A case of intermittent CT imaging for up to 2 hours following asymptomatic air emboli due to a CT-guided lung biopsy.

Air emboli represent rare but severe complications of computed tomography (CT)-guided lung biopsy (CTLB). No reports exist regarding the behavior of air during the early stages of air emboli. We present a case of air emboli following CTLB, evaluated by intermittent CT over a 2-hour period, spanning from onset to resolution. A man in his 60s underwent CTLB for diagnosis of a slowly enlarging pulmonary nodule in the right lower lobe. Immediately post-biopsy, chest CT revealed air emboli in the right coronary artery and apex of the ascending aorta. The patient was in the head-down position on the CT table, and intermittent CT scans were performed over a 2-hour period until the air emboli resolved. Subsequently, the patient was discharged without any complications.

Linked Color Imaging and the Kyoto Classification of Gastritis: Evaluation of Visibility and Inter-Rater Reliability.

BACKGROUND/AIMS: To compare white light imaging (WLI) with linked color imaging (LCI) and blue LASER imaging (BLI) in endoscopic findings of Helicobacter pylori presently infected, previously infected, and uninfected gastric mucosae for visibility and inter-rater reliability. METHODS: WLI, LCI and BLI bright mode (BLI-bright) were used to obtain 1,092 endoscopic images from 261 patients according to the Kyoto Classification of Gastritis. Images were evaluated retrospectively by 10 experts and 10 trainee endoscopists and included diffuse redness, spotty redness, map-like redness, patchy redness, red streaks, intestinal metaplasia, and an atrophic border (52 cases for each finding, respectively). Physicians assessed visibility as follows: 5 (improved), 4 (somewhat improved), 3 (equivalent), 2 (somewhat decreased), and 1 (decreased). Visibility was assessed from totaled scores. The inter-rater reliability (intraclass correlation coefficient) was also evaluated. RESULTS: Compared with WLI, all endoscopists reported improved visibility with LCI: 55.8% for diffuse redness; LCI: 38.5% for spotty redness; LCI: 57.7% for map-like redness; LCI: 40.4% for patchy redness; LCI: 53.8% for red streaks; LCI: 42.3% and BLI-bright: 80.8% for intestinal metaplasia; LCI: 46.2% for an atrophic border. For all endoscopists, the inter-rater reliabilities of LCI compared to WLI were 0.73-0.87. CONCLUSION: The visibility of each endoscopic finding was improved by LCI while that of intestinal metaplasia was improved by BLI-bright.

Improved Visibility of Barrett's Esophagus with Linked Color Imaging: Inter- and Intra-Rater Reliability and Quantitative Analysis.

BACKGROUND/AIMS: To evaluate the usefulness of linked color imaging (LCI) and blue LASER imaging (BLI) in Barrett's esophagus (BE) compared with white light imaging (WLI). METHODS: Five expert and trainee endoscopists compared WLI, LCI, and BLI images obtained from 63 patients with short-segment BE. Physicians assessed visibility as follows: 5 (improved), 4 (somewhat improved), 3 (equivalent), 2 (somewhat decreased), and one (decreased). Scores were evaluated to assess visibility. The inter- and intra-rater reliability (intra-class correlation coefficient) of image assessments were also evaluated. Images were objectively evaluated based on L* a* b* color values and color differences (ΔE*) in a CIELAB color space system. RESULTS: Improved visibility compared with WLI was achieved for LCI: 44.4%, BLI: 0% for all endoscopists; LCI: 55.6%, BLI: 1.6% for trainees; and LCI: 47.6%, BLI: 0% for experts. The visibility score of trainees compared with experts was significantly higher for LCI (p = 0.02). Intra- and inter-rater reliability ratings for LCI compared with WLI were "moderate" for trainees, and "moderate-substantial" for experts. The ΔE* revealed statistically significant differences between WLI and LCI. CONCLUSION: LCI improved the visibility of short-segment BE compared with WLI, especially for trainees, when evaluated both subjectively and objectively.

Therapeutic effect of intratumoral injections of dendritic cells for locally recurrent gastric cancer: a case report.

