Transabdominal impalement injury by an iron pipe - A case report.

Impalement injuries are rare and complex problems, often involving multiple organ injuries. An 18-year-old male was admitted to our emergency department after a car accident. Positioned in the right-side recumbent position, he had a 4.5 cm diameter pipe penetrating from his left abdomen to his back. Given the pipe's length exceeding the CT gantry's capacity, further imaging tests were not feasible. Consequently, the patient proceeded directly to the operating room without preoperative imaging. Before laparotomy, a left thoracotomy was conducted for aortic cross-clamping, anticipating uncontrollable bleeding during pipe removal. The subsequent laparotomy, with the patient in the right-side recumbent position, revealed the pipe impaling through the mesentery of the descending colon without evident major vessel injury. The pipe was cautiously extracted. The patient was subsequently discharged on day 26. The absence of imaging feasibility emphasized that current hemodynamic stability does not rule out the potential for significant vessel injury. Therefore, the sequential approach of left thoracotomy for aortic cross-clamping followed by laparotomy emerges as a potentially beneficial strategy in cases of transabdominal impalement. The impalement injury requires our preparedness and flexibility, which should be tailored to the individual case.

Impact of elemental diet on early recovery after laparoscopic colectomy: findings of a randomized controlled trial.

PURPOSE: An amino acid-containing elemental diet (ED) does not require digestion for nutritional absorption, making it a good option for patients with gastrointestinal malabsorption. We conducted a randomized trial to confirm that perioperative ED enhanced the recovery of patients undergoing laparoscopic colectomy. METHODS: Patients in the intervention arm received commercially available ED from the day prior to surgery until postoperative day (POD) 3, whereas patients in the control group received a conventional perioperative diet program. To verify the endpoints, "estimated minimum length of stay in hospital after surgery" (emLOS) was defined as the number of days necessary to reach all the five criteria; namely, "sufficient oral intake", "sufficient pain control", "withdrawal of intravenous alimentation", "no abnormal findings in routine examinations", and "no rise in fever". RESULTS: A total of 102 patients were randomized, 94 of whom were analyzed (ED 45, control 49). There was no morbidity or mortality. Shorter emLOS (POD 4 vs. POD 7; p = 0.018), earlier resumption of sufficient oral intake (POD 3 vs. POD 4; p = 0.034) and faster recovery to defecation (2.2 vs. 3.1 days; p = 0.005) were observed in the ED group vs. the control group. CONCLUSIONS: The perioperative ingestion of ED by patients undergoing laparoscopic colectomy is safe and can reduce the postoperative hospital stay by supporting the acceleration of oral intake.

[Transmanubrial Osteomuscular-sparing Approach for Resection of Superior Mediastinal Schwannoma].

Various approaches can be applied to resect superior mediastinal tumor. It is important to choose the procedure according to the location, size, and characteristics of the tumor in order to perform safe procedure surgery because of distinctive anatomy of this site. We hereby report on a case of Schwannoma of the superior mediastinum resected by the transmanubrial approach. A 67-year-old woman was referred to our department to examine an abnormal chest shadow found at a regular health checkup. Computed tomography revealed a tumor 58×52 mm in size extending from the left supraclavicular fossa to the upper border of the aortic arch. The surgery was performed under the diagnosis of neurogenic tumor using the transmanubrial approach. The tumor was resected safely and the pathological diagnosis was a Schwannoma. Transmanubrial approach was found to be quite useful in securing an adequate visual field and enabling the safe separation of blood vessels and nerves from the tumor.

Inhibition of Eph receptor A4 by 2,5-dimethylpyrrolyl benzoic acid suppresses human pancreatic cancer growing orthotopically in nude mice.

