Prognostic impact of lymph node metastasis in distal cholangiocarcinoma.

BACKGROUND: The aim of the study was to investigate the prognostic impact of lymph node metastasis in cholangiocarcinoma using three different classifications. METHODS: Patients who underwent pancreaticoduodenectomy for distal cholangiocarcinoma in 24 hospitals in Japan between 2001 and 2010 were included. Survival was calculated by means of the Kaplan-Meier method and differences between subgroups were assessed with the log rank test. The Cox proportional hazards model was used to identify independent predictors of survival. χ(2) scores were calculated to determine the cut-off value of the number of involved nodes, lymph node ratio (LNR) and total lymph node count (TLNC) for discriminating survival. RESULTS: Some 370 patients were included. The median (range) TLNC was 19 (3-59). Nodal metastasis occurred in 157 patients (42·4 per cent); the median (range) number of involved nodes and LNR were 2 (1-19) and 0·11 (0·02-0·80) respectively. Four or more involved nodes was associated with a significantly shorter median survival (1·3 versus 2·2 years; P = 0·001), as was a LNR of at least 0·17 (1·4 versus 2·3 years; P = 0·002). Involvement of nodes along the common hepatic artery, present in 21 patients (13·4 per cent), was also associated with a shorter survival (median 1·3 versus 2·1 years; P = 0·046). Multivariable analysis among 157 node-positive patients identified the number of involved nodes as an independent prognostic factor (risk ratio 1·87; P = 0·002). CONCLUSION: The number of involved nodes was a strong predictor of survival in patients with distal cholangiocarcinoma.

[Pulmonary pleomorphic carcinoma; report of 2 cases].

The 1st case was a 74-year-old male diagnosed as femoral neck fracture. Biopsy of the bone revealed metastatic adenocarcinoma. Chest computed tomography (CT) showed a mass lesion located in the right lower lobe. With a diagnosis of primary lung cancer (cT2N1M1), two-staged operation was performed. Pathological diagnosis was pleomorphic carcinoma [pT2N1M1 (OSS), stage IV]. He died 8 months after surgery due to metastasis to the thoracic spine. The 2nd case was a 80-year-old female who complained of lateral chest pain. Chest CT revealed a tumor in the right hilar region, which was diagnosed as adenocarcinoma by transbronchial lung biopsy. Only thoracic drainage was performed since metastases to the brain and the rib were demonstrated. She died 2 months after admission. Autopsy revealed pleomorphic carcinoma of the lung with metastasis to the brain, costa and mediastinal lymph nodes.

Ligand binding specificities of the eight types and subtypes of the mouse prostanoid receptors expressed in Chinese hamster ovary cells.

1. Eight types and subtypes of the mouse prostanoid receptor, the prostaglandin D (DP) receptor, the prostaglandin F (FP) receptor, the prostaglandin I (IP) receptor, the thromboxane A (TP) receptor and the EP1, EP2, EP3 and EP4 subtypes of the prostaglandin E receptor, were stably expressed in Chinese hamster ovary cells. Their ligand binding characteristics were examined with thirty two prostanoids and their analogues by determining the Ki values from the displacement curves of radioligand binding to the respective receptors. 2. The DP, IP and TP receptors showed high ligand binding specificity and only bound their own putative ligands with high affinity such as PGD2, BW245C and BW868C for DP, cicaprost, iloprost and isocabacyclin for IP, and S-145, I-BOP and GR 32191 for TP. 3. The FP receptor bound PGF2 alpha and fluprostenol with Ki values of 3-4 nM. In addition, PGD2, 17-phenyl-PGE2, STA2, I-BOP, PGE2 and M&B-28767 bound to this receptor with Ki values less than 100 nM. 4. The EP1 receptor bound 17-phenyl-PGE2, sulprostone and iloprost in addition to PGE2 and PGE1, with Ki values of 14-36 nM. 16,16-dimethyl-PGE2 and two putative EP1 antagonists, AH6809 and SC-19220, did not show any significant binding to this receptor. M&B-28767, a putative EP3 agonist, and misoprostol, a putative EP2/EP3 agonist, also bound to this receptor with Ki values of 120 nM. 5. The EP2 and EP4 receptors showed similar binding profiles. They bound 16,16-dimethyl PGE2 and 11-deoxy-PGE1 in addition to PGE2 and PGE1. The two receptors were discriminated by butaprost, AH-13205 and AH-6809 that bound to the EP2 receptor but not to the EP4 receptor, and by 1-OH-PGE1 that bound to the EP4 but not to the EP2 receptor. 6. The EP3 receptor showed the broadest binding profile, and bound sulprostone, M&B-28767, GR63799X, 11-deoxy-PGE1, 16,16-dimethyl-PGE2 and 17-phenyl-PGE2, in addition to PGE2 and PGE1, with Ki values of 0.6-3.7 nM. In addition, three IP ligands, iloprost, carbacyclin and isocarbacyclin, and one TP ligand, STA2, bound to this receptor with Ki values comparable to the Ki values of these compounds for the IP and TP receptors, respectively. 7. 8-Epi-PGF2 alpha showed only weak binding to the IP, TP, FP, EP2 and EP3 receptor at 10 microM concentration.

