除を行った. 術後経過は良好で, 術前2,685ng/mlと高値を示したAFPは3月後には3ng/mlと著明に低下した. 現在2年を経過するがAFPの上昇, 再発は認めていない. 肝細胞癌大動脈周囲孤立性リンパ節転移の報告はまれであり報告する.

Sentinel lymph node biopsy (SLNB) has been developed as a new diagnostic and therapeutic modality in melanoma and breast cancer surgery. The purpose of the SLNB include preventing the operative morbidity and improving the pathologic stage by focusing on fewer lymph nodes using immunocytochemic and molecular technology has almost achieved in breast cancer surgery. The prognostic meaning of immunocytochemically detected micrometastases is also evaluating in the SLN and bone marrow aspirates of women with early-stage breast cancer. SLNB using available techniques have suggested that the lymphatic drainage of the gastrointestinal tract is much more complicated than other sites, skip metastasis being rather frequent because of an aberrant lymphatic drainage outside of the basin exist. At the moment, the available data does not justify reduced extent of lymphadenectomy, but provides strong evidence for an improvement in tumor staging on the basis of SLNB. Two large scale prospective multi-center trials concerning feasibility of gamma-probe and dye detection for gastric cancer are ongoing in Japan. Recent studies have shown favorable results for identification of SLN in esophageal cancer. CT lymphography with endoscopic mucosal injection of iopamidol was applicable for SLN navigation of superficial esophageal cancer. The aim of surgical treatment is complete resection of the tumor-infiltrated organ including the regional lymph nodes. Accurate detection of SLN can achieve a selection of a more sophisticated tailor made approach. The patient can make a individualized choice from a broader spectrum of therapeutic options including endoscopic, laparoscopic or laparoscopy-assisted surgery, modified radical surgery, and typical radical surgery with lymph node dissection. Ultrastaging by detecting micrometastasis at the molecular level and the choice of an adequate treatment improve the postoperative quality of life and survival. However these issues require further investigation.

Lung cancer is the leading cause of cancer deaths in developed countries. Recently, autofluorescence bronchoscopy has been reported to improve the early detection of lung cancer in high-risk individuals. In the present study, we evaluated the efficacy of autofluorescence bronchoscopy for the early detection of bronchial premalignant and malignant lesions. From November 2000 through March 2004, 123 high-risk individuals (114 men and 9 women with a mean age of 68 years) were enrolled. Among 282 biopsy specimens, 93 (33.0%) were premalignant or malignant lesions. The sensitivity and negative predictive value for the detection of bronchial premalignant and malignant lesions were significantly higher with the addition of autofluorescence bronchoscopy than white light bronchoscopy alone. Moreover, the sensitivity for the detection of bronchial premalignant lesions was extremely higher with the addition of autofluorescence bronchoscopy than white light bronchoscopy alone, whereas there was no significant difference between autofluorescence bronchoscopy and white light bronchoscopy alone for the detection of non-malignant and malignant lesions. Autofluorescence bronchoscopy is a novel modality for the early detection of bronchial abnormality, especially for bronchial premalignant lesions.

症例は82歳, 女性. 咳嗽を主訴に近医受診, 胸部異常陰影を指摘され, 当科紹介となった. 胸部CT検査で左上葉の無気肺と左主気管支の閉塞を認め, 血液検査ではPro GRPの上昇を認めた. 気管支鏡を含む精密検査を行ったが, 確定診断を得ることができず, 肺癌を疑いPositron Emission Tomography (以下, PET) を施行した. PETでは左上葉とS状結腸に集積を認めた. 左上葉の病変は再検査での気管支洗浄液より結核菌が検出され, 気管支結核と診断した. 大腸内視鏡検査ではPET集積部に一致したS状結腸に4cm大のIp型の腫瘍を認め, PETで集積がなかった上行結腸に2型の腫瘍を認めた. S状結腸腫瘍に対しては内視鏡的粘膜切除術, 上行結腸腫瘍に対しては腹腔鏡補助下結腸右半切除術を施行した. S状結腸腫瘍は管状絨毛腺腫で, 上行結腸腫瘍は高分化腺癌であった. 結腸の同時性重複腫瘍で異なるPET所見を示した症例報告はなく, 若干の文献的考察を加えて報告する.