Ephrin receptor A4 (EphA4) is overexpressed in human pancreatic adenocarcinoma (PDAC) and activate cell growth. Recent studies have identified small molecules that block EphA4. In this study, we investigated the correlation between EphA4 expression and the prognosis of patients with PDAC. We also examined the cytostatic efficacy of 2,5-dimethylpyrrolyl benzoic acid (compound 1), a small molecule that blocks EphA4, in PDAC cells. Overall survival of patients with EphA4 positivity was significantly shorter than that of patients with EphA4 negativity (P = 0.029). In addition, multivariate analysis revealed that EphA4 expression was an independent prognostic factor in PDAC patients (P = 0.039). Compound 1 showed a cytostatic efficacy in PDAC cells expressing EphA4 in vitro and in vivo. Our study indicated that compound 1 suppressed both EphA4 and Akt phosphorylations, and induced apoptosis in PDAC cells expressing EphA4. In conclusion, compound 1 has a high potential as a therapeutic agent for patients with PDAC.

Paraneoplastic extralimbic encephalitis associated with thymoma: a case report.

Here we a report a rare case of extralimbic encephalitis associated with thymoma. A 66-year-old woman was admitted to our hospital with cramping in her right leg and inability to walk. Magnetic resonance imaging of the brain showed multifocal high intensity signals on T2 flare images in the cerebral cortex, and chest computed tomography showed a 5-cm anterior mediastinal mass, which was considered to be a thymoma. We speculated that she had paraneoplastic encephalitis associated with thymoma. She underwent a thymectomy and was diagnosed with type B1 thymoma. On postoperative day 6, her neurological symptoms began to improve. On postoperative day 31, she was discharged without complications. Limbic encephalitis is a paraneoplastic neurological syndromeassociated with thymoma, but extralimbic encephalitis has been described in the literature very rarely. We report the case of extralimbic encephalitis associated with thymoma along with a literature review.

Surgical resection of solid gallbladder adenocarcinoma presenting as a large mass: report of a case.

This report describes a case of a patient with a large solid gallbladder adenocarcinoma that was completely resected through aggressive surgery. The patient was a 57-year-old woman who had been diagnosed with advanced gallbladder cancer, had no indications for surgical resection and was scheduled to undergo systemic chemotherapy. She presented to our hospital for a second opinion. At the time of assessment, her tumor was large but was well-localized and had not invaded into the surrounding tissues, indicating that surgical resection was a reasonable option. Subsequently, the tumor was completely extracted via right hepatectomy with en bloc resection of the caudate lobe and extrahepatic bile duct. Histopathologically, the tumor was a solid adenocarcinoma. Although there are relatively few reports in the literature regarding solid gallbladder adenocarcinoma, well-localized growth appears to be a characteristic feature. On the basis of a tumor's progression behavior, aggressive surgical treatment might be indicated even when the tumor has grown to a considerable size.

Impact of the tumor microenvironment in predicting postoperative hepatic recurrence of pancreatic neuroendocrine tumors.

The disease frequency of pancreatic neuroendocrine tumors (PNETs) has been growing, and postoperative hepatic recurrence (PHR) is one of the factors affecting patient prognosis. The present study aimed to investigate biomarkers of PNETs in the primary disease site to predict PHR using immunohistochemical analysis for tumor-infiltrating lymphocytes (TILs: CD3, CD8 and CD45RO), human leukocyte antigen (HLA) class I, α-thalassemia/mental retardation X-linked (ATRX), death domain-associated protein (DAXX), mammalian target of rapamycin (mTOR) and phospho-mTOR (p-mTOR). Correlations were analyzed between TILs and the biomarkers, clinicopathological features and prognosis. Sixteen patients with PNETs who underwent radical surgery at our hospital were reviewed. We analyzed the correlation between PHR and immunohistochemical characteristics, and also between disease-free survival (DFS) or overall survival (OS) and the immunohistochemical characteristics. We found that PHR was associated with the expression patterns of DAXX and p-mTOR. No association was found between PHR and patient background, TILs or other biomarkers. DFS was found to be associated with ATRX, DAXX and p-mTOR. OS was associated only with p-mTOR. In conclusion, ATRX, DAXX and p-mTOR are useful molecular biomarkers for predicting PHR in patients who undergo radical surgery for PNETs. Use of these biomarkers will enable earlier decisions on which patients may benefit from adjuvant therapy.

Wnt inhibitor Dickkopf-1 as a target for passive cancer immunotherapy.