Expression of the prothymosin alpha mRNA correlated with that of N-myc in neuroblastoma.

Neuroblastoma is the most common malignant solid cancers in early childhood. Overexpression of the proto-oncogene, N-myc, has been reported to be correlated with more malignant course of the disease. Prothymosin alpha, a cellular proliferation-associated gene, is reported to be a target of myc and elevated in several malignant cells and tissues. Expression of prothymosin alpha and N-myc messenger RNAs were evaluated by real-time reverse transcription polymerase chain reaction (RT-PCR) assay in 18 tumor samples from neuroblastoma using LightCycler. The data was analyzed in reference to clinicopathological factors. There was a tendency that higher prothymosin alpha transcripts levels in the tumor samples from younger patients (<1year.) when compared to the older group (>1 year.) (P=0.0845). There was no relationship between prothymosin alpha gene expression and gender (P=0.3029), mass screening case or not (P=0.3007), or stage. The prothymosin alpha mRNA expression levels were correlated with N-myc mRNA levels (P=0.006). Thus we suggest that prothymosin alpha plays an active role as a target of N-myc in neuroblastoma.

Serum level of the periostin, a homologue of an insect cell adhesion molecule, in thymoma patients.

Periostin protein shares structural and sequence homology with fasciclin I, which is an insect adhesion molecule. Periostin has a typical signal peptide at the N-terminal end suggesting it is a secreted protein. Recently, we developed a novel sandwich chemiluminescence assay to determine serum concentrations of periostin. We investigated the serum periostin level in thymoma patients, and attempted to determine the correlation between serum periostin level and clinicopathological factors of thymoma patients who had undergone surgery between January 1994 and July 1996. Serum periostin levels were not significantly different between the thymoma patients (1264.4+/-122.9 ng/ml) and the normal control (962.0+/-118.6 ng/ml) (P=0.0877). There was no relationship between serum periostin level and age, gender or pathological subtype. However the serum periostin level of stage IV patients (1497.0+/-285.8 ng/ml) was significantly higher than normal control (P=0.0460). These data suggest that serum periostin level may indicate tumor invasion and progression of thymoma.

Expression of the cdc25B gene as a prognosis marker in non-small cell lung cancer.

There is an evidence to suggest that cdc25B phosphatase is an oncogenic. We hypothesized that cdc25B gene may be expressed in tumors of patients with non-small cell lung cancer (NSCLC) and affect their clinical outcome. Expression of cdc25B messenger RNA was evaluated by reverse transcription polymerase chain reaction in 55 non-small cell lung carcinomas and adjacent histological normal lung samples using LightCycler. The data was analyzed in reference to clinicopathological data and survival data. There was no difference of cdc25B expression level between the NSCLC tissue and normal lung tissue. There was no relationship between cdc25B gene expression and age, gender, N or T-status and clinical stage. However, the NSCLC patients with high cdc25B expression had significantly poor survival than the patients with low cdc25B expression (P=0.0173). Thus we suggest that cdc25B may predict poor survival.