A positive association between vascular endothelial growth factor-C (VEGF-C) expression and lymph node metastasis has been reported in several cancers. However, the relationship of VEGF-C and lymph node metastasis in some cancers, including non-small cell lung cancer (NSCLC), is controversial. We evaluated the VEGF-C and vascular endothelial growth factor receptor-3 (VEGFR-3) expression in NSCLC samples from patients who had undergone surgery between 1998 and 2002 using real-time quantitative RT–PCR and immunohistochemical staining. We failed to find a positive association between VEGF-C and VEGFR-3 mRNA expression and lymph node metastasis in NSCLC. An immunohistological study demonstrated that VEGF-C was expressed not only in cancer cells, but also in macrophages in NSCLC, and that VEGFR-3 was expressed in cancer cells, macrophages, type II pneumocytes and lymph vessels. The VEGF-C/VEGFR-3 ratio of the node-positive group was significantly higher than that of the node-negative group. Immunohistochemical staining showed that VEGFR-3 was mainly expressed in cancer cells. The immunoreactivity of VEGF-C and VEGFR-3 was roughly correlated to the mRNA levels of VEGF-C and VEGFR-3 in real-time PCR. VEGF-C mRNA alone has no positive association with lymph node metastasis in NSCLC. The VEGF-C/VEGFR-3 ratio was positively associated with lymph node metastasis in NSCLC. This suggests that VEGF-C promotes lymph node metastasis while being influenced by the strength of the VEGF-C autocrine loop, and the VEGF-C/VEGFR-3 ratio can be a useful predictor of lymph node metastasis in NSCLC.

Objective The capability of regeneration of lung tissues in adults is limited after chronic destruction. Bone marrow–derived stem cells, retinoic acid, growth factors, and other approaches have been attempted to promote or facilitate this process. We hypothesized that fetal lung tissues, with great potential for growth and differentiation, could be used for lung regeneration. Methods Day 17 fetal lung tissue fragments at the pseudoglandular stage of lung development from Lewis rats were implanted into adult Lewis rat lungs. For group 1, fetal lung fragments were injected into the adult left lung parenchyma; for group 2, fetal fragments were injected with the left lung partially resected; for group 3, adult fragments were injected; and for groups 4 and 5, fetal fragments were implanted into the omentum and subcutaneous tissue, respectively. Results The grafts implanted into pulmonary parenchyma were differentiated with opening of the alveolar space after 4 weeks and were advanced further with morphologic features similar to those of neonatal lungs after 8 and 12 weeks. The implants were connected with pulmonary circulation determined by means of perfusion with India ink. These changes appeared to be further enhanced in animals with partial lung resection that might have facilitated the maturation of implanted fetal lung tissues through mechanical factors, soluble factors, or both. Fetal lung tissues did not mature when implanted into the omentum or subcutaneous tissue. Adult lung fragments did not expand after being reimplanted back into the same animal. Conclusions Fetal lung tissue might be an option for further investigation into lung regeneration.

Objective To localize small and deeply situated pulmonary nodules during thoracoscopy with roentgenographic fluoroscopy, we developed a marking procedure that uses a metallic coil. Methods Nine patients underwent video-assisted thoracoscopic surgery for the removal of 11 pulmonary lesions. Fluoroscopy-assisted thoracoscopic surgery after computed tomography-guided bronchoscopic metallic coil marking was performed with an ultrathin bronchoscope, with simulation by means of virtual bronchoscopy. During thoracoscopy, a C-arm–shaped roentgenographic fluoroscope was used to detect the radiopaque nodules. Results The marking procedure took 15 to 60 minutes from insertion to removal of the bronchoscope. There were no complications from the marking, and all 11 nodules were easily localized by means of thoracoscopy. The metallic coil showed the nodules on the fluoroscopic monitor, which aided in nodule manipulation. Nodules were completely resected under thoracoscopic guidance, except in one case in which a minithoracotomy was performed at an early stage of the trial. The pathologic diagnosis was primary adenocarcinoma in 9 patients, pulmonary metastasis from colon cancer in 1 patient, and pulmonary lymph node in 1 patient. Two cases of bronchioloalveolar adenocarcinoma with an invasive component and a well-differentiated adenocarcinoma were converted to open thoracotomy to perform curative lobectomy. Conclusions In this pilot study computed tomography–guided transbronchial metallic coil marking with an ultrathin bronchoscope with virtual bronchoscopic simulation might be a useful method for the fluoroscopy-assisted thoracoscopic resection of pulmonary nodules.