Dickkopf-1 (DKK1) is an inhibitor of Wnt/beta-catenin signaling that is overexpressed in most lung and esophageal cancers. Here, we show its utility as a serum biomarker for a wide range of human cancers, and we offer evidence favoring the potential application of anti-DKK1 antibodies for cancer treatment. Using an original ELISA system, high levels of DKK1 protein were found in serologic samples from 906 patients with cancers of the pancreas, stomach, liver, bile duct, breast, and cervix, which also showed elevated expression levels of DKK1. Additionally, anti-DKK1 antibody inhibited the invasive activity and the growth of cancer cells in vitro and suppressed the growth of engrafted tumors in vivo. Tumor tissues treated with anti-DKK1 displayed significant fibrotic changes and a decrease in viable cancer cells without apparent toxicity in mice. Our findings suggest DKK1 as a serum biomarker for screening against a variety of cancers, and anti-DKK1 antibodies as potential theranostic tools for diagnosis and treatment of cancer.

Activation of an oncogenic TBC1D7 (TBC1 domain family, member 7) protein in pulmonary carcinogenesis.

To develop novel biomarkers and therapeutic agents for lung cancers, we screened molecules that were highly expressed in lung cancers by means of cDNA microarray analysis and found an elevated expression of TBC1 domain family, member 7 (TBC1D7) in the majority of lung cancers. Northern-blot analysis using mRNAs from 16 normal tissues detected its expression only in testis. Immunohistochemical staining using tumor tissue microarrays consisting of 261 archived non-small cell lung cancer (NSCLC) specimens suggested an association of TBC1D7 expression with poor prognosis for NSCLC patients (P = 0.0063). Treatment of lung cancer cells using siRNA against TBC1D7, suppressed its expression and resulted in inhibition of the cell growth. Furthermore, the induction of exogenous expression of TBC1D7 conferred growth-promoting activity at in vitro and in vivo conditions. We also identified TBC1D7 to interact with TSC1 protein in lung cancer cells. TSC1 introduction into cells increased the level of TBC1D7 protein, whereas knockdown of TSC1 expression decreased the level of TBC1D7 protein, suggesting that TBC1D7 is stabilized probably through interaction with TSC1. In addition, inhibition of the binding between TBC1D7 and TSC1 by a TBC1D7-derived 20-amino acid cell-permeable peptide (11R-TBC1D7(152-171)), which corresponded to the binding domain to TSC1, effectively suppressed growth of lung cancer cells. Selective suppression of TBC1D7 and/or inhibition of the TBC1D7-TSC1 complex formation could be promising therapeutic strategies for lung cancer therapy.

Activation of WD repeat and high-mobility group box DNA binding protein 1 in pulmonary and esophageal carcinogenesis.

PURPOSE: We attempted to identify novel biomarkers and therapeutic targets for lung and esophageal cancers. EXPERIMENTAL DESIGN: We screened for genes that were overexpressed in a large proportion of lung and esophageal carcinomas using a cDNA microarray representing 27,648 genes or expressed sequence tags. A gene encoding WDHD1, a WD repeat and high-mobility group box DNA binding protein 1, was selected as a candidate. Tumor tissue microarray containing 267 archival non-small cell lung cancers and 283 esophageal squamous cell carcinomas (ESCC) was used to investigate the clinicopathologic significance of WDHD1 expression. The role of WDHD1 in cancer cell growth and/or survival was examined by small interfering RNA experiments and cell growth assays. The mechanism of WDHD1 activation through its phosphorylation in cancer cells was examined by immunoprecipitation and kinase assays. RESULTS: Positive WDHD1 immunostaining was associated with a poor prognosis for patients with non-small cell lung cancer (P = 0.0403) as well as ESCC (P = 0.0426). Multivariate analysis indicated it to be an independent prognostic factor for ESCC (P = 0.0104). Suppression of WDHD1 expression with small interfering RNAs effectively suppressed lung and esophageal cancer cell growth. In addition, induction of the exogenous expression of WDHD1 promoted the growth of mammalian cells. AKT1 kinase seemed to phosphorylate and stabilize the WDHD1 protein in cancer cells. CONCLUSIONS: WDHD1 expression is likely to play an important role in lung and esophageal carcinogenesis as a cell cycle regulator and a downstream molecule in the phosphoinositide 3-kinase/AKT pathway, and that WDHD1 is a candidate biomarker and a promising therapeutic target for cancer.

