What factors determine the survival of patients with an acute exacerbation of interstitial lung disease after lung cancer resection?

PURPOSES: Acute exacerbation of interstitial pneumonia (AEIP) is a leading cause of death after lung cancer resection in patients with interstitial lung disease. METHODS: We retrospectively analyzed 1763 patients with non-small cell lung cancer with a clinical diagnosis of interstitial lung disease (ILD) who underwent lung cancer resection between 2000 and 2009 at 61 hospitals in Japan. AEIP occurred in 164 of 1763 (9.3%) patients with a mortality rate of 43.9% (72/164). Univariate and multivariate analyses were carried out to identify possible risk factors of fatal AEIP. We then analyzed the 164 patients who developed postoperative AEIP and identified the preoperative and postoperative risk factors. RESULTS: A multivariate regression analysis identified that the sex, percent vital capacity, neoadjuvant radiation, preoperative history of AEIP, preoperative use of steroids, usual interstitial pneumonia pattern on CT, and surgical procedures were independent preoperative risk factors for death due to AEIP. ILD patients with emphysema somehow showed a lower risk of fatal AEIP than those without emphysema in this study. CONCLUSIONS: This study revealed eight risk factors for fatal AEIP.

Feasibility Trial of Oral UFT after Platinum-based Adjuvant Chemotherapy in Patients with Resected Non-small Cell Lung Cancer.

We evaluated the feasibility of maintenance treatment using UFT (a combination of tegafur and uracil) after adjuvant platinum-based chemotherapy in patients with resected lung cancer. A prospective feasibility trial was conducted. Between 2010 and 2014, UFT was administered for 2 years sequentially after platinum-based adjuvant chemotherapy in 24 patients with resected Stage IIA-IIIA non-small cell lung cancer. The safety of UFT and the rate of treatment completion were then evaluated. The prior platinum-based chemotherapy regimens consisted of cisplatin+vinorelbine in 16 patients, carboplatin+paclitaxel in 5 and carboplatin+S-1 in one. During the subsequent UFT administration, a total of 3 patients required a dose reduction because of Grade 1 blood-stained sputum, Grade 2 numbness, and Grade 2 constipation, in one patient each. Eleven patients underwent the planned 2-year UFT administration, but 12 patients could not because of the recurrence of lung cancer in 5 patients, metachronous malignancy in one, and toxicities in 6. The completion rate for UFT administration was 64.7% (11/17). The most common type of toxicity was gastrointestinal toxicities. All of the toxicities were grade 1 or 2, and no severe toxicities were observed. UFT treatment after platinum-based chemotherapy was revealed to be feasible.

Changes in Post-Operative Complication and Mortality Rates after Lung Cancer Resection in the 20-Year Period 1995-2014.

We reviewed post-operative complication and mortality rates from 1995 through 2014 and evaluated the changes in those rates across that 20-year period. Two thousand and three hundred sixteen patients with lung cancer underwent resection at our institution between 1995 and 2014. This timespan was divided into four 5-year periods. Each patient's age, Charlson comorbidity index score, and extent of surgery in each 5-year period were summarized, and the changes in these factors over the 20-year span were evaluated. The complication and mortality rates were calculated for each 5-year period, and the changes in those rates over the 20-years were evaluated. The number of patients with higher Charlson comorbidity index scores increased during the 20-year period. Of the 455 patients who developed complications, 97 developed life-threating complications. There were 16 post-operative deaths and 23 in-hospital deaths. There were no significant changes in the complication rate or mortality rate during the 20-year period. Both rates were significantly correlated with the extent of resection. Although the number of patients with comorbidities increased in the 20-year period, the post-operative complication and mortality rates, as well as in-hospital mortality, did not change significantly.

A Case of Mediastinal Cystic Lymphangioma.