Background The histologic classification of thymoma has remained a subject of controversy for many years. In 1999, the World Health Organization Consensus Committee published a histologic typing system for tumors of the thymus. Methods We reclassified a series of 100 thymomas resected at Tokushima University Hospital and four affiliated hospitals in Japan between 1973 and 2001 according to the World Health Organization histologic classification and reported its clinicopathologic relationship and prognostic relevance. Results There were 8 type A, 17 type AB, 27 type B1, 8 type B2, 12 type B3, and 28 type C thymomas. The frequency of invasion to neighboring organs increased according to tumor subtype in the order A (0%), AB (6%), B1 (19%), B2 (25%), B3 (42%), and C (89%). There was no recurrence in patients with type A, AB, or B2 thymoma. The recurrence rates of patients with B1, B3, or C thymoma were 15%, 36%, and 47%, respectively. The disease-free survival rates were 100% for types A and AB, 83% for types B1 and B2, 36% for type B3, and 28% for type C thymoma at 10 years. There were significant differences in disease-free survival between types A and AB and types B1 and B2 ( p = 0.0436), and between type B3 and type C ( p = 0.042). By multivariate analysis, only Masaoka clinical stage ( p = 0.002) showed significant independent effects on disease-free survival. The 10-year survival rates of types A and AB, types B1 and B2, type B3, and type C thymoma were 100%, 94%, 92%, and 58%, respectively. Conclusions The current study confirmed the World Health Organization histologic classification as a good prognostic factor.

We examined the antitumour effect of a combination of betulinic acid (BA) and vincristine (VCR) on murine melanoma B16F10 cells in vitro and in vivo. Betulinic acid, a pentacyclic triterpene, showed a synergistic cytotoxic effect on melanoma cells by combinational use of VCR. Betulinic acid and VCR induced cell cycle arrest at different points (BA at G1 phase and VCR at G2/M phase) and caused apoptosis in B16F10 melanoma cells. In the in vivo study, VCR inhibited metastasis of tumour cells to the lung. The addition of BA to VCR augmented suppression of the experimental lung metastasis of melanoma cells in C57BL/6 mice. The number of lung nodules of more than 1 mm in diameter in mice treated with BA and VCR was less than that in mice treated with VCR alone. These results suggest that BA is an effective supplement for enhancing the chemotherapeutic effect on malignant melanoma.

BACKGROUND It is known that chromium is an inhaled carcinogen and an important risk factor in the development of lung carcinoma. METHODS The authors used a microscopic X-ray fluorescence analyzer with transmitted X-ray mapping imaging (Horiba, Kyoto, Japan) to measure the accumulation of chromium in 10 resected lung tissue specimens and 90 biopsy specimens from chromate workers. RESULTS The maximum chromium accumulation (mean ± standard deviation) in 10 resected lung tissue specimens was 197 ± 238 counts per second (cps)/mili ampere (mA) (range, 4–649 cps/mA). Chromium accumulation was scattered in six tissue specimens and diffuse in one specimen. Chromium accumulation in the proximal bronchi was less than in the bronchioles or subpleural regions of the lung. Chromium accumulation was detectable in 63 (70%) of 90 biopsy specimens, and the mean accumulation was 6.5 ± 9.2 cps/mA (range, 0–46.5 cps/mA). Chromium detected in bronchial tissue specimens was deposited in the bronchial stroma but not in the epithelium. The maximum chromium accumulations in dysplasic (n = 3), squamous metaplastic (n = 10), and normal bronchial epithelia (n = 9) in chromate workers and in normal bronchial epithelia (n = 3) in non-chromate workers were 20.2 ± 5.4, 18.3 ± 12.2, 13.2 ± 13.4, and 3.0 ± 1.8 cps/mA, respectively. The amount of chromium accumulation significantly increased according to the progression of malignant change of the bronchial epithelium (P = 0.003). CONCLUSIONS Previous studies found that lung carcinoma with chromate exposure exhibited a variety of genetic abnormalities. Considering genetic aberrations and chromium accumulation in these premalignant lesions is useful for elucidating the process of carcinogenesis in chromium-induced lung carcinoma. Cancer 2003. © 2003 American Cancer Society.

