Cognitive improvement effect of gintonin might be associated with blood-brain barrier permeability enhancement: dynamic contrastenhanced MRI pilot study

Along with the multiple neuroprotective effect, recent studies suggest that gintonin might increase the blood brain barrier permeability. We evaluated the effect of gintonin on the vascular permeability changes in different brain segments, using dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI). In this 8-week, randomized, open label pilot study, ten participants with subjective memory impairment but preserved cognitive function assigned to gintonin-enriched fraction (GEF) 300 mg/day or placebo groups. Korean versions of the Alzheimer's disease assessment scale (ADAS-K) and DCE-MRI parameters including Ktrans and Vp in different brain segments were evaluated at baseline and at 8 weeks after treatment. Nine participants completed the study protocol. No adverse events occurred during the observation period for 8 weeks in both groups. Following gintonin administration, increment trends of the brain permeability that did not reach a statistical significance were observed in the left hippocampus (Ktrans and Vp , both, p = 0.062), left thalamus and in left putamen (Ktrans , p = 0.062), and left insula and right amygdala (Vp , p = 0.062), but not in the control placebo group. The increment of the Ktrans value in the left thalamus from the baseline was highly correlated with the change of the ADAS scores (r = −0.900, p = 0.037). Gintonin might enhance the blood-brain barrier (BBB) permeability in the brain structures involved in cognitive functions. Further efficacy exploration for the synergistic effect of gintonin's BBB permeability enhancement to its other cognitive enhancing mechanisms are warranted.

A Case Report of Noonan Syndrome with Mental Retardation and Attention-Deficit Hyperactivity Disorder

Noonan syndrome is characterized by short stature, typical facial dysmorphology, and congenital heart defects. The main facial features of Noonan syndrome are hypertelorism with down-slanting palpebral fissures, ptosis, and low-set posteriorly-rotated ears with a thickened helix. The cardiovascular defects most commonly associated with this condition are pulmonary stenosis and hypertrophic cardiomyopathy. Other associated features are webbed neck, chest deformity, mild intellectual deficit, cryptorchidism, poor feeding in infancy, bleeding tendency, and lymphatic dysplasias. The patient is a 10-year-old boy. He had experienced repeated febrile convulsions. He had typical facial features, a short stature, chest deformity, cryptorchidism, vesicoureteral reflux, and mental retardation. His language and motor development were delayed. When he went to school, it was difficult for him to pay attention, follow directions, and organize tasks. He also displayed behavior such as squirming, leaving his seat in class, and running around inappropriately. Clinical observation is important for the diagnosis, so we report a patient who was diagnosed with Noonan syndrome, mental retardation, and attention-deficit hyperactivity disorder.

The Association Study between Mood Disorder Questionnaire and Bipolar Spectrum Disorder in Major Depressive Disorder / 신경정신의학

OBJECTIVES: This study was performed to evaluate the frequency of bipolar spectrum disorder (BSD) among patients who have been diagnosed with major depressive disorder. In addition, authors assessed the practical usefulness of the Mood Disorder Questionnaire (MDQ) to investigate the frequency of bipolar spectrum disorder in major depressive disorder. METHODS: The participants were 70 depressive patients who have never been diagnosed with bipolar disorders. The subjects were interviewed for diagnosis using the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision criteria and the Mini-International Neuropsychiatric Interview to exclude bipolar disorders from the subjects. BSD criteria (as defined by Ghaemi, et al. 2002), and Korean version of the Mood Disorder Questionnaire (K-MDQ) was used to investigate their bipolarity. Data were collected including family history of affective disorder, number of previous depressive episode, age of onset, history of suicide attempt, comorbid psychiatric illness, and drug and alcohol use. RESULTS: Among 70 subjects, 25 patients (35.7%) were classified as having bipolar spectrum disorder on BSD criteria, while other 45 patients (64.3%) as unipolar depression. Among the 25 patients who meet the BSD criteria, 24 patients (34.3%) scored more than 7 and only 1 patient (1.4%) scored less than 6 on K-MDQ. Among the 45 patients who don't meet BSD criteria, 40 patients (57.1%) scored less than 6 and only 5 patients (7.1%) scored more than 7 on K-MDQ. Early age of onset, recurrent depressive episode, brief depressive episode, bipolar family history, history of suicide attempt, antidepressant induced hypomania, hyperthymic temperament, atypical depressive symptom, psychotic depressive symptom, and antidepressant "wear off" were found to be highly related with MDQ positive subjects and BSD subjects among the depressive subjects. CONCLUSION: The result of this study demonstrates the high frequency of BSD in depressive patients who have never been diagnosed with bipolar disorders. Some BSD criteria can be used to differentiate BSD subjects from the subjects with major depressive disorder. Also these results indicate that K-MDQ is useful for screening of bipolar spectrum disorder.

