The fungal metabolite (+)-terrein abrogates osteoclast differentiation via suppression of the RANKL signaling pathway through NFATc1.

Pathophysiological bone resorption is commonly associated with periodontal disease and involves the excessive resorption of bone matrix by activated osteoclasts. Receptor activator of nuclear factor (NF)-κB ligand (RANKL) signaling pathways have been proposed as targets for inhibiting osteoclast differentiation and bone resorption. The fungal secondary metabolite (+)-terrein is a natural compound derived from Aspergillus terreus that has previously shown anti-interleukin-6 properties related to inflammatory bone resorption. However, its effects and molecular mechanism of action on osteoclastogenesis and bone resorption remain unclear. In the present study, we showed that 10 µM synthetic (+)-terrein inhibited RANKL-induced osteoclast formation and bone resorption in a dose-dependent manner and without cytotoxicity. RANKL-induced messenger RNA expression of osteoclast-specific markers including nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), the master regulator of osteoclastogenesis, cathepsin K, tartrate-resistant acid phosphatase (Trap) was completely inhibited by synthetic (+)-terrein treatment. Furthermore, synthetic (+)-terrein decreased RANKL-induced NFATc1 protein expression. This study revealed that synthetic (+)-terrein attenuated osteoclast formation and bone resorption by mediating RANKL signaling pathways, especially NFATc1, and indicated the potential effect of (+)-terrein on inflammatory bone resorption including periodontal disease.

Dynamics of Salivary Gland AQP5 under Normal and Pathologic Conditions.

AQP5 plays an important role in the salivary gland function. The mRNA and protein for aquaporin 5 (AQP5) are expressed in the acini from embryonic days E13-16 and E17-18, respectively and for entire postnatal days. Ligation-reopening of main excretory duct induces changes in the AQP5 level which would give an insight for mechanism of regeneration/self-duplication of acinar cells. The AQP5 level in the submandibular gland (SMG) decreases by chorda tympani denervation (CTD) via activation autophagosome, suggesting that its level in the SMG under normal condition is maintained by parasympathetic nerve. Isoproterenol (IPR), a ß-adrenergic agonist, raised the levels of membrane AQP5 protein and its mRNA in the parotid gland (PG), suggesting coupling of the AQP5 dynamic and amylase secretion-restoration cycle. In the PG, lipopolysaccharide (LPS) is shown to activate mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signalings and potentially downregulate AQP5 expression via cross coupling of activator protein-1 (AP-1) and NF-κB. In most species, Ser-156 and Thr-259 of AQP5 are experimentally phosphorylated, which is enhanced by cAMP analogues and forskolin. cAMP-dependent phosphorylation of AQP5 does not seem to be markedly involved in regulation of its intracellular trafficking but seems to play a role in its constitutive expression and lateral diffusion in the cell membrane. Additionally, Ser-156 phosphorylation may be important for cancer development.

Antimony, a novel nerve poison, triggers neuronal autophagic death via reactive oxygen species-mediated inhibition of the protein kinase B/mammalian target of rapamycin pathway.

Antimony (Sb), a naturally occurring metal present in air and drinking water, has been found in the human brain, and there is evidence of its toxic effects on neurobehavioral perturbations, suggesting that Sb is a potential nerve poison. Here, we provide the first study on the molecular mechanism underlying Sb-associated neurotoxicity. Mice exposed to antimony potassium tartrate hydrate showed significantly increased neuronal apoptosis. In vitro, Sb triggered apoptosis in PC12 cells in a dose-dependent manner. Mechanically, Sb triggered autophagy as indicated by increased expression of microtubule-associated protein 1 light chain 3-II (LC3-II) and accumulation of green fluorescent protein-tagged LC3 dots. Moreover, Sb enhanced autophagic flux and sequestosome 1 (p62) degradation. Subsequent analyses showed that Sb treatment decreased phosphorylation of protein kinase B (Akt) as well as the mammalian target of rapamycin (mTOR), while an Akt activator protected PC12 cells from autophagy. Moreover, the antioxidant N-acetylcysteine attenuated Sb-induced Akt/mTOR inhibition and decreased autophagy and apoptosis, with autophagy inhibition also playing a cytoprotective role. In vivo, mice treated with Sb showed higher expression of LC3-II and p62 in the brain, consistent with the in vitro results. In summary, Sb induced autophagic cell death through reactive oxygen species-mediated inhibition of the Akt/mTOR pathway.

