Video-assisted thoracoscopic lobectomy for clinical stage I non-small cell lung cancer: experience with 111 consecutive patients demonstrating comorbidity.

AIM: The outcomes of video-assisted thoracoscopic lobectomy for clinical stage I non-small cell lung cancer (NSCLC) patients with comorbidities were examined to determine the technical feasibility and safety of this procedure. METHODS: Between January 2002 and December 2007, 111 consecutive patients with suspected stage I lung cancer, who individually had one or more comorbidities cited in the modified Kaplan-Feinstein Index, were scheduled for a video-assisted thoracoscopic lobectomy. The demographic, perioperative, and outcome variables were assessed. RESULTS: One hundred of 111 patients had non-small cell lung cancer. Ninety-nine patients underwent successful video-assisted thoracoscopic lobectomies, while there was one conversion because of a hemorrhage from the pulmonary artery in the early stage. Including this one conversion, no patients required a blood transfusion during surgery or postoperatively. There were no intraoperative or in-hospital deaths. No complications occurred in 78 (78.8%) of 99 patients. Only one patient (1.0%) with a Kaplan-Feinstein Index Score of severe grade contracted pneumonia indicating grade 3 (severe), whereas the remaining 20 patients had grade 1 (mild) or 2 (moderate) complications. At a median follow-up of 40 months, the overall 3-year survival rates for postoperative stage IA (N.=52); IB (N.=26); and II or more (N.=21) were 100%; 78%; and 71%, respectively. CONCLUSION: A video-assisted thoracoscopic lobectomy is therefore considered to be a feasible and safe procedure for clinical stage I NSCLC even in patients with comorbidities.

Surgery versus stereotactic body radiotherapy for clinical stage I non-small-cell lung cancer: propensity score-matching analysis including the ratio of ground glass nodules.

PURPOSE: To investigate whether surgery and stereotactic body radiotherapy (SBRT) yield comparable outcomes for clinical stage (c-stage) I non-small-cell lung cancer (NSCLC), propensity score-matching (PSM) analysis was conducted. METHODS: This single-institutional retrospective study included patients who underwent surgery (n = 574) or SBRT (n = 182) between 2004 and 2014. PSM was performed based on tumor diameter, age, sex, performance status, forced expiratory volume, Charlson comorbidity index, and ground glass nodules (GGN) defined as cTis or cT1mi according to the 8th TNM classification. RESULTS: The median follow-up durations for the surgery and SBRT groups were 66 and 69 months, respectively. The multivariate analysis revealed that non-GGN was a significant factor for poorer overall survival (OS) and disease-free survival (DFS): hazard ratio (HR) 19.95% confidence interval (CI) 4.7-79, P < 0.001; and HR 28, 95% CI 6.9-110, P < 0.001, respectively. PSM identified 120 patients from each group. The 5-year OS and DFS rates of the surgery vs SBRT groups were 71% (95% CI 61-79) vs 64% (95% CI 54-72) (P = 0.41) and 63% (95% CI 53-72) vs 55% (95% CI 45-63) (P = 0.23) after PSM, respectively. CONCLUSION: The PSM analyses including the ratio of GGN demonstrated that the OS and DFS for patients with c-stage I NSCLC in the surgery group were slightly superior to those for those in the SBRT group, although both survivals were not significantly different between the two therapeutic approaches.

A comparison of the effect of large and small metal-on-metal bearings in total hip arthroplasty on metal ion levels and the incidence of pseudotumour: a five-year follow-up of a previous report.