An 80-year-old man with a history of gastric cancer and pulmonary emphysema underwent a distal gastrectomy for gastric cancer in 1997. In 2010, an endoscopic examination revealed a depressed-type lesion at the oral side of the anastomosis, which was diagnosed as signet-ring adenocarcinoma. Surgical management was considered, but was rejected because of obstructive and restrictive respiratory events. Chemotherapy was terminated because of adverse events. Endoscopy was used to administer intratumoral injections of dendritic cells (DCs) targeting synthesized peptides of Wilms tumor 1 (WT1) and mucin 1, cell-surface associated (MUC1). An immunohistochemical analysis of the tumor samples indicated positivity for WT1 and MUC1. One month after seven cycles of DC had been administered (between November 2010 and April 2011), no suspicious lesions were evident, and his biopsy results were normal. The patient has been in remission for 30 months. Intratumoral injections of DCs showed therapeutic effects in this patient, who could not undergo endoscopic submucosal dissection or surgery.

[Phase I study of CPT-11 and continuous 5-FU / l-leucovorin combination therapy(modified AIO regimen)in patients with metastatic colorectal cancer].

A combination of CPT-11, continuous 5-fluorouracil(5-FU)and leucovorin(LV), the Arbeitsgemeinschaft für Internistische Onkologie(AIO)regimen, is widely used for the treatment of metastatic CRC. The efficacy and toxicity of this regimen, however, have not been determined in Japanese patients with metastatic CRC. Our objective was to evaluate the safety of the AIO regimen plus CPT-11 in Japanese colorectal carcinoma(CRC)patients. We investigated the maximum tolerated dose(MTD), dose-limiting toxicity(DLT), and recommended dose(RD)for CPT-11 and continuous 5-FU. CPT-11, 5-FU, and l-LV were administered on days 1, 8, and 15 of a 28-day cycle. The dose of CPT- 11 was escalated from 40 mg/m2 (level 1)to 80 mg/m2 (level 3). The 5-FU dose was then escalated from 1,000 mg/m2 (level 4)to 2,000 mg/m2 (level 5). If neither level met the criteria for the MTD, the recommended dose was defined as level 5, and the dose escalation was discontinued, because the maximum approved weekly dose of CPT-11 alone in Japan is 80 mg/m2 and the dose of 5-FU in the original AIO regimen was 2,000 mg/m2. A total of 18 patients were enrolled in this study. Hematological and non-hematological toxicity were infrequent and mild. There were no toxicities greater than grade 2 at each dose level. Level 5 did not meet the MTD criteria. Our results confirm that the modified AIO plus CPT-11 regimen is safe for Japanese patients. The recommended doses in the present study were CPT-11 80 mg/m2, 5-FU 2,000 mg/m2, and l-LV 250 mg/m2.

[A case of sigmoid colon cancer with metastases of para-aortic lymph nodes treated with curative resection after irinotecan plus 5-fluorouracil and l-leucovorin combination chemotherapy].

A 54-year-old woman visited our hospital with a chief complaint of lower abdominal pain and melena. The patient was diagnosed with sigmoid colon cancer using colonoscopy. Abdominal CT revealed metastases to para-aortic lymph node, so our diagnosis was unresectable sigmoid colon cancer. She underwent a transverse colostomy to avoid stenosis. Two weeks after surgery, she underwent a 1-week chemotherapy regimen (CPT-11 80 mg/m(2)/week+5-FU 2,000 mg/m(2)/week+l-LV 250 mg/m(2)/week) modified AIO regimen combined irinotecan for 3 weeks, followed by a 1-week rest interval as one course. Throughout the period of treatment, there was no adverse event, and this regimen has been maintained for 5 courses. After 5 courses of chemotherapy, primary tumor and metastases to para-aortic lymph nodes were remarkably reduced on colonoscopy and abdominal CT. So, she could undergo curative resection. Pathological efficacy was Grade 3, a complete response. This combination therapy may well be useful for advanced colon cancer patients.

Mitochondrial Extrusion through the cytoplasmic vacuoles during cell death.