Expression of the MTA1 mRNA in thymoma patients.

The MTA1 gene is a recently identified metastasis-associated gene which has been implicated in the signal transduction or regulation of gene expression. We examined the mRNA expression levels of the MTA1, the human homologue of the rat mta1 gene in thymoma. Expression of MTA1 mRNA was evaluated by reverse transcription polymerase chain reaction (RT-PCR) in 30 thymoma samples using LightCycler. The data was analyzed in reference to clinicopathological data. There was no relationship between MTA1 gene expression and age and gender. MTA1/GAPDH mRNA level in stage IV thymoma (6.431+/-3.404) was significantly higher than the level in stage I thymoma (2.592+/-1.902, P=0.0081). There was a tendency towards higher MTA1/GAPDH mRNA level in stage IV thymoma when compared to stage II thymoma (3.746+/-3.292, P=0.072). Thus our results show that the expression of the MTA1 gene is closely related to invasiveness in thymoma. The gene MTA1 could potentially provide information on the mechanism of tumor invasion and metastasis.

Differential diagnosis of thymic carcinoma and lung carcinoma with the use of antibodies to cytokeratins.

There are few specific pathologic findings that can be relied on to distinguish primary thymic carcinomas from lung carcinomas with mediastinal extension or showing metastasis to the anterior mediastinum. The immunohistochemical reactivity on frozen sections of thymic carcinomas and lung carcinomas, which are histologically similar to each other, was examined with the use of monoclonal antibodies to cytokeratins 7 and 13. Among keratinizing squamous cell carcinomas, all thymic carcinomas reacted with antibody specific for cytokeratin 7 (9/9, 0%), whereas no staining reaction was seen in lung carcinomas (0/5, 0%) (p < 0.01). This finding can be used as a diagnostic aid in primary thymic keratinizing squamous cell carcinomas to expedite treatment and prognosis. Cytokeratin 7 and cytokeratin 13 monoclonal antibodies reacted with almost all cases of thymic carcinoma. Applications of monoclonal antibodies specific for certain cytokeratins, especially 7 and 13, may be helpful in the diagnosis of other subtypes of thymic carcinomas.

Esophageal tracheobronchoplasty for diseases of the central airway.

Three infants with congenital tracheal stenosis and three adults with various diseases of the central airway underwent esophageal tracheobronchoplasty to repair long-segment stenoses and defects. The primary operative goal was enlargement of the stenosis (n = 4), repair of the defect (n = 1), or both (n = 1). Cardiopulmonary support was required in two cases. All three infants were operated on for generalized congenital tracheal stenoses. There was one postoperative death on the fifth day. Another infant died of pneumonia 3 months after operation. Tracheal patency was excellent in two infants. One infant is well without symptoms 6 years after the operation, although balloon dilation was required three times during the first postoperative year. In the three adult patients, the primary diseases were congenital tracheal stenosis, iatrogenic injury associated with relapsing polychondritis, and malignant mediastinal tumor involving the trachea. All lesions involved both the trachea and main stem bronchi. Postoperative airway patency was excellent in all three adults, although expandable metallic stents had to be inserted in one patient. Postoperative pulmonary function was improved, particularly forced expiratory volume in 1 second and peak expiratory flow rate. Although the postoperative mortality rate was still high, especially among the infants, and prolonged postoperative ventilatory support was required for five of the six patients, long-term patency and postoperative pulmonary functional improvement are encouraging.

Surgical therapy for apical invasive lung cancer: different approaches according to tumor location.

