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Nadolol is a hydrophilic and non-selective β-adrenoceptor blocker with a bioavailability of 30%, relatively longer half-life, negligible metabolism, and predominant renal excretion. Previous studies have reported that nadolol is a substrate of P-glycoprotein, and the coadministration with itraconazole, a typical P-glycoprotein inhibitor, results in elevated plasma concentrations and cumulative urinary excretion of nadolol. In this study, we assessed whether measurements of urinary-excreted nadolol can be an alternative method of plasma pharmacokinetics for P-glycoprotein-mediated drug interactions in humans. We re-analyzed the pooled data set of plasma concentration and urinary excretion of nadolol from our previous clinical studies in a total of 32 healthy Japanese adults. The area under the plasma concentration-time curve from 0 to infinity (AUC0-∞ ) of nadolol in individual subjects was significantly correlated with the maximum plasma concentration (P < 0.01, r = 0.80), and the cumulative amount excreted into urine (Ae ) at 4 (P = 0.01, r = 0.51), 8 (P < 0.01, r = 0.63), 24 (P < 0.01, r = 0.75), and 48 hours (P < 0.01, r = 0.77). Significant correlations were also observed between the AUC and Ae during the same respective time periods. In the drug interactions of nadolol with itraconazole, rifampicin, a well-known P-glycoprotein inducer, or grapefruit juice, there were significant correlations between the differences in AUC0-48 and those in Ae, 0-48 from the controls in individual subjects. These results suggest that the measurements of urinary excretion of nadolol can be employed as a sensitive and reliable alternative to plasma pharmacokinetics for the evaluation of P-glycoprotein-mediated drug interactions. This article is protected by copyright. All rights reserved.

Background: There is little evidence regarding the risk of hepatitis B virus (HBV) reactivation in solid tumor patients without hepatitis B surface antigen (HBsAg), but with antibodies against hepatitis B core antigen (anti-HBc) and/or antibodies against HBsAg (anti-HBs) who received systemic chemotherapy. Methods: We conducted two retrospective studies; a single-center retrospective study to measure the incidence of HBV reactivation in 1,376 HBsAg-negative patients with solid tumors who received systemic chemotherapy, and a multicenter retrospective study to clarify the clinical features of HBV reactivation in HBsAg-negative patients with solid tumors who received systemic chemotherapy at 5 institutions. HBV reactivation was defined as reappearance of HBsAg or detection of HBV DNA levels of 1.3 log IU/mL or more in both studies.Results: With a median follow-up time of 607 days, HBV reactivation was confirmed in 2 of 218 patients with resolved HBV infection in the single-center study. Of the 12 patients with HBV reactivation who were diagnosed at a median HBV DNA of 1.3 log IU/mL in the multicenter study, no HBV-related hepatitis was observed. The median time from the first chemotherapy to confirmed HBV reactivation was 141 days. Of the 11 patients in whom both anti-HBc and anti-HBs were measured, all were seropositive for anti-HBc, and 7 were seronegative for anti-HBs at baseline.Conclusions: The risk of HBV reactivation was estimated to be 0.9% in HBsAg-negative patients with solid tumors who received systemic chemotherapy. Seronegativity for anti-HBs at baseline may be an important risk factor for HBV reactivation in these patients.

Background and Purpose— Several studies suggested that statins during hospitalization were associated with better disability outcomes in patients with acute ischemic stroke, but only 1 small randomized trial is available. Methods— We conducted a multicenter, open-label, randomized controlled trial in patients with acute ischemic strokes in 11 hospitals in Japan. Patients with acute ischemic stroke and dyslipidemia randomly received statins within 24 hours after admission in the early group or on the seventh day in the delayed group, in a 1:1 ratio. Statins were administered for 12 weeks. The primary outcome was patient disability assessed by modified Rankin Scale at 90 days. Results— A total of 257 patients were randomized and analyzed (early 131, delayed 126). At 90 days, modified Rankin Scale score distribution did not differ between groups ( P =0.68), and the adjusted common odds ratio of the early statin group was 0.84 (95% confidence interval, 0.53–1.3; P =0.46) compared with the delayed statin group. There were 3 deaths at 90 days (2 in the early group, 1 in the delayed group) because of malignancy. Ischemic stroke recurred in 9 patients (6.9%) in the early group and 5 patients (4.0%) in the delayed group. The safety profile was similar between groups. Conclusions— Our randomized trial involving patients with acute ischemic stroke and dyslipidemia did not show any superiority of early statin therapy within 24 hours of admission compared with delayed statin therapy 7 days after admission to alleviate the degree of disability at 90 days after onset. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT02549846.

