晚期糖基化终末产物的临床病理机制及抑制剂的研究进展

在糖尿病患者体内以及衰老进程中晚期糖基化终末产物 (AGEs)是不断积累的 ,其可以通过直接或间接的方式对机体产生病理作用。本文概述了AGEs对各种组织或细胞包括心血管组织、肾脏、大脑和骨组织等的间接病理作用和机制、介导该作用的AGEs受体或其他结合蛋白 。

Clinical Study of Photodynamic Therapy for Upper Gastrointestinal Tract Cancers

Objective： To evaluate the clinical effectiveness and adverse effects of photodynamic therapy （PDT） for the upper gastrointestinal tract cancers. Methods： 56 patients with upper gastrointestinal cancers in different clinical stages were treated with PDT. Diode laser （630 nm） was used as the light source and the parameters were as follows： power density 200 to 400 mW/cm, energy density 100 to 300 J/cm. PHOTOFRIN was used as photosensitizer, which was given in a dose of 2 mg/kg intravenously 12-24 h before irradiation. Results： Evaluation of the 56 patients＇ therapeutic effectiveness showed that 6 patients （10.7%） had a complete response （CR）, 33 patients （58.9%） partial response （PR）, 12 patients （21.4%） mild response （MR）, and 5 patients （8.9%） no response （NR）. The total response rate （CR＋PR） was 69.6%. No patients had severe adverse effects in this group. Conclusion： PDT is an effective and safe palliative modality for upper gastrointestinal tract cancers.

In vitro Study of Interstitial Combination Chemotherapy in the Treatment of Glioma

Objective： To investigate the inhibitory effects of combination chemotherapy of Carboplatin （CBP）, Teniposide （Vm-26）, Methasquin （MTX）, and Nimodipine （NIM） on glioma, and to explore the sensitivity of glioma cells to different treatment regimens so as to provide some clues for clinical usage of interstitial combination chemotherapy. Methods： MTT assay and 3H-TdR incorporation assay were performed to evaluate the inhibitory effects upon the proliferation of glioma cells, and to compare the sen- sitivity of glioma cells to administration of CBP, Vm-26, MTX, and NIM with that of the administration of CBP＋NIM, Vm-26＋NIM, MTX＋NIM, CBP＋Vm-26＋MTX, or CBP＋Vm-26＋MTX＋NIM, respectively. Results： The inhibition rate of CBP＋Vm-26＋MTX＋NIM combination administration against glioma cells was 96.64%, higher than that of CBP＋NIM （69.03%）, Vm-26＋NIM （71.53%）, MTX＋NIM （52.75%）, CBP＋Vm-26＋MTX （78.59%） （P〈0.01）, and the dosage of CBP, Vm-26, and MTX was declined to 1/10- 1/100 that of respective use of CBP, Vm-26, and MTX. Conclusion： The curative effect of combination administration of CBP, Vm-26, MTX, and NIM was much better than that of respective administration, suggesting a higher inhibition rate and a lower dosage use.

Clinical Analysis of 81 Cases of Benign Retroperitoneal Schwannoma

Objective： To analyze the clinical manifestations of retroperitoneal schwannoma in order to improve the diagnosis and treatment of this rare disease. Methods： Between January 1951 and September 2004, 81 patients with retroperitoneal schwannoma were retrospectively analyzed. Results： All cases received operative therapy. Sixty cases （74.1%） received a total resection; 12 cases （14.9%） subtotal resection, and 9 cases （11.1%） exploration. During the surgical operation, a single tumor was found in 77 cases （95.1%）, and multiple tumors in 4 cases （4.9%）. Most of the retroperitoneal schwannomas located beside the spine. The tumor was a fusiform, round or oval mass that was sharply circumscribed and encapsulated. Pathologic results showed all 81 cases were benign schwannoma. In the 4 cases of multiple tumors, 2 （2.5%） were diagnosed as double-primary tumors associated with ascending colon adenocarcinoma and lung squamous-cell cancer. One case recurred postoperatively. Conclusion： Retroperitoneal schwannoma was rare and preoperative diagnosis was difficult. Most of retroperitoneal schwannoma were benign and the surgical treatment was the first choice.

