[Treatment strategy and outcomes of invading apical lung cancer].

Invading apical lung cancers are generally the non-small-cell lung cancers (NSCLCs) which involve the apex of the chest wall. These tumors should be classified into 2 types based on the main location of tumor because of the difference of involved surrounding structures ; (1) the superior sulcus tumor origi nally termed Pancoast tumor which involves posterior region of the apex and (2) the anterior apical tumor which involves anterior region of the apex. Previously, these NSCLCs were considered to be inoperable showing a dismal prognosis. With the development of combined modality therapies for locally advanced NSCLCs, the prognosis of invading apical NSCLCs has been improved, especially since intro duction of the neoadjuvant chemoradiotherapy. Surgical resection for invading apical NSCLCs is 1 of challenging procedures for thoracic surgeons. The point is the anatomical complication of the small apex surrounding vital structures. Several approaches have been developed such as the posterior Paul-son's approach or anterior Masaoka's approach. In particular, the approach from anterior chest has been modified or devised to achieve safe and complete resection of tumors invading anterior structures like subclavian vessels. In this article, we reviewed our 13 cases of invading apical NSCLCs, especially from the view point of surgical approach. Thoracic surgeons should understand the properties of each approach and master them for complete resection avoiding serious complications.

[Histoculture drug response assay guided concurrent chemoradiotherapy for non-small cell lung cancer].

Retrospective analysis was done to evaluate concurrent chemoradiotherapy (CCRT) using chemotherapeutic agents judged to be sensitive by histoculture drug response assay (HDRA) for non-small cell lung cancer (NSCLC). We treated 21 NSCLC patients with CCRT using senstivie agents judged by HDRA from 1999 to 2004. Objective response was evaluated in 20 patients. They were consisted of 1 complete response (CR) case, 18 partial response (PR) cases, and 1 stable disease (SD) case. The response rate was 95%. Ten cancer related deaths were observed during 816 +/- 861 (60-2,780) days follow-up. Median survival time was 604 days. One- and 5-year survival rates were 73.9% and 40.3%, respectively. In conclusion, HDRA may improve efficacy of CCRT for NSCLC.

Usefulness of mini-tracheostomy and torque controlled insertion of applicator in fractionated endobronchial brachytherapy.

Endobronchial brachytherapy was developed as effective treatment of endobronchial cancer and fractionated schedule is applied to decrease late toxicity. However, repeated bronchofiberscopy is onerous to the patient and restricts the treatment schedule itself. We applied mini-tracheostomy for a ready access route, and a torque controlled technique for easy insertion of the endobronchial applicator. Eight patients with tracheobronchial cancer invasion were treated with endobronchial brachytherapy of 18-30 Gy/3-5 fractions/1.5-2.5 weeks (median 24 Gy/4 fractions/2 weeks) at reference points of 5 mm from the bronchial surface. The averaged individual irradiation and single session times were 4 min and 24 min, respectively. There were no procedure-related complications. These technical improvements may facilitate flexible fractionated dose prescriptions.

[Surgical stabilization of multiple rib fracture and flail chest].

The experience of 14 cases with surgical stabilization of multiple rib fracture and flail chest was reported. They were 11 men and 3 women of 31 to 87 years of age. Paradoxical chest movement was noted in 10 patients. Thirteen of 14 patients successfully weaned from the ventilator less than 7 days after surgery. Of 14, 4 cases were treated with internal fixation and the others were with acetabular reconstruction plates with or without rib stapler. No case of death was experienced. Ten patients who were performed fixation with acetabular reconstruction plate weaned from the ventilator earlier than cases treated by internal fixation, suggesting the superiority of the acetabular reconstruction plate. Improvement of rib stapler and the development of a titanium plate of specific use for rib is expected in the future.

Long-term results of fractionated strontium-90 radiation therapy for pterygia.