The Importance of Clinical Indicators for Detecting Postoperative Complications Following Laparoscopic Sleeve Gastrectomy

PURPOSE: The significant drastic complications of performing laparoscopic sleeve gastrectomy (LSG) in morbidly obese patients are gastric staple line leakage and bleeding. The aim of our study is to evaluate the efficacy of the clinical data for detecting postoperative complications after LSG. METHODS: The study enrolled 150 consecutive patients who underwent LSG from January 2003 to July 2006. When abnormal data (heart rate > or = 10/min, or temperature > or = 7.5degrees C) was detected on postoperative day 1, then laboratory tests (blood, urine, chest X-ray and abdominal sonogram) and water soluble gastrografin UGIS were performed to detect the postoperative complications after LSG (group A). The patients who had normal postoperative clinical data (group B) were compared with group A. RESULTS: Of the 150 patients who underwent LSG, 9 patients (6%) had postoperative complications. Two patients had major complications: 1 case of leakage (0.6%) and 1 case of delayed bleeding (0.6%), and 4 patients had minor complications in group A. But no major complications were detected in group B (P 39degrees C). CONCLUSION: Evidence of tachycardia or a high body temperature may be useful to detect major complications after LSG. We also recommend performing laboratory test and UGIS when clinically indicated.

The 3-Year Results of Laparoscopic Sleeve Gastrectomy for the Treatment of Korean Morbid Obesity

PURPOSE: In Asia, the types and the main causes of morbid obesity are different from those in western society. Therefore, the treatment plan should be different, and surgery for morbid obesity should be carefully chosen. The 3-year results for isolated laparoscopic sleeve gastrectomy (LSG) performedin the Korean population are reported. METHODS: We retrospectively reviewed 112 patients that underwent LSG from January 2003 to July 2006. Eighty-three of these patients had more than 3 years follow-up, and represent the subjects of this report. Sleeve gastrectomy was performed laparoscopicaly using the Endo-GIA stapler to create a lesser curve gastric tube over a 48-Fr bougie. RESULTS: The preoperative body mass index (BMI) was 36.4+/-5.2 (30.0~56.1). The mean excess BMI was 13.4+/-5.2. The percentage of excess weight loss (%EWL) in the postoperative first, second, and third year was 72.4+/-23.5, 69.5+/-29.4, and 66.8+/-33.4. The percentage of excess BMI loss (%EBMIL) was 74.1+/-25.6, 71.4+/-32.0, and 68.7+/-32.7. In 83 patients postoperatively after 3 years, 37 patients (44.6%) had >75% EBMIL, 22 patients (26.5%) had 50~75% EBMIL, 14 patients (16.9%) had 25~50% EBMIL, and 10 patients (12.0%) had less than 25% EBMIL. There was no 30-day peri-operative mortality. Two major complications (1 delayed bleeding, 1 leakage) occurred. CONCLUSION: LSG without the duodenal switch operation has been an effective single weight reducing surgical procedure thus far in most of the Korean patients.

