Endovascular Treatment for Very Early Hepatic Artery Stenosis Following Living-Donor Liver Transplantation: Report of Two Cases.

BACKGROUND: Some literature has reported on endovascular treatment for very early hepatic artery stenosis (HAS; within 2 weeks after liver transplantation, and has deemed endovascular treatment to be a contraindication because out of serious complications associated with the procedure. We report on 2 cases of very early HAS successfully treated with endovascular treatment after living-donor liver transplantation (LDLT). CASE 1: A 54-year-old woman underwent LDLT with a left liver graft. The native right gastric artery and left hepatic artery (LHA) of the donor were anastomosed. On postoperative day (POD) 13, HAS was suspected and multidetector computerized tomographic angiography (MDCTA) was performed, which revealed 90% stenosis of the arterial anastomosis and 50% stenosis of the LHA in the graft. We performed percutaneous balloon arterioplasty (PBA) without any complications. The artery was patent with a postoperative follow-up of 60 months without the need for repeat intervention. CASE 2: A 67-year-old woman with a history of repeated transarterial chemoembolization for hepatocellular carcinoma underwent LDLT with a left liver graft. The native A4 and LHA of the donor were anastomosed. We performed MDCTA on POD 11, which revealed 70% stenosis of the native hepatic artery. We performed PBA followed by stent placement on POD 11 without complication. The artery was patent with a postoperative follow-up of 40 months without the need for repeated intervention. CONCLUSIONS: Endovascular treatment has the potential to avoid the need for repeated surgical interventions or retransplantation, and it can be safely performed in carefully selected patients.

Dynamics of M1 macrophages in oral mucosal lesions during the development of acute graft-versus-host disease in rats.

The role of macrophage infiltrates in oral mucosal acute graft-versus-host disease (AGVHD) remains unclear, although clinical studies suggest that macrophage infiltration correlates directly with the severity of AGVHD. In this study, we investigated the role of M1 macrophage infiltration in the oral mucosa of rats with AGVHD. Lewis rat spleen cells were injected into (Lewis × Brown Norway) F1 rats to induce systemic GVHD. Tongue samples were evaluated using histology, immunohistochemistry, dual immunofluorescence, real-time reverse transcription-polymerase chain reaction, Transwell migration assays and Stamper-Woodruff binding assays. At the onset of oral mucosal AGVHD, dual immunofluorescence and migration assays revealed that M1 macrophages had accumulated in the basement membrane (BM) region via the laminin/CD29 ß1 integrin pathway. Macrophage-secreted matrix metalloproteinase-2 was related to BM degradation. The adhesion of macrophages to the oral epithelium could be inhibited by pretreating macrophages with a CC chemokine receptor 2 (CCR2) antibody and/or pretreating lesion sections with monocyte chemoattractant protein-1 (MCP-1) antibody. Our data show that the migration and adhesion of M1 macrophages are associated with oral mucosal AGVHD, which is mediated in part by both laminin/CD29 ß 1 intern and MCP-1/CCR2 pathways. Therefore, our study provides additional support for the contribution of macrophage infiltrate to the development of oral mucosal AGVHD.

Older Adults with Fear of Falling Show Deficits in Motor Imagery of Gait.

OBJECTIVE: Understanding of the underlying mechanisms of Fear of Falling (FoF) could help to expand potential treatments. Given the nature of motor performance, the decline in the planning stage of motor execution may be associated with an expression of FoF. The aim of this study was to assess the planning/prediction accuracy in motor execution in people with FoF using gait-related motor imagery (MI). DESIGN: Cross-sectional case/control study. SETTING: Three health centers in Japan. PARTICIPANTS: Two hundred and eighty-three community-dwelling older adults were recruited and stratified by presence of FoF as FoF group (n=178) or non-FoF group (n=107). MEASUREMENTS: Participants were tested for both imagery and execution tasks of a Timed Up and Go (TUG) test. The participants were first asked to imagine the trial (iTUG) and estimate the time it would take, and then perform the actual trial (aTUG). The difference between iTUG and aTUG (Δ TUG) was calculated. RESULTS: The FoF group was significantly slower in aTUG, but iTUG duration was almost identical between the two groups, resulting in significant overestimation in the FoF group. The adjusted logistic regression analysis showed that increased Δ TUG (i.e., tendency to overestimate) was significantly associated with FoF (OR = 1.05; 95% CI = 1.02-1.10). Low frequency of going outdoors was also associated with FoF (OR 2.95; 95% CI: 1.16-7.44). CONCLUSIONS: Older adults with FoF overestimate their TUG performance, reflecting impairment in motor planning. Overestimation of physical capabilities can be an additional explanation of the high risk of falls in this population.