背景. 肺癌副腎転移は剖検例では高頻度に見られるが, 治癒切除可能な症例は少なかった. しかし近年画像診断の進歩により転移発見動機が増加し, 外科治療の結果長期生存が得られたとの報告例も散見される. 今回, 我々は肺癌手術後の副腎転移2例に対し摘出術を行ったので報告する. 症例1. 68歳男性.66歳時, 右上葉切除術を施行した. pT1N0M0, stage LAであった. 1年3ヵ月後の定期的なCT検査にて左副腎腫瘍があり, 転移と考えたが本人の希望で経過観察していた. その後他疾患で開腹術の際, 同時に副腎摘出術を行った. 病理診断で肺癌の転移と診断された. 副腎摘出術後3年9ヵ月経過し, 再発を認めていない. 症例2. 65歳男性.64歳時, 右中下葉切除術を施行した. pT1N2M0, stage IILへであった. 1年後, 右側腹部痛があり, CTにて右副腎腫瘍を発見した. 副腎単独転移と診断, 摘出術を施行した. その7ヵ月後, 胸部の広範囲に再発, 最終的に副腎摘出術から1年3ヵ月後死亡した. 結論. 副腎単独転移の場合, 摘出術によって長期予後が得られることがあり, 可能ならば手術も積極的に選択すべきである.

症例は80歳,男性.自覚症状は特になかったが,大腿骨骨折入院時胸部レントゲン写真で異常影を指摘された. CT上,腫瘤は右上葉にあり46×32mm大で,壁側胸膜への直接浸潤が疑われた. 2カ月後のCTで,腫瘤は59×55mmと増大していた.経気管支鏡下肺生検では悪性所見を認めなかったが,肺癌が疑われたため,手術を行った.右上葉の腫瘤は肺尖部で胸膜と炎症性に癒着していた.組織学的には紡錘形の組織球様細胞がstoriform patternを示し,炎症細胞を伴っていた.免疫染色で, α1-antitrypsin, α1-antichimotrypsinが陽性であったことから,炎症型MFHと診断された.術後3年あまり経過したが再発の徴候なく経過良好である.

BACKGROUND A distinction between noninvasive, invasive, and metastatic thymoma on the basis of the cytologic features is difficult. The current study investigated whether the expression of MMP and TIMP was correlated with tumor invasiveness and prognosis in patients with thymoma. METHODS Tumor tissue samples were obtained from 42 patients with thymic epithelial tumors between 1974 and 2001 at Tokushima University Hospital. Three-micrometer-thick, formalin-fixed, paraffin-embedded tissue sections were immunostained using specific antibodies against MMP-2, MMP-9, TIMP-1, and TIMP-2. RESULTS MMP-2 expression was detected in 30 tumors (71%), and TIMP-2 expression was detected in 31 tumors (74%). MMP-9 expression was detected in 22 of 36 tumors (61%), and TIMP-1 expression was detected in only 7 tumors (19%). MMP-2 and TIMP-2 expression levels were very low (10% and 0%, respectively) in noninvasive tumors but were very high (91% and 97%, respectively) in invasive tumors. In thymic epithelial tumors, the more progressive the clinical stage of tumor, the higher the strongly positive rate of MMP-2 and TIMP-2 expression. There was no correlation between positivity for MMP-9 and stage. Twenty-five percent of Type AB thymomas and 50% of Type B1 thymomas expressed MMP-2 and TIMP-2. Most of Type A, Type B2, Type B3, and Type C thymomas expressed MMP-2 and TIMP-2. There were significant differences in disease-free survival at 5 years between patients without and with MMP-2 expression (91% vs. 55%, respectively) and patients without and with TIMP-2 expression (100% vs. 53%, respectively). CONCLUSIONS MMP-2 and TIMP-2 are key enzymes for invasiveness of thymic epithelial tumors. The expression of these proteins can predict a poor outcome in patients with thymoma. Cancer 2003. © 2003 American Cancer Society.

A 53-year-old female with pemphigus vulgaris received treatment with prednisolone for 3 years. On chest computed tomography performed at follow-up, an anterior-mediastinal tumor (4 cm × 3 cm) was detected and diagnosed as a thymoma. Although amyosthenia was absent, the patient's anti-acetylcholine-receptor antibody level was high, and she was positive for anti-desmoglein 3 antibodies. She underwent extended thymectomy in the same year, following which both the anti-acetylcholine receptor antibody and the anti-desmoglein 3 antibody levels were normalized. The patient's skin symptoms improved, and the steroid dose was gradually lowered and finally discontinued 4 years postoperatively. Extended thymectomy may be an effective therapy for treating patients with pemphigus.