The Establishment and Characterization of a Continuous Cell Line of Mouse Cervical Carcinoma

OBJECTIVE To establish a murine uterine cervical cancer cell line and to define its biological characters. METHODS Transplanted tumor tissue was used for in vitro primary culture of U14 cervical carcinoma cells. After 20 passages, we examined its morphology, chromosomes, tumorigenicity and produced a growth curve. CK was detected by immunohistochemistry, the cell cycle determined by flow cytometry and the metastatic potential assessed in 615 and C57BL/c mice. We also transfected the cells with the pEGFP-N1 plasmid. RESULTS A newly established murine cell line was passaged 50 times over a period of 10 months. The cells grow as a partially suspended culture, and are immunohistochemically CK（＋）. The cell line is characterized by a hypotetraploid karyotype, a chromosomal number of 64-68 and a doubling time of 21.8 h. Exponential growth occurs by the third and forth day of culture. Cell cycle analysis showed G1 34%, G2 26%, and 40% in the S phase. The tumorigenicity was 100% upon implantation. No mycoplasma contamination was detected. A monoclonal continuous U14-GFP cell strain which was 100% GFP （＋） was also produced. CONCLUSION We successfully established a new murine cervical U14 carcinoma cell line and an U14-GFP monoclonal strain. These cell lines are ideal for combined in vivo and in vitro tumor research.

Local Recurrence of Low-Grade Myofibroblastic Sarcoma of the Chest Wall:Report of a Case and Literatures Review

Myofibroblastic sarcoma, composed primarily of myofibroblast, is a rare malignant tumor. Low-grade myofibroblastic sarcoma （LGMS） has been defined properly as a distinct entity in the 2002 WHO classification of soft tissue tumors. Primary sarcoma of the chest wall is also a rare disease. This article describes a case of locally recurrent LGMS of the chest wall.

Microproteinuria in patients with inflammatory bowel disease:Is it associated with the disease activity or the treatment with 5-aminosalicylic acid?

AIM： To investigate whether microproteinuria in patients with inflammatory bowel disease （IBD） is associated with the disease activity or the treatment with 5-aminosalicylic acid （5-ASA）. METHODS： We prospectively studied microproteinuria in 86 consecutive patients with IBD, 61 with ulcerative colitis （UC） and 25 with Crohn＇s disease （CD）, before as well as 2 and 6 months after their inclusion in the study. Forty-six patients received 5-ASA for a period of 28.8 months （range 1-168 too）. Microalbuminuria （mALB） and urine levels of the renal tubular proteins β2-microglobulin （β2mGLB） and β-N-acetyI-D-glucosamidase （β-NAG） as well as the creatinine clearance were determined in a 12-h overnight urine collection. Tumor necrosis factor-α （TNF-α） serum levels were also measured. RESULTS： A total of 277 measurements （194 in UC patients and 83 in CD patients） were performed. The prevalence of abnormal microoproteinuria in UC and CD patients was 12.9% and 6.0% for mALB, 22.7% and 27.7% for B2mGLB, and 11.3% and 8.4% for β-NAG, respectively, mALB was not associated with IBD activity. β2mGLB and B-NAG urine levels were correlated to UC activity （UCAI： P〈0.01; UCEI： P〈0.005）. mALB in UC patients and β-NAG urine levels in CD patients were related to TNF-α serum levels. An association was noticed between microproteinuria and smoking habit. Treatment with 5-ASA was not correlated to the severity of microproteinuria or to the changes of creatinine clearance.CONCLUSION： Microproteinuria is mainly associated with UC and its activity but not affected by 5-ASA.