[Clinical examination of challenge test to local anesthetics].

BACKGROUND: Although adverse reactions to local anesthetics are often diagnosed as local anesthetic allergy, there is evidence that most of these reactions occur via non-allergic mechanisms. METHODS: To evaluate allergic reactions to local anesthetics, challenge tests were performed in 20 patients who had a history of adverse events to local anesthetics for whom dental treatment was planned. The diagnostic protocol of this challenge test consisted of skin prick and intracutaneous tests, as well as subsequent incremental subcutaneous challenge tests with local anesthetics such as lidocaine. RESULTS: 17 patients (85%) showed no immediate allergic response to lidocaine, which could then be used for dental treatment. Three patients (15%) reacted positively to lidocaine: one had local erythema at the site of the skin prick, and two reacted to subcutaneous challenge. CONCLUSION: The proportion of immediate-type reactions to local anesthetics is small but not rare in patients suspected of having local anesthetic allergy. This result suggests that the diagnostic approach to confirm allergy to local anesthetics is clinically important and requires further study in a larger population.

Activation of placenta-specific transcription factor distal-less homeobox 5 predicts clinical outcome in primary lung cancer patients.

PURPOSE AND EXPERIMENTAL DESIGN: To identify novel biomarkers and therapeutic targets for lung cancers, we screened for genes that were highly transactivated in lung cancers using a cDNA microarray representing 27,648 genes. DLX5 gene, a member of the human distal-less homeobox transcriptional factor family that is expressed during early embryonic development, was found to be overexpressed in the great majority of lung cancers. Tissue microarray consisting of archival non-small cell lung cancer samples from 369 patients was applied to examine the clinicopathologic significance of DLX5 protein. A role of DLX5 in cancer cell growth and/or survival was investigated through small interfering RNA experiments. RESULTS: Northern blot and immunohistochemical analyses detected expression of DLX5 only in placenta among 23 normal tissues examined. Immunohistochemical analysis showed that positive immunostaining of DLX5 was correlated with tumor size (pT classification; P = 0.0053) and poorer prognosis of non-small cell lung cancer patients (P = 0.0045). It was also shown to be an independent prognostic factor (P = 0.0415). Treatment of lung cancer cells with small interfering RNAs for DLX5 effectively knocked down its expression and suppressed cell growth. CONCLUSIONS: These data implied that DLX5 is useful as a target for the development of anticancer drugs and cancer vaccines as well as for a prognostic biomarker in clinic.

Activation of Holliday junction recognizing protein involved in the chromosomal stability and immortality of cancer cells.

We identified a novel gene HJURP (Holliday junction-recognizing protein) whose activation seemed to play a pivotal role in the immortality of cancer cells. HJURP was considered a possible downstream target for ataxia telangiectasia mutated signaling, and its expression was increased by DNA double-strand breaks (DSB). HJURP was involved in the homologous recombination pathway in the DSB repair process through interaction with hMSH5 and NBS1, which is a part of the MRN protein complex. HJURP formed nuclear foci in cells at S phase and those subjected to DNA damage. In vitro assays implied that HJURP bound directly to the Holliday junction and rDNA arrays. Treatment of cancer cells with small interfering RNA (siRNA) against HJURP caused abnormal chromosomal fusions and led to genomic instability and senescence. In addition, HJURP overexpression was observed in a majority of lung cancers and was associated with poor prognosis as well. We suggest that HJURP is an indispensable factor for chromosomal stability in immortalized cancer cells and is a potential novel therapeutic target for the development of anticancer drugs.

[Prognostic significance of neutrophil elastase inhibitor in patients with acute lung injury and interstitial pneumonia].