A 35-year-old Japanese man's routine chest radiography revealed an abnormal opacity. Chest computed tomography and magnetic resonance imaging showed a 5.5 cm in dia. cystic tumor located at the left anterior mediastinum. The tumor was suspected to be an asymptomatic thymic cyst, and we chose observation for the tumor. At the 3-year follow up, the cystic tumor had gradually enlarged to 7.5 cm in dia. and we thus performed a surgical resection via left video-assisted thoracic surgery. An immunohistochemical analysis showed that the cystic tumor was not a thymic cyst but rather a mediastinal cystic lymphangioma. Mediastinal cystic lymphangiomas are very rare, and they are difficult to diagnose preoperatively. Complete surgical resection is proposed for the treatment of such tumors.

A rare case of inflammatory myofibroblastic tumor of the diaphragmatic parietal pleura with dissemination.

Inflammatory myofibroblastic tumor (IMT) is a rare neoplasm that occurs at different sites in the body. Pleural IMT in particular is especially rare. IMTs infrequently tend to have malignancy. We report a rare case of advanced diaphragmatic parietal pleural IMT with dissemination. A 30-year-old woman complained of right upper abdominal pain. Computed tomography showed a large lobulated mass over the right diaphragm, but no disseminated nodules were noted. Intraoperatively, we found the primary tumor arising from the diaphragmatic parietal pleura and a dozen disseminated nodules, and we removed them completely. The histopathological and immunohistochemical diagnosis was IMT.

[Pulmonary non-tuberculous mycobacteriosis complicated with lung cancer].

A 54-year-old man with pulmonary non-tuberculous mycobacteriosis( pulmonary NTM) who had been treated by antituberculous chemotherapy, developed a new nodule of 1.3 cm in size in the segment 1/2 of the right upper lobe. The cavity of 3.5 cm in size in the segment 6 of the right lower lobe from which Mycobacterium intracellulare was bronchoscopically detected, was suspected to be pulmonary NTM lesion. Since lung cancer was highly suspected by radiological examinations, right upper lobectomy and S6 segmentectomy were performed. Pathological diagnosis for the right upper lobe nodule was adenocarcinoma.

Aberrant expression of the transcription factor Twist in adult T-cell leukemia.

Adult T-cell leukemia (ATL) is a T-cell malignancy etiologically associated with human T-cell leukemia virus type 1 (HTLV-1). Twist, a highly conserved basic helix-loop-helix transcription factor, is a newly identified oncogene. However, there are no reports on Twist expression in ATL. To define the role of Twist in leukemogenesis of ATL, we examined its expression in T-cell lines and PBMC. HTLV-1-infected T-cell lines and ATL cells expressed high levels of Twist compared with uninfected T-cell lines and normal PBMC. Immunohistochemistry showed immunostaining for Twist in ATL cells in ATL lymph nodes and skin lesions. Infection of normal PBMC with HTLV-1 induced Twist expression. Induction of the viral protein Tax in a human T-cell line led to upregulation of Twist. Tax-induced Twist expression involved the NF-kappaB and CREB signaling pathways. Twist augmented Tax-mediated HTLV-1 LTR and NF-kappaB activation. Short interfering RNA against Twist inhibited cell growth of HTLV-1-infected T-cell lines and downregulation of Twist expression in an HTLV-1-infected T-cell line inhibited the expression of Akt1, interleukin-2 receptor alpha chain, and Tax as well as the known target genes of Twist, YB-1 and Akt2. In conclusion, the results suggest that Tax-induced induction of Twist contributes to leukemogenesis of ATL.

Overexpression of caveolin-1 in adult T-cell leukemia.

