Clinicopathological features of cytokeratin 5-positive pulmonary adenocarcinoma.

Cytokeratin 5 (CK5) is a marker for pulmonary squamous cell carcinoma; however, CK5 is sometimes present in pulmonary adenocarcinoma (ADC), and there is insufficient information regarding the clinicopathological features of CK5-positive ADC. We aimed to explore the clinicopathological characteristics of CK5-positive ADC using immunohistochemistry. We prepared the following two cohorts: a resected cohort containing 220 resected tumours for primarily studying the detailed morphological characteristics, and a tissue microarray (TMA) cohort containing 337 samples for investigating the associations of CK5 expression with other protein expressions, genetic and prognostic findings. CK5-positive ADC was defined to have ≥ 10% tumour cells and presence of CK5-positive tumour cells in the resected and TMA cohorts, respectively. CK5-positive ADCs were identified in 91 (16.3%) patients in the combined cohort. CK5-positive ADCs had male predominance (P = 0.012), smoking history (P = 0.001), higher stage (P < 0.001), histological high-grade components (P < 0.001), vascular invasion (P < 0.001), mucinous differentiation (P < 0.001), spread through airspaces (P < 0.001), EGFR wild-type (P < 0.001), KRAS mutations (P < 0.001), ALK rearrangement (P < 0.001) and ROS1 rearrangement (P = 0.002). In the resected cohort, more than half the CK5-positive ADCs (19 cases, 65.5%) showed mucinous differentiation; the remaining cases harboured high-grade components. In the TMA cohort, CK5-positive ADCs correlated with TTF-1 negativity (P = 0.002) and MUC5B, MUC5AC and HNF4alpha positivity (P < 0.001, 0.048, < 0.001). Further, CK5-positive ADCs had significantly lower disease-free and overall survival rates than CK5-negative ADCs (P < 0.001 for each). Additionally, multivariate analysis revealed that CK5 expression was an independent poor prognostic factor. CK5-positive ADCs showed aggressive clinical behaviour, with high-grade morphology and mucinous differentiation.

Potential egg contamination by Salmonella enterica serovar Typhimurium definitive type 104 following experimental infection of pullets at the onset of lay.

The present study investigated the potential of Salmonella enterica serovar Typhimurium (Salmonella Typhimurium) definitive type 104 (DT104) to contaminate eggs in vivo. Of 10 strains of Salmonella Typhimurium DT104, none caused egg contamination when hens were inoculated orally. Three passages of the strains through recovery from the reproductive organs of intravenously infected laying hens resulted in no egg contamination after oral infection of the hens. Feed and water withdrawal for 24 h at 5 and 10 d after oral infection with Salmonella Typhimurium DT104 slightly decreased egg production but did not lead to egg contamination. Finally, oral infection of pullets at the onset of lay (approximately 50% of egg production) resulted in egg contamination (1.7%) in 2 wk. In conclusion, the Salmonella Typhimurium DT104 strains used in the present study have a low possibility of causing egg contamination; however, because infection at the onset of lay can cause egg contamination, the introduction of Salmonella Typhimurium DT104 into the layer houses should be prevented, especially when hens start laying eggs.

Significance of tumor recurrence before pulmonary metastasis in pulmonary metastasectomy for soft tissue sarcoma.

BACKGROUND: Resection for pulmonary metastasis from soft tissue sarcomas is an accepted method for treatment, but it is still debatable which patients will benefit from surgical intervention. To find an entity of patients benefiting from pulmonary metastasectomy, we reviewed our institutional experience. METHODS: Between 1990 and 2007, 23 patients with pulmonary metastases from soft tissue sarcomas underwent complete pulmonary resection. All patients had obtained locoregional control of their primary tumors. Various perioperative variables were investigated retrospectively to confirm the role of pulmonary metastasectomy and to identify possible prognostic factors for survival after metastasectomy. RESULTS: Overall survival rate after metastasectomy was 43% and 29% at 5 and 10 years, respectively. Disease-free survival rate was 9% at 1 year after pulmonary resection. On multivariate analysis, no tumor recurrence (neither locoregional recurrence nor extrapulmonary metastasis) before pulmonary metastasis provided a significantly favorable overall survival (P=0.038). In addition, repeat metastasectomy for recurrent pulmonary metastasis also provided a favorable overall survival (P=0.041). CONCLUSIONS: Our data suggested that patients most likely to benefit from pulmonary metastasectomy for soft tissue sarcoma have no tumor recurrence before pulmonary metastasis. Furthermore, patients with repeat metastasectomy for recurrent pulmonary metastasis also presented a significantly longer survival.