Adult Onset Still's Disease Misunderstood as Sepsis with Bile Peritonitis

Adult onset Still's disease (AOSD) is a rare systemic inflammatory disorder of an unknown etiology, and its major clinical manifestations include high spiking fever, polyarthralgia, salmon-colored evanescent rash and neutrophilic leukocytosis. We describe here a 41 year old woman with AOSD who presented with non-remitting high fever, polyarthralgia, sore throat, skin rash, splenomegaly, thrombocytopenia, neutrophilic leukocytosis, hyperferritinemia and coagulopathy with disseminated intravascular coagulation (DIC). The patient had a history of laparoscopic cholecystectomy due to acalculous cholecystitis prior to admission. We suspected sepsis due to bile peritonitis after the previous laparoscopic cholecystectomy. Yet we could not detect infectious organisms on the cultures or serologic studies. Finally, we suspected AOSD-associated hemophagocytic syndrome (HS). So, intravenous immunoglobulin and pulse methylprednisolone treatment brought about transient improvement of the fever and the neutrophilic leukocytosis, but the disease progressed and the patient expired due to acute renal failure. HS is a fatal cause of AOSD. If a patient has DIC and sepsis and these fail to respond to conservative treatment, then AOSD should be added to the differential diagnosis of sepsis and DIC.

Pregnancy after Isolated Sleeve Gastrectomy in Morbidly Obese Patient

Bariatric surgery is the best known procedure for treating severe obesity and the majority of patients who received surgical weight loss procedure were at childbearing age. Female patients who successfully lost weight following bariatric procedure, become pregnant and those are need to be evaluated carefully due to various operative procedures and to ensure intake of quality nutrition. A 35-year-old female, gravida 4, para 2, treated for morbid obesity with vertical sleeve gastrectomy performed 14 months earlier, presented 7 weeks of gestation. Before surgery, she had weighed 92.4 kg (body mass index (BMI); 32.9 kg/m(2)); she had gradually reduced her weight to 65.5 kg (BMI; 23.5 kg/m(2)) postoperatively at 14 months. For the first trimester of pregnancy, her average intake was 698.6 kcal/day from food, and 840~1352.8 kcal/day in second and third trimester. During pregnancy, significant iron, cobalamin and vitamin B12 deficiencies were not founded. She has gained a total of 8 kg. She delivered a healthy female infant at full term. Nutritional supplementation following bariatric surgery and close supervision during pregnancy can prevent nutrition-related complications and improve maternal and fetal health.

Overexpression of Estrogen Receptor in Female Patients with Varicose Vein of Lower Extremities

PURPOSE: The high frequency of varicose veins in female suggests the involvement of female sex hormone in pathophysiology of varicose vein. We investigated the presence of estrogen receptor in the wall of normal and varicose veins, and compared their expression between male and female. METHODS: Twenty normal veins were obtained from patient undergoing peripheral artery bypass surgery. Forty varicose segment and non-varicose segment of varicose veins in same patients were obtained from patient during operation. Using immunohistochemistry, we measured estrogen receptor expression rate and compared the estrogen receptor expression of varicose vein with that of normal vein. RESULTS: There is no difference on estrogen receptor expression between normal vein and varicose vein. The positive rate of estrogen receptor expression was higher in varicose segment of varicose vein than in non-varicose segment of varicose vein (P=0.039). In varicose segments in female, estrogen receptor positive rate was higher than non-varicose segment (P=0.022), and than normal vein (P=0.017). The estrogen receptor positive rate of varicose segment in varicose vein was higher in female than male (P=0.008). But there is no statistical significance for the estrogen receptor positive rate of non-varicose segment in varicose vein between male and female. CONCLUSION: The gender difference may be related to hormonal action. Also, these finding suggested the involvement of female sex hormone in varicosity and provides a basis for the finding of causes of primary varicose veins.

Excision of Benign Breast Disease by Ultrasound-Guided Vacuum Assisted Biopsy Device (Mammotome)

PURPOSE: The mammotome biopsy is a new surgical technique that is a minimally invasive, image guided procedure, requiring just one small incision and without the need for multiple insertions in the breast. The aim of this study was to evaluate the efficacy and the safety of mammotome biopsy device in the percutaneous removal of breast masses using ultrasound guidance. METHODS: From Jan. 2003 to sept. 2004, a total of 1003 US-guided excisional mammotome biopsy were performed in 827 patients at Kangnam Cha hospital. Lesions with BI-RADS category 3 and 4a features by ultrasonography were included in this study. Lesions below 1.0 cm were removed by 11 gauge probe, and lesions above 1.0 cm were removed by 8 gauge probe. Ultrasonographic follow-up were performed on 3~6 months later to assess residual tissue and scarring. RESULTS: Mean patient age was 36.2 years(range 14-75 years). The average size of lesion was 1.21cm (SD+- 0.43cm). The majority of lesions, 63.5%, were nonpalpable and 36.5% were palpable. The majority of specimens (99.2) were benign. Most of benign specimens (75.7) consisted of fibroadenoma and fibrocystic changes. 8 lesions (0.8%) were malignant. Mean time required to perform mammotome procedures was 6.4+/-3.9 minutes and mean number of cores removed were 14.2+/-7.9 pieces. No bleeding or infections occurred postoperatively. CONCLUSIONS: This study demonstrates that percutaneous breast biopsy using mammotome system is feasible, effective and safe method for the diagnostic and therapeutic management of benign breast lesions with minimal morbidity. And it allows for the complete excision of the lesions less than 3 cm in size. A breast surgeon can use Mammotome to replace open biopsy and core needle procedure for the initial biopsy of breast lesions.

