Tuberculosis of the esophagus.

We report a case of a patient with esophageal tuberculosis, a very uncommon form of extrapulrhonar tuberculosis. Initially, because of constitutional symptomatology and radiological findings of mediastinal lymph node enlargement, lymphoma was considered. However, the endoscopic findings of ulcerative masses and a sinus tract revealed by esophagram were suspicious of tuberculous origin. Diagnosis was achieved after bacterial examination of smear samples from esophageal ulcers that revealed bacillus tuberculous and histological demonstration of caseating granulomas in cervical lymph nodes. Tuberculous mediastinal lymphadenitis was thought to be source of the spread to esophagus.The patient was successfully treated with a three antituberculous drugs regimen. In spite of its rarity, even in patients without risk factors, the diagnosis would be considered in the differential diagnosis of uncertain esophageal lesions.

Multicentred surgical site infection surveillance using partitioning analysis.

BACKGROUND: Surgical site infection (SSI) is an ongoing major public health problem throughout the world that increases healthcare costs. Utilizing a methodology that can help clinicians to continuously collect data about SSIs, analyse it and implement the feedback into routine hospital practice has been identified as a top national priority in Japan. AIM: To conduct an intervention study through 'operations research' using partitioning at multiple facilities, and to reduce the incidence and consequences of SSI. METHODS: The Setouchi SSI Surveillance Group, which consists of seven institutes, started SSI surveillance in 2006. Until May of 2008, there were four surveillance periods (A-D). In all, 3089 patients underwent gastrointestinal surgery and were followed up for 30 days after their operations. Twenty-six factors that have been reported to be related to SSI were evaluated for all patients. The top three factors from each surveillance period were determined and then actual practice improvements were planned for each subsequent period. FINDINGS: The total SSI occurrence was 6.9% for period A, 6.3% for period B, 6.4% for period C and 3.9% for period D. Comparing periods A and D, there was a statistical significance in the decrease of SSI occurrence (P = 0.012). CONCLUSION: Using the results and partitioning analysis of active SSI surveillance to contribute to action plans for improving clinical practice was effective in significantly reducing SSIs.

Oesophageal squamous cell carcinoma may develop within a background of accumulating DNA methylation in normal and dysplastic mucosa.

BACKGROUND: Oesophageal squamous cell carcinoma (OSCC) often arises from preceding dysplastic lesions in the oesophageal epithelium. However, the molecular changes occurring in premalignant lesions are not well understood. An epigenetic change is an example of OSCC that may occur within the epithelium. AIM: To investigate the methylation status of multiple promoters in cancer-derived DNA, as well as in the background epithelium of OSCC, including dysplastic lesions and non-neoplastic mucosa. The normal epithelium from patients without cancer was also examined. The findings were correlated with the mutational status of p53. PATIENTS AND METHODS: 56 patients with advanced OSCC, 21 patients with intraepithelial neoplasia (IEN), 56 patients with a background of non-neoplastic epithelium, adjacent to the OSCC, and 42 normal control epithelia from healthy volunteers were studied. The promoter methylation status of SFRP1, SFRP2, DCC, APC, p16(INK4a), p14(ARF), MINT1, MINT2, MINT31, CACNA1G, COX2, DAPK, hMLH1 and MGMT was examined by methylation-specific single polymerase chain reaction or combined bisulphite restriction analysis. The mutation of p53 by direct sequencing was assessed. RESULTS: DNA methylation was observed in OSCC and in its background epithelium. The frequency of CpG island methylation increased from a baseline level in the background non-neoplastic epithelium, through IEN, to advanced OSCC. However, mutations in p53 were almost exclusively observed in IEN and OSCC. More extensive DNA methylation was seen in the neoplastic lesions (OSCC or IEN) having a p53 mutation than in those with wild-type p53. CONCLUSION: DNA methylation is present at low levels in the non-neoplastic oesophageal epithelium and appears to contribute to the progression of the dysplasia-carcinoma sequence in OSCC carcinogenesis.

Intra-aortic stent graft in oesophageal carcinoma invading the aorta. Prophylaxis for fatal haemorrhage.

In patients with advanced oesophageal carcinoma with aortic invasion, any therapy potentially causes fatal haemorrhage. We describe here the successful application of intra-aortic stent graft to prevent haemorrhage before radical oesophagectomy for advanced oesophageal cancer. Four patients with advanced oesophageal cancer complicated by invasion of the aorta. Under general anaesthesia, aortic invasion is evaluated by an intravascular sonography. The stent graft is passed through the right femoral artery into the descending aorta. Subsequently, the stent graft is released to expand in the thoracic aorta during an artificial cardiac arrest. Aortography is performed to check for any stent migration or endoleakage. This procedure was successful in all four patients without any complications. All patients underwent radical oesophagectomy following aortic stent-grafting. One patient survived more than 2 years after stent grafting and operation. This procedure is safe and applicable for the patient with aortic invasion before radiochemotherapy or operation.