Purpose Intracranial hemorrhage after thrombectomy using a catheter to treat acute major cerebral artery occlusion is known to exacerbate patient outcomes. This study was performed to determine the relationship between middle cerebral artery (MCA) tortuosity and postoperative hemorrhage. Methods We examined 111 consecutive patients who underwent acute thrombectomy for major intracranial artery occlusion in the anterior circulation at our hospital between September 2013 and June 2016. Patients in whom intracranial hemorrhage or subarachnoid hemorrhage was seen on head computed tomography 12-24 hours after surgery were assigned to the hemorrhagic group, whereas all the other patients were assigned to the nonhemorrhagic group. The groups were compared for tortuosity of the MCA, which was evaluated by finding the top-to-bottom (TB) distance of the M1 segment on anterior–posterior view angiograms. A modified Rankin scale score of 0-2 at 3 months after onset was considered a favorable prognosis. Results The hemorrhagic group comprised 28 patients (25.2%) and the nonhemorrhagic group comprised 83 patients (74.8%). No significant difference in patient characteristics was seen between the groups. The hemorrhagic group displayed significantly fewer patients with a favorable prognosis (17.9% versus 43.4%, P = .016). The TB distance was significantly greater in the hemorrhagic group (hemorrhagic group, 9.7 mm; nonhemorrhagic group, 7.6 mm; P = .002); multivariate analysis also identified a TB distance over 8.8 mm as a factor independently associated with postoperative intracranial hemorrhage (P = .001). Conclusions Post-thrombectomy hemorrhage was significantly correlated with TB distance. A solution is needed for selecting and combining devices used in patients with a TB distance over 8.8 mm.

Patients with amyotrophic lateral sclerosis (ALS) present an increased risk of postoperative respiratory failure after general anesthesia. We report the case of a 71-year-old man with ALS who underwent emergency laparotomy for small bowel strangulation. After surgery, he remained intubated and was transferred to the high care unit under mechanical ventilation, due to unstable hemodynamics requiring inotropic support. On postoperative day (POD) 3, he was extubated under stable hemodynamics and respiratory status. Immediately after extubation, bilevel positive airway pressure (bilevel PAP) was prophylactically applied to prevent postoperative respiratory failure, which may have been caused by respiratory muscle fatigue, attributed to general anesthesia and surgical stress. On POD 7, bilevel PAP was smoothly weaned off because no signs and symptoms of respiratory failure were observed. On POD 10, he achieved 30 m-walk without rest. No postoperative complications were observed up to one month after surgery. Postoperative respiratory failure may lead to death in patients with neuromuscular disorder. Non-invasive ventilation (NIV) reduces respiratory muscle fatigue, resulting in easy sputum expectoration, promoting CO2 washout, and better oxygenation. Consequently, the prophylactic use of NIV to avoid postoperative respiratory insufficiency should be considered in patients with ALS after emergency operation under general anesthesia.

The clinical efficacy and outcomes of pazopanib treatment for metastatic extraosseous Ewing sarcoma remain unclear. We herein report a case of heavily pre-treated metastatic extraosseous Ewing sarcoma in which pazopanib treatment achieved a significant improvement. A 17-year-old girl was referred to our hospital due to metastatic extraosseous Ewing sarcoma. The initial cytotoxic chemotherapy was temporarily effective, however, her disease eventually progressed, and she was subsequently treated with pazopanib. The recurrent tumor showed a marked response to pazopanib therapy; the therapeutic effect has lasted for more than 26 months. The present case suggests that pazopanib may be a therapeutic option for extraosseous Ewing sarcoma.

A 56-year-old man was diagnosed with advanced adenocarcinoma of the esophagogastric junction. He received 1 course of neoadjuvant chemotherapy with S-1. After neoadjuvant chemotherapy, the primary tumor showed a remarkable decrease in size. Subtotalesophagectomy, D2 lymph node dissection, and reconstruction with a gastric tube through the posterior mediastinal route were performed. Pathological examination showed that most of the cancer cells had been destroyed, with a part where adenocarcinoma mucosa was seen. We successfully treated a case of advanced adenocarcinoma of the esophagogastric junction, with neoadjuvant S-1 chemotherapy and surgicalresection.

In the manufacture of tablets, especially in direct tableting processes, the flowability of excipient powders and formulated powders is one of the most important characteristics. In the past two decades, orally disintegrating tablets (ODTs) have been prepared as popular solid dosage forms for elderly patients. Many types of mannitol granules have been developed and marketed as new pharmaceutical excipients for ODTs, owing to the solubility and palatability of mannitol. Characterizing the flow behaviors of these mannitol granules is essential to their use. The flowability of mannitol excipients was the focus of the present study. A fine crystalline mannitol powder, eight commercial types of mannitol granules and four types of mannitol mixture granules were evaluated. Two flowability testers were used for comparing and analyzing the samples' flowabilities. A variety of methodologies were used: an assessment using Carr's index, a shear test and a dynamic flow test. Mannitol powder showed the lowest Carr's index, meaning the lowest flowability. Spherical mannitol granules showed the lowest angle of internal friction in the shear test and extremely low basic flow energy in the dynamic flow test. Larger granules showed relatively high values for Carr's index, but also a relatively high total flow energy.

Purpose We developed a new technique, sutureless mesh fixation, using 2-octyl cyanoacrylate (Dermabond®, a surgical tissue adhesive) for incisional hernia repair. The objective of this article is to introduce the new technique and to examine whether the technique provides sufficient resistance to abdominal pressure.

Background and Aim The feasibility of TDM-621, the synthetic infectious agent-free peptides, was tested in hemostasis of the bleeding after endoscopic treatments of the gastric tumors. Methods The patients who underwent endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) were enrolled in the present study. The subject of hemostasis was the oozing after the EMR or ESD. The hemostatic effect, the secondary hemorrhage from one postoperative day to the day before discharge and operability were studied. Results The hemostatic effects were assessed in 12 patients. It was “remarkably effective” in 11 patients and “effective” in 1 patient. The operability was “very easy” in two patients, “easy” in eight patients and “acceptable” in two patients. No secondary hemorrhage was observed in all of 12 patients. No adverse effect considered to be related to TDM-621 was observed. Conclusion It was shown that hemostasis using TDM-621 was feasible after endoscopic treatments of the gastric tumors without any technical trouble or adverse event.