Clinical features of surgical resection for pulmonary metastasis from breast cancer.

BACKGROUND AND OBJECTIVES: Metastatic breast cancer has been defined as a systemic disease. The discussion concerning the resection of lung metastases in patients with breast cancer is controversial. To confirm the role of resection of pulmonary metastases from breast cancer and to identify possible prognostic factors, we reviewed our institutional experience. METHODS: Between 1991 and 2007, 41 patients with pulmonary metastases from breast cancers underwent complete pulmonary resection. All patients had obtained or had obtainable locoregional control of their primary tumors. Various perioperative variables were investigated retrospectively to confirm the role of metastasectomy and to analyze prognostic factors for overall survival after metastasectomy. RESULTS: All patients were female with a median age of 55 years (range, 35-81 years). The overall survival rate after metastasectomy was 51% at 5 and 10 years. On multivariate analysis, fewer than four pulmonary metastases and a disease-free interval of more than 3 years were significantly favorable prognostic factors for overall survival (p=0.023 and 0.024, respectively). CONCLUSIONS: The current practice of pulmonary metastasectomy for breast cancers in our institution was well justified. Pulmonary metastasectomy in patients with previous breast cancer might be justified when fewer than four pulmonary metastases or a disease-free interval of more than 3 years.

[Mediastinal aberrant goiter; report of a case].

A 54-year-old woman was admitted to our hospital because of an abnormal shadow on chest X-ray. Chest computed tomography (CT) scan and magnetic resonance imaging (MRI) demonstrated an anterior mediastinal tumor. The tumor was resected completely through a median sternotomy. The tumor was dissected successfully from the surrounding vessels in spite of the heavy adhesion to them. The blood supply of the tumor was from a branch of the brachiocephalic artery. The tumor was 9 x 8 x 3 cm in size, and was diagnosed as an aberrant mediastinal goiter since it showed no communication to the thyroid gland. An aberrant mediastinal goiter is a quite rare entity of diseases and its removal through the neck would result in uncontrolled blood loss because its blood supply usually derives from intrathoracic vessels.

Determination of low tetanus or diphtheria antitoxin titers in sera by a toxin neutralization assay and a modified toxin-binding inhibition test.

A method for the screening of tetanus and diphtheria antibodies in serum using anatoxin (inactivated toxin) instead of toxin was developed as an alternative to the in vivo toxin neutralization assay based on the toxin-binding inhibition test (TOBI test). In this study, the serum titers (values between 1.0 and 19.5 IU) measured by a modified TOBI test (Modi-TOBI test) and toxin neutralization assays were correlated (P < 0.0001). Titers of tetanus or diphtheria antibodies were evaluated in serum samples from guinea pigs immunized with tetanus toxoid, diphtheria-tetanus or triple vaccine. For the Modi-TOBI test, after blocking the microtiter plates, standard tetanus or diphtheria antitoxin and different concentrations of guinea pig sera were incubated with the respective anatoxin. Twelve hours later, these samples were transferred to a plate previously coated with tetanus or diphtheria antitoxin to bind the remaining anatoxin. The anatoxin was then detected using a peroxidase-labeled tetanus or diphtheria antitoxin. Serum titers were calculated using a linear regression plot of the results for the corresponding standard antitoxin. For the toxin neutralization assay, L+/10/50 doses of either toxin combined with different concentrations of serum samples were inoculated into mice for anti-tetanus detection, or in guinea pigs for anti-diphtheria detection. Both assays were suitable for determining wide ranges of antitoxin levels. The linear regression plots showed high correlation coefficients for tetanus (r(2) = 0.95, P < 0.0001) and for diphtheria (r(2) = 0.93, P < 0.0001) between the in vitro and the in vivo assays. The standardized method is appropriate for evaluating titers of neutralizing antibodies, thus permitting the in vitro control of serum antitoxin levels.