Caveolin-1 is implicated in the regulation of signal pathways. Adult T-cell leukemia (ATL) is a T-cell malignancy causatively associated with human T-cell leukemia virus type 1 (HTLV-1). To determine the role of caveolin-1 in leukemogenesis, we examined caveolin-1 expression levels in HTLV-1-infected T-cell lines and ATL cells. These cells expressed high levels of caveolin-1 compared with uninfected T-cell lines and normal peripheral blood mononuclear cells (PBMCs). Caveolin-1-positive ATL cells were detected in ATL lymph nodes and skin lesions, and caveolin-1 was also detected in the plasma of patients with ATL. Infection of a human T-cell line, an epithelial cell line, and normal PBMCs with HTLV-1 induced caveolin-1 expression. The viral protein Tax transcriptionally activated caveolin-1 gene through nuclear factor-kappaB and cAMP response element binding protein signal pathways. HTLV-1-infected T-cell lines, and ATL cells are known to be resistant to transforming growth factor beta (TGF-beta)-induced growth inhibition. Caveolin-1 was colocalized with TGF-beta type I receptor in HTLV-1-infected T-cell lines and suppressed TGF-beta signaling. Caveolin-1 knockdown in an HTLV-1-infected T-cell line exhibited susceptibility to TGF-beta. Thus, we describe a new function for Tax, repression of TGF-beta signaling through caveolin-1 expression, which may play a critical role in ATL leukemogenesis.

[Current status of adjuvant chemotherapy for resected lung cancer at our institute--focus on clinical trial enrollment].

Adjuvant chemotherapy after complete resection in Stage I B-III A non-small cell lung cancer is recommended. Several clinical trials of adjuvant chemotherapy are now underway in Japan. Our institute also participates in adjuvant clinical trials, but slow patient recruitment is a problem. In this paper, we reported the current status of adjuvant chemotherapy and recruitment for clinical trials at our institute. Between August 2001 and December 2008, candidates for adjuvant chemotherapy were 315 patients. Among them 186 who received adjuvant chemotherapy were younger and had less co-morbidity than those who did not receive adjuvant chemotherapy. Twenty-five of the 186 patients participated in the clinical trials. The major reason of refusal of a clinical trial was that patients preferred to choose their own treatment and disliked randomized trials.

Relationships among pulmonary capillary wedge pressure, dry weight and natriuretic peptide in patients undergoing hemodialysis: a three-dimensional speckle tracking echocardiography study.

BACKGROUND: Although the evaluation of fluid status in hemodialysis (HD) patients is useful, relationship among pulmonary capillary wedge pressure (PCWP), dry body weight (DW) and natriuretic peptide has not been elucidated. In addition, there has been no objective marker for instantaneously monitoring hemodynamic improvement in response to HD. We previously reported that PCWP and time constant of left ventricular pressure decline (Tau) can be noninvasively estimated (ePCWP and eTau) by speckle tracking echocardiography (STE). The aim of this study was to elucidate the relationship among ePCWP, eTau, DW and natriuretic peptide in patients undergoing HD. METHODS: We measured ePCWP and body weight (BW) by STE in 81 patients and ANP and BNP by blood examination in 31 patients just before and after HD during sinus rhythm. RESULTS: The ePCWP decreased after HD, and this was associated with reductions in ln ANP, eTau and BW (r = 0.523, 0.271 and 0.814, respectively, p < 0.05). The % change in ePCWP was not correlated with the % change in ln BNP (p = 0.47). The change in ePCWP had a stronger correlation with the % change in BW than the change in any other parameters. CONCLUSIONS: The ePCWP is more sensitive to estimate the change in BW during HD than any other parameters such as ANP and BNP. These results indicated that a substantial amount of excess fluid can be assessed real-time by STE using ePCWP.

Anti-adult T-cell leukemia/lymphoma effects of indole-3-carbinol.