Aims: The purpose of this study was to compare two different types of metal-on-metal (MoM) bearing for total hip arthroplasty (THA): one with a large femoral head (38 mm to 52 mm) and the other with a conventional femoral head (28 mm or 32 mm). We compared clinical outcome, blood metal ion levels, and the incidence of pseudotumour in the two groups. Patients and Methods: Between December 2009 and December 2011, 62 patients underwent MoM THA with a large femoral head (Magnum group) and 57 patients an MoM THA with a conventional femoral head (conventional group). Clinical outcome was assessed using the Harris Hip score, University of California, Los Angeles (UCLA) activity score and EuroQol-5D (EQ-5D). Blood metal ion levels were measured and MRI scans were analyzed at a minimum of five years postoperatively. Results: No acetabular component was implanted with more than 50° of inclination in either group. The Harris Hip Score, UCLA activity score, and EQ-5D improved postoperatively in both groups; no significant clinical differences were noted between the groups. The blood cobalt ion levels in the conventional group continued to rise postoperatively to five years while reaching a plateau at two years postoperatively in the Magnum group. At five years, the mean cobalt ion level of 1.16 µg/l (sd 1.32) in the Magnum group was significantly lower than the 3.77 µg/l (sd 9.80) seen in the conventional group (p = 0.0015). The incidence of moderate to severe pseudotumour was 4.7% in the Magnum group and 20.6% in the conventional group. There were no dislocations in the Magnum group and two in the conventional group. One patient in the Magnum group underwent revision for pseudotumour at 4.7 years postoperatively. Conclusion: At five years, a well-positioned large head MoM THA has a significantly lower level of metal ion release and a lower incidence of moderate to severe pseudotumour than a MoM bearing of conventional size. Cite this article: Bone Joint J 2018;100-B:1018-24.

[Pneumonectomy for lung cancer in a patient with acute respiratory failure; report of a case].

A 58-year-old man had developed acute respiratory failure because of deterioration of the pneumonia, and had been on a mechanical ventilator. Bronchoscopy showed tumor occlusion of the left main stem of the bronchus. For the purpose of weaning from ventilatory support and prevention of progress of the pneumonia, we performed a pneumonectomy and systematic hilar and mediastinal lymph node dissection using a thoracoscopy. The patient could be weaned from ventilatory support, and we could improve his quality of life by minimally invasive surgery.

[Coronary artery bypass grafting in patients with dialysis-dependent renal failure].

From January 1995 to May 2003, 36 patients with dialysis-dependent renal failure underwent coronary artery bypass grafting. We performed the operation with cardiopulmonary bypass (group On) in 17 cases and without cardiopulmonary bypass (group Off) in 19 patients [off-pump coronary artery bypass grafting (OPCAB) 15, minimally invasive direct coronary artery bypass (MIDCAB) 4]. There were no statistical differences regarding mean age, sex, duration of dialysis, preoperative hypertension, diabetes and peripheral and cerebral vascular diseases. Mean operation time and the number of bypass grafts were 315 +/- 53 minutes, 2.8 +/- 0.8 grafts in group On and 284 +/- 78 minutes, 2.4 +/- 1.1 grafts in group Off, respectively (not significant). Seventeen patients (100%) of group On and 12 patients (63%) needed blood transfusion. Hospital stay after operation was significantly longer in group On (40 days) of group Off than that in group Off (26 days). After the operation, continuous hemodiafiltration (CHDF) was used in 10 cases (59%) in group On and 3 cases (16%) in group Off. In coronary artery bypass grafting (CABG) on dialysis patient, it is very effective to have various operation techniques, such as off-pump bypass and on-pump beating bypass. Also control of water-electrolyte balance using early postoperative CHDF is useful. However, off-pump cases could be controlled by conventional hemodialysis.

Intravenous dexmedetomidine for cesarean delivery and its concentration in colostrum.

BACKGROUND: Dexmedetomidine is a sedative agent with high α2-adrenoreceptor selectivity. We investigated intravenous dexmedetomidine administration during scheduled cesarean delivery under neuraxial anesthesia; and its concentration in the colostrum. METHODS: Twenty-seven participants having elective cesarean delivery under combined spinal-epidural anesthesia were enrolled. After delivery and cord clamping, 6µg/kg/h of intravenous dexmedetomidine was administered for 10minutes, followed by a dose of 0.7µg/kg/h until peritoneal closure. Sedation, vital signs and side effects were recorded. Blood and colostrum samples were collected from each participant at 6, 12, and 24h after dexmedetomidine administration. Samples were analysed using liquid chromatography tandem-mass spectroscopy. RESULTS: Colostrum samples were collected from 10 patients. The median [95% CI] plasma dexmedetomidine concentration was 333 [303-534] pg/ml at 0h and 19.7 [13.5-25.8] pg/ml at 6h. The colostrum concentration was 12.3 [8.1-20.1] pg/ml at 6h. The dexmedetomidine completely disappeared from both within 24h. The calculated milk-to-plasma ratio at 6h was 0.76 [0.57-0.86]. The relative infant dose was 0.034% [0.020-0.062%]. At dexmedetomidine discontinuation, the Richmond Agitation-Sedation Scale score was -2 (range,-4 to -1). During surgery, no patients complained of nausea, peritoneal irritation or afterbirth pain. CONCLUSIONS: The dexmedetomidine milk-to-plasma ratio did not exceed 1 in any participant, and the relative infant dose was very low. Maternal sedation using dexmedetomidine is unlikely to be harmful for the infant.