PURPOSE: The long-term safety and effectiveness of fractionated strontium-90 radiation therapy (RT) for pterygium were reviewed retrospectively. METHODS AND MATERIALS: Between 1984 and 1996, 399 patients with 490 pterygia were treated with a strontium-90 eye applicator following surgical removal of the pterygium. The median follow-up period was 61 months (range 2-178). Of the 490 pterygia, 452 were fresh, 17 were recurrences after surgical removal alone, and 21 were recurrences after surgical removal plus postoperative RT. Fractionated RT of 31-42 Gy/4-5 fractions/22-29 days was given for 95.1% of the pterygia. RESULTS: In total, 58 (11.8%) local recurrences of pterygia were noted. The median time of local recurrences was 10 months, ranging from 2 to 93 months, and 16 recurrences (28%) were noted later than 24 months after treatment. The interval between surgery and the start of RT (1-3 days vs. >3 days) and recurrent pterygia were significant variables for local control in the multivariate analysis, while total RT dose (7-29 Gy vs. 31-50 Gy) was a marginally significant variable. Late toxicities that may be associated with strontium-90 RT were scleromalacia (scleral thinning) in 4 eyes, adhesion of eyelids in 3 eyes, and scleral ulcer in 2 eyes. CONCLUSION: Fractionated strontium-90 RT of approximately 40 Gy/4-5 fractions was safe and effective for preventing recurrence of pterygia, when RT was started within 3 days of surgery.

Evaluation of effect of lung resection on lobar ventilation and perfusion using intrabronchial capnography.

Intrabronchial capnography was applied in 11 lung cancer patients to investigate the effects of lobectomy on regional lung function. Spirometry and intrabronchial capnography were performed before surgery (PRE), and during the early (POST1,19 +/- 5 POD) and late (POST2, 184 +/- 98 POD) postoperative periods. End-tidal carbon dioxide concentration (EtCO2) and Smidt's velocity profile index (V-index) were calculated from each lobar capnogram obtained bronchoscopically. The V-index of lobes without cancer on the operated-on side increased after surgery (PRE, 10.7 +/- 5.0%; POST1, 14.3 +/- 9.4%, NS; POST2, 16.8 +/- 8.6%, p < 0.05), while the V-index on the unoperated-on side decreased after surgery (PRE, 10.5 +/- 5.3%; POST1, 7.9 +/- 3.5%, p < 0.05; POST2, 7.2 +/- 2.9%, p < 0.05). EtCO2 after surgery was lower on the operated-on side (POST1, 5.1 +/- 1.1%; POST2, 4.6 +/- 1.1%) than on the unoperated-on side (POST1, 5.4 +/- 0.9%, p < 0.05; POST2, 5.0 +/- 0.9%, p < 0.01). Since the V-index and EtCO2 are compatible with the expiratory flow rate and the perfusion/ventilation ratio, respectively, we concluded that the air flow decreased on the operated-on side and increased on the unoperated-on side postoperatively and that perfusion on the operated-on side was more severely reduced than ventilation. These findings suggest that intrabronchial capnography is useful for assessing the ventilation and perfusion of the individual lobes as single units.

Intrapleural administration of a large amount of diluted fibrin glue for intractable pneumothorax.

OBJECTIVE: Pleurodesis using chemical agents has been applied to high-risk patients with pneumothorax. This treatment, however, is sometimes unsuccessful in patients with intractable pneumothorax or intrapleural dead space. We developed a technique for the intrapleural administration of diluted fibrin glue as a treatment for such patients. METHODS: Fibrin glue was diluted fourfold with saline solution and/or contrast medium. Pleurodesis with a large amount of the diluted fibrin glue was performed in 40 high-risk patients with intractable pneumothorax and in 13 postthoracotomy patients with persistent air leakage associated with an intrapleural dead space. RESULTS: The air leaks were stopped by administration of the glue in all patients of both groups. During the follow-up period, a recurrence rate of 12.5% was observed in the former group. These recurrent pneumothoraces also were successfully treated by glue administration with no further recurrence. In the 13 postthoracotomy patients, there was no recurrence after the initial treatment. Pyrexia (12.5%) and chest discomfort (4.1%) were observed as side effects, but there were no findings of severe chest pain or thoracic empyema. CONCLUSIONS: These results suggest that intrapleural administration of a large amount of diluted fibrin glue is a useful treatment for intractable pneumothoraces in high-risk or postthoracotomy patients who have an intrapleural dead space.