Correlation between luminescence intensity and cytotoxicity in cell-based cytotoxicity assay using luciferase.

The luciferase reporter assay has become one of the conventional methods for cytotoxicity evaluation. Typically, the decrease of luminescence expressed by a constitutive promoter is used as an index of cytotoxicity. However, to our knowledge, there have been no reports of the correlation between cytotoxicity and luminescence intensity. In this study, to accurately verify the correlation between them, beetle luciferase was stably expressed in human hepatoma HepG2 cells harboring the multi-integrase mouse artificial chromosome vector. We showed that the cytotoxicity assay using luciferase does not depend on the stability of luciferase protein and the kind of constitutive promoter. Next, HepG2 cells in which green-emitting beetle luciferase was expressed under the control of CAG promoter were exposed to 58 compounds. The luminescence intensity and cytotoxicity curves of cells exposed to 48 compounds showed similar tendencies, whereas those of cells exposed to 10 compounds did not do so, although the curves gradually approached each other with increasing exposure time. Finally, we demonstrated that luciferase expressed under the control of a constitutive promoter can be utilized both as an internal control reporter for normalizing a test reporter and for monitoring cytotoxicity when two kinds of luciferases are simultaneously used in the cytotoxicity assay.

Switching from singlet-oxygen-mediated oxidation to free-radical-mediated oxidation in the pathogenesis of type 2 diabetes in model mouse.

Oxidative stress plays a key role in the development of type 2 diabetes. However, it is still unknown what kind of oxidative stress underlies the development of type 2 diabetes. We investigated hydroxyoctadecadienoic acid (HODE) isomers, which have been proposed as a biomarker for evaluating oxidative stress in vivo, during the development of diabetes in Tsumura Suzuki Obese Diabetes (TSOD) mouse, a type 2 diabetes model. It was revealed that glucose tolerance and insulin resistance index HOMA-IR in TSOD mice at 5 weeks of age were approximately normal, namely, the mice were in the prediabetic state, but these levels were significantly exacerbated from 8 weeks of age compared with those in Tsumura Suzuki Non Obesity (TSNO) mice (control). Concomitantly, the plasma levels of free-radical-mediated oxidation products, 9- and 13-(E,E)-HODE and 7ß-hydroxycholesterol, in TSOD mice were significantly higher than those in TSNO mice at 8, and 8 and 11 weeks of age, respectively. Interestingly, the plasma levels of 10- and 12-(Z,E)-HODE, which are produced specifically by singlet-oxygen-mediated oxidation, in TSOD mice were higher than those in TSNO mice only at 5 weeks of age, and not at 8, 11, and 13 weeks of age. We demonstrated that singlet-oxygen-mediated oxidation occurred in TSOD mice before development of the diabetic phenotypes, including impaired glucose tolerance and insulin resistance. These results suggest that excessive singlet-oxygen-mediated oxidation plays an important role in the pathogenesis of type 2 diabetes.

Minimal deviation endometrioid adenocarcinoma of the endometrium and its MRI findings.

Minimal deviation endometrioid adenocarcinoma (MDA-E) of the endometrium is a rare pathological entity, and its radiological features are rarely documented. A 73-year-old Japanese woman was referred to the authors when an endometrial biopsy revealed moderately differentiated endometrioid adenocarcinoma. Preoperative radiological examinations, including ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) showed no evidence of cancer nests. In the hysterectomy specimen, mildly atypical glands were scattered throughout the entire depth of the myometrium, without stromal desmoplastic reaction, and a tiny focus of typical, ruptured, endometrioid adenocarcinoma glands was found in the atrophic endometrium. MRI had not been able to identify this unusual, scattered, myometrial invasion. It should be kept in mind that in cases showing Stage IA endometrial carcinoma without endometrial thickening on MRI, this rare form of invasion may be present.