Heparanase expression correlates with malignant potential in human colon cancer.

PURPOSE: Heparanase cleaves carbohydrate chains of heparan sulphate proteoglycans and is an important component of the extracellular matrix. This study was designed to determine the relation between heparanase expression and prognosis of patients with colon cancer. METHODS: The study included 54 patients (35 males and 19 females) who underwent colorectal resection for colorectal cancer between January 1992 and December 1994. Expression of heparanase protein and mRNA were determined and correlated with various clinicopathological parameters. In vitro studies were also performed to examine tumor invasion and to test the effects of heparanase inhibition, and in vivo studies were performed to examine tumor metastasis and prognosis. RESULTS: Heparanase expression was detected in the invasion front of the tumor in 37 of 54 (69%) colon cancer samples, whereas 17 of 54 (31%) tumors were negative. Expression of heparanase was significantly more frequent in tumors of higher TNM stage (P=0.0481), higher Dukes stage (P=0.0411), higher vascular infiltration (P=0.0146), and higher lymph vessel infiltration (P=0.0010). Heparanase expression in colon cancers correlated significantly with poor survival (P=0.0361). Heparanase-transfected colon cancer cells exhibited significant invasion compared with control-transfected colon cancer cells (P=0.001), and the peritoneal dissemination model also showed the malignant potential of heparanase-transfected cells, as assayed by number of nodules (P=0.017) and survival (P=0.0062). Inhibition of heparanase significantly reduced the invasive capacity of cancer cells (P=0.003). CONCLUSIONS: Heparanase is a marker for poor prognosis of patients with colon cancer and could be a suitable target for antitumor therapy in colon cancer.

Impedance pharyngography to assess swallowing function.

We evaluated impedance pharyngography (IPG), a new method to assess swallowing function based on changes in the electrical impedance of the neck during swallowing. The electrical impedance of the neck, recorded by the 4-electrode method, changed with the equivalent cross-sectional area of the route of the electric current due to reflex activities of related organs during swallowing. IPG waveforms accurately recorded the swallowing process, therefore. We recommend IPG for assessing swallowing function because we expect IPG to provide the following advantages over conventional diagnostic techniques: it is a quantitative method that allows for the objective assessment of swallowing function; it is a simple procedure that is convenient for the patient and could be used for screening; it is inexpensive and non-invasive, so could be performed repeatedly in situations such as rehabilitation; and it uses highly portable equipment suitable for community use.

Esophageal cancer associated with right aortic arch: report of two cases.

Esophageal carcinoma associated with a right aortic arch is very rare. In such cases, the dissection of right paratracheal lymph nodes is difficult. Herein, we report two cases of thoracic esophageal carcinoma with right aortic arch, for which the left door open method was used to provide a good surgical view. Postoperative chemotherapy and radiotherapy were used for both cases and no evidence of recurrence or metastasis has been noted in the 24-month postoperative period.

Two cases of superficial basaloid squamous carcinoma of the esophagus.

. Basaloid squamous carcinoma of the esophagus is very rare. We report two cases of basaloid squamous carcinoma of the esophagus. Both tumors histologically consisted of solid cell nests with intervening fibromyxoid stroma. In some tumor nests were comprised of pseudoglandular structures containing myxoid matrix, and displayed focal immunoreactivity for laminin. Thoracic esophagectomy with lymph node dissection was followed by intrathoracic esophagogastrostomy in both patients. The patients had uneventful postoperative courses. Regular periodic follow-up showed no evidence of recurrence or metastasis in the 22-month postoperative period.

TNF combined with IFN-alpha accelerates NF-kappaB-mediated apoptosis through enhancement of Fas expression in colon cancer cells.