Mutations of the p53 gene as a predictor of poor prognosis in patients with non-small-cell lung cancer.

BACKGROUND: Inactivation of the p53 tumor suppressor gene (also known as TP53) through a point mutation and/or loss of heterozygosity is one of the most common genetic changes found in various types of human tumors. PURPOSE: Our purpose was to investigate the relationship between the presence of p53 gene mutations and survival of patients with non-small-cell lung cancer (NSCLC) of all stages who underwent surgery with preoperative curative intent as a routine therapeutic intervention. The prognostic significance of factors like sex, age, tumor histology, and the stage of the disease was also evaluated. METHODS: We analyzed 120 tumor specimens from patients with histologically confirmed NSCLC for p53 mutations occurring in exons 5 through 8 by polymerase chain reaction-single-strand conformation polymorphism assay of genomic DNA. Univariate and multivariate analyses were performed to assess the association between p53 mutations and the survival of the NSCLC patients. RESULTS: Fifty-one (43%) of 120 tumor specimens showed p53 mutations. Overall, the p53 mutations did not correlate with sex, age, or the clinical stage of the disease but showed frequent association with tumors of squamous cell histology. Univariate analysis revealed that the patients with p53 mutations survived for a significantly shorter period of time after surgery than those without the mutations (P = .0100, logrank test). The presence of p53 mutations was a significant prognostic factor in the patients with advanced disease (stages IIIA through IV) (P = .0091) but not in those with early disease (stages I and II) (P = .2837). Multivariate analysis using the Cox proportional hazards model found independent prognostic significance for p53 mutations (hazards ratio [HR] = 1.84; P = .018) and advanced disease stage (HR = 2.20; P = .003). The model also predicted the lower risk for female patients (HR = 0.51; P = .040). CONCLUSION: The occurrence of p53 mutations in some NSCLC tumors may be independently associated with a shortened overall survival and may be of somewhat more prognostic significance in patients with advanced stage than in those with early stage of the disease. IMPLICATION: Detection of p53 mutations may help in the selection of NSCLC patients suitable for appropriate investigational therapeutic strategies in view of improving their survival and quality of life.

[Successful surgical management of papillary muscle rupture following acute myocardial infarction in an elderly patient].

Papillary muscle rupture is rare but catastrophic complication of acute myocardial infarction. We report a 91-year-old woman who underwent successful management of papillary muscle rupture following acute myocardial infarction. She was transferred to our hospital because of severe pulmonary edema and cardiogenic shock. Echocardiography revealed severe mitral valve regurgitation due to total rupture of anterolateral papillary muscle. After intubation, intraaortic balloon pumping (IABP) and percutaneous cardiopulmonary support (PCPS) insertion, mitral valve replacement was successfully performed. She was discharged 134 days after operation. In papillary muscle rupture deteriorating hemodynamics, early diagnosis and immediate cardiopulmonary support are required before surgical treatment. She was, to the best of our knowledge, the oldest among the reported cases of successful surgical treatment of papillary muscle rupture in Japan.

Therapeutic Effect of Sirolimus for Lymphangioleiomyomatosis Remaining in the Abdominopelvic Region After Lung Transplantation: A Case Report.