Haemophilic pseudotumour of the mandible in a 5-year-old patient.

A haemophilic pseudotumour was identified in the mandible of a 5-year-old male with severe haemophilia A. The patient initially experienced painless swelling of the mandible. Computed tomography revealed a marked enlargement of the lower right mandibular border, which was associated with a low-density area, and irregular absorption of the lingual cortex bone. A malignant tumour was suspected, and a biopsy was performed after the administration of coagulation factor (Factor VII). A histopathologic diagnosis of haemophilic pseudotumour was made and the patient subsequently underwent surgical treatment. A cavity was created in the multilocular bone cyst and surgical curettage and irrigation were performed with the same haemorrhagic control as in the biopsy procedure. The multilocular cyst was contained within a haematoma and was surrounded by thin granular tissue. Three years after surgery, no abnormal signs have been detected by radiography during follow-up examinations. This case involved a rare haemophilic pseudotumour located in the mandible; the pathogenetic mechanism was attributed to pressure necrosis due to intraosseous bleeding.

Metastatic tumor extending through the inferior vena cava into the right atrium: a case report of carcinoma of the uterine cervix with para-aortic lymph node metastases.

Carcinoma of the uterine cervix with cardiac metastasis is not uncommon in autopsy cases. However, an intraatrial tumor extending through the inferior vena cava (IVC) from the site of para-aortic lymph node metastasis has never been reported. A 57-year-old Japanese woman was admitted to an emergency care unit complaining of mild chest pain and shortness of breath. She had progressive multiple lymphatic metastases of stage IIIB squamous cell carcinoma of the uterine cervix that had initially been treated with concurrent chemoradiation. Echocardiogram showed pedunculated tumor in the right atrium (RA), and computed tomography demonstrated multiple pulmonary tumor embolism. Surgical specimen from the RA showed squamous cell carcinoma resembling the primary cervical tumor, and the peduncle appeared to originate from within the IVC. Postoperative ultrasonography showed severe stenosis of the abdominal IVC due to the invasive growth of para-aortic lymph node metastases. The stalk of the tumor originated from this lesion. We present an extremely unusual case of intraatrial metastatic tumor originating from the para-aortic lymph nodes of cervical cancer.

Endometrial extension of adenosquamous carcinoma of the uterine cervix.

Endometrial in situ extension of cervical cancer is extremely uncommon. Previous reports only present the cases of squamous cell carcinoma or related category. This report presented adenosquamous carcinoma of the uterine cervix that showed a paradoxical extension of each component in a 72-year-old patient. Main tumor in the cervix was revealed to be adenosquamous carcinoma. The glandular component extended to the vagina, while the squamous component grew into the entire uterine cavity and replaced the glandular epithelium. We presented the first case of adenosquamous carcinoma of the uterine cervix with vaginal and endometrial extension. Furthermore, the endometrium was replaced with squamous component, while the vagina was invaded by glandular component. The observed paradoxical extension of the present case was extremely rare.

Adult case of squamous cell carcinoma arising on congenital esophageal stenosis due to fibromuscular hypertrophy.

This study relates to an adult case of squamous cell carcinoma arising on congenital esophageal stenosis. The patient was a 65-year-old man who had suffered from dysphagia and vomiting since birth and was diagnosed as having congenital esophageal stenosis. The patient had not received any treatment because his symptoms were mild. The patients suffered from severe dysphagia since he was 20 years old and had received balloon therapies several times; however, the effects were transient. After admission to our hospital, he underwent a transhiatal esophagectomy without thoracotomy. Histopathological examination of the resected specimen revealed a thick muscular mucosae associated with hypertrophic fibromuscular components and poorly to moderately differentiated squamous cell carcinoma in the region of stenosis. This case report is the first of a patient with squamous cell carcinoma arising on congenital esophageal stenosis.

Predicting initial recurrence pattern of esophageal cancer after neoadjuvant chemotherapy.