Refractory esophageal ulcerations occur rarely after cardiovascular surgery, occasionally leading to perforation. There is little consensus on their optimal management. Herein, we present a case of refractory esophageal ulceration after cardiovascular surgery. A 62-year-old woman with Marfan’s syndrome was referred to our hospital with cardiac failure due to aortic regurgitation. She underwent root replacement by the modified Bentall method. Refractory esophageal ulceration developed 3 months later and persisted for 3 months despite conservative therapy. With the patient’s informed consent, Kirschner bypass surgery was performed. A jejunostomy using a 20 Fr. Nelaton catheter was made in the Roux-en-Y loop of the jejunum for postoperative endoscopy. The postoperative course was uneventful and transjejunostomal endoscopy revealed excellent healing of the ulceration. Esophageal bypass surgery and transjejunostomal endoscopy were very effective in this patient with refractory esophageal ulceration.

The HyperEye Medical System is a newly developed device that allows for the visualization of the fluorescent image of indocyanine green enhanced by near-infrared light among the surrounding vivid color images. We recently applied this system to confirm the blood flow of an esophageal substitute, and for sentinel node navigation during esophagectomy. Five consecutive patients with thoracic esophageal cancer who underwent a subtotal esophagectomy between June 2010 and May 2011 were enrolled in the study. The esophageal substitute used for reconstruction was the stomach and ileocecum in four and one cases, respectively. In all cases with a reconstructive stomach, fine arterial blood flow and venous perfusion were observed. The blood flow of the reconstructive colon was poor before microvascular anastomosis, however, it dramatically increased after anastomosis. Concerning the sentinel node navigation, the fluorescence of lymph nodes, lymphatic vessels, and the tumor site were detected. The postoperative courses of all cases were uneventful, with no mortalities or anastomotic leakage occurring.

Background and Aim: We seek for the accurate and simple method for detecting sentinel nodes of gastric cancer which can be popularized in community hospitals. The indocyanine green (ICG) fluorescence-guided method is reported to be sensitive. However, the ordinal fluorescence cameras have gray scale imaging and require a dark room. We have developed a new device, Hyper Eye Medical System (HEMS) which can simultaneously detect color and near-infrared rays and can be used under room light. This study was planned to examine whether submucosal injection of 0.5 mL × 4 of 50 µg/mL ICG on the day before operation is the adequate administration for detecting sentinel nodes using HEMS in the gastric cancer surgery. Methods: The patients underwent gastrectomy for clinical T1a (mucosa)–T2 (muscularis propria) and clinical N0 were enrolled in the present study. As a preliminary trial, one case each of the ICG 25 and 100 µg/mL, injected on the day before operation and intraoperative injection, was examined. Then, 10 cases injected 50 µg/mL ICG on the day before operation were examined. Results: The ICG fluorescence of the patient injected 100 µg/mL was too intense and that of the patient injected 25 µg/mL was too faint. Sentinel lymph nodes were detected in all of 10 cases injected 50 µg/mL, the day before operation and number of sentinel lymph nodes per patient was 3.6 ± 2.1. Metastasis was observed in one case. All of ICG fluorescence-positive sentinel nodes were positive for the metastasis. In the patient who underwent intraoperative injection, sentinel lymphatic basins could be identified. Conclusion: The present study shows that HEMS-guided abdominal surgery is feasible under room light. Submucosal injection of 0.5 mL × 4 of 50 µg/mL ICG on the day before operation is the adequate administration for detecting sentinel nodes using HEMS in the gastric cancer surgery.

Background and Aims: The most effective treatment would be neoadjuvant chemoradiotherapy (NACRT) plus surgery with three-field lymphadenectomy, if tolerability and complications are acceptable. The aim of this prospective study was to evaluate the tolerability of NACRT+ systematic three-field lymphadenectomy. Methods: A total of 127 cases of advanced esophageal carcinoma were objected, among which 32 had NACRT, being the cases suspected to cT3–T4 or

Esophageal neuroendocrine carcinomas are rare, aggressive and have a poor prognosis. Combined therapy using chemotherapy, radiotherapy and/or surgery appear effective for them. Upper gastrointestinal endoscope of a 65-year-old male revealed a localized ulcerative lesion in the middle esophagus. Histology of biopsy specimens indicated a neuroendocrine carcinoma. A computed tomography showed an esophageal tumor with enlarged mediastinal lymph nodes. The patient was administered neoadjuvant chemotherapy consisting of 5-fluorouracil and cisplatin, which led to partial response. Subtotal esophagectomy with three-field lymphadenectomy was performed. Pathologically, the tumor was 25 mm and infiltrated the proper muscle layer. The tumor cells were arranged in microtubular structures, with small and round cells containing scanty cytoplasm, and exhibited intense mitosis 51/10 HPF. They were positive for synaptophysin and chromogranin A, and Ki-67 labeling index was 70% - 80%. These findings led to the diagnosis of neuroendocrine carcinoma of small cell type. The patient was administered adjuvant chemotherapy using cisplatin and CPT-11, and he is now alive disease-free at the time of this writing.