BACKGROUND: Adult T-cell leukemia/lymphoma (ATLL) is a malignancy derived from T cells infected with human T-cell leukemia virus type 1 (HTLV-1), and it is known to be resistant to standard anticancer therapies. Indole-3-carbinol (I3C), a naturally occurring component of Brassica vegetables such as cabbage, broccoli and Brussels sprout, is a promising chemopreventive agent as it is reported to possess antimutagenic, antitumorigenic and antiestrogenic properties in experimental studies. The aim of this study was to determine the potential anti-ATLL effects of I3C both in vitro and in vivo. RESULTS: In the in vitro study, I3C inhibited cell viability of HTLV-1-infected T-cell lines and ATLL cells in a dose-dependent manner. Importantly, I3C did not exert any inhibitory effect on uninfected T-cell lines and normal peripheral blood mononuclear cells. I3C prevented the G1/S transition by reducing the expression of cyclin D1, cyclin D2, Cdk4 and Cdk6, and induced apoptosis by reducing the expression of XIAP, survivin and Bcl-2, and by upregulating the expression of Bak. The induced apoptosis was associated with activation of caspase-3, -8 and -9, and poly(ADP-ribose) polymerase cleavage. I3C also suppressed IkappaBalpha phosphorylation and JunD expression, resulting in inactivation of NF-kappaB and AP-1. Inoculation of HTLV-1-infected T cells in mice with severe combined immunodeficiency resulted in tumor growth. The latter was inhibited by treatment with I3C (50 mg/kg/day orally), but not the vehicle control. CONCLUSION: Our preclinical data suggest that I3C could be potentially a useful chemotherapeutic agent for patients with ATLL.

NF-kappaB activation by Helicobacter pylori requires Akt-mediated phosphorylation of p65.

BACKGROUND: The inflammatory response in Helicobacter pylori-infected gastric tissue is mediated by cag pathogenicity island (PAI)-dependent activation of nuclear factor-kappaB (NF-kappaB). Phosphatidylinositol 3-kinase (PI3K)/Akt signaling is known to play a role in NF-kappaB activation, but little information is available on the relationship between H. pylori and PI3K/Akt signaling in gastric epithelial cells. We examined whether H. pylori activates Akt in gastric epithelial cells, the role of cag PAI in this process and the role of Akt in regulating H. pylori-induced NF-kappaB activation. RESULTS: Phosphorylated Akt was detected in epithelial cells of H. pylori-positive gastric tissues. Although Akt was activated in MKN45 and AGS cells by coculture with cag PAI-positive H. pylori strains, a cag PAI-negative mutant showed no activation of Akt. H. pylori also induced p65 phosphorylation. PI3K inhibitor suppressed H. pylori-induced p65 phosphorylation and NF-kappaB transactivation, as well as interleukin-8 expression. Furthermore, transfection with a dominant-negative Akt inhibited H. pylori-induced NF-kappaB transactivation. Transfection with small interference RNAs for p65 and Akt also inhibited H. pylori-induced interleukin-8 expression. CONCLUSION: The results suggest that cag PAI-positive H. pylori activates Akt in gastric epithelial cells and this may contribute to H. pylori-mediated NF-kappaB activation associated with mucosal inflammation and carcinogenesis.

An intradialysis diagnostic test for restless legs syndrome: a pilot study.