症例は43歳,女性. 1992年7月,検診で右乳腺の腫瘤を指摘され,精査のため当科受診した.穿刺吸引細胞診はclass 1であったが臨床的に悪性を否定できず,生検が施行された.病理組織学的に非浸潤性小葉癌と診断されたため,追加切除が施行された.切除標本の多数切片の検索で断端陽性であったが,本人とのインフォームドコンセントに基づき経過観察とした.以後3カ月毎に超音波検査, 6カ月毎にマンモグラフィを施行した. 1996年2月に超音波検査で前回の切除部分に径5mmの低エコーの腫瘤像を認めた.穿刺吸引細胞診ではclass1であった.その後腫瘤は次第に大きくなり, 1997年7月には腫瘤は径8mmとなったため腫瘤摘出術が施行された.切除標本は病理組織学的に浸潤性小葉癌と診断され,乳腺全切除術が施行された.非浸潤性小葉癌を臨床的病理学的に5年間観察し浸潤性小葉癌に進展したことを確認し得たのは貴重と思われ報告した.

Background and Objectives Organ specificity has been demonstrated in the mode of CD44 expression among several cancers. Methods We examined the expressions of CD44 standard (CD44s) and CD44 variants (CD44v) in 14 cell lines (small cell lung cancer (SCLC): 5, non-small cell lung cancer (NSCLC): 9 and 20 surgically resected samples (SCLC: 7, NSCLC: 13) of lung cancer using reverse transcription-polymerase chain reaction and immunohistochemistry. Results Although both NSCLC and SCLC expressed CD44s, the frequency and intensity of CD44s expression in NSCLC were different from those in SCLC: cell lines, 89% vs. 40%; tumor samples, 100% (diffusely stained) vs. 57% (focally stained). CD44s expression was partially or completely repressed in SCLC. However, NSCLC frequently expressed CD44v, but SCLC expressed infrequently: cell lines, 67% vs. 20%; tumor samples, 69% vs. 0%. The N-417 line, which only expressed some CD44v in SCLC, falls SCLC and NSCLC both in biomarkers and in growth patterns. Conclusions CD44 expression was repressed in SCLC but was enhanced in NSCLC. J. Surg. Oncol. 1998;69:128–136. © 1998 Wiley-Liss, Inc.

OBJECTIVES: To re-evaluate the efficacy of fluoroscopy-assisted thoracoscopic resection after computed tomography (CT)-guided bronchoscopic metallic coil marking (FATS-CM), which was our original method for small peripheral pulmonary lesions. METHODS: Fifty-eight patients with 63 lesions underwent FATS-CM. A metallic coil was installed in the bronchus nearest to the lesion under CT fluoroscopic guidance with ultrathin bronchoscopy. The virtual bronchoscopic navigation (VBN) system was used in 14 cases. Afterwards, we basically performed wide wedge resection (WWR) using a C-arm-shaped roentgenographic fluoroscope during thoracoscopic surgery initially, and then the final procedure was determined by intraoperative histological diagnosis. Moreover, we prospectively treated ground-glass opacity (GGO) lesions of

1987年から1995年までの9年間,209樹のキウイフルーツ花腐細菌病の発生と開花日を調査し,開花日からさかのぼって60日前までを10日ごとにステージ1から6に類別し,各ステージでの発病率と10種気象要因(気温,最高気温,最低気温,気温較差(最高-最低気温),湿度,最低湿度,日照時間,日射量,降水量および降雨日数)との関係について検討した。開花日と発病率との関係では正の相関(危険率5%)が認められた。ステージ別気象要因と発病率との相関で0.5以上の相関係数を示した要因は,ステージ2の気温,最高気温,湿度,降水量および降雨日数,ステージ3の気温差,湿度,最低湿度および日射量,ステージ4の最低気温,ステージ5の気温および最高気温の12要因であった。この12種要因を用い,変数増加法による重回帰分析を行った結果,ステージ2の降水量,ステージ2の最高気温,ステージ3の気温較差および湿度,ステージ5の気温の5気象要因に有意差が認められ,かつそれらの要因の寄与率は61.2%と極めて高かった。このことから,開花10日から29日前の気象要因,特に前述の5要因が本病発生に強く影響を及ぼすことが明らかとなった。