Background and Purpose— The hemodynamic factors of aneurysms were recently evaluated using computational fluid dynamics in a static vessel model in an effort to understand the mechanisms of initiation and rupture of aneurysms. However, few reports have evaluated the dynamic wall motion of aneurysms due to the cardiac cycle. The objective of this study was to quantify cardiac cycle-related volume changes in aneurysms using 4-dimensional CT angiography. Methods— Four-dimensional CT angiography was performed in 18 patients. Image data of 1 cardiac cycle were divided into 10 phases and the volume of the aneurysm was then quantified in each phase. These data were also compared with intracranial vessels of normal appearance. Results— The observed cardiac cycle-related volume changes were in good agreement with the sizes of the aneurysms and normal vessels. The cardiac cycle-related volume changes of the intracranial aneurysms and intracranial normal arteries were 5.40%±4.17% and 4.20±2.04%, respectively, but these did not differ statistically ( P =0.12). Conclusions— We successfully quantified the volume change in intracranial aneurysms and intracranial normal arteries in human subjects. The data may indicate that cardiac cycle-related volume changes do not differ between unruptured aneurysms and normal intracranial arteries, suggesting that the global integrity of an unruptured aneurysmal wall is not different from that of normal intracranial arteries.

The aim of this study was to investigate the efficacy of diagnosing depth of wall invasion of gastric cancer on endoscopic images using computer-aided pattern recognition. The back propagation algorithm was used for computer training. Data of 344 patients who underwent gastrectomy or endoscopic tumor resection between 2001 and 2010 and their 902 endoscopic images were collected. The images were divided into ten groups among which the number of patients and images were almost equally distributed according to T staging. The computer learning was performed using about 800 images from all but one group, and the accuracy rate of diagnosing the depth of wall invasion of gastric cancer was calculated using the remaining group of about 90 images. The various numbers of input layers, hidden layers, and learning counts were updated, and the ideal setting was decided. Similar learning and diagnostic procedures were repeated ten times using every group and all 902 images were tested. The accuracy rate was calculated based on the ideal setting. The most appropriate setting was a resolution of 16 × 16, a hidden layer of 240, and a learning count of 50. In the next step, using all the images on the ideal setting, the overall accuracy rate was 64.7%. The diagnostic accuracy was 77.2, 49.1, 51.0, and 55.3% in the T1, T2, T3, and T4 stagings, respectively. The accuracy was 68.9% in T1a(M) staging and 63.6% in T1b(SM) staging. The positive predictive values were 80.1, 41.6, 51.4, and 55.8% in the T1, T2, T3, and T4 staging, respectively. It was 69.2% in T1a(M) staging and 68.3% in T1b(SM) staging. Computer-aided diagnosis is useful for diagnosing depth of wall invasion of gastric cancer on endoscopic images.

A 56-year-old man was diagnosed with esophageal cancer by upper gastrointestinal endoscopy for examination of dysphagia. The patient had undergone total gastrectomy and jejunal interposition 4 years previously for a gastric cancer at the pT1N0M0 stage according to the UICC-TNM classification. Enhanced CT findings revealed a 3-cm-diameter mass located near the superior mesenteric artery. We conducted subtotal esophagectomy associated with partial jejunectomy including mesojejunectomy. The mass was histologically diagnosed to be mesojejunal lymph node metastasis from esophageal cancer. Mesojejunal lymph node metastasis from esophageal cancer developing after total gastrectomy has been reported in only three cases including ours. The present lymph node metastases may have occurred via the newly developed lymphatic drainage route through the esophagojejunostomy, and this metastatic lymph node can be considered the regional lymph node. Therefore, resection of the interposed jejunal limb with mesojejunectomy may be rational in surgery on esophageal cancer developing after total gastrectomy.

In an attempt to improve survival of patients with locally advanced esophageal cancer, chemoradiotherapy consisting of cisplatin, 5-fluorouracil (5-FU), and irradiation has recently been used. For such patients, concurrent chemoradiotherapy using docetaxel in combination with cisplatin and 5-FU has been introduced and is under evaluation. We herein report an esophageal cancer patient with concomitant distant lymph node metastasis in whom a complete response was achieved by chemoradiation therapy. A 46-year-old man was diagnosed as having stage IV A esophageal cancer with synchronous bulky metastasis in the celiac lymph node, and concurrent chemoradiotherapy was started. Chemotherapy consisting of docetaxel (30 mg/m2 on days 1, 8), cisplatin (60 mg/m2 on day 1), and 5-FU (200 mg/m2/day, continuous infusion on days 1–14) was performed for 2 cycles. At the same time, irradiation therapy (1.8 Gy/day on 1–5 days every week for 6 weeks) was employed for both local and metastatic lesions. Although the patient experienced severe hematological toxicity throughout the course, chemoradiotherapy resulted in complete regression of both local and metastatic disease. Subsequently, he was followed as an outpatient without any maintenance therapy, and he has been free of disease for 38 months after completion of the combination therapy. Thus, concurrent chemoradiotherapy may be effective for esophageal cancer, even with visceral metastasis.