BACKGROUND: Restless legs syndrome (RLS) is common in dialysis patients, but a simple diagnostic test is not available. STUDY DESIGN: Diagnostic test study. SETTING & PARTICIPANTS: 32 patients with RLS and 29 patients without RLS in 2 dialysis centers. INDEX TEST: The suggested immobilization test (SIT) was performed during dialysis for at least 30 minutes, and periodic limb movements (PLMs) were assessed by means of electromyography of the anterior tibialis muscles using a Holter monitor as an electromyographic monitoring device. We also assessed changes in number of leg movements on the 30-minute SIT (SIT-PLM) after 4 weeks of treatment with the dopamine agonist pergolide. REFERENCE TEST OR OUTCOME: Clinical review by a neurologist, International RLS Rating Scale (IRLSRS) score, and changes in IRLSRS score after pergolide treatment. RESULTS: PLMs on the 30-minute SIT during dialysis were identified in 20 of 32 patients with RLS and 3 of 29 control participants. Sensitivity and specificity of PLMs on the 30-minute SIT during dialysis for RLS diagnosis were 63% and 90%, respectively. SIT-PLM correlated with IRLSRS total score at diagnosis (r = 0.53; P = 0.03), suggesting that SIT-PLM measures the general severity of RLS in uremic patients. Treatment with the dopamine agonist pergolide significantly reduced the IRLSRS total score (from a mean of 24.9 +/- 9.1 [SD] to 9.5 +/- 6.8; P < 0.01) and SIT-PLM (from 41.9 +/- 24.2 to 11.3 +/- 12.3; P < 0.01), but correlation between changes in SIT-PLM and those in IRLSRS score was not significant (r = 0.27; P = 0.3). LIMITATIONS: Poor correlation may be caused by the small sample size. Time available for the SIT was limited because of the patient's condition during dialysis. Time of day during SIT, mental-alerting activities during SIT, or hemodialysis therapy itself may influence the severity of PLMs. CONCLUSIONS: A Holter-monitored SIT during dialysis is a valid method for the diagnosis of RLS and to evaluate the effect of treatment with pergolide in uremic patients.

Evaluation of video-assisted thoracoscopic surgery for pulmonary metastases: 11-years of experience.

BACKGROUND: Although video-assisted thoracoscopic surgery (VATS) has been applied to pulmonary resection for pulmonary metastases, the clinical validity of this approach remains controversial. The purpose of this study was to evaluate the validity and problems of VATS for pulmonary metastasectomy. METHODS: From January 1993 to December 2003, VATS for pulmonary metastasectomy was performed in 53 resections for 48 patients at our institution. The medical records of these patients were retrospectively reviewed. RESULTS: The primary tumor was colorectal cancer in 23 patients, renal cell carcinoma in 6, breast cancer in 6, germ cell tumor in 5, head and neck cancer in 2, and others in 6. Thirty-six cases had a solitary lesion, 8 had unilateral multiple lesions, and 9 had bilateral multiple lesions. The following procedures were performed: 7 lobectomies, 5 segmentectomies, and 41 wedge resections. There was no major postoperative morbidity related to VATS. At a median follow-up period of 29.0 months, 13 patients were alive without recurrences. The 3-year overall survival rate and the 3-year intrathoracic disease-free survival rate were 59.8% and 33.4%, respectively. Five cases had recurrence at the surgical stump or at the port sites, but these recurrences have not been found in the recent period since June 1997. Intrathoracic recurrences within 3 months after VATS occurred in four. CONCLUSION: VATS for pulmonary metastases is not superior to the conventional open thoracotomy and is not recommended as a standard procedure. Further studies with a larger number of cases performed by skilled surgeons familiar with VATS are needed.

Re-classification of pTNM staging for lung cancer: single-institution report at a Japanese comprehensive cancer hospital.

Among the major cancer sites, the lung has the most complicated pTNM description. Reclassification of International Union Against Cancer (UICC)-pTNM grading of 262 lung cancers resected at Shikoku Cancer Center was done using microscopy and audit of pathology reports. Of the 262 lung cancers, 222 were obtained at operation from 1999 to 2004 and 40 additional cases from 2006. Among 666 pTNM components of the former cases, 37 components (31T, 3N, 3M) in 35 cases were revised to different categories. The concordance rate (CR) of the original stage to the reclassified stage was 90% (210/222) in the five-group staging system (5GSS) without subdivisions and 84% (187/222) in the 8GSS with subdivisions such as IA and IB. It decreased in advanced cases. For example, the CR was higher in stage I (97%, 158/163) than in stage II-IV (88%, 51/59) in five-GSS (chi(2) test, P < 0.05). The CR in 8GSS of the additional 40 cases, which were diagnosed after the review of the former 222 cases, was 98% (39/40), indicating that the knowledge gained from the review improved the accuracy significantly (chi(2) test, P < 0.05). It is necessary to assess disparities in the accuracy of pTNM for lung cancer at each institution. This is also true for cancers at other sites.