We report a patient treated for malignant melanoma of the left planta who developed pulmonary metastases after a disease-free interval of 10 years. Metastatectomy was performed after observing progress for 12 months. However, 18 months later, pretracheal and right axillary lymph node metastases occurred. Because pulmonary metastasis from malignant melanoma may occur after 10 years or more, we observe patients carefully. If it does occur, an operation should be considered under limited indications. We should also recognize that recurrence may occur within a short interval after metastatectomy as well.

Summary Background Photodynamic therapy (PDT) using Talaporfin is an attractive treatment for central-type early lung cancer. It was noted that some patients had altered levels of arterial oxygen saturation as indicated by pulse oximeter (SpO 2 ) and arterial oxygen saturation levels in blood gas analysis (SaO 2 ) during PDT. The present experiments were designed to provide an explanation for these findings. Methods The influence of Talaporfin on SpO 2 using in vitro and in vivo experiments, and clinically, was examined. Results Our in vitro and in vivo experiments showed a linear relationship between Talaporfin concentration in the plasma and the SpO 2 level ( R = 0.9957 and 0.9837). The apparent SpO 2 level decreased according to the increase of Talaporfin concentration in the plasma. In two patients with PDT, SpO 2 levels at 4–6 h and 24 h after Talaporfin administration were 93% and 97%, respectively. Conclusions Talaporfin raised blood absorbance at 660 nm with a pulse oximeter. It appeared that the presence of the drug falsely decreased the level of SpO 2 since SpO 2 did not actually change.

A 55-year-old-male patient underwent subtotal esophagectomy for esophageal cancer (pT1b, N0, M0, stage II) in April 2005. The patient received postoperative chemotherapy (docetaxel 40 mg/body, 5-fluorouracil 750 mg/body, cisplatin 10 mg/body : administered every 4 weeks) for 3 months. Six months postoperatively, routine follow up CT demonstrated multiple metastatic tumors in the bilateral lungs. Under the diagnosis of multiple lung metastases, the patient was hospitalized and received intensive chemotherapy with docetaxel 40 mg/ week (day 1), 5-fluorouracil 500 mg/ day (days 1-5), cisplatin 10 mg/ day (days 1-5). After two weeks administration, the patient eagerly hoped for outpatient treatment. The treatment was changed to outpatient chemotherapy with S-1 100 mg/ day (continuous administration for 3 weeks followed by rest for 1 week) and cisplatin 20 mg/ every week. The treatment enabled the patient to keep working. Follow up CT showed disappearance of all tumors two months after TS-1/cisplatin chemotherapy. There were no obvious signs of recurrence 5 months after chemotherapy. The S-1/cisplatin therapy in the outpatient was thought to be one of the effective treatments in maintaining quality of life for the patient.

To evaluate the effects of drugs in clinical settings, an animal model of lung cancer similar to clinical cancer is necessary. Our previous studies described an SCID mouse model using orthotopic implantation of the human lung cancer cell line which mimicked the lymph node metastasis of patients with lung cancer. In this study, we made animal models that reflected various metastatic forms of lung cancer in humans. We applied our procedure to 6 lung cancer cell lines. Suspensions of 2.0 x 10(4) cancer cells were injected into the left lung of SCID mice. We evaluated the mRNA expressions of 52 proteins related to the metabolism of and resistance to anticancer drugs of each tumor cell line and its orthotopically implanted tumor using a customized cDNA array. Three lung cancer cell lines had the potential of lymphogenous metastasis and 3 cell lines had the potential of hematogenous metastasis in this model system. The A549 line showed multiple metastases, and Ma2 line showed solitary metastasis. The expression of 52 genes in each implanted tumor was closely correlated with that in each cell lines (correlation coefficients: 0.8883-0.9533), and the gradient of the regression line was more than 0.9. This model was similar to the metastatic form in patients with lung cancer. The similar expression of proteins in each tumor cell line in vitro and implanted tumor in vivo gives an advantage in evaluating the effects of molecular-targeted drugs and the relationship between specific genes and tumor potential in preclinical studies.