We report a rare case of leiomyosarcoma of the lower esophagus that was treated by endoscopic resection. A 56-year-old man was referred to our hospital in October 2005 because of mild discomfort around the lower esophagus upon swallowing for 2 months. The esophagogram showed a filling defect at the lower esophagus. It revealed a giant polyp tumor arising from the right wall of the lower esophagus. The diameter of the top of the tumor was 25 mm. Upper gastrointestinal endoscopic study revealed that the lesion was a tumor with a large stalk at the right side in the lower esophagus. The lesion was at 38 cm from the incisors. Histological study of the biopsy samples revealed the tumor was a leiomyosarcoma by morphological features of the tumor in hematoxylin and eosin stain. Computerized tomographic (CT) scan showed the tumor protruded into the lumen of the lower esophagus but into none of the lymph nodes, nor was distant metastasis seen. Endoscopic resection was performed with an electric snare. The tumor was completely resected without any trouble. The tumor was composed of spindle cells with irregular nuclei and numerous mitotic figures were present. The immunohistochemical staining showed positive for p53. The Ki67 labeling index was 8.7%, which was consistent with leiomyosarcoma. It also showed positive for smooth muscle actin, caldesmon, and calponin but negative for c-kit, CD34, and S-100. These histopathological findings disclosed a leiomyosarcoma. The patient is asymptomatic and disease free after a 2-year follow up. We believe that endoscopic resection will be an option for an intraluminal polypoid form of esophageal leiomyosarcoma.

Undifferentiated carcinoma of the esophagus (UEC) is an uncommon esophageal malignancy, and patients with UEC have an especially poor prognosis because of extensive metastasis even at an early stage. A standard treatment regimen for UEC has not yet been established. We have experienced a case with UEC (T2N1, stage II) that achieved complete remission by chemoradiotherapy [cisplatin (CDDP) + 5-fluorouracil (5-FU), 50 Gy]. A 67-year-old man with a 4-cm type 1 tumor in the middle thoracic esophagus was diagnosed as UEC (non-small cell type) histologically. Computerized tomographic (CT) scan of the chest showed metastatic lesions at the right recurrent nerve lymph nodes. Although the lesion was diagnosed as T2, N1, and stage II, the patient was judged to be a severe case because surgical control of UEC is almost impossible even at the early stages. Chemoradiotherapy (CRT; CDDP + 5-FU, and radiation) was selected for this case. In the first course of CRT, the patient was given CDDP (20 mg/m2) and 5-FU (700 mg/m2) for 5 days and concurrent external-beam irradiation (30 Gy, 2 Gy/day × 15 days) in the “long-T” field including the cervical and mediastinal lymph nodes. The second course was the same chemotherapy (CDDP 20 mg/m2/day + 5-FU 700 mg/m2/day, 5 days) with externalbeam irradiation (2 Gy/day) for 10 days (5 days/week, 2 weeks). After the first course of CRT, the patient already had achieved complete remission (CR). An upper gastrointestinal endoscopic study showed the tumor had almost disappeared and was covered by normal epithelium. Histological study from the biopsy samples showed there were no viable cancer cells at the lesion. CT scan of the chest showed the metastatic lesions at the right recurrent nerve lymph nodes had reduced. After the second course of CRT had been completed, the patient was discharged from the hospital. The patient is still alive with no cancer relapse at 2.5 years after the treatment. Further studies to clarify the response rate and survival effect of CRT in patients with UEC are expected.

In Nagoya City University Hospital, a two-week training program for senior students in pharmacy training was carried out up until 1999. The large majority of senior students took a passive role in this pharmacy training course and therefore did not understand that importance of such training. Therefore, the pharmacy training period was extended from two-weeks to four-weeks in 2000. We thus evaluated what differences there were after the training was increased from two-weeks to four-weeks.The four-week training program was found to increase student motivation toward the pharmacy training. Our survey concluded that approximately 69 % of all senior students were interested in pharmacy training and 75% of senior students understood the role of the pharmacist. In addition, 87% of senior students had an improved image of pharmacists after the new pharmacy training. The reason for such an increase was that the senior students gained a better understanding of the reasons for training and also obtained practical experience in pharmaceutical care. These findings suggest that the four-week training program with self-learning exercises was useful for normally passive senior students. It also enabled hospital pharmacists to make an even greater contribution to the pharmacy training program.

Foreign bodies in the oral and maxillofacial region frequently result from trauma and dental treatment. We describe a foreign body, suspected to be a fish bone, in the submandibular gland. A 63-yearold man had a swelling in the left submandibular region. Computed tomography revealed a radiopaque spot, 1mm in diameter, in the gland. Removal of the submandibular gland was performed. The swelling was found to be a foreign body, not a salivary calculus. The foreign body measured 16×1mm and resembled a needle. How this foreign body entered the submandibular gland was unclear. The clinical course suggested that the foreign body had penetrated into the submandibular gland through the oral mucosa.

This study was to examine the utility of a modified double-stapling end-to-end gastroduodenostomy method ('Tornado' anastomosis) compared to a method with an additional gastrotomy ('Anterior Incision' method) in laparoscopy-assisted distal gastrectomy.Forty-two patients with gastric cancer who underwent laparoscopy-assisted distal gastrectomy were analyzed retrospectively. Billroth-I using an additional gastrotomy was performed in 24 patients (AI group) and Billroth-I without an additional gastrotomy was performed in 18 (TOR group). Clinicopathological features, operative outcomes (lymph node dissection, operative time, operative blood loss) and postoperative outcomes (complications, postoperative hospital stay, and body weight loss at one year after surgery) were evaluated and compared between groups.Operative time was significantly shorter in the TOR group (251 min) than in the AI group (282 min) (p0.01). There were no statistically significant differences in operative blood loss, postoperative complications, and hospital stay between the 2 study groups. Body weight loss at one year after surgery was -5.8 kg in the TOR group and -6.5 kg in the AI group, without a statistically significant difference.Completion time for Billroth-I anastomosis was significantly shorter with Tornado anastomosis than with the Anterior Incision method, with safety equal between the two methods.