Early Results of Laparoscopic Isolated Sleeve Gastrectomy without Duodenal Switch in the Treatment of Korean Morbid Obesity

PURPOSE: In Korea due to cultural background (food, life style) and environmental factors, type of obesity and previously defined operative indication is different from western country. Therefore, surgical procedure also must be applied differently under pattern of obesity. In this report we are trying to introduce our early results of laparoscopic sleeve gastrectomy without duodenal switch in Korean morbid obesity. METHODS: We retrospectively reviewed 60 consecutive patients who underwent laparoscopic sleeve gastrectomy between January 2003 and May 2004. Four 12mm ports and one 15mm port are placed. The sleeve gastrectomy was done as routine fashion using ligasure and endo-GIA stapler to create a lesser curve gastric tube over 48 French bougie. RESULTS: Excess weight loss was achieved in 71.6% during first six months postoperatively and 83.3% within 12 months. Body mass index (kg/cm2) was decreased average 9.2 during first 12 months postoperatively. Median weight loss at 12 months was 24.6 kg. Postoperative dyslipidemia was improved in 75% of patient within 12 months of operation. Diabetes as a co-morbidity was disappeared 100% of patient within 6 months postoperatively. Hypertension was disappeared in 92.9%, improved in 100% of patients within 12 months postoperatively. Arthritis and joint pain were improved 100% of patient within 12 months postoperatively. Weight loss plateaued at 12 months for the majority of patients. CONCLUSION: Additional studies and further follow up are needed to determine the best surgical treatment for Korean morbid obesity patient. However sleeve gastrectomy without duodenal switch operation can be an effective single weight loss procedure especially in Korea

Changes in Anthropometric Indices and Lipid Profile after Isolated Vertical Sleeve Gastrectomy in Morbid Obesity

Purpose: Generally, morbid obesity has accompany with co-morbidities including dyslipidemia. Bariatric operation has shown various degree of effectiveness and different mechanism on weihgt loss. The effectiveness of sleeve gastrectomy in lipid profile is not revealed until now. Therefore, we have investigated and evaluated the efficacy of sleeve gastrectomy on weight loss and serum lipid profile. METHODS: We retrospectively reviewed 42 patients who underwent laparoscopic sleeve gastrectomy. All the patient was divided into two groups (group A (n=35): >50% excessive weight loss (EWL) in 6 months postoperatively, and group B (n=7): <50% (EWL)). Anthropometric Indices and serum lipid profile were measured before sleeve gastrectomy and postoperatively in 6 months. RESULTS: EWL of all the patients was 74.1+/-21.9% in 6 months postoperatively, group A was 80.4+/-18.2%, group B was 39.7+/-6.4%. Waist circumference, hip circumference, percent of body fat and visceral fat area were decreased in group A than B (P <0.05). Especially the visceral fat area of group A was reduced (-38.6%). Significant reduction of atherogenic index and triglyceride was observed (P <0.001) and increment of HDL cholesterol (P <0.001) was observed in both Groups. The moderate reduction of total cholesterol was observed in group A (P <0.05) but in not group B. LDL cholesterol level was mildly decreased but not statistically significant (group A: P=0.82, group B: P=0.746). Conclusion: Isolated vertical sleeve gastrectomy in morbid obesity patients is a effective surgical procedure. It offers excellent results in weight loss, anthropometric Indices and lipid profiles in short period of time. Eventually, it reduces the risk of coronary disease.