Successful third renal transplantation in a child with an occluded inferior vena cava: A novel technique to use the venous interposition between the transplant renal vein and the infrahepatic inferior vena cava.

A girl aged 11 years and 3 months with occlusion of the inferior vena cava had experienced two renal transplant graft failures since birth. The third renal transplant from a live donor was carried out. Preoperative evaluation showed that the arteries from the right common to the right external iliac artery were absent, and the ilio-caval vein was occluded below the level of the renal vein. The donor's renal artery was anastomosed to the aorta. The donor's ovarian and large saphenous veins were used to extend the transplant renal vein to the recipient's patent inferior vena cava. The present report concludes that the extension of a short donor renal vein using other donor veins is a viable therapeutic option for pediatric patients with vascular occlusions.

Past-behavioural versus situational questions in a postgraduate admissions multiple mini-interview: a reliability and acceptability comparison.

BACKGROUND: The Multiple Mini-Interview (MMI) mostly uses 'Situational' Questions (SQs) as an interview format within a station, rather than 'Past-Behavioural' Questions (PBQs), which are most frequently adopted in traditional single-station personal interviews (SSPIs) for non-medical and medical selection. This study investigated reliability and acceptability of the postgraduate admissions MMI with PBQ and SQ interview formats within MMI stations. METHODS: Twenty-six Japanese medical graduates, first completed the two-year national obligatory initial postgraduate clinical training programme and then applied to three specialty training programmes - internal medicine, general surgery, and emergency medicine - in a Japanese teaching hospital, where they underwent the Accreditation Council for Graduate Medical Education (ACGME)-competency-based MMI. This MMI contained five stations, with two examiners per station. In each station, a PBQ, and then an SQ were asked consecutively. PBQ and SQ interview formats were not separated into two different stations, or the order of questioning of PBQs and SQs in individual stations was not changed due to lack of space and experienced examiners. Reliability was analysed for the scores of these two MMI question types. Candidates and examiners were surveyed on this experience. RESULTS: The PBQ and SQ formats had generalisability coefficients of 0.822 and 0.821, respectively. With one examiner per station, seven stations could produce a reliability of more than 0.80 in both PBQ and SQ formats. More than 60% of both candidates and examiners felt positive about the overall candidates' ability. All participants liked the fairness of this MMI when compared with the previously experienced SSPI. SQs were perceived more favourable by candidates; in contrast, PBQs were perceived more relevant by examiners. CONCLUSIONS: Both PBQs and SQs are equally reliable and acceptable as station interview formats in the postgraduate admissions MMI. However, the use of the two formats within the same station, and with a fixed order, is not the best to maximise its utility as an admission test. Future studies are required to evaluate how best the SQs and PBQs should be combined as station interview formats to enhance reliability, feasibility, acceptability and predictive validity of the MMI.

Successful treatment with mycophenolate mofetil and tacrolimus in juvenile severe lupus nephritis.

Lupus nephritis (LN) of juvenile onset often has severe disease presentation. Despite aggressive induction therapy, up to 20% of patients with LN are resistant to initial therapy and up to 44% suffer a renal relapse. However, there is no consensus on an appropriate therapeutic regimen for refractory LN. We report a 13-year-old girl with recurrent LN who was not taking her medications. At age of 11 years, she was diagnosed with LN classified as International Society of Nephrology/Renal Pathology Society (ISN/RPS) class IV G (A) + V. She was treated with prednisolone and MMF after nine methylprednisolone pulses. Nineteen months later, she was admitted to the hospital with generalized edema. Her symptoms were nephrotic syndrome and acute renal dysfunction. She received three methylprednisolone pulses for 3 days, followed by oral prednisolone and MMF. Twenty-seven days after the three methylprednisolone pulses, her acute renal dysfunction was improved, but the nephrotic syndrome was not improved. A second biopsy showed diffuse lupus nephritis classified as the predominant finding of ISN/RPS class V. We added tacrolimus to the MMF. Four months after adding tacrolimus, the nephrotic syndrome improved. We conclude that adding tacrolimus to the treatment regimen for LN resistant to MMF is effective.