The prognostic significance of a neutrophil elastase inhibitor, sivelestat sodium hydrate (SSH), was evaluated in patients on mechanical ventilation due to acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) associated with systemic inflammatory response syndrome (SIRS). We studied 20 consecutive patients in our hospital, where patients complicated with interstitial pneumonia (IP) were separately analyzed (ARDS group, n = 10; IP group, n = 10). There was no significance difference between the two groups in the average lung injury score (3.0 in the ARDS group versus 2.8 in the IP group), the mean P/F ratio (96.3 mmHg in the ARDS group versus 96.7 mmHg in the IP group), plateau pressure (30.5 mmHg in the ARDS group versus 27.0 mmHg in the IP group), ventilator-free days, the duration of intensive care unit stay, and the hospitalization period. Four ARDS patients and 5 IP patients were treated with SSH within 3 days from SIRS onset. In the ARDS group, 5 patients (50%) were complicated with 4 or more organ dysfunctions and 3 patients (30%) died. IP patients all received corticosteroid, but the mortality was significantly higher among patients with IP than among those with ARDS by Kaplan-Meier survival curves. Of the clinical variables, only the diagnosis of IP was found to be independently related to mortality by a multivariate Cox proportional-hazards analysis. We conclude that IP patients have poor life expectancy if they are treated with SSH.

[A pregnant woman with severe asthma effectively treated by inhalational lidocaine therapy].

We report a case of a pregnant woman with severe asthma that was not controlled with ordinary medications but was effectively treated by inhalational lidocaine treatment. The case was a 27-year-old woman who had been repeatedly hospitalized due to acute asthma since her infancy. The patient had an episode of asthma attack caused by the use of aspirin. The daily medication for controlling her asthma included 1.5mg betamethasone. In February, 2004, she was hospitalized because of asthma exacerbation during her 11th week of pregnancy. Despite intensive treatments including repetition of inhaled beta2-agonist and anti-cholinergic drugs, intravenous injection of betamethasone and theophylline, and a leukotriene receptor-antagonist, no obvious improvement in severe cough, wheeze, or hypoxemia was observed for more than 3 weeks. Then inhalational lidocaine was introduced according to the method described by Mayo Clinic, USA. Namely, following inhalation of beta2-agonist, 40 to 100mg lidocaine was given via an ultrasonic nebulizer 5 times a day. Interestingly, symptoms such as wheezing or cough and also her hypoxemia dramatically improved following this treatment and reduction of systemic corticosteroid became possible. Finally, she was delivered of a girl by caesarean section. Nebulized lidocaine treatment may be an useful option as supplementary treatment for refractory asthma especially in pregnant cases.

Hyaline vascular-type Castleman's disease in the hepatoduodenal ligament: report of a case.

Castleman's disease is an uncommon lymphoproliferative disorder, which occurs most commonly in the mediastinum. Sporadic reports of its occurrence in the hepatoduodenal ligament and other extrathoracic locations have also been documented. Ultimately, Castleman's disease can develop anywhere lymphoid tissue is found, and the preoperative diagnosis is often difficult. We report a case of hyaline vascular-type Castleman's disease in the hepatoduodenal ligament. An asymptomatic 26-year-old woman was admitted to our hospital for further examination of a mass found on ultrasonography. A contrast-enhanced computed tomography scan confirmed a hypervascular mass in the hepatoduodenal ligament, and angiography showed that the mass was receiving its blood supply from various arteries. These findings suggested a diagnosis of Castleman's disease and we removed the tumor without resecting any other organs. Computed tomography and angiography were helpful in establishing a correct preoperative diagnosis, which minimized the magnitude of surgery.

[A case of pulmonary Mycobacterium avium complex disease, mimicking hot tub lung].