Early Management of Type 2 Diabetes Mellitus after Sleeve Gastrectomy in Morbid Obesity

PURPOSE: Obesity is a frequent cause of insulin resistance and poses a major risk for diabetes. The effects of sleeve gastrectomy on diabetes have not elucidated. This report documents that the sleeve gastrectomy provides control for diabetes, prior to significant body weight losses. METHODS: We retrospectively reviewed 14 type 2 diabetic patients who underwent laparoscopic isolated sleeve gastrectomy between May 2003 and October 2004. Fourteen patients had type 2 diabetes treated by oral hypoglycemic agents. Preoperative, 4 weeks and 3 months following surgery, all patients checked weight, body mass index(BMI), waist circumference, hip circumference, blood pressure, HbA1c and fasting glucose. RESULTS: Fourteen patients with a mean preoperative body mass index (BMI) of 39.1+/-4.2 kg/m2 (31.9~47.5 kg/m2) underwent laparoscopic sleeve gastrectomy. Changes in mean BMI were minimal (preop: 39.1+/-4.2 kg/m2, postop (4 week): 35.5+/-3.8 kg/m2), but there are significant decrease in blood fasting glucose (P<0.001), HbA1c (P<0.001), systolic blood pressure (P<0.001), diastolic blood pressure (P=0.009). Ten patient did not require medications after surgery (4 week), the other 4 patient stop the medications after surgery (3 month). CONCLUSION: Further evaluation is needed to analyze effect of sleeve gastrectomy in treating type 2 diabetes mellitus. But just with restrictive procedures as isolated sleeve gastrectomy also can control early type 2 diabetes mellitus in morbidly obese patients.

Clinical Effectiveness of Diagnosis Using Immunohistochemistry and New Grade in Gastrointestinal Stromal Tumors (GISTs)

PURPOSE: Paraffin-embedded tissue samples from the gastrointestinal tract, which had been diagnosed as tumors of a mesenchymal origin, were reviewed by an immunohistochemical staining method. The prognostic significances of the immunohistochemical subtypes and anatomical locations were also investigated. GIST, as a new grading system, was compared with the pre-existing system for its useful prognostic significance. METHODS: 122 cases were evaluated and classified by immunohistochemical staining for KIT, CD34, actin, desmin, vimentin, S-100 protein and NSE. RESULTS: Positivity for both KIT and CD34 of 92.6 and 73.8%, respectively, indicated that KIT was more effective for the diagnosis of GISTs. The stomach (62.3%) and small bowel (23.7%) were most common organs of GIST. There was no difference in the prognosis between these two organs. Immunophenotypically, the uncommitted, myoid, combined and neural types were 37.7, 23.7, 20.2 and 7%, respectively. There was no significant difference in the prognosis between these types. The old grading system showed no difference between the borderline and malignant groups (P=0.14), whereas, the new grading system showed a significant difference between the intermediate and high risk groups (P=0.01). CONCLUSION: KIT is more useful for the diagnosis of GOSTs. The immunophenotypical classification and anatomical location showed no prognostic significance in GISTs. Therefore, the new grading system might be more useful than older system.

Robot Assisted Laparoscopic Surgery and Bariatric Surgery

Laparoscopic operations are a primary component of general surgery. Opportunities to perform laparoscopic operations currently vary widely between surgical training programs. As utilization of minimal access procedures increases in the future, doctors will more readily learn the skills necessary to safely accomplish these operations. Recently robotic surgery has been developed amazingly, and now tele-robotic, laparoscopic abdominal surgery is feasible with its initial outcomes being compatible with those obtained from traditional laparoscopic surgery. Therefore, the tele-robotic and robotic surgical systems are believed to overcome some of the limitations inherent to the traditional laparoscopic surgeries and to increase the number of surgeons who could perform complex laparoscopies in the future. Laparoscopic bariatric surgery is a well known procedure in western countries. It appears as effective as other laparoscopic operations and has been shown to provide excellent long term outcomes. Therefore I am trying to introduce bariatric surgery which is not much familiar in Asian countries.