Under various conditions, noxious stimuli damage mitochondria, resulting in mitochondrial fragmentation; however, the mechanisms by which fragmented mitochondria are eliminated from the cells remain largely unknown. Here we show that cytoplasmic vacuoles originating from the plasma membrane engulfed fragmented mitochondria and subsequently extruded them into the extracellular spaces in undergoing acute tumor necrosis factor alpha-induced cell death in a caspase-dependent fashion. Notably, upon fusion of the membrane encapsulating mitochondria to the plasma membrane, naked mitochondria were released into the extracellular spaces in an exocytotic manner. Mitochondrial extrusion was specific to tumor necrosis factor alpha-induced cell death, because a genotoxic stress-inducing agent such as cisplatin did not elicit mitochondrial extrusion. Moreover, intact actin and tubulin cytoskeletons were required for mitochondrial extrusion as well as membrane blebbing. Furthermore, fragmented mitochondria were engulfed by cytoplasmic vacuoles and extruded from hepatocytes of mice injected with anti-Fas antibody, suggesting that mitochondrial extrusion can be observed in vivo under pathological conditions. Mitochondria are eliminated during erythrocyte maturation under physiological conditions, and anti-mitochondrial antibody is detected in some autoimmune diseases. Thus, elucidating the mechanism underlying mitochondrial extrusion will open a novel avenue leading to better understanding of various diseases caused by mitochondrial malfunction as well as mitochondrial biology.

Ulcerative colitis accompanied with sarcoidosis and dermatomyositis: report of a case.

We report a rare case of ulcerative colitis with sarcoidosis and dermatomyositis. A 33-year old woman had a ten-year history of ulcerative colitis and dermatomyositis. After nine-year maintenance treatment with sulphasalazine and steroids, she underwent a proctocolectomy and ileal pouch-anal anastomosis because of deterioration of ulcerative colitis. One year after the operation, she noticed some subcutaneous masses in the right forearm and left lower leg. A total biopsy of the mass was performed, and noncaseous epithelioid granulomas were found in the specimen. Chest roentgenogram and chest computed tomography showed hilar adenopathy and a diffuse granular shadow. The diagnosis of sarcoidosis was made. Concomitant development of ulcerative colitis and sarcoidosis may not be incidental, and there may be a common factor in the two diseases. Ulcerative colitis also may be a part of a systemic disorder associated with abnormal immune reactions. Complications by disorders associated with other immunologic abnormalities, as noted in this patient, should be kept in mind in the management of ulcerative colitis.

Granulocytic sarcoma presenting as a thrombosed external hemorrhoid in a patient with myelodysplastic syndrome overt leukemia.

A 67-year-old Japanese man complained of a painful lump in his anus. He had a 15-month history of myelodysplastic syndrome (MDS) and had been diagnosed with MDS overt leukemia. A solid lump measuring 1.0 cm in diameter was detected in the anal verge. Under a diagnosis of a thrombosed external hemorrhoid, thrombectomy was performed under local anesthesia. One week after thrombectomy, the wound had not healed, and grayish-green tissue was seen at the bottom. A biopsy of the wound revealed atypical mononuclear cell infiltration. Myeloperoxidase and lysozyme were positive on immunohistochemical staining. Finally, the diagnosis of granulocytic sarcoma (GS) was made. Though it is well known that perianal complications occur quite often in patients with leukemia, it is unusual for a diagnosis of GS of the anus to be definitely established. To our knowledge, there has not been a previous report of GS presenting as a thrombosed external hemorrhoid. The development of GS should be considered during the management of such lesions, especially in patients with bone marrow disorders, such as acute myeloid leukemia (AML) or high-risk MDS.

Crohn's disease-associated colorectal cancer in Japan: report of four cases.

PURPOSE: We report four cases of Crohn's disease (CD)-associated colorectal cancer (CRC) in our department. CASE 1: A 42-year-old Japanese man had a 14-year history of ileocolon CD. He had a history of an ileocecal resection and a stricture plasty. At the age of 42, sigmoid colostomy was performed because of the deterioration of the anal stenosis. After this operation, the perianal pain had remained, and a magnetic resonance imaging scan revealed a rectal tumor. CASE 2: A 30-year-old Japanese man had a 13-year history of ileocolon CD. He had a history of an ileostomy, a subtotal colectomy, and ileo-rectal anastomosis. At the age of 30, he had perianal pain, and a colonoscopy revealed a rectal cancer. An abdomino-perineal resection of the remnant rectum was performed. CASE 3: A 46-year-old Japanese man had a 9-year history of ileocolon CD. He experienced abdominal fullness. Colonoscopy revealed an ascending colon cancer. He underwent a subtotal colectomy and ileo-rectal anastomosis. CASE 4: A 33-year-old Japanese woman had a 16-year history of ileocolon CD. She had no changes in symptoms of CD. Surveillance colonoscopy revealed a transverse colon cancer. She underwent a subtotal colectomy and ileo-rectal anastomosis. CONCLUSION: As the number of patients with CD and with CD-associated CRC has increased in Japan, CD-associated CRC, as noted in these patients, should be kept in mind in the management of patients with CD. In addition, a surveillance system of patients with CD should be established and should prompt further study about CD-associated CRC.