BACKGROUND/AIMS: No report has reviewed which clinicopathological factors including 3-field dissection and the response to neoadjuvant chemotherapy can predict the recurrence pattern of an esophageal carcinoma. The aim of this study was to reveal clinicopathological predictors for the initial recurrence pattern of a thoracic esophageal carcinoma. METHODOLOGY: Sixteen parameters derived from 98 patients who underwent a curative esophagectomy with neoadjuvant chemotherapy for a squamous cell carcinoma of the thoracic esophagus were examined using univariate and multivariate logistic regression analyses. RESULTS: Thirty-seven (37.8%) of the 98 patients had recurrences (hematogenous; 16, lymphatic; 13, others; 8). Univariate analyses revealed that the completion of 3-field dissection was the only factor for suppressing the lymphatic recurrence (P = 0.009; odds ratio: 0.2). Multivariate analyses showed that the number of positive nodes was a significant predictor for recurrence including all modalities (P = 0.02; odds ratio: 1.2) and both the number of positive nodes (P = 0.04; odds ratio: 1.1) and the poor response to neoadjuvant chemotherapy (P = 0.02; odds ratio: 6.9) were significant predictors for the hematogenous recurrence. CONCLUSIONS: The number of positive nodes and the response to neoadjuvant chemotherapy could predict the hematogenous recurrence of esophageal carcinoma.

Accelerated growth signals and low tumor-infiltrating lymphocyte levels predict poor outcome in T4 esophageal squamous cell carcinoma.

BACKGROUND: Little is known about the biological nature of T4 esophageal carcinoma growth signals and host defenses. METHODS: Paraffin-embedded sections from 78 patients with T2 to T4 esophageal squamous cell carcinoma who underwent operation were analyzed with immunohistochemistry. RESULTS: Positive cyclin A showed a significantly greater increase in T4 tumors than in those of other stages, and negative p27 showed a significantly greater decrease in T4 tumors than in large T3 stage tumors (tumor size > or = 4.0 cm). Patients with low-grade tumor-infiltrating lymphocyte (TIL) density showed a significantly greater decrease in T4 than in T2. The combination of p27 and cyclin A was a significant independent prognostic factor among T and N factors in multivariate analysis. TIL density was an independent prognostic factor among immunonutritional variables such as serum albumin concentration and the number of total blood lymphocytes. CONCLUSIONS: T4 esophageal squamous cell carcinoma has a poor prognosis, which is associated with increased p27-negative and cyclin A-positive growth signals in the tumor and with low TIL density in the host.

[Vascular anastomoses in free jejunal reconstruction to the neck vessels: an experience of consecutive 20 cases without using surgical microscope].

Twenty consecutive cases of pharyngoesophageal cancer who underwent free jejunal reconstruction were reported. The common carotid or external carotid artery was used for a feeder of the free graft. The internal jugular vein were served as a drainage vein. All anastomoses were performed in an end-to-side fashion without using surgical microscopes. Mean carotid artery clamping time was 16 minutes and no neurological complications were noticed postoperatively. Graft failure was occurred in 1 patient. The presenting technique, showing 95% success rate, is recommended as a simple option for vascular anastomosis in free jejunal reconstructive surgery.

Chemotherapy-induced apoptosis of lymphocytes in esophageal cancer worsens outcome.

BACKGROUND/AIMS: Chemotherapy has been shown to induce apoptosis in esophageal cancer. However, no windows of opportunity exist to selectively kill tumor cells without killing host cells. Due to the concern that tumor-infiltrating lymphocytes may be killed by chemotherapy, we examined the significance of the effect of treatment on the density of tumor-infiltrating lymphocytes and apoptosis in the tumor itself and in the tumor-infiltrating lymphocytes. METHODOLOGY: In 93 patients with esophageal cancer including 50 with neoadjuvant chemotherapy, esophagectomy specimens were examined for density of tumor-infiltrating lymphocytes and for apoptosis in both tumor cells and tumor-infiltrating lymphocytes. RESULTS: Apoptotic index was increased by neoadjuvant chemotherapy only in tumor-infiltrating lymphocytes, apoptotic index was > or = 4 only in chemotherapy patients. The density of tumor infiltrating lymphocytes was a significant positive prognostic factor in chemotherapy and non-chemotherapy groups, and the high apoptotic index in tumor-infiltrating lymphocytes was an independent negative prognostic factor in the chemotherapy group. CONCLUSIONS: Apoptosis in tumor-infiltrating lymphocytes was induced by chemotherapy in some patients in association with a poor prognosis. Unexpectedly, chemotherapy did not increase apoptosis in tumor cells. Both findings suggest a need for improved regimes and individualized treatment.