Laparoscopic Appendectomy is Feasible for All Forms of Appendicitis

PURPOSE: Acute gangrenous and perforated appendicitis are associated with an increased risk for intraoperative conversion, postoperative complications and have been considered a relative contraindication for laparoscopic appendectomy. The objective of this study was to analyze the feasibility of the laparoscopic approach in all forms of appendicitis. METHODS: A retrospective review of 101 patients who underwent laparoscopic appendectomy for uncomplicated and complicated appendicitis (perforated appendicitis and periappendiceal abscess) between June 2000 and May 2001 was performed. RESULTS: There were 84 patients with uncomplicated appendicitis (group A), 11 patients with perforated appendicitis (group B) and 16 patients with periappendiceal abscess (group C). The mean age of the patients was 42 (12~79) years and there were 47 men and 54 women. The mean operation time was 43, 67 and 105 minutes in groups A, B and C, respectively. Oral intake commenced at 1.4, 2.2 and 2.9 days and the hospital stay was 2.5, 2.9 and 5.2 days in groups A, B and C, respectively. There was no conversion to open surgery in groups A and B; however 4 patients in group C were converted. Complications were noted in 3 patients, one for each group. The overall complication rate was 2.9% and conversion rate, 0.9%. CONCLUSION: Although our experience is limited, the laparoscopic appendectomy seems to be a feasible and safe procedure for all forms of apppendicitis, including periappendiceal abscess.

Early Gastric Cancer Accompanied with a Giant Metastatic Abdominal Lymph Node

Lymph node metastasis is found in 10-15% of patients with early gastric cancer; however, metastatic nodes forming giant abdominal masses or distant metastases are extremely rare. A 51-year-old male, HBs Ag-positive patient presented with an incidentally found huge upper abdominal mass. Imaging studies showed a 7 cm-sized epigastric mass consistent with hepatocellular carcinoma. His serum -fetoprotein level was also significantly elevated (330.6 ng/ml). Endoscopic studies revealed a suspicious early gastric carcinoma located on the lesser curvature and the anterior wall of the antrum. He was operated on with a preoperative diagnosis of hepatocellular carcinoma coexisting with an early gastric carcinoma. However, the actual abdominal tumor was a metastatic lymph node resulting from a gastric carcinoma which was located around the hepatic artery. Accordingly, he underwent a subtotal gastrectomy with the D2 lymph node dissection and the removal of the metastatic node. Postoperatively, he did well without any complications. His serum -fetoprotein level decreased to 49.3 ng/ml one week after the surgery and was completely normalized 3 months later. To date, one year and 4 months after the operation, he is in good conditions without evidence of recurrence on endoscopic and imaging studies.

Strabismus with Ocualr Motility Disturbance after Molteno Implant

PURPOSE: We experienced a case of ocular motility disturbance with esotropia and hypotropia, following implantation of Molteno to the superotemporal quadrant. METHODS: The patient recovered to orthophoria after removal of implant and fibrotic scar tissue with recession and resection. RESULTS: Multiple complications have been reported in association with Molteno implantation, including hypotony, cataract, choroidal hemorrhage, retinal detachment, endophthalmitis, hyphema, phthisis. However ocular motility disturbances have been documented in only a few cases and never in Korea to our knowledge. Therefore, we report this case with the review of related literatures.

Clinical Evaluation of Recurrence Rate of Pterygium Operation according to Mitomycin C Concentration

PURPOSE: The authors compared the recurrence rate and complications of primary pterygium operation with respect to mitomycin C concentration. METHODS: Four hundred twenty three eyes with primary pterygium underwent surgery using the bared sclera method. One hundred nineteen eyes randomly chosen were treated with 0.02% mitomycin C (Group I) twice a day for 5days, 138 eyes were treated with 0.01% mitomycin C (Group II), and 166 eyes were treated with 0.005% mitomycin C (Group III). RESULTS: During the mean follow-up period of 6 months, the overall recurrence rate was 14.7% (62 eyes). Recurrence rates in each group : 8.4% (10 eyes) in Group I , 13.7% (19 eyes) in Group II , and 19.9% (33eyes) in Group III . Complications seen in Group I were corneal abrasion (1 eye), symblepharon (1 eye), and postoperative corneal scar (1 eye). Complications seen in Group II were symblepharon (1 eye), and postoperative corneal opacity (2 eye) and seen in Group III were symblepharon (1 eye), and postoperative corneal opacity (1 eye). We conclude that a higher concentration of mitomycin C (0.2 mg/ml) reduces the recurrence rate of pterygium. CONCLUSIONS: We recommend the use of mitomycin C concentration of 0.02% twice a day for 5days to lower the recurrence rate and complications after excision of primary pterygium