Exercise capacity of thoracotomy patients in the early postoperative period.

OBJECTIVE: We investigated the mechanism involved with the initial drop and subsequent recovery of exercise capacity in the early postoperative period of thoracotomy patients. METHODS: Sixteen patients (13 who had undergone lobectomy, 3 who had undergone pneumonectomy) underwent a routine pulmonary function test (PFT) and a cardiopulmonary exercise test preoperatively, within 14 postoperative days (POD; post-1; mean +/- SD, 9 +/- 2 POD), and after 14 POD (post-2; mean, 26 +/- 12 POD). RESULTS: After surgery on post-1, PFT results of FVC, FEV(1), and maximum ventilatory volume (MVV) significantly decreased. Oxygen uptake (VO(2)) at a venous blood lactate level of 2.2 mmol/L (La-2. 2), which was adopted as the empirical anaerobic threshold, and maximum V O(2) (VO(2)max) decreased significantly to 88.2 +/- 7.9% and 73.1 +/- 15.4% of the preoperative values, respectively. La-2.2 min ventilation (VE)/ MVV and maximum VEmax)/MVV increased significantly from 0.36 +/- 0.08 to 0. 66 +/- 0.20 and from 0.58 +/- 0.14 to 0.80 +/- 0.09, respectively. On post-2, though La-2.2 VO(2) did not change, VO(2)max improved significantly to 81.5 +/- 19.7% of the preoperative values, in association with significant increases in maximal tidal volume and VEmax, which were produced by significant increases in the PFT results. La-2.2 VE/MVV also decreased significantly to 0.49 +/- 0.13, which indicated a sufficient recovery of respiratory reserve at submaximal exercise. CONCLUSIONS: The initial drop of exercise capacity after lung resection seems to be derived from both circulatory and ventilatory limitations. Further, the subsequent recovery within 1 month seems to be produced by an improvement in ventilatory limitation, which was caused by the surgical injury to the chest wall.

MxA expression in patients with viral infection after allogeneic stem cell transplantation.

Many patients suffer febrile diseases soon after allogeneic stem cell transplantation (SCT). Some of the symptoms of viral infections and acute GVHD are often difficult to distinguish. However, an accurate diagnosis is important since the treatments for these conditions are different. It is known that MxA protein is specifically induced in patients with several viral infections. We investigated the cytoplasmic expression of MxA in the peripheral blood mononuclear cells (PBMCs) of patients with fever after allogeneic SCT using a newly generated monoclonal antibody (KM1135) and flow cytometry. The level of MxA expression was significantly higher in patients diagnosed with viral infections (n=6, cytomegalovirus in three, Epstein-Barr virus in one, human herpesvirus-6 in one, adenovirus in one) than control individuals (n=9) (P<0.05, Mann-Whitney test). The level of MxA in patients with aGVHD (n=7) was identical to that in controls. The level of MxA correlated well with the amount of the cytomegalovirus antigen-positive cells in the presence of acute GVHD in two patients. The measurement of MxA is simple and useful in distinguishing viral disease from acute GVHD after allogeneic SCT.

Successful treatment of natural killer (NK) cell leukemia following a long-standing chronic active Epstein-Barr virus (CAEBV) infection with allogeneic bone marrow transplantation.

The optimal treatment for natural killer (NK) cell leukemia after chronic active Epstein-Barr virus (CAEBV) infection has not been determined. A 15-year-old boy presented with NK cell leukemia following CAEBV infection for 5 years. The peripheral blood and BM had an increased number of CD3(-)CD56(+) large granular lymphocytes and a monoclonal integration of the EBV genome was detected. Chemotherapy was not sufficiently effective to control the disease. Allogeneic BMT from an HLA-identical sister was performed using a conditioning regimen consisting of total body irradiation, cyclophosphamide and thiotepa. The patient is disease-free with a perfect performance status 24 months after BMT. This is the first report to show that allogeneic BMT is potentially able to cure NK cell leukemia after CAEBV infection.