Gastro-esophageal reflux disease symptoms are more common in general practice in Japan

To accurately assess the prevalence of GERD symptoms in general practice. METHODS： 4139 consecutive patients （2025 men and 2114 women with a mean age of 43 years）, who first attended the Outpatient Department of General Medicine and Emergency Care at Toho University Omori Hospital, were asked to respond to the F-scale questionnaire regardless of their chief complaints. The questionnaire is a self-report instrument, written in a simple and easy-to- understand language, containing 12 questions. RESULTS： Of 4139 subjects, 1554 patients （37.6%） were identified as GERD according to their F-scale score （〉 7）. However, there were only 45 consultations （1.1%） for typical GERD symptoms. Although GERD symptoms are common in adults of all ages, the prevalence of GERD was highest in the 20-29 years age group and the age group 70-79 years had the lowest prevalence for both males and females. CONCLUSION： Although there was a high rote indicating GERD in our primary care population, only 1.1% of outpatients attended our hospital with a chief complaint of GERD symptoms. Since about one-third of GERD patients are affected by atypical symptoms, general physicians need to be cautious about extrapolating these results to patients with a chief complaint other than typical GERD symptoms.Watanabe T, Urita Y, Sugimoto M, Miki K. Gastro-esophagea reflux disease symptoms are more common in genera practice in Japan. World J Gastroenterol 2007; 13（31） 4219-4223

Augmenter of liver regeneration promotes hepatocyte proliferation induced by Kupffer cells

AIM： To observe the effects of augmenter of liver regeneration （ALR） on Kupffer cells and to determine whether ALR promotes hepatocyte proliferation induced by Kupffer cells. METHODS： Kupffer cells and hepatocytes were cultured in vitro and various concentrations of recombinant rat ALR （rrALR） were added. ^3H-thymidine, BrdU and ^3H-leucine incorporation was determined in cultured Kupffer cells and hepatocytes, in hepatocytes conditioned by Kupffer cells, and in associated medium, rrALR was labeled by iodination and used to determine its binding activity by Scatchard analysis in Kupffer cells and primarily cultured rat hepatocytes. RESULTS： rrALR stimulated DNA replication in Kupffer cells and protein synthesis both in cells and in medium in a non-concentration-dependent manner. The effect was significant at the concentration of 1μg/L ALR. However, rrALR had no effect on primarily cultured hepatocytes, when hepatocytes were cultured with the Kupffer cell medium conditioned by ALR, DNA replication and protein synthesis in hepatocytes increased significantly at the concentration of 1μg/L ALR. When the ALR concentration was increased, its effect on hepatocyte proliferation decreased to the basal level. Scatchard analysis indicated the presence of a single class of high affinity receptors with a dissociation constant （Kd） of 0.883 nmol/L and a maximum binding capacity （Bmax） of 126.1 pmol/g protein in the rat Kupffer cells. CONCLUSION： ALR can promote hepatocyte proliferation induced by Kupffer cells, which is associated with the concentration of ALR, suggesting that Kupffer cells play a dual role in liver regeneration.

Different profile of cytokine synthesis according to the severity of acute pancreatitis

AIM: To evaluate the cellular synthetic ability of cytokines involved in pro- and anti-inflammatory reactions in patients with AP.METHODS: Sixty-seven patients with AP (16 severe,51 mild) and 10 controls were included in the study.Cultures of whole blood were performed in samples obtained within the first 72 h from the onset of pain.Serum levels of interleukins (IL) 6, 8, 10, and TNF-α were measured at baseline and in the supernatant of cultures with (functional reserve) or without stimulation with phytohemaglutinin.RESULTS: Basal levels of cytokines were significantly higher in patients with severe AP. A significant increase of all pro-inflammatory cytokines vs basal levels was observed in the supernatant after 24 h of whole blood cultures in patients, but not in controls. In contrast, IL-10 increased significantly in the supernatant of cultures only in patients with mild AP. Cells showed a statistically significant functional reserve for all IL in patients with mild, but only for pro-inflammatory cytokines in patients with severe AP.CONCLUSION: A marked activation of immune system may be observed in patients with AP, being balanced between pro- and anti-inflammatory cytokines in patients with mild but not severe AP. A reduced functional reserve for the synthesis of IL-10 may be observed in patients with severe AP, which might lead to a worst prognosis.

