Preliminary experimental outcomes of induced hypercapnia in treatment of obstinate singultus.

BACKGROUND: Our team found that abolishing the venous-arterial CO2 gradient can cease singultus (hiccups), in which the CO2 pressure in blood reaches no less than 50 mmHg. In order to precisely investigate the target level as a preliminary study, we made a combination gas consisting of 10% CO2 and 90% O2 to generate the conditions instantly and safely. METHODS: Thirty-five cases consisting of 26 patients with long-term chronic singultus were treated using the gas. The group consisted of 21 males and 5 females with mean singultus duration of 8.0±13.1 years. A standard oxygen mask was used for delivery of the gas to the patients, and patients breathed in the gas until they felt relief. The duration of the procedure was measured from the beginning to the point at which singultus ceased. A blood test was performed to measure the partial pressure of CO2 in venous blood at the point at which singultus ceased. RESULTS: Singultus ceased in all patients in a mean time of 5.3±1.5 minutes, with complete recurrence observed in two cases. The mean partial pressure of CO2 in the venous blood at the point the singultus stopped was 60.8±6.8 mmHg. No life-threatening complications were found in any patient. CONCLUSIONS: One of the definitive conditions for ceasing singultus is acute CO2 retention in the body, the target of which is around 60 mmHg of CO2 in venous blood. We believe that targeting acute hypercapnia can always stop singultus, although further neuroscientific investigation is necessary to reveal the physiological mechanism.

[Pulmonary Mucormycosis with Reversed Halo Sign on Computed Tomography of Patient with Leukemia].

The patient was a male in his 60s, who had undergone bone marrow transplantation because of lymphoblastic leukemia. He suffered from chest pain two weeks after the transplantation. A chest computed tomography(CT) showed reversed halo sign( RHS) in the right upper lobe of the lung. A bronchoscopic lung biopsy revealed mycelia, and the patient was diagnosed with pulmonary mucormycosis. Although antifungal drugs were administered, no significant improvements were observed. A right upper lobectomy of the lung was successfully performed, and no postoperative complications occurred. Pathological examination found nodular lesions with extensive necrotic foci inside, and inflammatory granulation tissue and mucormycosis with hyphae (+) were found through Grocott staining. RHS in leukemia patients with neutropenia is specific to pulmonary mucormycosis. Pulmonary mucormycosis is a life-threatening disease, and urgent treatment intervention including surgical treatment is advisable.

[Surgically Managed Flail Chest Caused by Resuscitation].

A 84-year-old man who had experienced cardiac arrest in the ambulance was brought to the emergency room. He had been followed at outpatient after surgery for colon cancer and known to be suffered from mild renal impairment. The cardio pulmonary arrest was likely to be caused by acute exacerbation of that. He was resuscitated and immediately recovered without severe hypoxic encephalopathy or deterioration of renal function. However, the flail chest by manual cardiac compression sustained. It urged him to be managed under the ventilator and he seemed difficult to leave from that within a couple of weeks. So we decided to perform surgery. The course after surgery was favorable.

Pulmonary resection after chemoradiotherapy for advanced non-small cell lung cancer: the impact of presurgical radiation therapy.

PURPOSE: Chemoradiation therapy (CRT) is recommended as standard care for stage III non-small cell lung cancer (NSCLC), but some patients experience local recurrence after the treatment. Surgical resection after CRT involves high surgical risk, but is expected to increase the curability. This study was performed to investigate the impact of presurgical CRT on the postoperative outcome, focusing especially on the effect of radiation therapy. METHODS: Twenty-six patients with stage III (N2 or T3-4) NSCLC underwent pulmonary resection after CRT. A radiation dose up to 40-70 Gy was given with concurrent chemotherapy. The morbidity, mortality and survival after surgical resection were examined. RESULTS: Lung resection was performed as lobectomy (73 %) or pneumonectomy (19 %). Postoperative complications occurred in 12 patients (morbidity 46.1 %). The overall 5-year survival of the entire cohort was 69.7 %. The factors associated with favorable long-term survival included a pathological complete response (CR) and mediastinal node negative condition after CRT, and microscopic complete resection. CONCLUSION: Surgical resection for stage III patients after CRT may provide a survival benefit with acceptable morbidity. The surgical morbidity may be increased by prior radiation therapy, thus, surgeons should be familiar with the available countermeasures to reduce the surgical risk.