Anti-adult T-cell leukemia effects of brown algae fucoxanthin and its deacetylated product, fucoxanthinol.

Adult T-cell leukemia (ATL) is a fatal malignancy of T lymphocytes caused by human T-cell leukemia virus type 1 (HTLV-1) infection and remains incurable. Carotenoids are a family of natural pigments and have several biological functions. Among carotenoids, fucoxanthin is known to have antitumorigenic activity, but the precise mechanism of action is not elucidated. We evaluated the anti-ATL effects of fucoxanthin and its metabolite, fucoxanthinol. Both carotenoids inhibited cell viability of HTLV-1-infected T-cell lines and ATL cells, and fucoxanthinol was approximately twice more potent than fucoxanthin. In contrast, other carotenoids, beta-carotene and astaxanthin, had mild inhibitory effects on HTLV-1-infected T-cell lines. Importantly, uninfected cell lines and normal peripheral blood mononuclear cells were resistant to fucoxanthin and fucoxanthinol. Both carotenoids induced cell cycle arrest during G(1) phase by reducing the expression of cyclin D1, cyclin D2, CDK4 and CDK6, and inducing the expression of GADD45alpha, and induced apoptosis by reducing the expression of Bcl-2, XIAP, cIAP2 and survivin. The induced apoptosis was associated with activation of caspase-3, -8 and -9. Fucoxanthin and fucoxanthinol also suppressed IkappaBalpha phosphorylation and JunD expression, resulting in inactivation of nuclear factor-kappaB and activator protein-1. Mice with severe combined immunodeficiency harboring tumors induced by inoculation of HTLV-1-infected T cells responded to treatment with fucoxanthinol with suppression of tumor growth, showed extensive tissue distribution of fucoxanthinol, and the presence of therapeutically effective serum concentrations of fucoxanthinol. Our preclinical data suggest that fucoxanthin and fucoxanthinol could be potentially useful therapeutic agents for patients with ATL.

Anti-adult T-cell leukemia effects of a novel synthetic retinoid, Am80 (Tamibarotene).

Clinical trials for treatment of adult T-cell leukemia (ATL) caused by human T-cell leukemia virus type I (HTLV-I) using all-trans-retinoic acid (ATRA) have shown satisfactory therapeutic responses, although efficacies were limited. Recently, many synthetic retinoids have been developed and among them, a novel synthetic retinoid, Am80 (Tamibarotene) is an RARalpha- and RARbeta-specific retinoid expected to overcome ATRA resistance. The present study examined the inhibitory effects of Am80 on HTLV-I-infected T-cell lines and ATL cells. Am80 had negligible growth inhibition of peripheral blood mononuclear cells but marked growth inhibition of both HTLV-I-infected T-cell lines and ATL cells. Am80 arrested cells in the G1 phase of the cell cycle and induced apoptosis in HTLV-I-infected T-cell lines. It inhibited also the phosphorylation of IkappaBalpha and NF-kappaB-DNA binding, in conjunction with reduction of expression of proteins involved in the G1/S cell cycle transition and apoptosis. Am80 also inhibited the expression of JunD, resulting in suppression of AP-1-DNA binding. Furthermore, severe combined immunodeficient mice with tumors induced by subcutaneous inoculation of HTLV-I-infected T cells, responded to Am80 treatment with partial regression of tumors and no side-effects. These findings demonstrate that Am80 is a potential inhibitor of NF-kappaB and AP-1, and is a potentially useful therapeutic agent against ATL.

A modified version of galectin-9 induces cell cycle arrest and apoptosis of Burkitt and Hodgkin lymphoma cells.