Determination of low tetanus or diphtheria antitoxin titers in sera by a toxin neutralization assay and a modified toxin-binding inhibition test

A method for the screening of tetanus and diphtheria antibodies in serum using anatoxin (inactivated toxin) instead of toxin was developed as an alternative to the in vivo toxin neutralization assay based on the toxin-binding inhibition test (TOBI test). In this study, the serum titers (values between 1.0 and 19.5 IU) measured by a modified TOBI test (Modi-TOBI test) and toxin neutralization assays were correlated (P < 0.0001). Titers of tetanus or diphtheria antibodies were evaluated in serum samples from guinea pigs immunized with tetanus toxoid, diphtheria-tetanus or triple vaccine. For the Modi-TOBI test, after blocking the microtiter plates, standard tetanus or diphtheria antitoxin and different concentrations of guinea pig sera were incubated with the respective anatoxin. Twelve hours later, these samples were transferred to a plate previously coated with tetanus or diphtheria antitoxin to bind the remaining anatoxin. The anatoxin was then detected using a peroxidase-labeled tetanus or diphtheria antitoxin. Serum titers were calculated using a linear regression plot of the results for the corresponding standard antitoxin. For the toxin neutralization assay, L+/10/50 doses of either toxin combined with different concentrations of serum samples were inoculated into mice for anti-tetanus detection, or in guinea pigs for anti-diphtheria detection. Both assays were suitable for determining wide ranges of antitoxin levels. The linear regression plots showed high correlation coefficients for tetanus (r² = 0.95, P < 0.0001) and for diphtheria (r² = 0.93, P < 0.0001) between the in vitro and the in vivo assays. The standardized method is appropriate for evaluating titers of neutralizing antibodies, thus permitting the in vitro control of serum antitoxin levels.

Endovascular treatment of ruptured anterior communicating artery aneurysms. Results and technical considerations.

SUMMARY: The aim of this paper is to provide a review of our experience in using the endovascular treatment of ruptured anterior communicating artery (ACoA) aneurysms. Between March 1997 and May 2004, 211 ruptured aneurysms were treated with Guglielmi detachable coil (GDC) system in Mito Medical Center, 73 were located at the ACoA.Two cases were incomplete embolization, and performed microsurgical clipping. In the initial embolization for the 71 aneurysms, complete occlusion was achieved in 44 aneurysms, neck remnant in 11 aneurysms and body filling in 16 aneurysms. Intra-operative complication was occurred in six cases (8.2%). Aneurysm perforation was occurred in three cases (4.1%), thromboembolic complication was occurred in three cases (4.1%). Acute rebleeding were observed in two cases (2.7%). Endovascular treatment is an effective technique for treating ACoA aneurysms, and 3D-rotational angiography is important diagnostic tool for evaluating the ACoA complex.

Mutations in the epidermal growth factor receptor gene are linked to smoking-independent, lung adenocarcinoma.

Epidermal growth factor receptor (EGFR) mutations are a potential predictor of the effectiveness of EGFR inhibitors for the treatment of lung cancer. Although EGFR mutations were reported to occur with high frequency in nonsmoking Japanese adenocarcinoma patients, the exact nature has not been fully elucidated. We examined EGFR gene mutations within exons 18-21 and their correlations to clinico-pathological factors and other genetic alterations in tumour specimens from 154 patients who underwent resection for lung cancer at Kyoto University Hospital. Epidermal growth factor receptor mutations were observed in 60 tumours (39.0%), all of which were adenocarcinoma. Among the patients with adenocarcinoma (n=108), EGFR mutations were more frequently observed in nonsmokers than former smokers or current smokers (83.0, 50.0, 15.2%, respectively), in women than men (76.3 vs 34.0%), in tumours with bronchio-alveolar component than those without bronchio-alveolar component (78.9 vs 42.9%), and in well or moderately differentiated tumours than poorly differentiated tumours (72.0, 64.4, 34.2%). No tumours with EGFR mutations had any K-ras codon 12 mutations, which were well-known smoking-related gene mutations. In conclusion, adenocarcinomas with EGFR mutation had a distinctive clinico-pathological feature unrelated to smoking. Epidermal growth factor receptor mutations may play a key role in the development of smoking-independent adenocarcinoma.

Angiographical change of guglielmi detachable coils. Treated cerebral aneurysm in acute stage.

SUMMARY: Acute angiographical changes for preventing acute rebleeding on GDC treated cerebral aneurysms were evaluated. From December 2000 to November 2002, 48 total aneurysms in 44 consecutive patients with acute SAH. Acute angiographical evaluations were carried out in 46 aneurysms, including 42 ruptured and 4 unruptured aneurysms. Two cases were excluded because of poor medical condition. In this series, there were no rebleeding cases in acute stage. In the initial embolization for the 46 aneurysms, CO was achieved in eight aneurysms, NR in 15 aneurysms and BF in 23 aneurysms. Acute angiographical observations showed progressive thrombosis in 17 aneurysms (37%). No changes were observed in remaining 29. No recanalization was observed in this series. Only one case of BF, inside the aneurysm bleb was still observed during follow up. Additional embolization was carried out. Progressive thrombosis was frequently observed in GDC treated cerebral aneurysms during acute stage. This angiographical finding seems to show prevention of rebleeding, which is considered important for the management of GDC treatment in acutely ruptured cerebral aneurysm.