Immunostaining and EMSA revealed that NF-kappaB was activated strongly by TNF/IFN-alpha compared to TNF alone in a human colon adenocarcinoma cell line, RPMI4788. Although inhibition of activated NF-kappaB, by using an NF-kappaB decoy, reduced cell viability after treatment with TNF only, NF-kappaB decoy resulted in recovery of cell viability after TNF/IFN-alpha treatment. Caspase-3 activity was increased in cells induced by TNF/IFN-alpha, while suppression of caspase-3 activity was observed in cells transfected with NF-kappaB decoy and then treated by TNF/IFN-alpha. On the other hand, Fas expression was strongly enhanced by TNF/IFN-alpha, and inhibition of TNF/IFN-alpha-induced NF-kappaB activation, by using NF-kappaB decoy, decreased Fas expression. Cell viability and caspase-3 activity decreased in cells treated with TNF/IFN-alpha and anti-FasL antibody. Taken together, our findings suggest that activated NF-kappaB induced by the crosstalk between TNF and IFN-alpha is a novel pro-apoptotic signal acting via enhancement of Fas expression.

Apoptosis in normal tissues induced by anti-cancer drugs.

To investigate the damage mediated by anti-cancer drugs in normal cells, we examined the effect of such drugs on apoptosis of normal cells of the small intestinal epithelium and the bone marrow by in situ DNA end-labelling and transmission electron microscopy. Mice received a single dose of 5-fluorouracil (5-FU) or cisplatin, or repeated daily doses of 5-FU for 7 days. In mice treated with a single dose of 5-FU 50 mg/kg or cisplatin 5 mg/kg, the number of apoptotic cells appearing in the small intestine 12 h after injection was relatively small, but increased steadily reaching a peak after 36 h and then decreasing to close to that in the control group by 48 h. In bone marrow cells, results were similar in mice treated with single doses of 5-FU 50 mg/kg but apoptosis increased much less in those treated with cisplatin 5 mg/kg. The proportion of apoptotic cells reached peak values earlier at higher concentrations of 5-FU or cisplatin both in small intestine and in bone marrow. In the mice treated repeatedly with 5-FU 50 mg/kg, the proportion of apoptotic small intestinal epithelial cells reached a succession of peaks at 48-h intervals. Mice treated repeatedly with 5-FU 50 mg/kg also showed a rapid increase in diarrhoea symptoms and a steady decrease in the height of villi. Our results suggest it may be possible to prevent the side-effects of anti-cancer drugs by inhibiting apoptosis in the gastrointestinal tract.

Antisense-mediated suppression of human heparanase gene expression inhibits pleural dissemination of human cancer cells.

Heparan sulfate proteoglycans is a major component of the cell surface and extracellular matrix and functions as a barrier against cationic molecules and macromolecules. Heparanase is an endoglucuronidase capable of specifically degrading heparan sulfate, and its activity is associated with the metastatic potential of tumor cells. To inhibit human heparanase expression in human cancer cells, we constructed an adenoviral vector carrying a full-length human heparanase cDNA in an antisense orientation (Ad-AS/hep). Increased heparanase expression in T.Tn human esophageal cancer cells and A549 human lung cancer cells after infection with an adenovirus vector expressing the human heparanase gene (Ad-S/hep) was specifically inhibited by simultaneous infection with Ad-AS/hep in a dose-dependent manner. A modified Boyden chamber assay demonstrated that infection with Ad-AS/hep significantly inhibited in vitro invasion of A549 cells after Ad-S/hep infection. Moreover, intrathoracic administration of Ad-AS/hep reduced the number and size of heparanase-expressing A549 tumors implanted intrathoracically into BALB/c-nu/nu mice. Our results suggest that heparanase contributes to the invasive phenotype of tumor cells, and that antisense-mediated inhibition of heparanase activity may be efficacious in the prevention of pleural dissemination.

Leiomyosarcoma arising in a remnant esophagus after esophagectomy: a case report.

We report an extremely rare case of leiomyosarcoma arising from a remnant esophagus. A 52-year-old Japanese man was referred to our hospital for treatment of a tumor arising from the remnant esophagus. Four years earlier, he underwent a subtotal esophagectomy for esophageal squamous cell carcinoma (well differentiated squamous cell carcinoma, T1N0M0 Stage I) located in the lower esophagus. After preoperative studies, partial esophagectomy with laryngeal preservation and reconstruction using a free graft from the jejunum were performed. Histopathological and immunohistochemical examination revealed leiomyosarcoma without metastasis. Immunohistochemical examination showed that most tumor cells were positive for smooth muscle actin and vimentin, but were negative for cytokeratin and S100. The deeply biopsied specimens are helpful for preoperative histological diagnosis. Mitotic activity has been considered an important criterion of malignancy. However, some cases with minimal mitosis in the tumor grow rapidly and were associated with poor prognosis. Therefore, we advocate that the clinical behavior is the only true indication of malignancy. We also provide a review of 64 cases of esophageal leiomyosarcoma reported in the Japanese literature with available data between 1969 and 1999, including the present case, and discuss their clinicopathological features. Asynchronous occurrence of leiomyosarcoma and squamous cell carcinoma in the esophagus is most unusual and has never been reported. Patients with infiltrating type leiomyosarcoma measuring more than 5 cm in diameter tend to have a poor prognosis. Chemotherapy did not exhibit any survival benefits. In the present patient, no recurrence has been noted for 23 months after surgery.