[Mycophenolate mofetil in induction and maintenance therapy for juvenile onset severe lupus nephritis].

OBJECTIVE: The aim of the present study was to evaluate the efficacy of mycophenolate mofetil (MMF) in the induction and maintenance therapy for juvenile onset severe lupus nephritis. METHODS: Children with severe focal, and diffuse proliferative lupus nephritis were treated with prednisolone (initial dose; 1 mg/kg/day, maximum dose; 60 mg/day) and MMF (initial dose; 300 mg/m2/day, increased to 1 g/m2/day) for 24 months after high-dose intravenous methylprednisolone (30 mg/kg/day). Urinalysis was performed, and renal function, and albumin were evaluated. Serum anti-double-stranded DNA antibody, and also serum C3 and C4 were measured. The duration of induction therapy was defined as the initial 6 months after treatment. The duration of maintenance therapy was defined as 18 months after induction therapy. RESULTS: Twelve children (mean age 12.6 +/- 1.7 years)were treated with induction therapy. With 6 months of induction therapy, urine protein, and serum anti-double-stranded DNA antibody, decreased significantly (p < 0.05), renal function improved, and albumin, serum C3 and C4 increased significantly (p < 0.05). Ten children received maintenance therapy. No patients had renal flares during maintenance therapy. The mean prednisolone dose was tapered to 9.2 +/- 2.3 mg/day. Among 5 patients who had a second biopsy after MMF therapy, 4 showed a significant reduction and one had no change in histology. Major infection episodes occurred in 5 patients: Herpes zoster in 3 patients, bacteremia in 2, and hair loss in 3, respectively. No patients discontinued MMF therapy. CONCLUSIONS: MMF is an effective induction and maintenance therapy for juvenile onset severe lupus nephritis.

The relationship between clinicopathological factors and the reduction of pyrimidine nucleoside phosphorylase activity after preoperative administration of 5'-deoxy-5-fluorouridine.

AIM: The response to fluoropyrimidine chemotherapeutic drugs is different in individual tumors. Predictive biomarkers of antitumor effects by these drugs are unknown. 5'-Deoxy-5-fluorouridine (5'-DFUR), a fluoro-pyrimidine chemotherapeutic drug, is converted to 5-fluorouracil (5-FU) by pyrimidine nucleoside phosphorylase (PyNPase). It is suggested that 5'-DFUR will efficiently exert antitumor effects via PyNPase in tumor tissues. The change of PyNPase activity in tumor tissues following 5'-DFUR administration may reflect antitumor effects, and may be useful for detecting predictive factors of antitumor effects. The aim of this study was to search for predictive factors of antitumor effects by analyzing the relationship between clinicopathological factors and the change of PyNPase activity in colorectal tumor tissues after preoperative 5'-DFUR administration. PATIENTS AND METHODS: PyNPase activity in colorectal tissues from 45 patients with colorectal tumors was measured using an ELISA method. RESULTS: The reduction rate of PyNPase activity in colorectal tumor tissues after preoperative 5'-DFUR administration was correlated with significant differences in lymphatic invasion, stage, and histologic classification. It is suggested that lymphatic invasion, stage (distant metastasis), and histologic classification may be predictive factors for evaluating antitumor effects and selecting 5-FU-based chemotherapeutic drugs for patients with colorectal tumors.

Body mass index influences long-term outcome in patients with colorectal cancer.