Successful treatment of relapsed blastic natural killer cell lymphoma with unrelated cord blood transplantation.

The prognosis for blastic natural killer (NK) cell lymphoma is generally dismal. We report a patient who was successfully treated with unrelated cord blood transplantation (UCBT). A 15-year-old boy was diagnosed as having blastic NK cell lymphoma in the cervical lymph nodes. Autologous peripheral blood stem cell transplantation was performed on achieving a complete remission. However, the disease recurred in the bone marrow 6 months later. Chemotherapy induced a second remission and the patient received UCBT with a conditioning regimen consisting of total body irradiation, thiotepa and cyclophosphamide. Chronic GVHD of the lung occurred, but it was well controlled with steroids. At the time of writing, he remains in remission 18 months after UCBT with an excellent performance status. UCBT may be an option for patients with blastic NK cell lymphoma.

Prompt and durable hematopoietic reconstitution by unrelated cord blood transplantation in a child with Fanconi anemia.

We describe here the case of an 8-year-old girl with Fanconi anemia (FA) whose hematopoiesis was successfully restored by unrelated umbilical cord blood (UCB) transplantation. The patient became resistant to androgen therapy, and developed intracranial hemorrhage and dyserythropoiesis. Her hematopoietic recovery after the transplantation was excellent and a complete chimerism has been durably maintained. UCB should be considered as a stem cell source for transplantation when a patient with FA does not have an HLA-identical unaffected sibling donor.

Improvement in bronchiolitis obliterans organizing pneumonia in a child after allogeneic bone marrow transplantation by a combination of oral prednisolone and low dose erythromycin.

We report a 13-year-old boy who developed dyspnea at rest 1 year after the occurrence of cGVHD following an allogeneic bone marrow transplant (BMT). Pulmonary function data, imaging studies, lung biopsy, and bronchoalveolar lavage were consistent with the diagnosis of bronchiolitis obliterans organizing pneumonia (BOOP). Although reports suggest that oral methylprednisolone or methylprednisolone pulse therapies improve BOOP after BMT, we treated our patient with a combination of oral prednisolone (1 mg/kg) and low dose erythromycin (10 mg/kg) to avoid the side-effects of high-dose steroids. With this therapy, our patient showed clinical and radiological improvements within 1 week. The steroids were tapered off 12 months later and erythromycin was given for 14 months. We conclude that therapy consisting of a combination of oral prednisolone and low-dose erythromycin for BOOP after BMT may minimize the dose and duration of steroid use.

Enhancement of the response to levodopa therapy after intrastriatal transplantation of autologous sympathetic neurons in patients with Parkinson disease.

OBJECT: There is growing evidence to indicate that tissue transplantation can potentially be a restorative neurosurgical treatment for patients with Parkinson disease (PD). In this study the authors investigated the clinical effect of unilateral intrastriatal grafting of autologous sympathetic neurons in patients with PD. METHODS: Four patients with PD who had been observed for 1 year after graft placement of autologous sympathetic neurons were selected for an analysis of the effect of that procedure. Sympathetic ganglion tissue was endoscopically excised from the thoracic sympathetic trunk and grafted into the unilateral caudate head and putamen of the PD patients. No changes were made in the patients' preoperative regimens of antiparkinsonian medications, and clinical evaluations were made principally according to those established by the Core Assessment Program for Intracerebral Transplantation Committee. Whereas the sympathetic neuron grafts failed to affect clinical scores reflecting the patients' motor performance, which was evaluated during either the "on" or "off' phases, the grafts significantly increased the duration of the levodopa-induced on period with consequent reduction in the percentage of time spent in the off phase. This beneficial effect may be explained by the results of the present in vitro experiment, which show that human sympathetic neurons have the ability to convert exogenous levodopa to dopamine and to store this synthesized dopamine. CONCLUSIONS: Sympathetic neuron autografts were found to improve performance status in patients with PD by reducing the time spent in the off phase. This clearly indicates that sympathetic ganglion tissue, the use of which involves few ethical issues, can be an efficacious donor source in cell transplantation therapy for PD. Further studies are needed to determine whether the grafts may provide long-lasting clinical benefits.