Combination of tumor necrosis factor alpha and interferon alpha induces apoptotic cell death through a c-myc-dependent pathway in p53 mutant H226br non-small-cell lung cancer cell line.

We investigated the role of wild-type p53 and c-myc activity in apoptosis induced by a combination of natural human tumor necrosis factor alpha (TNF-alpha) and natural human interferon alpha (IFN-alpha). Studies were performed with two human non-small-cell lung cancer cell lines, H226b, which has wild-type p53, and H226br, which has a mutant p53. The combination of IFN-alpha and TNF-alpha significantly inhibited cell growth and induced apoptotic cell death of both H226b and H226br, compared with IFN-alpha or TNF-alpha alone. Treatment with one or both cytokines did not affect the expression level of p53 in both cell lines. These results suggest that the combination of IFN-alpha/TNF-alpha induces apoptotic cell death through a p53- independent pathway. The c-myc oncogene is known to be involved in apoptosis induced by TNF. Antisense c-myc oligonucleotides have been reported to modulate cell growth or apoptosis in several cell lines. Antisense oligodeoxynucleotides were added to the culture of H226br cells before the addition of IFN-alpha/TNF-alpha. Antisense c-myc inhibited IFN-alpha/TNF-alpha cytotoxicity and apoptotic cell death. In conclusion, this study provides support for the speculation that TNF-alpha/IFN-alpha induce apoptosis through a c-myc-dependent pathway rather than a p53-dependent pathway. (c)2001 Elsevier Science.

Genetic alterations of candidate tumor suppressor ING1 in human esophageal squamous cell cancer.

Overexpression of ING1, a candidate tumor suppressor gene, efficiently blocks cell growth or induces apoptosis in different experimental systems. ING1 maps to chromosome 13q33-34, and because loss of the terminal region of chromosome 13q has been implicated in esophageal squamous cell cancer (ESCC), we examined ESCC for genetic alterations of ING1. Among 31 informative cases of ESCC, 58.9% of the tumors showed allelic loss at chromosome 13q33-34, and we detected four tumor-specific missense nucleotide changes. These alterations were found within the PHD finger domain and nuclear localization motif of the ING1 and may be functionally involved in the development of ESCC. Because immunohistochemical study revealed that all of the ESCC samples showed loss of ING1 protein expression, genetic or epigenetic alterations that abrogate the normal function of ING1 may contribute to esophageal squamous cell carcinogenesis.

A family of multiple endocrine neoplasia type 2A with the RET proto-oncogene mutation in codon 618 (Cys-->Arg).

Multiple endocrine neoplasia type 2 (MEN-2) is a hereditary syndrome characterized by medullary thyroid carcinoma (MTC), pheochromocytoma and hyperplasia or adenoma of the parathyroid gland with hyperparathyroidism. Recent genetic studies have identified the presence of germline missense mutations in the RET proto-oncogene in almost 100% of MEN-2 patients. We report here three generations of one MEN-2 family with rare missense mutation at codon 618 (Cys-->Arg) of the RET proto-oncogene. The first patient was surgically treated at the age of 63 years but died of bone metastasis. His two children (29-year-old daughter and 25-year-old son) were treated surgically for MTC and neck lymph node metastasis. Germline mutations of the RET proto-oncogene of these three MTC patients and two children of the 29-year-old daughter (9-year-old female and 7-year-old male) were examined. Three MTC patients and the 9-year-old female possessed the mutation. The phenotype of the family with this rare point mutation of the RET proto-oncogene is reported.

Advanced gastric cancer with multiple lymph node metastasis successfully treated with etoposide, adriamycin and cisplatin.