PURPOSE: Sirolimus (SRL) is used to treat pulmonary lymphangioleiomyomatosis (P-LAM). There is limited evidence that SRL has systemic efficacy for the patients with extrapulmonary lymphangioleiomyomatosis (E-LAM) remaining after lung transplantation (LT) for P-LAM. This report examines the efficacy of SRL treatment for the patient with E-LAM remaining after an LT for P-LAM. CASE SUMMARY: The course of the patient's recovery from an LT for P-LAM was complicated by lymphedema in the left femoral region that was caused by two E-LAM lesions remaining in the left pelvic cavity and in the retroperitoneal area. After the LT was performed, the patient started SRL treatment to reduce the E-LAM lesions. The daily SRL dose, selected based on the standard SRL dose for P-LAM, was initiated at 1 mg/d and was maintained at 2 mg/d. The remaining E-LAM lesions and lymphedema in the left femoral region improved in approximately 9 months after the LT with the administration of both SRL and the standard immunosuppressive therapy used by Okayama University Hospital, including tacrolimus, mycophenolate mofetil, and prednisolone. The SRL and tacrolimus trough concentrations in whole blood were maintained within the therapeutic window for the next 1.5 years after initiation of SRL treatment. The patient experienced no severe adverse events that required discontinuation of the SRL treatment during this time. CONCLUSION: The patients with remaining E-LAM lesions may receive SRL treatment to improve the quality of life after LT for P-LAM as effective therapy in cases where the patient's recovery is complicated by E-LAM lesions.

Minamata disease (organic mercury poisoning): neuroradiologic and electrophysiologic studies.

We studied 10 patients with Minamata disease (organic mercury poisoning) who have been followed for over 20 years. CT revealed a bilateral, symmetric, low-density area in the visual cortex and diffuse atrophy of the cerebellar hemispheres and vermis, especially the inferior vermis. Computerized quantitative analysis of the tremor of these patients showed a peculiar frequency of 7.075 Hz on postural tremor and 7.501 Hz on action tremor. On studies of short-latency somatosensory evoked potential, all patients showed a lack of the N20 component, the potential of the somatic sensory area.

Fas expression in non-small cell lung cancer: its prognostic effect in completely resected stage III patients.

The aim of this study was to examine Fas expression in non-small cell lung cancer (NSCLC) and examine its correlation with clinicopathological features and prognosis. Fas expression was determined by an immunohistochemical analysis using the labelled streptavidin-biotin method from 220 paraffin specimens of completely resected primary stage I-III NSCLC. 80 (36%) of 220 cases were positive for Fas immunostaining. These 80 cases included 44 adenocarcinomas (33%) and 30 squamous cell carcinomas (40%). 33 stage I (33%) 13 (43%) stage II and 34 (37%) stage III tumours were Fas positive. No statistically significant differences were observed regarding the Fas status with respect to age, sex, histological type, or stage of disease. There was no significant difference in survival between early stage (stages I-II) disease patients with positive Fas expression and those with a negative expression (P = 0.719). However, for patients with completely resected stage III tumours, the patients with positive Fas staining were found to survive for a longer period than those with negative staining (P = 0.026).

Heterogeneous distribution of benzodiazepine receptors among rat neostriatal neurones.

1. The effects of benzodiazepine receptor (BZR) agonist were investigated in dissociated rat neostriatal neurones by a conventional whole-cell patch recording configuration at room temperature. 2. The dissociated neurones, with a longest somatic diameter of larger than 25 microns, were classified as 'large neurones', while those having soma measuring less than 15 microns were described as 'small neurones'. Large neurones were intensely positive for acetylcholinesterase staining, whereas the small ones were not. 3. CL218,872 enhanced the GABA response in both the large and small neurones with similar EC50S. However, the potentiation efficacy of CL218,872 in large neurones was larger than that of small ones. 4. Zolpidem also potentiated the GABA response in both neuronal populations with similar EC50S. This compound also enhanced the GABA response more strongly in large neurones than in small ones. 5. Zopiclone exerted a prominent potentiation in large neurones, although no difference was seen in the EC50S in the large and small neurones. 6. It was concluded that the BZR in large neurones had a different pharmacological property from that in small ones and that the BZR agonists showed a prominent difference, not in EC50, but in the potentiation efficacy between these neuronal populations.

Maximum length of tracheal autografts in dogs.

When a primary anastomosis of the trachea is not feasible, grafting is required. We assessed the maximum length of tracheal autografts in 25 dogs. We used the autografts in this experimental study to avoid the immunologic complexity of allografts. Sections of cervical trachea ranging in length from 2.4 cm (6 rings) to 5.9 cm (14 rings) were excised and reimplanted as autografts. To increase the blood supply, we wrapped each graft in the greater omentum, which was brought up through the diaphragm. Grafts longer than 4.0 cm (8 to 10 rings) frequently showed stenosis, dissolution, or both in the middle part of the graft as a result of ischemia in that area, as demonstrated by laser blood flowmetry and injection study. We conclude that there is a limit to the length of a tracheal autograft, even if the blood supply has been increased by wrapping with omentum.