A 56-year-old man in whom reticulonodular shadows had been noted on a previous chest radiography study was admitted to our hospital with complaint of exertional dyspnea in March 2004. His thoracic computed tomography (CT) showed diffuse ground-glass opacities and multiple centrilobular small nodules in both lung fields. Lymphocytes occupied a high proportion in the cells recovered from the bronchoalveolar lavage fluid. These findings were compatible with those for hypersensitivity pneumonitis. Histopathological findings observed in the video-assisted thoracoscopic surgical biopsy specimens included necrotizing granulomas, organizing pneumonia associated with collective epithelioid cell granulomas without necrosis, and alveolar septal thickening with lymphocyte infiltration that showed a centrilobular distribution. These findings were also compatible with those for hot tub lung. Further information that supported the diagnosis were the identifications of Mycobacterium avium complex in his sputum by acid-fast bacteriological culture as well as positive for Mycobacterium avium polymerase chain reaction in lung specimen. He responded well to corticosteroid therapy, resulting in improvement in his clinical condition as well as in his chest radiographs. He was later put on an antituberculosis therapy, and the corticosteroid therapy was discontinued. This led to an exacerbation of his disease and corticosteroid therapy was restarted. It is not long time since the disease was first recognized, and thus few cases have been reported in Japan. Our report may provide valuable information on the disease in this country.

Serum IgG and IgA antibodies to Chlamydia pneumoniae and severity of emphysema.

OBJECTIVE: Chronic Chlamydia pneumoniae infection has been identified serologically in patients with COPD. The aim of this study was to examine whether the severity of emphysema is related to elevated antibody titres against C. pneumoniae. METHODOLOGY: We measured antibody titres against C. pneumoniae using ELISA, and assessed the severity of emphysema by the percentage of low attenuation area (%LAA) using high resolution (HR) CT in patients with COPD and in non-smoking control subjects. RESULTS: The mean %LAA was 2.2% in non-smoking controls (n = 28) and 13.3% in COPD patients (n = 94). COPD patients with a high IgG antibody index to C. pneumoniae (> or =2.0, n = 42) had a significantly higher %LAA (16.8%) than those with a low IgG index (<2.0, n = 52) (10.6%, P = 0.01). In addition, COPD patients with a high IgA antibody index (> or =2.0, n = 46) had a significantly higher %LAA (15.9%) than those with a low IgA index (<2.0, n = 48) (10.9%, P = 0.048). COPD patients with a high IgA antibody index also had a significantly lower %DLco than that associated with a low IgA index (68.1% and 80.3%, respectively, P = 0.007). There were no significant differences in age, smoking index or FEV(1)/FVC between these groups. CONCLUSION: These results suggest that high antibody titres against C. pneumoniae are linked with the severity of emphysema on high resolution CT and decreased diffusing capacity to carbon monoxide.

High resolution CT and bronchial reversibility test for diagnosing COPD.

BACKGROUND: COPD is defined by airflow limitation that is not fully reversible and is associated with relevant risk factors. The diagnosis requires that other causes of chronic airflow limitation (CAL) be excluded. We assessed the diagnostic utility of high resolution thoracic CT (HRCT) and bronchodilator reversibility to assist in making a diagnosis of COPD. METHODOLOGY: We investigated 516 consecutive patients whose FEV1/FVC was less than 70% after inhalation of bronchodilator. HRCT was performed on all subjects and a final diagnosis was made only after 3 months of treatment and repeated spirometry. RESULTS: Of 516 cases, 54.3% had COPD, 19.8% had asthma plus emphysema, and 13.2% had chronic asthma. The remaining 12.7% of patients with CAL had diffuse panbronchiolitis, bronchiectasis, bronchiolitis obliterans, or other miscellaneous diseases. In these minor diseases HRCT was essential in making a definitive diagnosis. The sensitivities of emphysema on HRCT and of absence of bronchodilator response for the diagnosis of COPD were 81% and 90%, respectively, and the specificities of the tests were 57% and 37%, respectively. In addition, HRCT revealed considerable heterogeneity of COPD. Emphysema was not recognized on HRCT in 18.6% of COPD patients. HRCT also revealed that 17.5% of COPD patients had other pulmonary complications including lung fibrosis compatible with usual interstitial pneumonia in the lung bases. CONCLUSIONS: HRCT and the bronchial reversibility test had reasonable sensitivities but low specificities for diagnosing COPD. HRCT has some additional advantages in detecting heterogeneity and concomitant lung diseases in COPD.