[Surgical management for lung cancer in less than 1 cm].

Recently, the greater utilization of computed tomography (CT) has led to an increasing proportion of small-sized stage I A lung cancer in less than 1 cm in diameter. However, a treatment strategy for these small-sized lung cancers has not yet been defined. The aim of this study was to investigate surgical outcomes regarding these lung cancers. A total of 123 patients who underwent complete surgical resection for lung cancer in less than 1 cm between January 1995 and March 2010 were retrospectively evaluated. The 123 study subjects consisted of 54 male and 69 female patients. The mean age was 64.0 (43~82) years. The mean tumor size was 0.9( 0.3~1.0) cm. In this study, 70 patients underwent lobectomy (56.9%). Segmentectomy and wedge resection were underwent 23( 18.7%) and 30 patients( 24.4%), respectively. The 3-, 5- and 10-year survival rates were 95.7, 92.3 and 85.7%, respectively, after the operation for lung cancer in less than 1 cm. There were no significant difference between sublobar resection and lobectomy. However, 2 patients( 1.6%) had recurrent cancer and 7 patients (5.7%) had lymph node metastasis. We suggested surgical procedure for patients with lung cancers in less than 1 cm should be selected with the greatest care, because recurrent cancer and lymph node metastasis can occur in patients.

Effectiveness of near-infrared spectroscopy during surgical repair of tracheo-innominate artery fistula.

Monitoring regional cerebral oxygen saturation (rSO(2)) by use of near-infrared spectroscopy (NIRS) is a useful method for detecting cerebral ischemia. Tracheo-innominate artery fistula is a rare but life-threatening complication of tracheostomy. The surgical procedures for management of tracheo-innominate artery fistula include direct or patch closure of the fistula, ligation or division of the innominate artery, and anatomical or extra-anatomical reconstruction of the flow of the innominate artery. Division of the innominate artery is the best method to prevent postoperative recurrence of bleeding and infection. However, cutting off the innominate artery flow may cause brain ischemia. We present the case of a patient with tracheo-innominate artery fistula successfully treated by dividing the innominate artery while the rSO(2) was monitored. In this case report, we have shown that NIRS is a useful method for deciding the surgical maneuver for tracheo-innominate artery fistula.

Micropapillary pattern and grade of stromal invasion in pT1 adenocarcinoma of the lung: usefulness as prognostic factors.

Recently, the stromal invasion grading system was proposed for small adenocarcinomas of < or =2.0 cm. The system is based on the presence or absence of a fibrotic focus, and the extent of invasion into the fibrotic focus. Although stromal invasion grading system closely correlated with the prognosis, stromal invasion grade 3, representing stromal invasion into the center of a fibrotic focus, was the largest group of tumors and showed variable prognosis. In this study, we investigated whether stromal invasion grading system could be applied to and validated in pT1 adenocarcinomas as the TNM classification is the most universally used system. Furthermore, we investigated whether stromal invasion grade 3 cases could be subclassified according to the presence and absence of micropapillary pattern. The study included 120 cases of pT1 lung adenocarcinomas, of which 81 (68%) cases were stromal invasion grade 3. Micropapillary pattern was positive in 80% of grade 3 cases. For stromal invasion grade 3 cases, the 5-year survival rate of patients with micropapillary pattern-positive carcinomas was 63%, which was significantly worse than 94% of those with micropapillary pattern-negative carcinomas (P=0.0196). The latter was very close to that for patients with stromal invasion grade 0-2 (95%). Moreover, small cluster invasion was observed at sites of stromal invasion significantly more often in micropapillary pattern-positive cases than negative cases. Thus, the stromal invasion grading system is reproducible and correlates with prognosis even in pT1 lung adenocarcinomas. Moreover, among patients with stromal invasion grade 3 carcinomas, favorable prognosis is noted in micropapillary pattern-negative cases. The micropapillary pattern subclassification provides an advantage to the stromal invasion grading system and reconfirms the importance of micropapillary pattern as a prognostic marker. Our study is the first to point to the possible association of micropapillary pattern-positive carcinomas and small cluster invasion.