BACKGROUND/AIMS: The influence of high Body Mass Index (BMI) on long-term outcome is scarcely known in patients with colorectal carcinoma. METHODOLOGY: In the present study was analysed 356 consecutive patients with colorectal carcinoma, in order to address the impact of BMI on patients' characteristics, surgical procedures, and clinical outcomes following radical resection. Patients were divided into the following 3 categories according to BMI; high BMI group (BMI > or = 24.0 kg/m2), middle BMI group (21.0 < or = BMI < 24.0 kg/ m2), and low BMI group (BMI < 21.0 kg/m2). RESULTS: Low BMI was significantly correlated with advanced tumor stage compared with middle BMI group (p < 0.05). The mean number of lymph node dissected per patients of the high BMI group was significantly lower than the middle BMI group (p < 0.05). The 5-year disease-free survival rates of both high and low BMI groups were significantly lower than middle BMI group, respectively. Low and high BMI also became worse independent prognostic factors by multivariate analysis, respectively (p < 0.01; low vs. middle, p < 0.05; high vs. middle). CONCLUSIONS: Both high and low BMI became independent prognostic factors of disease recurrence in patients with colorectal carcinoma, as low BMI was correlated with tumor progression and high BMI influenced the number of lymph node dissected.

Increased levels of soluble cytokine receptors in the synovial fluid of temporomandibular joint disorders in relation to joint effusion on magnetic resonance images.

PURPOSE: The purpose of this study is to clarify the significance of joint effusion (JE) on T2-weighted magnetic resonance images of the temporomandibular joint (TMJ) in comparison to various soluble cytokine receptors in the synovial fluid of patients with temporomandibular disorders (TMDs). PATIENTS AND METHODS: Magnetic resonance imaging of 55 TMJs of 55 patients with TMD was performed, and synovial fluid samples were obtained on the same day. The grade of JE was evaluated on a scale from 0 to 3, with grade 0 indicating the absence of JE and grades 1 to 3 indicating the presence of JE. Correlations were measured between JE and the concentrations of soluble tumor necrosis factor receptors I and II, interleukin (IL) 6 soluble receptor, IL-1 soluble receptor type II, and IL-1 receptor antagonist and protein in the synovial fluid samples. RESULTS: The mean concentrations of cytokine receptors in the synovial fluid were significantly higher in the 30 joints with JE than in the 25 joints without JE. There were no correlations between the JE grade and the level of any mediators. CONCLUSION: Increased levels of cytokine receptors are likely to influence the expression of JE and may play important roles in the pathogenesis of TMD. These results also suggest that JE may reflect synovial inflammation of the TMJ.

Multicenter safety study of mFOLFOX6 for unresectable advanced/recurrent colorectal cancer in elderly patients.

BACKGROUND: Combination chemotherapy with oxaliplatin plus 5-fluorouracil/leucovorin (FOLFOX) has become a standard regimen for colorectal cancer. An increase of adverse events with combination chemotherapy is predicted in elderly patients, and it remains controversial whether they should receive the same chemotherapy as younger patients. Accordingly, this study of modified FOLFOX6 (mFOLFOX6) therapy was performed to compare its safety between elderly and non-elderly patients. METHODS: We prospectively studies 14 non-elderly patients aged <70 years old and 8 elderly patients aged >or= 70 years with unresectable advanced/recurrent colorectal cancer who received mFOLFOX6 therapy during the period from March 2006 to March 2007. Adverse events and the response to treatment were compared between the elderly and non-elderly groups. RESULTS: The main adverse events were neutropenia and peripheral neuropathy, which occurred in 62.5% (>or= grade 3) and 87.5% (>or= grade 1) of elderly patients. The grade and frequency of adverse events were similar in the elderly and non-elderly groups. In some patients with neutropenia, treatment could be continued without reducing the dose of oxaliplatin by deleting bolus 5-fluorouracil. A correlation was found between the cumulative dose of oxaliplatin and the severity of neuropathy, and there were 2 elderly and 3 younger patients in whom discontinuation of treatment was necessary due to peripheral neuropathy. The median number of treatment cycles was 10.0 and 9.5 in the non-elderly and elderly groups, respectively. The response rate was 60.0% in the non-elderly and 50.0% in the elderly group, while the disease control rate was 100% and 83.3% respectively, showing no age-related difference. CONCLUSION: mFOLFOX6 therapy was well-tolerated and effective in both non-elderly and elderly patients. However, discontinuation of treatment was sometimes necessary due to peripheral neuropathy, which is dose-limiting toxicity of this therapy.