Normal aspects of colorectal motility and abnormalities in slow transit constipation

Human colonic motility is a relatively difficult topic to investigate. However, the refinement of manometric techniques in recent years enabled us to study both the proximal and distal segments of the viscus. The present paper reviews our knowledge about normal aspects of colorectal motility in man and the abnormalities found in slow transit constipation (STC), one of the most frequent and difficult to treat subtypes of constipation. An internetbased search strategy of the Medline and Science Citation Index was performed using the keywords colon, colonic, colorectal, constipation, slow transit, motility, rectal, rectum in various combinations with the Boolean operators AND, OR and NOT. Only articles related to human studies were used, and manual cross-referencing was also performed. Most of colonic motor activity is represented by single nonpropagated contractions, rarely organized in bursts; this activity is maximal during the day, especially after waking and following meals. In addition, a specialized propagated activity with propulsive features is detectable, represented by high-and low-amplitude propagated contractions. In the severe form of constipation represented by the slow transit type, the above motor activity is completely deranged. In fact, both basal segmental activity (especially in response to meals) and propagated activity (especially that of high amplitude) are usually decreased, and this may represent a physiologic marker of this disorder. Human colonic motor activity is quite a complex issue, still only partly understood and investigated, due to anatomic and physiological difficulties. In recent years, however, some more data have been obtained, even in proximal segments. These data have helped in elucidating, although only in part, some pathophysiological mechanisms of chronic constipation, and especially of the STC subtype.

Giant appendiceal mucocele: Report of a case and brief review

Mucocele of the appendix is a rare lesion, characterized by distension of the lumen due to accumulation of mucoid substance. This disease is often asymptomatic and pre-operative diagnosis is rare. If untreated, one type of mucocele may rupture producing a potentially fatal entity known as pseudomyxoma peritonei. The type of surgical treatment is related to the dimensions and to histology of the mucocele. Appendectomy is used for simple mucocele or for cystadenoma. Right hemi-colectomy is recommended for cystadenocarcinoma. In this paper, we report a case of a 51-year-old woman with a mobile, painless mass in the right lower quadrant of abdomen caused by a giant appendiceal mucocele. Imaging showed a larger tubular, cystic structure extending below from the inferior wall of the cecum. Surgery revealed a giant retro-cecal appendix measuring 17 cm in length and 4 cm in diameter. The final pathologic diagnosis was mucocele caused by mucinous cystadenoma.

Liver cell adenoma:A case report with clonal analysis and literature review

We report a case of liver cell adenoma （LCA） in a 33-year-old female patient with special respect to its clonality status, pathogenic factors and differential diagnosis. The case was examined by histopathology, immunohistochemistry and a clonality assay based on X-chromosomal inactivation mosaicism in female somatic tissues and polymorphism at androgen receptor focus. The clinicopathological features of the reported cases from China and other countries were compared. The lesion was spherical, sizing 2 cm in its maximal dimension. Histologically, it was composed of cells arranged in cords, most of which were two-cell-thick and separated by sinusoids. Focal fatty change and excessive glycogen storage were observed. The tumor cells were round or polygonal in shape, resembling the surrounding parenchymal cells. Mitosis was not found. No portal tract, central vein or ductule was found within the lesion. The tumor tissue showed a positive reaction for cytokeratin （CK） 18, but not for CK19, vimentin, estrogen and progesterone receptors. Monoclonality was demonstrated for the lesion, confirming the diagnosis of an LCA. Clonality analysis is helpful for its distinction from focal nodular hyperplasia.K

Metastatic bone cancer as a recurrence of early gastric cancer - characteristics and possible mechanisms

The surgical outcome of most early gastric cancer （EGC） is usually satisfactory. Some cases show bone metastasis even though the depth of cancer invasion is confined to the mucosa. The most frequent site for recurrence of EGC is the liver. Cases of EGC with bone metastasis are reviewed to clarify the clinicopathological characteristics of EGC giving rise to bone metastasis. Possible mechanisms and risk factors underlying this rare condition are proposed. Forty-six cases of bone metastasis from EGC are reviewed from published reports and meeting proceedings in Japan. This investigation suggests that risk factors for bone metastasis from EGC include depressed-type signet-ring cell carcinoma, poorly differentiated carcinoma, and/or the likely involvement of lymph node metastasis, even though the cancer is confined to the gastric mucosa. The risk factors do not include recurrence of EGC in the liver. We speculate that the mechanism of bone metastasis from EGC is via lymphatic channels and systemic circulation. Postoperative follow-up of cases should consider the development of bone metastasis from EGC. We propose the use of elevated alkaline phosphatase levels for the detection of bone metastasis and recommend bone scintigraphy in positive cases. 2005 The WJG Press and Elsevier Inc. All rights reserved