Possible mechanism of metastasis in lung adenocarcinomas with a micropapillary pattern.

Micropapillary differentiation in adenocarcinomas has recently been associated with poor prognosis because these tumors are more likely to metastasize. However, no clear explanation exists as to why the presence of a micropapillary pattern is associated with metastasis. A case of primary lung adenocarcinoma with a prominent micropapillary pattern is presented here, with special reference to the immunohistochemical expression of the E-cadherin-mediated system and IQGAP1. Histologically, the tumor was diagnosed as a moderately differentiated papillary adenocarcinoma, showing an extensive micropapillary pattern, with intrapulmonary metastases, pulmonary disseminations, lymphovascular invasions, and lymph node metastases. Immunohistochemically, positive staining for the adhesion molecules E-cadherin, alpha-catenin, and beta-catenin was detected in both the micropapillary and non-micropapillary areas, whereas IQGAP1 was detected in the micropapillary, but not in the non-micropapillary, area. The adhesive function of E-cadherin depends on the integrity of the entire cadherin-catenin-actin network, and thus the expression of IQGAP1 may lead to adherens junction disassembly, and consequently, the release of carcinoma cells organizing in a micropapillary pattern. This is the first report to suggest correlation between adenocarcinoma with a micropapillary pattern and the presence of adhesion molecules, and offers an intriguing first glimpse on the role of the micropapillary pattern in the process of metastasis.

Inflammatory myofibroblastic tumor of the posterior mediastinum: an older adult case with anaplastic lymphoma kinase abnormalities determined using immunohistochemistry and fluorescence in situ hybridization.

Inflammatory myofibroblastic tumor (IMT) is a rare neoplasm that usually occurs in children and young adults. Anaplastic lymphoma kinase (ALK) abnormalities in IMT, determined using immunohistochemistry and/or molecular genetic studies, including fluorescence in situ hybridization (FISH), have almost been limited to children and young adults. In elderly cases of IMT, these ALK abnormalities are very rare. We report on a case of IMT arising in the posterior mediastinum of a 59-year-old Japanese man that showed ALK abnormalities determined using immunohistochemistry and FISH, suggesting the neoplastic nature of a subset of IMTs in older patients similar to those in younger ones and the presence of an additional mechanism(s) that allows them to start to grow late.

Apoptosis- and cell cycle-associated gene expression profiling of histiocytic necrotising lymphadenitis.

Cell death is of two types; necrosis and apoptosis. In histiocytic necrotising lymphadenitis (HNL), apoptosis is the main form of cell death. Apoptosis results in the formation of nuclear debris, which is one of the characteristic features of HNL. We previously reported that in HNL it is predominantly CD8-positive cytotoxic T cells that undergo apoptosis; however, the majority of proliferating cells are also CD8-positive T cells. Recent advances in technical and analytical methods have facilitated the parallel quantitation of expression of numerous genes using DNA microarrays. The technology is particularly well suited to compare differences in gene expression between normal tissues and inflammatory disease. To investigate the apoptosis- and cell cycle-associated gene expression in HNL, we analysed five cases each of HNL and non-specific lymphadenitis (NSL), using ready-made microarrays, including cyclins and caspases, and immunohistochemical staining of caspase-3, ssDNA, bcl-2 and NF-kappaB. Caspase-3- and ssDNA-positive apoptotic cells were frequently detected in HNL, but were rare in NSL. However, bcl-2- and NF-kappaB-positive cells were rare in HNL. Gene expression tree analysis of DNA microarrays showed different clustering of HNL and NSL. In comparison with NSL, HNL exhibited diffuse upregulation of these gene profiles, particularly of cyclins and caspases (ratio; cyclin A2, 2.72; caspase-6, 2.43; caspase-3, 2.02); whereas, Mcl-1, which has been shown to delay apoptosis, was downregulated (ratio, 0.71), as confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR). Almost all apoptosis-associated genes, especially caspases, were upregulated, and apoptosis inhibitory genes, including bcl-2 by immunohistochemistry, were downregulated in all five cases with HNL. In addition, cell cycle-associated genes were upregulated in all. These findings confirm that both apoptosis and proliferation are simultaneously present in HNL lesions.