Thirty-one patients with apical invasive lung cancer were reviewed. The tumor occupied the anterior portion of the lung apex in four, the middle portion in one, the posterior portion in 17, and the entire apex in nine. Nine patients were treated by irradiation alone. Twenty-two patients underwent en bloc resection of the apical chest wall and the lung. Seventeen patients were operated on by different approaches: anterior and hook, according to the location of the lesion. Nine patients were operated on by the anterior approach and eight by the hook approach. Another five patients were operated on by the conventional postero-lateral approach. Lesions of the sternum and subclavian vessels and ipsilateral supraclavicular lymph nodes were resected by the anterior approach. Lesions of the vertebrae, brachial plexus, subclavian vessels and ipsilateral supraclavicular lymph nodes could be resected by the hook approach. The anterior approach was suited for lesions in the anterior portion or middle portion and the hook approach for lesions in the middle or posterior.

Overexpression of Hrad17 gene in non-small cell lung cancers correlated with lymph node metastasis.

We used palindromic PCR-driven cDNA differential display technique to identify and isolate a gene, human homologue of the Schizosaccharomyces pombe checkpoint gene rad17, from colon cancer tissues. The loss of checkpoint control in mammalian cells results in genomic instability, leading to the amplification, rearrangement, or loss of chromosomes, events associated with tumor progression. We hypothesized that the Hrad17 may be expressed in non-small cell lung cancer (NSCLC). We attempted to determine the influence of Hrad17 expression on clinicopathological features for patients with NSCLC who had undergone surgery. Expression of Hrad17 messenger RNA was evaluated by reverse transcription-polymerase chain reaction (RT-PCR) in 102 non-small cell lung carcinomas and adjacent histologically normal lung samples from patients for whom follow up data were available. Hrad17 transcripts were detected in 26 (25.5%) of the tumor samples, although some of the paired normal lung samples showed weak expression. There was no relationship between Hrad17 gene expression and age, gender or T-status. About 13 of 31 (41.9%) NSCLC patients with Hrad17 overexpressions were node positive, on the other hand, 13 of 76 (18.3%) cases without Hrad17 overexpressions were node positive. Thus the expression of Hrad17 mRNA correlated with lymph node metastasis (P=0.0231) from NSCLC. Hrad17 protein was highly expressed at the advancing margin of the tumor of lung cancer tissue but not within the normal lung tissue by immunohistochemistry. Thus the expression of Hrad17 might correlate with more advanced NSCLC.

Expression of the antiapoptosis gene, AAC-11, as a prognosis marker in non-small cell lung cancer.

Inhibition of programmed cell death (apoptosis) is associated with increased tumor aggressiveness. We hypothesized that a novel apoptosis inhibitor gene, antiapoptosis clone 11 (AAC-11), may be expressed in tumors of patients with non-small cell lung cancer (NSCLC) and affect their clinical outcome. Expression of AAC-11 messenger RNA was evaluated by reverse transcription polymerase chain reaction (RT-PCR) in 94 non-small cell lung carcinomas and adjacent histologically normal lung samples. The data was analyzed in reference to clinicopathological and survival data. AAC-11 transcripts were detected in 12 (12.7%) of the tumor samples, although five of paired normal lung samples showed very weak expression. There was no relationship between AAC-11 gene expression and age, gender, N or T-status. AAC-11 was preferentially expressed in squamous cell carcinoma (26.9% of squamous cell carcinoma vs. 7% of adenocarcinoma). The NSCLC patients with AAC-11 expression had significantly poor survival than the patients without AAC-11 expression (P=0.0360). Although the AAC-11 gene was not expressed in a majority of NSCLC tumors, we suggest that AAC-11 may predict poor survival.

Increased matrix metalloproteinase 9 activity and mRNA expression in lung ischemia-reperfusion injury.