Recurrent nerve nodal involvement is associated with cervical nodal metastasis in thoracic esophageal carcinoma.

BACKGROUND: Because three-field dissection for esophageal carcinoma is one of the most invasive operations, this procedure should be selected only when strictly indicated; but there are no useful criteria for it. The goal of this study was to identify the useful clinicopathologic factors for indicating three-field dissection. STUDY DESIGN: In this study, we reviewed the survival of patients after three-field dissection and identified factors associated with metastases in cervical nodes (CN), especially internal jugular nodes and supraclavicular nodes. Eighty-six patients who underwent curative esophagectomy with three-field dissection for squamous cell carcinoma of the thoracic esophagus were enrolled in this study. Survival rates were compared with respect to the presence of nodal metastasis. The relationship between recurrent nerve nodal (RNN) involvement and CN metastasis (bilateral internal jugular nodes, supraclavicular nodes, or both) was examined. Clinicopathologic factors possibly influencing CN metastasis were studied by multivariate logistic regression analysis. RESULTS: The overall 5-year survival rate was 45.1%. The 5-year survival rate for patients without metastatic nodes was 67.5%, for patients with one to four metastatic nodes it was 53.1%, and for patients with five or more it was 9.1 %. The prognosis of those with five or more metastatic nodes was significantly poorer than those of the other two groups. In the positive-node group, the 5-year survival rate for patients with RNN metastasis was 21.7%, and for patients with negative RNN it was 47.0% (p = 0.2). In the positive-node group, the 5-year survival rate for patients with positive CN was 13.7% and for patients with negative CN it was 45.8% (p = 0.01). Fifty-six (88.9%) of 63 patients without RNN metastasis had no CN metastasis in contrast to 13 of 23 patients (56.5%) with RNN metastasis who had no CN metastasis (p = 0.001). The positive predictive value, negative predictive value, sensitivity, and specificity were 43.5%, 88.8%, 58.8%, and 81.2%, respectively. The number of metastatic nodes (5 or more versus 0-4) (odds ratio: 2.9, 95% Confidence Interval (CI) = 1.6-5.5, p = 0.0008) and RNN involvement (odds ratio: 4.5, 95% CI = 1.3-15.9, p = 0.02) were the significant factors associated with CN metastasis in the multivariate analysis. CONCLUSIONS: RNN involvement is associated with CN metastasis as is the number of metastatic nodes and may be an indicator for the selection of three-field dissection in thoracic esophageal carcinoma.

Prognostic value of mitotic metaphase rate in oesophageal cancer.

OBJECTIVE: To assess the prognostic value of the mitotic metaphase rate in patients with oesophageal cancer. DESIGN: Retrospective study. SETTING: University hospital, Japan. SUBJECTS: 41 patients with oesophageal cancer. INTERVENTIONS: We calculated the ratio of mitotic metaphase to anaphase cells among tumour cells in sections stained with haematoxylin and eosin, a ratio that shows the status of mitotic metaphase-anaphase transition. The DNA ploidy pattern was examined by flow cytometry. MAIN OUTCOME MEASURE: Correlation between survival and mitotic metaphase rate. RESULTS: A high mitotic metaphase rate was correlated with vascular invasion and is expected to be a useful prognostic factor. DNA diploidy combined with a low rate was an independent favorable prognostic factor. CONCLUSION: Mitotic metaphase rate is a useful index of malignant potential, independent of DNA ploidy. It can distinguish high malignant potential from low in a diploid tumour, which has a poor prognosis that is equal to that of the aneuploidy tumour.

Endoscopic decompression procedure in acute obstructing colorectal cancer.