Short-course immunosuppression after tracheal allotransplantation in dogs.

It is desirable to minimize immunosuppression after allotransplantation. We examined the usefulness of a short course of immunosuppression after tracheal allotransplantation in 35 dogs. Five animals with six-ring tracheal autografts served as controls (group I, n = 5). Thirty animals with six-ring tracheal allografts were randomly classified into five groups as follows: no immunosuppression (group II, n = 6), azathioprine for only 1 postoperative week (group III, n = 7), azathioprine for 2 postoperative weeks (group IV, n = 7), azathioprine for 3 postoperative weeks (group V, n = 5), and mizoribine for 3 postoperative weeks (group VI, n = 5). All allografts in groups II through VI sustained rejection, but there was no difference in mononuclear cell infiltration of the grafts among the groups. The only grafts with long-term viability were those in groups I and VI, as demonstrated by graft patency and epithelialization. We conclude that immunosuppression with mizoribine for only a short course after transplantation may allow long-term viability of tracheal allografts.

Serum level and tissue expression of c-erbB-2 protein in lung adenocarcinoma.

Serum levels of c-erbB-2 protein were measured by an enzyme immunoassay in 64 patients with lung adenocarcinoma. Immunohistochemical staining was performed in 40 of these tumors. The mean serum concentration was 16.5 +/- 8.5 U/mL (range: 3.4 to 49.0) in patients with lung adenocarcinoma, whereas it was 14.0 +/- 3.7 U/mL (range: 6.9 to 20.9) in 15 controls (1 U/mL = 0.61 ng/mL). Elevated concentrations (> or = 22.0 U/mL, control mean + 2 SD) were observed in 17/64 lung adenocarcinoma patients (26.6%), as compared with none of the control subjects (p < 0.05). Patients with stage IIIB or T4 disease had increased serum levels. The serum concentration was decreased significantly by surgical tumor ablation. Tissue overexpression was obtained in 17/40 cases (42.5%), and serum levels in patients with tissue overexpression were higher than in patients without overexpression. Serum c-erbB-2 protein may be a useful indicator of tumor burden in patients with lung adenocarcinoma.

Optimal dose of basic fibroblast growth factor for long-segment orthotopic tracheal autografts.

When a primary anastomosis of the trachea is not feasible, extensive grafting is required. However, despite the use of omental wrapping for revascularization, long-segment tracheal grafts frequently do not maintain structural integrity because of insufficient blood supply. We examined the use of basic fibroblast growth factor for preservation of long-segment tracheal autografts after orthotopic transplantation with omental wrapping in 23 dogs. All animals received orthotopic tracheal transplantation, with 14-ring autografts that occupied a major part of the thoracic trachea, and omental wrapping. The 23 animals were classified randomly into six groups as follows: no treatment (group I, n = 3), topical administration of fibrin glue alone (group II, n = 4), fibrin glue enriched with 1 microg/cm2 basic fibroblast growth factor (group III, n = 4), fibrin glue enriched with 5 microg/cm2 basic fibroblast growth factor (group IV, n = 4), and fibrin glue enriched with 10 microg/cm2 basic fibroblast growth factor (groups V and VI, each n = 4). The omentum that was used to wrap the autografts was fed by the right gastroepiploic artery in groups I to V and by both the right gastroepiploic artery and splenic artery in group VI. All autografts in groups I and II showed dissolution. Ten of 12 autografts in groups III, V, and VI did not maintain long-term structural integrity. By contrast, all autografts in group IV showed long-term viability, as demonstrated by graft patency, epithelialization, cartilage morphology, and vascularity. We conclude that treatment with fibrin glue enriched with 5 microg/cm2 basic fibroblast growth factor in combination with omental wrapping may prolong the viability of long-segment tracheal autografts.

Feasibility of cryopreserved tracheal xenotransplants with the use of short-course immunosuppression.