Differential expression of chemokines, chemokine receptors, cytokines and cytokine receptors in diffuse large B cell malignant lymphoma.

Host immunity, particularly T cell immunity (Th1/Th2 balance), plays an important role in clinicopathological features of malignant disease. However, the T cell immunity has not been fully investigated in patients with lymphoid malignancies. Recent studies suggested the important role of dysregulation of the endogenous immune system in lymphomagenesis. The relationships between cytokines/chemokines and their receptors, are important in determining the selectivity of local immunity. To investigate differences in the endogenous immune system of diffuse large B cell lymphoma (DLBL), we performed gene expression profiling using cDNA microarrays of cytokines/chemokines and their receptors. We studied 5 cases each of primary central nervous system lymphomas (PCNSL), extranodal and nodal lymphomas. PCNSL exhibited diffuse down-regulated profiles, compared to normal peripheral blood lymphocytes. While extranodal and nodal lymphomas also exhibited diffuse down-regulated profiles, some genes displayed up-regulated profiles. Hierarchical clustering analysis separated PCNSL and extranodal lymphomas into distinct groups based on their gene expression profiles, as well as extranodal and nodal, but not PCNSL and nodal. PCNSL exhibited significantly lower expression of BLC/BCA-1 and CCR-3 (Th2 type), and higher expression of IL-8 and MIP-1beta (Th1 type) than extranodal lymphomas. Immunohistochemistry and RT-PCR revealed frequent CCR-3 and BLC/BCA-1 expression in extranodal lymphomas, compared with PCNSL. Our results provide new insights into the pathogenesis of each DLBL. A better understanding of the immune response in each DLBL could help in the design of novel therapeutic strategies based on cytokines/chemokines and their receptors.

Differential chemokine, chemokine receptor, cytokine and cytokine receptor expression in pulmonary adenocarcinoma: diffuse down-regulation is associated with immune evasion and brain metastasis.

Pulmonary adenocarcinoma is frequently associated with brain metastasis at some stage during the disease course. Host immunity, particularly T cell immunity, plays an important role in the clinicopathological features of carcinoma proliferation and metastasis. Cytokines and chemokines are members of a family of small secreted proteins. The relationships between the cytokines and cytokine receptor (R), and between chemokines and chemokine R are important determinants of selectivity in local immunity. RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) and Fas ligand (FasL) are present in neoplastic cells, induce apoptosis of NK/T cells, and play a role in immune evasion. To investigate differences in host immunity between pulmonary adenocarcinoma with and without brain metastasis, we performed gene expression profiling, using chemokine, chemokine R, cytokine and cytokine R DNA chips. In addition, to assess the extent of immune evasion, we examined the expression of RCAS and FasL. We studied five cases of pulmonary adenocarcinoma with brain metastasis (meta) and five cases without brain metastasis (non-meta). The brain meta cases exhibited diffuse down-regulated profiles, in comparison with normal non-carcinomatous lungs, which were used as controls. Non-meta cases also displayed diffuse down-regulation, however the degree was variable. Expression of RCAS and FasL was detected in almost all cases, but was stronger in meta than non-meta cases. Our findings suggested that tumor cells evaded host immunity. In the gene tree analysis, brain meta cases and non-meta cases exhibited distinct clustering. Brain meta cases exhibited significantly lower expression of interleukin 13 receptor alpha2 (IL-13Ralpha2) than non-meta cases. The reduction of IL-13Ralpha2 expression was confirmed by RT-PCR. Immunohistochemically, non-meta adenocarcinoma cells frequently expressed IL-13Ralpha2, however, IL-13Ralpha2 expression was rare or weak in adenocarcinomas with meta. Our results suggested that, in addition to immune evasion, the characteristics of the adenocarcinoma tumors themselves were important for brain metastasis. However, our study demonstrated the enormous potential of gene expression profiling in clarifying the pathogenesis of brain metastasis in pulmonary adenocarcinoma.