A retrospective analysis of therapeutic modalities used in postoperative recurrent esophageal cancer.Among 43 esophageal cancer patients who underwent esophagectomy between 2003 and 2010, recurrence was found in 15. Best supportive care was given to two patients and another patient was referred to another hospital. The remaining 12 patients were treated by the following modalities: Surgical resection: 2 cases; chemoradiotherapy: 7 cases; chemotherapy: 2 cases; and radiotherapy: 1 case. The median survival time, 1-year survival rates, and response rates were examined. Data from 13 esophageal cancer patients who underwent chemoradiotheray as an initial therapy in the same period were collected and compared with recurrent cases treated with chemoradiotherapy.For all 12 patients, the median overall survival time was 19.5 months, and the 1-year survival rate was 83%. Among 7 chemoradiotherapy patients, the response rate was 57%. The median survival time was 23 months, and the 1-year survival rate was 86%. The response rate of 13 patients receiving chemoradiotherapy as an initial therapy was 69%. The median overall survival time was 12 months and the 1-year survival rate was 54%.Re-operation and chemoradiotherapy for recurrent esophageal cancer might be as effective as the same treatment used initially.

Surgeries for cancer of the esophagus are still associated with a high rate of postoperative morbidity. There are few reports of perioperative nutritional support for patients undergoing esophageal cancer surgery, and there is insufficient evidence to recommend routine use of immunonutrition in these patients. The aim of this study was to determine whether preoperative immunonutrition positively influences key clinical outcomes such as postoperative infectious complications, mortality, length of hospital stay, and short-term survival in this population.We undertook a retrospective investigation of the effects of preoperative nutritional support on the postoperative course of esophageal cancer surgery at the Department of Gastroenterological Surgery, International University of Health and Welfare Mita Hospital, Tokyo, Japan.Fifty-five patients who underwent esophagectomy for esophageal cancer were included in this study. Of the 55 patients, 26 patients consumed a liquid dietary supplement (IMPACT group) before surgery and 29 patients did not (STANDARD group).Before surgery, the IMPACT group consumed 750 ml (3 packs)/day of Impact for 5 consecutive days.The analysis was based on postoperative complications, hospital mortality, length of hospital stay, and short-term survival.Significantly fewer patients developed postoperative infections in the IMPACT group compared with the STANDARD group (p=.007): 4 of 21 patients in the IMPACT group and 10 of 29 patients in the STANDARD group. Either an infectious complication or another complication developed in 8 patients in the IMPACT group and 13 patients in the STANDARD group, with the result that 6 patients in the STANDARD group died of postoperative complications (p=.001). The duration of hospitalization was 34 days in the IMPACT group and 48 days in the STANDARD group; hence, hospitalization was significantly shorter in patients treated with Impact (p=.008). The mean 6-month survival rates for the IMPACT group and the STANDARD group were 92% (24/26) and 72% (21/29), respectively (p=.028).Simple preoperative supplementation significantly improved outcome. Administration of the supplemental diet before esophageal surgery appeared to be an effective strategy in reducing infectious complications, mortality, and hospitalization, and improving short-term survival.

Neurothekeoma (NT) including nerve sheath myxoma (NSM), is a benign neoplasm derived from the peripheral nerve sheath that occurs very rarely in the oral cavity. We describe two cases of a distinctive variant of NT arising in the buccal mucosa and the tongue. Histologically, one of the lesions showed the coexistence of ill-circumscribed hypocellular and myxoid lobules and hypercellular fibrous fascicles, and the other demonstrated a scattered distribution of the tumor cells in myxoid matrix in various sizes of nests. These findings, together with immunohistochemical characteristics, suggest that the former lesion is a mixed variant of NT, and the latter is a myxoid variant of it. A review of the literature revealed 16 previous reports of NTs arising in the oral cavity.

Hemodynamics is considered to be one of the indices to evaluate the effects of the treatment by coil embolization for cerebral aneurysms. For the sake of detailed analysis of hemodynamics in coil-embolized aneurysms, we develop a virtual coil model based on the mechanical theory that the coil deforms toward minimizing the elastic energy, and represent a realistic configuration of the embolized coils in the aneurysm by the insertion simulation. Then, the blood flow analysis is done by solving the N.S. and continuity equations numerically with the finite volume method using polyhedral mesh. The coil insertion simulation demonstrated that almost uniform distribution of the coil in the aneurysm was achieved at over 10% packing density of the coil. The blood flow analysis using the virtual coil model showed that the flow momentum inside the aneurysm was reduced to less than 10% by coil embolization with a packing density over 20%. In comparison to the simulation results using a porous media model for the embolized coil, there was no significant difference in the reduction ratio of the flow momentum in the aneurysm by coil embolization. However, local flow dynamics evaluated by the flow vorticity was different in the virtual coil model and the porous media model, in particular at the neck region of the aneurysm.Copyright © 2013 by ASME