Lymph node classification of esophageal squamous cell carcinoma and adenocarcinoma.

The lymphatic channels of the esophagus run vertically along the axis of the esophagus and some of them drain into the cervical lymph glands upwards and into the abdominal glands downwards, and the pattern of lymph node metastasis of esophageal carcinoma is widespread. In various classifications of pattern of lymphatic spread, four classifications were proposed; location, number, ratio, and size. No definite survival advantage of aggressive lymph node dissection during esophagectomy has been proved compared with less dissection. Stage migration, micrometastasis, and sentinel lymph node concept all make it possible to individualize surgical management of esophageal carcinoma as a part of various multimodal treatments. Early diagnosis, standardization of surgery including routine lymph node dissection, and perioperative management of patients have all led to better survival rates of esophageal carcinoma.

Clinicopathologic features of superficial esophageal cancer: results of consecutive 100 patients.

BACKGROUND: The depth of tumor penetration is a crucial factor in determining the prognosis of patients with esophageal carcinoma. Patients with superficial esophageal carcinoma (SEC) have a far more favorable clinical course compared with those with advanced cancers. The outcome for patients with mucosal cancer is excellent with a 5-year survival rate exceeding 80%. On the other hand, submucosal cancer often metastasizes to regional and/or distant lymph nodes or other organs, and the prognosis of these patients are far from satisfactory. METHODS: Among 334 patients with esophageal cancer who underwent surgery between December 1980 and December 2006, 100 patients (30%) had SEC confined to the epithelium, lamina propria mucosa, or submucosa. Patient and tumor characteristics of those 100 patients were studied. RESULTS: The prevalence of SEC has increased from 13% (8 of 61) in the initial 5-year period (1985-1989) to 44% (41 of 93) in the recent 7-year period (2000-2006). Subjective symptoms were present in 7 (14%) of 51 mucosal cancers and in 13 (27%) of 49 submucosal cancers. The remaining 80 patients (80%) had no subjective symptoms. Ninety-one patients (91%) were diagnosed to have the lesions by endoscopy at the time of screening for gastric problems, and only nine were detected by gastrointestinal series. Four of 51 patients with mucosal cancer had venous or lymph vessel invasion, and among those, only one (2%) had a solitary perigastric lymph node metastasis. In 49 patients with submucosal cancer, 35 (71%) had lymph vessel invasion, 28 (57%) had venous invasion, and 16 (33%) had lymph node metastases. In particular, 15 of 35 patients with positive lymph vessel invasion had lymph node metastasis, whereas only 1 of 14 with negative lymph vessel invasion had lymph node metastasis (P < .05). Among 17 patients with nodal involvement, 4 patients with upper thoracic SEC had upper mediastinum and/or cervical nodal metastases, 11 patients with middle thoracic SEC had widespread upper and lower mediastinal and abdominal metastases, and 2 patients with lower thoracic SEC had lower and abdominal lymph node metastases. Seventy-nine patients were alive without recurrence at last follow-up. Five of 49 patients with submucosal cancer died of recurrent disease, and 4 of these developed regional nodal recurrence around the bilateral laryngeal recurrent nerves. Forty-two patients (42%) developed double cancers during the follow-up period, and 5 died of a second cancer. The 3- and 5-year survival rates of all 100 patients were 85% and 73%, and those disease-specific survival rates were 96% and 93%, respectively. The 3- and 5-year survival rates for patients with mucosal cancer were 89% and 83%, and those for submucosal cancer were 80%, and 64%, respectively. CONCLUSIONS: Esophagectomy with extensive lymphadenectomy should be carried out particularly for upper thoracic submucosal cancer, whereas esophagectomy with moderate lymphadenectomy may be preferred for mucosal cancer. Patients with SEC should be examined for another primary cancer preoperatively and periodically during follow-up.