Expression of Matrix Metalloproteinase-2, Cathepsin D and E-cadherin in Human Gastric Adenocarcinomas

PURPOSE: The prognosis of gastric cancer depends on the depth of invasion, lymph-node metastasis, invasion to adjacent tissues, and distant metastasis. Recently, it is known that tumor-associated proteases and adhesion molecules have been shown to play a relevant role in the process of progression and metastasis. The purpose of our study was to demonstrate the value of MMP-2 (matrix metalloproteinase), cathepsin D and E-cadherin as prognostic factors. MATENRIALS AND METHODS: In this study, formalin-fixed, paraffin-embedded tissue blocks from 69 patients with gastric cancer were immunohistochemically studied using antibodies to MMP-2, cathepsin D, and E-cadherin, and their expressions were analyzed according to the pathologic stage, lymph-node metastasis, histological differentiation, and patient survival. The medical records of these patients were retrospectively reviewed. RESULTS: Increased expression of MMP-2 significantly correlated with advanced pathologic stage (P=0.026). Patients with lymph-node metastasis also had increased expression of MMP-2. Those patients with increased expression of MMP-2 showed a poorer survival; nevertheless, it was not statistically significant. Increased expression of cathepsin D significantly correlated with advanced pathologic stage (p= 0.029). However, no correlation was observed between advanced pathologic stage and either lymph-node status or histological differentiation. Patients with increased expression of cathepsin D had a poorer survival, but that result was not statistically significant. No association was found between reduced expression of E-cadherin and pathologic stage, lymph-node status, or histological differentiation. Also, no correlation was found between the expression of E- cadherin and survival. In addition, when a combination of MMP-2 and cathepsin D expressions was analyzed, if both were negative, the survival seems to be longer, but it was not statistically significant. CONCLUSION: In patients with gastric cancer, expressions of MMP-2 and cathepsin D correlated with tumor stage; therefore, they may be considered as prognostic factors.

Detection of Micrometastases in the Sentinel Lymph Node from Patients with Early Gastric Cancer

PURPOSE: If the SLN (sentinel lymph node) is an accurate predictor of the lymph node status it should eliminate unnecessary lymph node dissection, resulting in a lower morbidity and mortality in patients with an early gastric cancer. The aim of this study was to investigate the feasibility of SLN biopsy for its location, accuracy and ability to sensitize the tumor cell detection, using reverse transcriptase-polymerase chain reactions (RT-PCR) for the cytokeratin 19 and CD44 variants. METHODS: SLN biopsies were performed in patients with early gastric cancer (n=33). After a gastrectomy to the apposite site, isosulfan blue dye (0.5-1.0 ml) was injected submucosal medially, laterally, superiorly and inferiorly, adjacent to the tumor site. Lymphatic channels were immediately apparent. Sentinel nodes were separately submitted, and evaluated with RT-PCR, using the cytokeratin 19 and CD44 variants. Following the removal of the sentinel node, the adjacent regional nodes were also removed. Both SLN and non-SLN were examined with H&E stain and RT- PCR. RESULTS: Sentinel nodes could be identified in 26 of 33 patients (79%). The average number of sentinel nodes detected was 1.4 and were chiefly perigastric nodes. Of these 26 patients, 6 had micrometastasis in their sentinel nodes by RT-PCR detection using the cytokeratin 19 and CD44 variants. The specificity of the SLN status in the diagnosis of the lymph node status was 95% (20/21). One patient (4%) had skip metastasis. CONCLUSION: A SLN biopsy, using indocyanine green, can be performed with a high success rate. A focused examination of the sentinel nodes detected by indocyanine green with RT-PCR will resolve the underestimation of micrometastasis in regional lymph nodes, and improve the accuracy of the pathological staging. If the sentinel node concept is clinically feasible for early gastric cancer, we would perform not only accurate staging, but also effective surgical treatment, with minimally invasive techniques.