OBJECTIVE: We evaluated the feasibility of discordant xenotransplantation of the cryopreserved trachea with intermittent immunosuppression to help solve the shortage of donor tracheas. METHODS: Two experiments were performed with heterotopic transplantation models in 14 guinea pigs and 85 rats. So that the minimal dose of FK506 for viable fresh xenografts could be determined, FK506 was given in escalating doses (0, 1.5, 2.5, and 3.5 mg/kg) for recipient animals after xenogeneic transplantation. With the goal of obtaining a long-term survival of the xenografts, the effect of cryopreservation on xenografts was assessed and thereafter different cycles of immunosuppression every third week were evaluated in fresh or cryopreserved xenografts in the second experiment. RESULTS: An FK506 dosage of more than 2.5 mg/kg per day was much more effective than smaller dosages, as demonstrated by morphologic assessment. A higher dosage of FK506 potentially delayed the rejection of xenografts and can thus maintain tracheal xenograft viability for less than 4 weeks in rat recipients. In experiment 2, the cryopreserved xenografts showed less histologic viability than fresh xenografts but greater patency of the lumen. The patency of cryopreserved xenografts was favorably maintained for a longer period than that of fresh xenografts with either the same number or more cycles of immunosuppression. CONCLUSIONS: We conclude that the synergistic effect of cryopreservation and adequate intermittent immunosuppression may enable tracheal xenografts to remain viable over longer periods.

Experimental carinal autotransplantation and allotransplantation.

Grafting is required when a primary reconstruction of a carinal defect is not feasible. A series of experiments in 21 dogs was conducted to assess the possibility of carinal reconstruction with the use of carinal autografts and allografts, with or without omentopexy. Carinal autograft transplantations were done without omentopexy in group A (n = 6) and with omentopexy in group B (n = 6). In group C (n = 9), carinal allograft transplantations were done with omentopexy and FK 506 was administered after operation. Survival of grafts was seen in 50% of group A, 83% of group B, and 44% of group C dogs. Postoperative bronchoscopy revealed inflammatory changes in the surviving grafts; the changes resolved more rapidly in the dogs with omentopexy than in the dogs without omentopexy. These experiments suggest that omentopexy is an effective method of facilitating survival and healing in carinal grafts and that carinal reconstruction with carinal allografts with FK 506 is feasible.

Unfavorable prognosis of patients with stage II non-small cell lung cancer associated with macroscopic nodal metastases.

BACKGROUND: Patients with stage II-N1 non-small cell lung cancer (NSCLC) make up an intermediate group of patients with an unsatisfactory prognosis even though complete resection is usually possible. We retrospectively analyzed postoperative prognostic factors to devise guidelines for the proper management of this patient population. STUDY DESIGN: Among 546 patients with NSCLC who underwent surgical resection from 1979 to 1995, 43 patients were pathologically defined to be at stage II-N1 (T1-2N1M0). The influence of the following variables on postoperative survival was analyzed: gender, age, cell type, pathologic T factor, number of metastatic nodes, station of metastatic nodes (hilar or pulmonary nodes), status of nodal metastasis (macroscopic, gross involvement confirmed histologically; or microscopic, metastasis first defined by histologic examination), surgical methods, and adjuvant therapy (including 18 of chemotherapy and 2 of radiotherapy). RESULTS: The 5-year survival rates (5YSRs) of patients with microscopic (n = 21) and macroscopic nodal metastasis (n = 22) were 76.0% and 27.6%, respectively (p = 0.001). The 5YSRs of 20 patients who received adjuvant therapy and 23 who did not receive adjuvant therapy were 57.6% and 46.6%, respectively (p = 0.036). Other variables did not affect survival. The Cox proportional hazards model analysis indicated that the presence of a macroscopic nodal metastasis and postoperative adjuvant therapy were independent prognostic factors. Among patients with macroscopic N1 NSCLC, 9 patients who had undergone adjuvant therapy showed a more favorable prognosis than the 13 patients who had not received adjuvant therapy (3-year survival rate, 55.6% vs 18.5%; p = 0.037; and recurrence rate, 30.0% vs 77.8%), whereas no significant influence of adjuvant therapy on survival was observed among patients with microscopic N1 NSCLC. CONCLUSIONS: Stage II-N1 NSCLC was categorized into microscopic and macroscopic N1 diseases. The latter had a poor prognosis, which might be improved by adjuvant therapy, although a suitable regimen has not been established.