A resected case of liver metastasis from colon cancer that occurred 13 years after a colectomy.

A 73-year-old man, who underwent a potentially curative resection of cancer of the descending colon 13 years before, was found to have a well-defined hepatic tumor on ultrasonography. A lateral segmentectomy was performed for a solitary hepatic tumor. Histopathological examination of the tumor indicated well differentiated adenocarcinoma compatible with the metastasis from the previous descending colon cancer. There have been no signs of recurrence for 5 years after the hepatic resection. This case suggests that distant metastasis from colorectal could be found several years after operation like in this case, and consequently long-term and strict follow-up is required after curative resection of the primary lesion.

Expression of receptor activator of nuclear factor-kappaB ligand in synovial tissue: comparison with degradation of articular cartilage in temporomandibular joint disorders.

OBJECTIVE: The present study was performed to investigate the correlations between expression of the receptor activator of nuclear factor-kappaB ligand (RANKL) in synovial tissue and the degrees of synovitis, degeneration of articular cartilage, and adhesions in patients with internal derangement (ID) of the temporomandibular joint (TMJ). STUDY DESIGN: Expression of RANKL, detected immunohistochemically, and the severity of arthroscopic features (synovitis, degenerative changes of articular eminence, and adhesion) in 30 patients with ID of the TMJ were assessed and the correlations between them were analyzed statistically. RESULTS: RANKL expression was detected in the cytoplasm of synovial lining cells, endothelial cells, and fibroblast cells. However, there were no correlations between RANKL expression in any cell type and the severity of arthroscopic features. CONCLUSION: These observations indicated that the cellular source of osteoclastic differentiation exists in TMJ with ID and may provide insight into the mechanism of osteoclast differentiation.

Treatments for the activating macrophages that reduces surgical stress and postoperative mortalities from bacterial infections and tumor metastases.

BACKGROUND: Some of the mortalities caused by infectious diseases and/or distant metastases following surgery are thought to be due to immunological suppression. For this reason, techniques that reduce immunological suppression following surgery may reduce mortalities and/or incidences of micrometastases in distant organs. MATERIALS AND METHODS: Mice were anesthetized and their peritoneal cavities were opened for 30 min. Immunological suppression was estimated by the presence of tumor necrosis factor-a (TNF) after injection with OK-432 (dead bacterial bodies). The mice were administered with either Staphylococcus aureus or cancer cells of Meth A fibrosarcoma. Survival times and lung metastastic foci were then observed at 3 weeks. Results were compared for mice with or without treatment by OK432 or TNF prior to surgery. RESULTS: While significant suppression of TNF production was observed after laparotomy, administration of a macrophage-activating agent (TNF or OK-432) 3 h prior to laparotomy prevented immune suppression after the laparotomy. Laparotomy increased mortalities from bacterial infections and promoted the number of lung metastases. By contrast, administration of TNF or OK-432 3 h prior to the laparotomy decreased mortalities and metastases after the laparotomy. CONCLUSION: These results suggest that appropriate activation of macrophages prior to surgery is a method to reduce some of the detrimental effects caused by surgical operations.

Prognostic factors in arthrocentesis of the temporomandibular joint: Comparison of bradykinin, leukotriene B4, prostaglandin E2, and substance P level in synovial fluid between successful and unsuccessful cases.