An antiapoptotic protein, c-FLIPL, directly binds to MKK7 and inhibits the JNK pathway.

Inhibition of NF-kappaB activation increases susceptibility to tumor necrosis factor (TNF)alpha-induced cell death, concurrent with caspases and prolonged c-Jun N-terminal kinase (JNK) activation, and reactive oxygen species (ROS) accumulation. However, the detailed mechanisms are unclear. Here we show that cellular FLICE-inhibitory protein (c-FLIP) is rapidly lost in NF-kappaB activation-deficient, but not wild-type fibroblasts upon TNFalpha stimulation, indicating that NF-kappaB normally maintains the cellular levels of c-FLIP. The ectopic expression of the long form of c-FLIP (c-FLIPL) inhibits TNFalpha-induced prolonged JNK activation and ROS accumulation in NF-kappaB activation-deficient fibroblasts. Conversely, TNFalpha induces prolonged JNK activation and ROS accumulation in c-Flip-/- fibroblasts. Moreover, c-FLIPL directly interacts with a JNK activator, MAP kinase kinase (MKK)7, in a TNFalpha-dependent manner and inhibits the interactions of MKK7 with MAP/ERK kinase kinase 1, apoptosis-signal-regulating kinase 1, and TGFbeta-activated kinase 1. This stimuli-dependent interaction of c-FLIPL with MKK7 might selectively suppress the prolonged phase of JNK activation. Taken that ROS promote JNK activation and activation of the JNK pathway may promote ROS accumulation, c-FLIPL might block this positive feedback loop, thereby suppressing ROS accumulation.

[A case of retractile mesenteritis of the ileocecum].

Retractile mesenteritis is a rare inflammatory mesenteric disorder with unknown etiology. We reported a resected case of mass-forming retractile mesenteritis. A 64-year-old man noticed a mass with mild tender in the right lower abdomen. Colonoscopy revealed no abnormal findings. Computed tomography of the abdomen showed a solitary tumor of the ileocecal mesentery. Ileocecal resection was performed. Pathological findings were inflammatory change of the mesentery with marked fibrosis. Final diagnosis was retractile mesenteritis. He is doing well for 26 months after the operation.

Left paraduodenal hernia in an adult complicated by ascending colon cancer: a case report.

Paraduodenal hernia is the most common internal hernia. The clinical symptoms of paraduodenal hernia may be intermittent and nonspecific. Therefore, it is difficult to diagnose preoperatively. Abdominal computed tomography (CT) scan currently plays an important role in the evaluation and management of paraduodenal hernia before surgical operation. We report one unique case of preoperatively diagnosed left paraduodenal hernia complicated by advanced ascending colon cancer and reviews of Japanese literature.

Tumor necrosis factor alpha (TNFalpha) induces the unfolded protein response (UPR) in a reactive oxygen species (ROS)-dependent fashion, and the UPR counteracts ROS accumulation by TNFalpha.

Accumulation of unfolded proteins in the endoplasmic reticulum (ER) causes ER overload, resulting in ER stress. To cope with ER stress, mammalian cells trigger a specific response known as the unfolded protein response (UPR). Although recent studies have indicated cross-talk between ER stress and oxidative stress, the mechanistic link is not fully understood. By using murine fibrosarcoma L929 cells, in which tumor necrosis factor (TNF) alpha induces accumulation of reactive oxygen species (ROS) and cell death, we show that TNFalpha induces the UPR in a ROS-dependent fashion. In contrast to TNFalpha, oxidative stresses by H2O2 or arsenite only induce eukaroytic initiation factor 2alpha phosphorylation, but not activation of PERK- or IRE1-dependent pathways, indicating the specificity of downstream signaling induced by various oxidative stresses. Conversely, the UPR induced by tunicamycin substantially suppresses TNFalpha-induced ROS accumulation and cell death by inhibiting reduction of cellular glutathione levels. Collectively, some, but not all, oxidative stresses induce the UPR, and pre-emptive UPR counteracts TNFalpha-induced ROS accumulation.