Prognostic significance of microsatellite alterations at 1p36 in cholangiocarcinoma

AIM： To investigate loss of heterozygosity （LOH） and microsatellite instability （MSI） on the chromosomal region 1p36-pter in cholangiocarcinoma （CCA） patients and determine the association between microsatellite alterations and clinicopathological parameters. METHODS： Ten polymorphic microsatellite markers were determined for LOH and MSI using GS-3000 gel scan fragment autoanalyzer. RESULTS： Sixty-eight out of 90 cases （75.6%） showed LOH in one or more loci. LOH was found most frequently at DIS199 （40.0%）, DIS507 （34.6%）, DIS2845 （30.5%）, and DIS2734 （30.1%）. MSI was found in 34 of 90 cases （37.8%） at one or more loci. Fine mapping at lp36 showed two distinctive regions of common loss, which were D1S2845 and the 25.5-cM region between D1S507 and D1S2734, indicating the existence of putative tumor suppressor genes that is likely to play important roles in the development of CCA. Patients with LOH at D1S234 showed less lymphatic invasion （P = 0.017）, whereas patients with LOH at D1S2676 exhibited more lymphatic invasion than those without （P = 0.031）. LOH at D1S2845 showed a significant correlation with nerve invasion （P = 0.029）. Moreover, patients who demonstrated MSI at D1S228 showed a poor prognosis （P = 0.0026）. CONCLUSION： Allelic loss plays a major role in microsatellite alterations at chromosome lp36, which may contribute to carcinogenesis and pathogenesis of liver fluke related CCA and these alterations can be used as molecular prognostic indicators for CCA patients.

Progress in treatment of massive ascites and hepatorenal syndrome

Massive ascites and hepatorenal syndrome （HRS） are frequent complications of liver cirrhosis. Thus, effective therapy is of great clinical importance. This concise review provides an update of recent advances and new developments. Therapeutic paracentesis can be safely performed even in patients with severe coagulopathy. Selected patients with a refractory or recurrent ascites are good candidates for non-surgical portosysternic shunts （TIPS） and may have a survival benefit and improvement of quality of life. Novel pharmaceutical agents mobilizing free water （aquaretics） are currently under test for the therapeutic potential in patients with ascites. Prophylaxis of hepatorenal syndrome in patients with spontaneous bacterial peritonitis is recommended and should be considered in patients with alcoholic hepatitis. Liver transplantation is the best therapeutic option with long-term survival benefit for patients with HRS. To bridge the time until transplantation, TIPS or Terlipressin and albumin are good options. Albumin dialysis can not be recommended outside prospective trials.

Granular cell tumor of stomach: A case report and review of literature

Granular cell tumor （GCT） was described for the first time by Abrikosoff in 1926. It is a relatively rare neoplasm that may occur at many sites, but most commonly in the skin or soft tissues. The occurrence of GCT in the gastrointestinal tract is rare, accounting approximately for 8% of all tumors, among which the most common site is the esophagus, whereas gastric localization is very rare. Gastric GCTs can be solitary or, more frequently, associated with other gastrointestinal localization. Although GCTs are usually clinically and histologically benign, some malignant cases have been reported. Histologically, these tumors consist of polygonal and fusiform cells disposed in compact ＂nests＂ and immunohistochemical staining for S-100 protein supports the proposed derivation from Schwann cells. A correct preoperative diagnosis of this tumor can only be made in 50% of all patients and it is always based on endoscopic biopsy. Laparoscopic or conventional wedge resection represents the treatment of choice. In this study, the authors reported a case of a 49-year-old woman with a solitary granular cell tumor of the stomach with infiltrative pattern, successfully treated with surgical resection. A review of literature is also presented with emphasis on diagnostic criteria concerning the malignant form.