Retreatment of cerebral aneurysms after guglielmi detachable coil embolization.

SUMMARY: Of 175 patients with 181 aneurysms initially treated with Guglielmi Detachable Coils (GDC), 25 were retreated. All retreatments except one were performed on previously ruptured aneurysms. Thirteen aneurysms were retreated because of recurrence, and 12 aneurysms were retreated to complete initial insufficient embolization. Sixteen patients underwent re-embolization and 9 patients were operated upon surgically. No complications related to the retreatment were experienced. We consider that repeat embolization should be attempted before considering surgical treatment in case that additional therapy is required. However, it is difficult to retreat aneurysms having wide necks. In regard to surgical clipping, aneurysms without a coil in the neck are easier to treat with primary clipping, whereas aneurysms with a coil mass in the neck are difficult to surgical clip. We have never used temporary clipping and coil extraction if the distance between the coil and the parent artery was wider than 2 mm. Emerging new embolic agents or devices and technical improvement might decrease the need for retreatment and increase long-term efficacy after endovascular treatment.

Angiographic Follow-up of Embolization Using Guglielmi Detachable Coils for Cerebral Aneurysms.

SUMMARY: The purpose of this study is to evaluate the mid or long-term angiographical stability of Guglielmi Detachable Coils (GDC) after embolization for cerebral aneurysms. Between march 1997 and november 2001, 164 aneurysms, including 116 ruptured and 48 unruptured aneurysms, were treated using GDC at Mito National Hospital. Cerebral angiograms over one month after embolization were obtained in 111 aneurysms, including 71 ruptured and 40 unruptured aneurysms.At the time of initial GDC embolization of the 71 ruptured aneurysms, complete occlusion was achieved in 31 aneurysms, neck remnant in 18 aneurysms, and body filling in 22 aneurysms. Morphological changes were observed in 26 aneurysms (37%) in follow-up. Progressive thrombosis was obtained in 12 out of 71 aneurysms, no changes were shown in 45, and recanalizations occurred in 14. In the initial embolization of the 40 unruptured aneurysms, complete occlusion was achieved in 15 aneurysms, neck remnant in five and body filling in 20 aneurysms respectively. Morphological changes were observed in 12 aneurysms (30%), in which 12 aneurysms showed progressive thrombosis and 28 aneurysms were unchanged. There were significant differences of the longterm angiographical stability between ruptured and unruptured aneurysms. Rigorous follow-up angiography is mandatory when complete aneurysm occlusion is not achieved in ruptured aneurysms.

Treatment of a scalp arteriovenous malformation by a combination of embolization and surgical removal.

SUMMARY: The authors describe a 21-year-old man in whom a large arteriovenous malformation of the scalp was eliminated using a combined interventional, neuroradiological and neurosurgical approach. Embolization was utilized to reduce arterial blood supply to the malformation. Eudragit- E, as a liquid embolic material from a cationic polymer, methyl and butyl methacrylate, and dimethylaminoethyl methacrylate copolymer, was injected through the transarterial route and then by direct percutaneous puncture of the nidus. One week after embolization, the nidus was easily resected with minimal blood loss. A postoperative angiogram showed nearly total extirpation of the nidus as well as complete clinical recovery. Preoperative embolization in this case was a safe and effective ablative technique.

Thymoma. Analysis of prognostic factors.

OBJECTIVE: We evaluated the prognostic factors for thymoma that remain controversial. METHODS: We studied 72 consecutive patients treated for thymoma during the period between 1966 and 1997. Recurrence-free interval rates and overall survival rates calculated by the Kaplan-Meier method were compared using log-rank test by the Masaoka stage, extent of surgical resection, histology, or associated disease(s). Multivariate analysis was performed using Cox's proportional hazards model. RESULTS: Thirty-two thymomas were at Masaoka stage I, 9 at stage II, 15 at stage III, and 16 were at stage IV. There were 56 complete resections, 7 incomplete resections (2 at stage III and 5 at stage IV), and 9 biopsies (1 at stage III and 8 at stage IV). Forty-one thymomas were cortical, 16 medullary, and 15 were mixed form. Association of myasthenia gravis was found in 20 patients, and pure red cell aplasia in 7. After an average follow-up period of 103 months, the recurrence-free 5-, 10-, 15-year interval rate was 89%, 80%, 80%, respectively, and overall 5-, 10-, 15-year survival rate was 86%, 71%, 59%, respectively. Factors influencing the recurrence-free interval and overall survival included the Masaoka stage, extent of surgical resection, and association with pure red cell aplasia. Multivariate analysis revealed stage IV tumor and association with pure red cell aplasia as risk factors for recurrence. Pure red cell aplasia indicated poor prognosis for overall survival. CONCLUSIONS: Masaoka stage, extent of surgical resection, and association with pure red cell aplasia were prognostic factors for thymoma. Multidisciplinary treatment for stage IV tumors and better control of pure red cell aplasia, if associated, should be investigated.