Gastric cancer usually shows poor sensitivity to chemotherapy, and the presence of lymph node metastases is associated with extremely poor prognosis, especially when the number of such nodes is more than 10. We report here a case of advanced gastric cancer with histopathologically confirmed metastases in 15 regional lymph nodes, in which the recurrent tumor was sensitive to combination chemotherapy. Distal gastrectomy with lymphadenectomy was performed for the primary tumor. A hard (recurrent) tumor was detected in the upper abdomen 5 months postoperatively. Abdominal CT revealed two tumors measuring 3.5 x 1.8 and 3.3 x 2 cm in diameter at the front of the pancreatic head, which suggested recurrence. Etoposide, adriamycin and cisplatin (EAP) chemotherapy (20 mg/kg adriamycin, 100 mg/kg etoposide and 50 mg/kg cisplatin (CDDP)) was administered every 6 weeks. The tumors regressed and became undetectable on CT after four cycles. At that stage, CDDP was replaced with 400 mg/kg carboplatin, which was administered every 1 or 2 months. The patient had no recurrence 8 years after surgery. For treatment of advanced gastric cancer with multiple lymph node metastases, a wide resection of the tumor should be performed followed by treatment of the residual tumor cells with a suitable combination chemotherapy taking into consideration the characteristics of the tumor and the condition of the host. We present a patient with gastric cancer and histopathologically confirmed metastases in 15 regional lymph nodes, who was successfully treated by surgery followed by EAP adjuvant chemotherapy. The patient remains alive and well at 8 years after surgery.

Basaloid-squamous cell carcinoma of the esophagus: diagnosis based on immunohistochemical analysis.

Basaloid-squamous cell carcinoma of the esophagus (BSCC) is an extremely rare tumor. Histologically, this tumor should be differentiated from adenoid cystic carcinoma (ACC) and small cell undifferentiated carcinoma (SCUC). Biologically, this tumor is very aggressive, with a propensity for distant metastasis. We report a 64-year-old male with esophageal BSCC. The patient complained of dysphagia and was found to have a torous lesion in the esophagus on radiological examination. Upper gastrointestinal fiberscopy showed a localized ulcerative type tumor, which was diagnosed as squamous cell carcinoma (SCC) on biopsy. Surgery resulted in curative resection. A histological examination of the resected tumor showed features of BSCC. Immunohistochemical examination demonstrated AE3/1- and CAM 5.2-positive tumor cells, and laminin-positive cells in the periphery of the nests. These data were useful in differentiating this tumor from ACC and SCUC. Six months after surgery, the patient developed hepatic metastases, which were successfully treated by regional chemotherapy via the hepatic artery by using fluorouracil. The patient is currently being followed up at the outpatient clinic and shows no signs of any recurrence.

Retroperitoneal liposarcoma presenting a indirect inguinal hernia.

A 60-year-old man was admitted to our hospital with a right inguinal swelling that had been growing in size without any pain for 7 months. We diagnosed the growth as a right inguinal hernia and operated on him. The growth, however, was found to be a tumor it situated along the spermatic cord and testicular vessels. We diagnosed it as a lipoma. The tumor was resected near part of the internal inguinal ring. Histopathological diagnosis showed well-differentiated liposarcoma of the sclerosing type. Postoperative computed tomography (CT) revealed a large residual tumor in the retroperitoneum. We believed that the tumor was a retroperitoneal liposarcoma and that it developed in the inguinal region. The residue of the liposarcoma was resected onto the right inguinal tract. A periodic follow up has been performed and no evidence of recurrence or metastasis has been seen in the 4 years and 9 months since the second surgery. No adjuvant therapy was performed. Inguinal liposarcomas are relatively rare and in most cases these tumors are thought to originate in the spermatic cord. The origin of the tumor is believed to be the retroperitoneum.

Vacuolar hepatocyte degeneration induced by infusion of 20% glucose solution with insulin after hepatopancreatectomy in rats.

To investigate the causes of hepatic dysfunction after extensive resection of the liver together with pancreatectomy, rats were subjected to sham operation, to 68% hepatectomy alone, to 90% pancreatectomy alone, or to 68% hepatectomy combined with 90% pancreatectomy (hepatopancreatectomy). Solutions of 5% or 20% glucose were infused post-operatively for 48 h at a constant rate (250 ml/kg body weight/day) under fasting conditions. To improve the survival rates of pancreatectomized and hepatopancreatectomized rats given 20% glucose, it was necessary to use insulin. In hepatopancreatectomized rats, infusion of 20% glucose with insulin (1 U/5 g glucose) induced prominent hepatocyte vacuolar degeneration and mitochondrial swelling, associated with reduced hepatic protein content. The severity of histological changes was proportional to the insulin dose and the activity of hepatic glucokinase, a key glycolytic enzyme. were observed in These histological changes pancreatectomized rats albeit in a milder form, but not in sham-operated or hepatectomized rats given 20% glucose nor in any rats given 5% glucose. Our results suggest that hepatopancreatectomy followed post-operatively by a high glucose load and exogenously administered insulin enhances the development of hepatocyte swelling.