PURPOSE: To compare levels of bradykinin (BK), leukotriene B4 (LTB4), prostaglandin E2 (PGE2), and substance P (SP) between successful and unsuccessful cases of arthrocentesis of temporomandibular joint disorders (TMDs). PATIENTS AND METHODS: A total of 66 joints in 66 patients with TMDs who underwent arthrocentesis were evaluated in this study. Synovial fluid diluted with saline solution was aspirated from the superior joint compartment before arthrocentesis and their concentrations of BK, LTB4, PGE2, and SP were determined by enzyme-linked immunosorbent assay. The differences in the detection rate and concentration of each mediator between successful cases and unsuccessful cases of arthrocentesis were analyzed statistically. RESULTS: Arthrocentesis was successful for 77% (51/66) of the joints. The mean detection rate of LTB4 was significantly (P < .05) higher in the unsuccessful cases (47%) than in the successful cases (16%). The mean concentration of BK was significantly (P < .0005) higher in the unsuccessful cases (425 pg/mL) than in the successful cases (144 pg/mL). There was also a statistical correlation between the detection of LTB4 and PGE2 (P < .01). CONCLUSIONS: Increased levels of BK and LTB4 in the synovial fluid of patients with TMDs may indicate that arthrocentesis is less likely to be a successful treatment.

Specific expression of substance P in synovial tissues of patients with symptomatic, non-reducing internal derangement of the temporomandibular joint: comparison with clinical findings.

Our aim was to find out the extent of expression of substance P in synovial tissue from the human temporomandibular joints (TMJ) with symptomatic, non-reducing internal derangement, and to investigate the relationship between substance P and clinical findings. Fifty-four joints in 54 patients were examined immunohistochemically. Specimens of synovial tissue from 10 joints in 8 subjects with habitual dislocation of the TMJ with no pain were examined as controls. Cells that stained for substance P were found mainly among the endothelial cells in the blood vessels beneath the lining cells in synovial tissues from 47 of the 54 joints (87%) with internal derangement and from 5 of the 10 control joints. The extent score of cells that stained for substance P in joints with internal derangement was significantly higher than that in controls (p=0.02). The extent score of these cells did not correlate with pain in the joint or the degree of synovitis. These results suggest that substance P may have some roles in both the physiological and pathological conditions in patients with symptomatic internal derangement of the TMJ.

Surgical treatment of superficial esophageal cancer.

OBJECTIVE: The worldwide incidence of superficial esophageal cancer (SEC) is increasing. The aim of this study is to review the systematic surgical outcomes of esophagectomy for SEC. DATA SOURCES: Only manuscripts written in English and written between 1980 and 2003 were selected from MEDLINE. The keywords consisting of superficial esophageal cancer, early esophageal cancer, and early stage or superficial stage or stage I in esophageal cancer were searched. STUDY SELECTION: There were no exclusion criteria for published information relevant to the topics. The most representative articles were selected when there were several articles from the same institution. Case reports were excluded. DATA EXTRACTIONS: Thirty-two manuscripts were finally collected from MEDLINE and eight articles were also added from reference lists of the pertinent literatures. In evaluating the statistical analysis of the complications of the reported literature, collective method was used. DATA SYNTHESIS: The collected information was organized. CONCLUSIONS: The conclusions drawn from those articles showed that the overall prevalence of SEC accounted around 10% and increased to 25% in the 2000s. The overall incidence of lymph node metastasis of SEC was about 25% and its incidences in mucosal and submucosal cancer were 5 and 35%, respectively. The percentage of the cases of squamous cell carcinoma (SCC) vs adenocarcinoma (AC) widely varied depending on the geographic locations reported; most SCC cases were from the Asian countries and most AC cases were from the European countries. Clinical significance of multimodal treatment for SEC has dramatically developed in the recent era and could provide various potential therapeutic options for SEC. These concepts make it possible to individualize surgical management of SEC as part of various multimodal treatments. The operative approaches for SEC varied from minimally invasive thoracoscopic esophagectomy, limited transabdominal distal esophagectomy, conventional transthoracic esophagectomy, transhiatal esophagectomy without thoracotomy, en bloc esophagectomy, and to extended esophagectomy with a complete three-field lymph node dissection. A 5-year overall survival rate of SEC after esophagectomy was good (46 to 83%) to excellent (71 and 100%) for mucosal SEC, but far from satisfactory (33 and 78%) for submucosal SEC. Early diagnosis, development of multimodal treatment, standardization of the surgical procedure including routine lymph node dissection, and improved perioperative management of patients have led to a better survival for patients with SEC.