Acquisition of multidrug resistance in recurrent breast cancer demonstrated by the histoculture drug response assay.

Recurrent breast cancer has a very poor response rate to chemotherapy. To understand the degree of acquisition of multidrug resistance in recurrent disease, 24 recurrent breast tumors and 127 primary tumors were evaluated and compared for chemosensitivity in the histoculture drug response assay (HDRA). The evaluation rate was 98.8%. The HDRA utilizes 3-dimensional culture of human tumors on collagen-gel rafts. Doxorubicin (DXR), 5-fluorouracil (5-FU) and mitomycin C (MMC) were tested as standard agents and cisplatin (CDDP) as a candidate agent on surgical specimen of breast cancer in the HDRA. In vitro drug exposure in the HDRA was for 7 days. At the end of the assay, tumor response was assessed by the reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The mean inhibition rates of primary tumors vs. recurrent tumors were 57.9% and 38.6% for DXR (p<0.0005); 59.9% and 42.8% for MMC (p<0.01); 49.0% and 33.4% for 5-FU (p<0.01); and 34.5% and 16.0% for CDDP (p<0.005), respectively. The recurrent cases were pretreated clinically with CAF (cyclophosphamide, DXR and 5-FU), CEF (cyclophosphamide, epirubicin and 5-FU) or CMF (cyclophosphamide, methotrexate and 5-FU). In the CAF and CEF group, the HDRA sensitivity to CDDP was significantly lower in recurrent disease (p<0.005) than that of primary breast cancer suggesting that one agent can induce resistance to another. This is further suggested by the fact that 64.7% of the recurrent cases were resistant to all 4 agents tested as opposed to 27% of the primary cases and that only 5.9% of the recurrent cases were sensitive to three or more agents as opposed to 18% of the primary cases. The correlation of the HDRA results to clinical outcome in the study was 80.0% with 15 cases evaluated consisting of 5 true positives, 3 false positives, 7 true negatives and no false negatives. Thus, the HDRA gives useful clinical information, in particular for the specific individualized treatment design necessary to overcome the multidrug resistance problem of recurrent breast cancer.

Disappearance curves for tumor markers after resection of intrathoracic malignancies.

Determination of the standard elimination kinetics of tumor markers will be helpful in the diagnosis of malignancies. We analyzed the disappearance curves for serum tumor marker levels after resection of intrathoracic malignancies. Serum levels of CEA, SLX, AFP, CA 19-9, SCC, TPA and CYFRA were measured several times after surgery in a total of 40 patients. To obtain precise biological half-lives, we applied non-linear least square analysis, taking into consideration the possibility of residual tumor cells. Disappearance curves were monophasic for CEA, SCC, TPA, CYFRA and SLX and biphasic for CA 19-9 and AFP. Temporary elevation of serum levels after surgery was observed for SCC, TPA and CYFRA. The average half-lives of CEA, SLX, SCC, TPA and CYFRA were 1.5 days, 2.7 days, 2.2 hours, 2.5 hours and 1.5 hours, respectively. The average half-life of CA 19-9 was 0.5 days in the first compartment and 4.3 days in the second compartment, while that of AFP was 1.0 days and 6.3 days, respectively. These values will be helpful in the interpretation of serum tumor marker levels after surgery.

Long-term results of lipiodol-transcatheter arterial embolization with cisplatin or doxorubicin for unresectable hepatocellular carcinoma.