OBJECTIVES: In lung ischemia-reperfusion injury, neutrophil migration from the vasculature to the interstitial spaces plays a major role in tissue injury. Degradation of the basement membrane, which is composed of extracellular matrix (ECM) molecules, is necessary for neutrophil migration. Matrix metalloproteinases (MMPs) might play a role in ECM degradation in lung ischemia-reperfusion injury. We evaluated the changes in the activity of MMP-2 and MMP-9, and tissue inhibitor of metalloproteinase 1 (TIMP-1) gene expressions using rat lung transplantation models. METHODS: We divided animals into 4 groups. Groups I and II served as control groups with intact lungs (Group I) and 24-hour cold-preserved lungs (Group II). Groups III and IV received lung grafts after 24-hour cold preservation. The recipient animals were sacrificed 1 hour (Group III) or 24 hours (Group IV) after transplantation. We evaluated lung injury histologically. We assessed MMP activity using zymography. We assessed MMP-2, MMP-9, and TIMP-1 gene expression using biplex reverse transcriptase-polymerase chain reaction method. RESULTS: In Groups III and IV, we noted severe ischemia-reperfusion injury. We noted no significant difference in enzyme activity and gene expression of MMP-2 between Groups I and IV. The MMP-9 activity and gene expression were low during ischemia and increased on reperfusion. TIMP-1 gene expression was low during ischemia and at the early phase of reperfusion, and showed a dramatic increase at the late phase of reperfusion. CONCLUSIONS: Matrix metalloproteinase 9, but not MMP-2, may play an important role in ischemia-reperfusion injury. TIMP-1 increases at the late phase of reperfusion and may compensate for the activity of MMP-9.

Hepatic resection guided by needles inserted under ultrasonographic guidance.

BACKGROUND: Operative ultrasonography for orienting the direction of transection of the liver is often useful in obtaining an adequate disease-free surgical margin. We have devised a new technique for hepatectomy guided by needles inserted under ultrasonographic guidance. METHODS: One hundred two hepatectomies were performed between January 1987 and September 1991, and the hepatectomy with this technique was begun in January 1989. RESULTS: In 10 of 29 limited hepatectomies performed in the first phase of the period in which this technique was not available, disease-free surgical margin of less than 1 cm was left because of inadequately directed division. Disease-free surgical margin of more than 1 cm was left in 18 of 23 limited hepatectomies in the second phase of the period in which this technique was available. In the other five operations where disease-free surgical margin of less than 1 cm was left, carcinomas were located too close to the major hepatic vessels. The average blood loss during the limited hepatectomies was reduced by this technique. Two-year and 3-year survival of patients undergoing hepatectomy for hepatocellular carcinoma were more favorable in the second phase than in the first phase. CONCLUSIONS: Although the difference between the two groups was not significant, this technique is useful in performing adequate transection of the liver.

Experimental reconstruction of the mediastinal trachea with a wing-shaped reversed esophageal flap.

BACKGROUND: In cases of extensive tracheal resection in which direct end-to-end anastomosis is impossible there is a need for reconstruction. Nevertheless, with the present lack of reliable artificial trachea, no reconstruction method is available to assure safe replacement of the mediastinal trachea. METHODS: After tubular resection of the mediastinal trachea in mongrel dogs, the trachea was reconstructed using a wing-shaped reversed esophageal flap. A silicone tube was used as an internal stent. RESULTS: In group I (16 animals), three tracheal rings were resected; in group II (4 animals), six tracheal rings; in group III (6 animals), eight tracheal rings; and in group IV (5 animals), eight tracheal rings and the lining of the greater omentum. Safe reconstruction was accomplished in all cases in groups I and II, 2 of 6 cases in group III, and 2 of 5 cases in group IV. The omentopexy failed to prevent incomplete closure, yet served to minimize inflammation in the mediastinum. CONCLUSIONS: A reversed esophageal autograft can be considered as a tracheal replacement.

Subclavian artery branch ligation reduces hemorrhage during resection of pulmonary aspergilloma.

Treatment of a 71-year-old woman with recurrent massive hemoptysis secondary to an aspergilloma and pleural aspergillosis is reported. Branches of the subclavian artery were ligated using an anterior approach before performing the thoracotomy, and pleuropneumonectomy was accomplished after ligation of the costal arteries. This technique provided a relatively bloodless field and minimized blood loss.

Chondrosarcoma originating from the trachea.