Background: Fosaprepitant-associated injection site reaction (ISR) has been reported in patients treated with cisplatin, an irritant drug. We conducted this retrospective study to clarify the incidence and symptoms of fosaprepitant-associated ISR in patients treated with anthracycline. Patients and methods: Fifty six patients receiving 159 injections administering doxorubicin/cyclophosphamide (AC), fluorouracil/epirubicin/cyclophosphamide (FEC), or rituximab/cyclophosphamide/doxorubicin/vincristine/prednisolone (R-)CHOP regimen through a peripheral vein at ambulatory treatment centers reviewed for this study from patients’ medical records. Incidence of ISR was compared between 24 patients with fosaprepitant injection (fosaprepitant group) and 32 patients without fosaprepitant (control group). Frequency and symptoms of ISR per injection were also compared between 61 injections with fosaprepitant and 98 injections without fosaprepitant. Results: Both the ISR incidence rate per patient and per injection were significantly higher in the fosaprepitant group than in the control group (67% vs. 16%; P=0.0002, 34% vs. 8.2%; P

Here we report a case of successful treatment with combination chemotherapy of carboplatin(CBDCA)and paclitaxel for a patient undergoing hemodialysis(HD)with cancer of unknown primary, conducted by monitoring the observed AUC of ultrafilterable CBDCA. CBDCA was administered at a dose of 125 mg on day 1 in each course, an amount which had been calculated by the Calvert formula(GFR: 0, target AUC: 5). HD was started at a point in time one hour after the completion of each CBDCA administration, and performed for 5 hours in each course. Blood samples were collected during the first 3 courses of chemotherapy to measure the plasma concentration of free-platinum. The observed AUCs(o-AUC)of CBDCA in the first, second and third courses were 3. 03, 3. 44 and 3. 50mg·min/mL, respectively. The o-AUC in the first course was lower than that in the second course. The o-AUC in the second course was nearly equal to that in the third course, while each o-AUC was below the target AUC(t-AUC). Partial response was achieved after two courses of the CBDCA and paclitaxel combination chemotherapy, with adverse events of Grade 3 neutropenia and Grade 3 peripheral neuropathy observed in each course after the second course of chemotherapy. o-AUC of CBDCA administered to HD patients can not only be below t-AUC, as in this case, but also oppositely above t-AUC in cases with different doses of CBDCA or HD settings. Our results suggest that the monitoring of o-AUC of CBDCA is useful when practicing CBDCA-based chemotherapy safely and effectively in cancer patients undergoing HD.

Coil embolization is one of the most popular methods to treat cerebral aneurysms. We investigated hemodynamics in differently positioned aneurysms coiled at various volume embolization ratios (VER) to determine the effective VER in terms of flow stagnation. Simulations were conducted for patient specific aneurysm and idealized aneurysm. Porous media modeling was used to describe blood flow within the coil-embolized aneurysm. The ratio of flow stagnation volume to aneurysm volume (stagnant volume ratio, SVR) was analyzed to quantify the efficacy of coil embolization. The results showed that SVR tended to increase with increasing VER for both patient-specific and idealized aneurysms. For the idealized model, SVR was almost 100% at 20% of VER. In contrast, SVR in the patient specific aneurysm was approximately 40% for VER of 20%. These results suggested the importance of taking account of geometrical features of aneurysms when treating them by coil embolization.Copyright © 2012 by ASME

Coil embolization is performed to induce flow stagnation in cerebral aneurysms and enhance blood clot formation, thus preventing rupture and further growth. We investigated hemodynamics in differently positioned aneurysms coiled at various packing densities to determine the effective packing density in terms of flow stagnation. As a first step, hemodynamic simulations were conducted for idealized geometries of both terminal- and sidewall-type aneurysms. Porous media modeling was employed to describe blood flow in coil-embolized aneurysms. The stagnant volume ratio (SVR) was analyzed to quantify the efficacy of coil embolization. Regardless of aneurysm type and angle, SVR increased with increasing packing density, but the increase in SVR varied depending on type. For sidewall-type aneurysms, the packing density required to achieve 60 % SVR was 20 %, roughly independent of aneurysm angle; flow stagnation was achieved at low packing density. In contrast, in terminal-type aneurysms, the packing density required to achieve 60 % SVR was highly dependent on aneurysm angle, accomplishing a 20 % packing density only for lower angles. Indications are that a relatively high packing density would be required, particularly when these aneurysms are angled against the parent artery. The packing density required for flow stagnation varies depending on aneurysm type and relative position.

The most effective treatment would be neoadjuvant chemoradiotherapy (NACRT) plus surgery with three-field lymphadenectomy, if tolerability and complications are acceptable. The aim of this prospective study was to evaluate the tolerability of NACRT+ systematic three-field lymphadenectomy.A total of 127 cases of advanced esophageal carcinoma were objected, among which 32 had NACRT, being the cases suspected to cT3-T4 or,cT3 with multiple lymph node metastasis. ≥ T2 of 95 cases were treated by surgery alone (NACRT [-] case). The effect of NACRT was evaluated by histological examination and corrected with the clinicopathologic factors, including postoperative prognosis. After reports JCOG9907, we treated eight cases with neoadjuvant chemotherapy at stages II and III. We examined Musashi-1 staining for these eight cases.Histological good response to NACRT group showed good prognosis. Lymph node metastasis is a predictive factor for prognosis. In this additional study, Musashi-1 was positive after neoadjuvant chemotherapy in three cases. The histological response was grade 1 in all of them and recurrence was observed within a short period of time. Two cases of grade 3 were negative staining to Musashi-1 and showed no recurrence.This study shows that NACRT plus surgery with three-field lymphadenectomy is a feasible therapeutic approach for the cases with multiple lymph node metastases. Prognosis was significantly better in cases with marked histological improvement. It is important to find the predictive factors of histological improvement. Musashi-1 might be a candidate maker for histological response and prognosis, and further studies are needed to prove it.