The long-term effects of Lipiodol-transcatheter arterial embolization (Lp-TAE) combined with cisplatin (CDDP) or doxorubicin (ADM) on unresectable hepatocellular carcinoma (HCC) were analyzed. Eighty-four consecutive patients with unresectable HCC were treated with TAE. Of the 84, 38 patients were treated with CDDP-Lp-TAE (CDDP group), whereas the remaining 46 patients were treated with ADM-Lp-TAE (ADM group). No significant difference in characteristics of patients and tumors was noted between the groups. CDDP (50 mg) or ADM (20-50 mg) was administered with Lp followed by embolization of the feeding arteries using gelatin sponge particles. The mean number of TAE treatments was 3.3 in the CDDP group and 1.9 in the ADM group (p < 0.01). The 5-year overall survival rates of the CDDP group and the ADM group were 19% and 6%, respectively. The overall survival rate of the CDDP group was significantly higher than that of the ADM group (p < 0.05). No serious side effects were observed in either group. CDDP-Lp-TAE improved the prognosis of unresectable HCC compared with ADM-Lp-TAE, which may be attributable to the fact that CDDP-Lp-TAE treatment could be repeated more times than ADM-Lp-TAE.

Discoid lupus erythematosus (DLE)-like lesion induced by uracil-tegafur (UFT).

A mixture of uracil and tegafur (UFT) is a common antineoplastic agent in Japan. We report a 64-year-old Japanese woman with discoid lupus erythematosus (DLE)-like lesions which were induced by UFT. After surgery to treat lung cancer, UFT (300 mg/day) was administered and she developed round erythema on her right cheek. A skin biopsy specimen taken from the right cheek site revealed atrophy of the epidermis, a slight liquefaction of the basal cell layer, and patchy lymphocytic infiltration in the perivascular and perifollicular regions. A test for antinuclear antibody was weakly positive (80 fold), and rheumatoid factor was slightly elevated (7.6 IU/ml). After discontinuation of UFT, the erythema completely regressed within 2 months. We reviewed 17 cases of DLE-like lesions induced by fluorouracil agents and summarized the common features.

Bisphosphonate therapy for bone metastases from breast cancer: clinical results and a new therapeutic approach.

BACKGROUND: We evaluated the usefulness of bisphosphonate (BIS) monotherapy, the safety of rapid infusion of BIS and the efficacy of BIS-sequential therapy for bone metastases from breast cancer. PATIENTS AND METHODS: Twenty-nine patients with bone metastasis or invasion were treated with BIS monotherapy. Each BIS (pamidronate 30 mg, alendronate 10 mg, or incadronate 10 mg) was infused over 30 minutes every two weeks a median of 12 times. RESULTS: With BIS therapy, five patients (17%) showed partial response of the bone lesions, and eighteen patients (64%) had pain relief. Of the nine patients treated with BIS-sequential therapy, one (11%) showed a partial response of the bone metastases, three (33%) had pain relief, and one (11%) showed a decrease in the serum tumor marker level. CONCLUSION: BIS therapy is effective against bone metastases from breast cancer, and rapid infusion of BIS is both safe and convenient for patients. BIS-sequential therapy can be a unique therapeutic option in some cases.

Skin metastasis of neuroendocrine carcinoma derived from the mediastinum.

We report a 46-year-old Japanese man with a metastatic skin tumor on his left palmar region. He underwent resection for a mediastinal neuroendocrine carcinoma in February of 1998. After the operation, he immediately noticed an elevated tumor on his left palm. In September 1999, a brain tumor was discovered. The skin and brain tumors were subsequently removed surgically. Neuron specific enolase (NSE) in the serum was elevated to 25 ng/ml. A skin biopsy specimen from the left palmar site revealed multiple tumor nests which showed the same histological features as the primary mediastinal tumor. Immunostaining was positive for chromogranin, synaptophysin, and NSE but negative for S-100 protein and CD57. To our knowledge, this is the first report of cutaneous metastasis of a neuroendocrine tumor derived from the mediastinum.