The identification of galectin-9 as a ligand for T-cell immunoglobulin- and mucin-domain-containing molecule-3 (Tim-3), expressed on T-helper type-1 (Th1) cells, has established the Tim-3-galectin-9 pathway as a regulator of Th1 immunity. Whereas there is compelling evidence for the effects of galectin-9 on T-cell fate, limited information is available on the impact of galectin-9 on B lymphocytes. We found that protease-resistant galectin-9, hG9NC(null), but not galectin-1 or -8, prevented cell growth of malignant B cells, such as Burkitt lymphoma (BL) and Hodgkin lymphoma (HL). beta-galactoside binding was essential for galectin-9-induced cell growth suppression. hG9NC(null) induced cell cycle arrest by reducing the expression of cyclin D1, D2, B1, Cdk4, Cdc25C and c-Myc, and apoptosis by reducing the expression of XIAP, c-IAP2 and survivin. Most of the genes that encode these proteins are regulated by nuclear factor-kappaB (NF-kappaB), and constitutive activation of NF-kappaBeta is a common characteristic of both types of malignancies. hG9NC(null) inhibited IkappaBalpha phosphorylation, resulting in suppression of NF-kappaB. AP-1 has also been implicated in the control of cell survival. hG9NC(null) inhibited the expression of JunD, resulting in the suppression of AP-1. Our results suggest that hG9NC(null) is a potentially suitable agent for the management of BL and HL.

Very long-term outcomes of video-assisted thoracoscopic surgery for lung cancer.

BACKGROUND: The most critical parameter in the evaluation of the feasibility of video-assisted thoracoscopic surgery (VATS) lobectomy for lung cancer is long-term outcome. In this study, patients in whom more than 5 years had elapsed since they had undergone VATS lobectomy for lung cancer were identified, and the 5-year survival rate and frequency of recurrence were evaluated as the long-term outcomes; in addition, the frequency of perioperative complications were also evaluated as the short-term outcomes. METHODS: The stage, histology, perioperative complications, recurrence, and survival data were carefully reviewed in 198 patients who underwent VATS lobectomy for lung cancer between 1998 and 2002. RESULTS: Median postoperative follow-up period was 72.1 months. Of the 198 patients, 138 and 30 were diagnosed as having p-stage IA and IB disease, respectively, while the remaining 30 patients had more advanced disease. Perioperative complications were observed in 20 patients (10.1%), however, there were no perioperative mortalities. Recurrence was observed in 26 patients (13.1%): of these, 11 patients showed local recurrence, including malignant pleural effusion and mediastinal lymph node recurrence, and 16 patients showed distant metastasis, the lung being the commonest site of metastasis; six patients had both local recurrence and distant metastasis. During the study period, there were 26 deaths (13.1%), of which 17 were due to lung cancer and 9 were due to other causes. The 5-year overall survival rates of the patients with p-stage IA and IB disease were 93.5% and 81.6%, respectively. CONCLUSION: VATS lobectomy for the treatment of lung cancer is as feasible and safe as open lobectomy in terms of both very long- and short-term outcomes.

Downregulation of citrin, a mitochondrial AGC, is associated with apoptosis of hepatocytes.

Citrin is a mitochondrial aspartate-glutamate carrier primarily expressed in liver. Adult-onset type II citrullinemia is caused by mutations in the SLC25A13 gene that encodes for citrin, and patients with this condition do not express citrin. We found apoptotic hepatocytes in one such patient. This finding prompted us to investigate the role of citrin in hepatocyte survival. Knockdown of citrin by a vector-based short-hairpin RNA technique reduced cell viability and induced apoptosis of a hepatocellular carcinoma cell line, Hep3B cells. Caspase-3/7 and caspase-9 were activated, and PARP was cleaved. Citrin knockdown also increased the expression of Bax and Bak, and reduced expression of Bcl-xL and Bcl-2. These alterations resulted in the release of cytochrome c from the mitochondria. Our results indicated that citrin downregulation induces apoptosis of hepatocytes through the mitochondrial death pathway, highlighting the importance of citrin in survival of hepatocytes and maintenance of liver function.