We seek for the accurate and simple method for detecting sentinel nodes of gastric cancer which can be popularized in community hospitals. The indocyanine green (ICG) fluorescence-guided method is reported to be sensitive. However, the ordinal fluorescence cameras have gray scale imaging and require a dark room. We have developed a new device, Hyper Eye Medical System (HEMS) which can simultaneously detect color and near-infrared rays and can be used under room light. This study was planned to examine whether submucosal injection of 0.5 mL × 4 of 50 µg/mL ICG on the day before operation is the adequate administration for detecting sentinel nodes using HEMS in the gastric cancer surgery.The patients underwent gastrectomy for clinical T1a (mucosa)-T2 (muscularis propria) and clinical N0 were enrolled in the present study. As a preliminary trial, one case each of the ICG 25 and 100 µg/mL, injected on the day before operation and intraoperative injection, was examined. Then, 10 cases injected 50 µg/mL ICG on the day before operation were examined.The ICG fluorescence of the patient injected 100 µg/mL was too intense and that of the patient injected 25 µg/mL was too faint. Sentinel lymph nodes were detected in all of 10 cases injected 50 µg/mL, the day before operation and number of sentinel lymph nodes per patient was 3.6 ± 2.1. Metastasis was observed in one case. All of ICG fluorescence-positive sentinel nodes were positive for the metastasis. In the patient who underwent intraoperative injection, sentinel lymphatic basins could be identified.The present study shows that HEMS-guided abdominal surgery is feasible under room light. Submucosal injection of 0.5 mL × 4 of 50 µg/mL ICG on the day before operation is the adequate administration for detecting sentinel nodes using HEMS in the gastric cancer surgery.

Gastric neuroendocrine carcinomas are rare and have a poor prognosis, and the diagnostic criteria for this disease have recently changed. We herein report a case of sporadic gastric neuroendocrine carcinoma. A 75-year-old man was referred to our hospital with epigastric pain. Endoscopic examination revealed a localized ulcerative lesion (diameter, 4 cm) at the upper stomach. The diagnosis on biopsy was neuroendocrine carcinoma. Total gastrectomy with D2 lymphadenectomy, splenectomy, and cholecystectomy was performed. Pathologically, the tumor infiltrated the subserosal layer, and 6/49 lymph nodes were involved. The tumor was uniform in shape and arranged in a rosette-like structure to form solid nests, with medium-sized, round-to-cuboid-shaped tumor cells and intense mitosis 46/10 HPF. It was positive for synaptophysin and chromogranin A, and the Ki-67 labeling index was 70–80%. The diagnosis of neuroendocrine carcinoma was made according to the WHO 2010 criteria. The patient was followed up for three years without recurrence.

In Japan, the first gastro camera was introduced as a trial in 1950, and has improved continuously. On the other hand, in Europe, it was earlier that the first laparoscopic examination was tried in 1901 by Kelling. After that, laparoscopic surgery was developed by originating in a gynecologic surgery. The historical moment came in 1987, Prof. Mouret has succeeded in laparoscopic cholecystectomy, and for 20 years, endoscopic has been developing rapidly with progress of related devices. This remarkable advance is based on the collaboration between basic medicine and clinical medicine, in other words, the concept of engineering based medicine.

To investigate the phenomenon of remnant gastric motility and emptying after local resection.Fifteen dogs were divided into three groups: a control (CONT) group, a group that underwent local resection of the greater (GREAT) curvature, and a group that underwent resection of the lesser (LESS) curvature. We conducted a strain gauge force transducer study, a [(13)C]octanoic acid breath test ((13)C-OBT), and a mosapride citrate effect test. Based on these results, we worked out the receptive relaxation (RR), motility index (MI), and postprandial period (PP) in the postprandial state, and the frequency, duration, and MI of phase III in the fasted state. The half emptying time (T (1/2)) of (13)C-OBT was also calculated. The MI was compared according to the mosapride effect test results.Postprandial RR, antro-pyloro-duodenal coordination, and fasting contractions were maintained in all three groups. Receptive relaxation was significantly shorter in the LESS group than in the other groups. Motility index was significantly lower in both treatment groups than in the CONT group. The PP was significantly longer in the GREAT group than in the other two groups. The (13)CO(2) excretion curves did not differ significantly among the groups. The duration of phase III was remarkably less in the treatment groups than in the CONT group, and MI was significantly lower in the LESS group than in the other groups in the fasted state. The MI increased remarkably after mosapride administration in the CONT group, showing no differences in other objective groups.Gastric function was maintained after gastric local resection, although its motility decreased.

In the Nagoya City University Hospital, we started an Anti-cancer drug prescription support system according to which physicians input the injection prescription order from the regimen, together with the Outpatient Oncology Unit established in May, 2007. In order to prepare the anti-cancer drug more safely, we constructed a new Anti-cancer drug preparation support system(new system) at the same time. We investigated and evaluated the time and accuracy required for the preparation between the old and new systems. In the old system, we used electronic calculators or manual methods to perform calculations in the prescription procedure. In the new system, notes are automatically printed out with the kind, amount, and extraction amount of the dissolution liquid according to the dosage of the given anti-cancer drug for the injection prescription. Therefore, even a person with little experience in the preparation can confirm the preparative procedure accurately and promptly. Moreover, this system improves the efficiency of the preparation and it is thought that the utility is high as a part of the risk management.