Prognostic factors in patients with node-negative gastric carcinoma:A comparison with node-positive gastric carcinoma

AIM： To identify the clinicopathological characteristics of lymph node-negative gastric carcinoma, and also to evaluate outcome indicators in the lymph node-negative patients.METHODS： Of 2848 gastric carcinoma patients, 1524 （53.5%） were lymph nede-negative. A statistical analysis was performed using the Cox model to estimate outcome indicators. RESULTS： There was a significant difference in the recurrence rate between lymph nede-negative and lymph node-positive patients （14.4% vs 41.0%, P〈0.001）. The 5-year survival rate was significantly lower in lymph node-positive than in lymph node-negative patients （31.1% vs 77.4%, P〈0.001）. Univariate analysis revealed that the following factors influenced the 5-year survival rate： patient age, tumor size, depth of invasion, tumor location, operative type, and tumor stage at initial diagnosis. The Cox proportional hazard regression model revealed that tumor size, serosal invasion, and curability were independent, statistically significant, prognostic indicators of lymph node-negative gastric carcinoma. CONCLUSION： Lymph node-negative patients have a favorable outcome attributable to high curability, but the patients with relatively large tumors and serosal invasion have a poor prognosis. Curability is one of the most reliable predictors of long-term survival for lymph nodenegative gastric carcinoma patients.

Carcinoma in situ arising in a tubulovillous adenoma of the distal common bile duct: A case report

Tubulovillous adenomas are common in the colon and rectum, but are rare in the common bile duct. Biliary adenomas may produce obstructive jaundice, which can be easily confused with a malignant neoplasm or stone. We report a case of a carcinoma in situ arising in a tubulovillous adenoma of the distal common bile duct causing obstructive jaundice. A 55-year-old male presented with a 10-d history of pruritus and progressive jaundice. Abdominal sonography and computed tomography showed a mass in the distal common bile duct. Endoscopic retrograde cholangiopancreatography showed luminal narrowing of the bile duct due to a polypoid mass. Positron emission tomography demonstrated no abnormal uptake. It was thought that this mass was a malignant tumor, thus a pylorus-preserving panceaticoduodenectomy was performed. The final pathology showed a tubulovillous adenoma with carcinoma in situ of the distal common bile duct. At follow-up 8 mo later, endoscopy showed multiple polyps in the rectum, colon and stomach. The polyps were removed by endoscopic mucosal resection and shown to be tubular adenomas with high grade dysplasia. Biliary adenomas require careful follow-up for early detection of recurrence and malignant transformation.

Patients with Helicobacter pylori positive and negative duodenal ulcers have distinct clinical characteristics

AIM: To assess the clinical characteristics of Helicobacterpylori(H pylori) negative duodenal ulcer.METHODS: Patients with an endoscopic diagnosis of duodenal ulcer between 1996 and 2002 were included in the present study. Patients were considered to be negative for Hpylori, if both histological examination and rapid urease test of biopsy specimens were negative. A comparison was made between patients with H pyloripositive and negative duodenal ulcers.RESULTS: A total of 1 343 patients were studied. Their mean age was 54.7±0.5 years. There was a male preponderance (M:F = 2.5:1). Three hundred and ninetyeight patients (29.6%) did not have H pylori infection. The annual proportion of patients with H pylori negative duodenal ulcers increased progressively from 1996 to2002. On multivariate analysis, patients with H pylorinegative duodenal ulcer were more likely to be older, have concomitant medical problem, pre-existing malignancy, recent surgery, underlying sepsis, or taken non-steroidal anti-inflammatory drugs. In terms of clinical presentations, patients with H pylori negative duodenal ulcer were more likely to present with bleeding, multiple ulcers and larger ulcers.CONCLUSION: The proportion of patients with H pylori negative duodenal ulcers is on the rise because of a continued drop in incidence of H pylori positive duodenalulcers in recent years. Such patients have distinct clinical characteristics and it is important to ascertain the H pylori status before starting eradication therapy.