The molt-inhibiting hormone in the American crayfish Procambarus clarkii: its chemical synthesis and biological activity.

The molt-inhibiting hormone of the American crayfish Procambarus clarkii (Prc-MIH), a 75-residue polypeptide containing three disulfide bridges, was synthesized by chemical ligation of two peptides, i.e., synthetic Prc-MIH(1-39) and Prc-MIH(40-75)-NH(2), and by subsequent folding to form the native disulfide-containing peptide molecule. The synthetic peptide was comparable to the natural Prc-MIH in inhibiting ecdysteroid secretion by in vitro bioassay and shared features with the natural Prc-MIH in some biochemical analyses. These results indicate that the chemical ligation method can be used for the synthesis of Prc-MIH. Furthermore, it was demonstrated that synthetic Prc-MIH has hyperglycemic activity, although the activity was weaker than that of the authentic crustacean hyperglycemic hormone in the American crayfish. To examine the structural requirement of the Prc-MIH for eliciting biological activity, an antibody raised against the C-terminal region (residues 55-75) and two synthetic peptides, i.e., a core region (residues 1-54) containing three disulfide bridges and the C-terminal region, were utilized. It is suggested that Prc-MIH exerts its activities through coordination between the core region and the C-terminal region.

Long-term local hyperthermia in the treatment of advanced breast cancer (case report).

BACKGROUND: It is difficult to control non-resectable locally advanced primary and recurrent breast cancer by conventional modalities. Recently, hyperthermia (HT) has been recognized as an effective adjuvant to radiotherapy (RT) and chemotherapy (CT) in treatment of various malignancies, including breast cancer. PATIENT AND METHODS: The patient was a 58-year-old female Japanese, with breast cancer, T4N2M0, stage IIIb (papillo-tubular carcinoma). Previous treatment included RT and neoadjuvant CT Local HT was performed with a total number of 87 sessions given over 12 months. The mean time of each session was 40 minutes. Elevation of temperature to a tumoricidal level of 43 degrees C was confirmed. The patient received cyclophosphamide (50 mg p.o./day) and tamoxifen (20 mg p.o./day) during the whole period of HT. Due to the decreased amount of WBC, further CT was not possible, except for one course of CMF performed 3 months after the start of HT. RESULTS: The patient had a decrease in the intensity of pain even after the first 3 sessions. In one month, movement in the right shoulder became possible in an anterio-posterior direction. By 5 months, the healing of ulceration became evident. At present, the patient is in continuous CR for 15 months after HT. The movement in the shoulder joint is markedly improved in all directions. In addition, HT did not cause any notable complications. CONCLUSION: Long-term HT may be useful in the management of locally advanced breast cancer and these results should encourage further clinical study.

Revascularization Using an Extracorporeal Pump for the Treatment of Cerebral Embolism in the Acute Stage. For Protection of the Brain Tissue from Irreversible Change due to Cerebral Embolism.

SUMMARY: Object. For patients with cerebral embolism, we are using an extracorporeal pump to rev ascularize the more peripheral brain tissues far from the thrombus, proceeding the microcatheter beyond the thrombus, and dissolving the thrombus during a satisfactory time as required. Methods. As the critical cerebral blood flow is thought to be below 30 mlllOOglmin, in the case of middle cerebral artery occlusion at the Ml portion, over 15mllmin. of arterial blood is necessary to protect the brain tissue from irreversible change. One thousand and eight hundred mmHg (about 2 atoms) of pump pressure is necessary to send l5mllmin. of blood through the microcatheter (110 cm, FastTrucker 18, Boston). It was confirmed by laboratory and clinical data that hemolysis of the pump action is not sufficient to aggravate kidney function. Conclusion. This method enables the protection of brain tissues from irreversible change after cerebral embolism, and extends the time sufficiently for thrombolysis.