BACKGROUND AND STUDY AIMS: In the treatment of acute obstructing colorectal cancer, a nasoenteric ileus tube is not capable of providing sufficient decompression of the enlarged intestine immediately, and it may cause the patients throat pain. We therefore assessed the effectiveness of an endoscopic decompression procedure using a transanal ileus tube for acute obstructing colorectal cancer. PATIENTS AND METHODS: Five patients (five women, mean age 62) with colorectal cancer ileus underwent endoscopic decompression procedures between July 1994 and March 1999. The stricture was first negotiated using a guide wire 300 cm in length, and was then dilated using 8 Fr and 26 Fr dilating catheters. Immediately after a transanal ileus tube 120 cm in length with an outside diameter of 22 Fr was inserted, the intestinal tract was cleaned. RESULTS: No leakage from a colorectal anastomosis occurred during this endoscopic decompression procedure. Immediately after insertion of a decompression procedure tube, radical surgery could be performed after adequate preoperative examination and colorectal preparation. CONCLUSIONS: This procedure may be helpful in allowing immediate preoperative examination and scheduling of a radical operation for acute obstructing colorectal disease.

Continuous intra-arterial 5-FU chemotherapy in a patient with a repeated recurrence of rectal cancer: report of a case.

PURPOSE: We report a patient with a recurrent pelvic tumor after abdominoperineal resection of a rectal carcinoma who was treated sufficiently by repeated intra-arterial infusions of 5-fluorouracil. METHODS: A continuous, 24-hour 5-fluorouracil administration was made through the bilateral internal iliac artery at a dosage of 250 mg/m2/day by the subcutaneous reservoir located at both upper legs using a Baxter infusor. RESULTS: In this patient pain in the hip and pelvis was relieved. A complete regression in the infused field of pelvic tumor was observed not only with computed tomography and magnetic resonance imaging but also confirmed by operative findings at the seventh month after the intra-arterial infusion. The abnormal serum level of carcinoembryonic antigen and carbohydrate antigen 19-9 was decreased to within the normal range at the 19th and 3rd week respectively. When the repeated recurrence was suspected in follow-up, normalization of the re-elevated carcinoembryonic antigen and carbohydrate antigen 19-9 levels was also obtained by repeating the same treatment. The side effects and complications were tolerable, consisting of local skin erosion on the hips and lower extremity neuropathy caused by the 5-fluorouracil. CONCLUSIONS: Clinical local regression of a pelvic recurrence was observed in a patient with rectal recurrent tumor who received continuous intra-arterial chemotherapy. Local recurrence of rectal cancer may be controlled effectively and safely by repeating long-term, continuous, intra-arterial 5-fluorouracil infusion.

Electrophysiological studies of a child with presumed botulism.

Electrophysiological studies of a child with presumed botulism showed that the amplitude of the serially and electrically elicited blink reflexes Rl, R2 and R2' was reduced during recovery. These findings suggest a conduction block of the facial nerves. Other nerve conduction studies and an incremental response to repetitive stimulation demonstrated a block of the presynaptic neuromuscular transmission. Results of the biological tests were negative, but those of electrodiagnosis and clinical examination favored a diagnosis of botulism. A combination of electrically elicited blink reflexes and rapid repetitive stimulation of the peripheral nerves was found to be a sensitive method of assessing the integrity of neuromuscular junctions and the subclinical impairment of muscle nerves.

Is upper mediastinal lymphadenectomy necessary in squamous carcinoma of the lower thoracic oesophagus?

AIM: We examined the indication of upper mediastinal lymphadenectomy for a squamous cell carcinoma of the lower thoracic oesophagus. METHODS: 49 patients underwent a curative oesophagectomy with upper mediastinal lymphadenectomy for a squamous cell carcinoma of the lower thoracic oesophagus. Node status and clinicopathological characteristics of these patients were reviewed retrospectively. RESULTS: 16 (94.1%) of 17 patients with superficial tumours had no positive node in the upper mediastinum. Nine (29.0%) of 31 patients with transmural tumours had positive nodes in the upper mediastinum (P = 0.04). Ten (20.4%) of 49 patients had many positive nodes in the upper mediastinum. Of these 10 patients, 6 patients had 5 or more positive nodes in all. The 5-year survival rate for patients with 5 or more positive nodes was 7.7%, which was significantly poorer than patients with 4 or fewer positive nodes. CONCLUSIONS: Upper mediastinal lymphadenectomy is unnecessary in most of the superficial squamous carcinomas of the lower thoracic oesophagus.