We report a tracheal chondrosarcoma in a 54-year-old man, treated with neodymium:yttrium-aluminum garnet laser vaporization via fiberoptic bronchoscopy followed by surgical resection. Chondrosarcomas of the trachea are extremely rare tumors. To our knowledge, there are 9 cases of chondrosarcoma of the trachea reported in the English-language literature, to which we add the tenth.

A case of gallbladder cancer associated with a common bile duct neuroma, and a cystic lesion of the liver with histologic findings similar to those of an inflammatory pseudotumor.

We report a rare case of gallbladder cancer associated with a common bile duct neuroma, and a cystic liver lesion with histologic findings similar to an inflammatory pseudotumor, in a patient who had had no previous abdominal surgery. The patient was a 62-year-old man whose major complaint was fever. Ultrasonography and a computed tomography scan revealed gallstones, an elevated lesion in the gallbladder, and a cystic liver lesion. Endoscopic retrograde cholangiopancreatography demonstrated stenosis of the common bile duct. Cultures of the cystic fluid and gallbladder bile were positive for Staphylococcus aureus. The patient underwent hepatectomy (inferior S4, S5, and S6), cholecystectomy, resection of the common bile duct, and right hemicolectomy. The resected specimens revealed gallbladder cancer with the microscopic appearance of a papillary adenocarcinoma, and a 12 x 4.5 x 3.5 cm cystic liver lesion with a wall 7 mm thick. Histologic studies of the wall of the cystic liver lesion revealed infiltration by histiocytes and plasma cells, and the presence of fibrous connective tissue, which findings are characteristic of inflammatory pseudotumors. A 9 x 6 mm elevated lesion, with the microscopic appearance of a neuroma, was resected from the common bile duct.

Gallbladder cancer associated with cholesterosis.

We report herein two cases of carcinoma in situ of the gallbladder associated with cholesterosis. The patient in case 1 was an 81-year-old man who underwent a cholecystectomy for cholelithiasis. The resected specimens revealed gallbladder cancer in the fundus which was diagnosed histologically as mucinous carcinoma. Other findings included 13-mm, 12-mm, and 5-mm polypoid lesions in the neck of the gallbladder which macroscopically appeared to be cholesterol polyps, but histologically demonstrated carcinoma in situ with cholesterosis. The patient in case 2 was a 76-year-old man in whom ultrasonography revealed a highly echogenic, elevated lesion in the gallbladder. Cholecystectomy was performed, and a 33 x 28-mm papillary, elevated lesion with cholesterosis was resected from the neck of the gallbladder. Histologically, this was demonstrated to be papillary adenocarcinoma in situ with cholesterosis surrounded by glandular dysplasia. The distribution of the carcinomas and cholesterosis in both of these patients suggests that the adenoma or carcinoma of the gallbladder had occurred first. Then, the tumor epithelium absorbed cholesterol from the bile, and foamy cells were produced. Thus, when treating cholesterol polyps, it should be remembered that it is often difficult to distinguish between cholesterol polyp and gallbladder cancer with cholesterosis.

Expression of Id2 mRNA in neuroblastoma and normal ganglion.

AIMS: Inhibitors of DNA binding 2 (Id2) has been reported to be overexpressed in neuroblastoma cell lines carrying extra copies of the N-myc gene. It has been suggested that Id2 may be involved in the disturbed regulation of cell cycle by interfering with retinoblastoma protein. METHODS: In this report we assessed Id2 gene expression in 20 neuroblastoma samples and eight normal ganglion tissues using quantitative reverse transcription-PCR (RT-PCR). Id2 expression in resected clinical samples of neuroblastoma needs to be studied. RESULTS: Id2 messenger RNA (mRNA) was expressed in all the neuroblastoma samples. The level of Id2 mRNA expression was not influenced by the patient's age, gender, tumor's clinical stage, DNA ploidy pattern, histological pattern, the level of N-myc mRNA expression and whether the patient was found by mass screening or by symptom. Id2 was also expressed in comparable levels in normal differentiated sympathetic ganglion in adult. CONCLUSION: Our data suggest that Id2's role in the oncogenesis or progression of neuroblastoma is minimal.