Gut Microbiota in Health and Probiotics in Functional Bowel Disease / 이화의대지

Microorganisms coexist in the human body and its function is essential to maintain normal physiology and homeostasis. Microbiota refers to the entire population of microorganisms that colonizes a particular location; includes not just bacteria but also other microbes. Gut microbiota is vast and complex. It could be changed dynamically according to the variable factors. Well balanced host-microbial symbiotic state is a harmonious ecosystem in the stable individual. But, dysbiosis is a state of deviation in composition or function from the usual gut microbiota. It has been found that this condition is associated with many gastrointestinal, metabolic, allergic and the other diseases. Dysbiosis plays an important role in the pathophysiology of functional bowel disease, such as irritable bowel syndrome and functional constipation. Probiotics is microorganism which, when administrated in adequate amounts, confer a health benefit on the host. Probiotics have beneficial effects to reduce several symptoms of functional bowel diseases. Currently, complementary and alternative medicine therapies with probiotics is recommended for symptomatic relief from functional bowel disease.

Relationship between Microsatellite Instability and Dihydropyrimidine Dehydrogenase Expression as a Predictor of Response to 5-Fluorouracil Chemotherapy for Colorectal Cancer

PURPOSE: Dihydropyrimidine dehydrogenase (DPD) is a rate-limiting enzyme in 5-FU catabolism, so the enzymatic activity of DPD reflects the 5-FU response. Moreover, recent studies have revealed that microsatellite instability (MSI) status correlates well with the prognosis and the 5-FU chemosensitivity in colorectal cancer (CRC). This study aimed to determine whether DPD mRNA expression is related with the MSI status of primary CRC as a prognostic predictor. METHODS: Tumor samples and adjacent normal colonic mucosal tissues were collected from 59 patients. DPD mRNA expression was calculated by using the real-time RT-PCR method. The MSI status was examined by using multiplex fluorescent PCR with five reference markers. The results of DPD mRNA expression and MSI status were compared with the clinicopathologic variables and with each other. RESULTS: The mean age of the 59 patients was 59 (range: 36~81) years. In 55 patients (93.2%), the colorectal cancers were histologically well or moderately differentiated. Forty-nine of the tumors (49, 83.1%) were located distal to the splenic flexure, and 46 patients (78%) had TNM stage II (n=17) or stage III (n=29) cancer. The DPD mRNA expression level was informative in all 59 cases. The median expression level was 2.5 (range: 0~67.33). There was no correlation between the DPD mRNA expression level and age, gender, location, or TNM stage. MSI status was informative in 43 cases (72.9%). Thirty-six cases (36, 83.7%) were microsatellite-stable (MSS), 4 cases (9.3%) showed low-level microsatellite instability (MSI-L), and 3 cases (7.0%) showed high-level microsatellite instability (MSI-H). Proximal CRC showed a higher proportion of MSI-H than distal CRC (25% vs. 2.9%, P=0.03). We could not find any correlation between the DPD mRNA expression level and the MSI status in tumor tissues (r=0.29, P=0.09). CONCLUSIONS: The expression level of DPD mRNA raried among the tumors studied. The relatively low frequency of MSI in distal CRC prohibits the use of MSI status as a predictor of 5-FU chemosensitivity. We suggest that a well-designed large-scale study would be helpful to confirm the relation between DPD mRNA expression and MSI status as a predictor of 5-FU chemosensitivity in CRC patients.

Benign Anal Diseases on Patients with HIV Disease

PURPOSE: The number of patients with HIV disease has been increasing rapidly, with anorectal discomfort being the most common complaint of these patients. However, there are no data on HIV disease relating to the benign anorectal area in Koreans. METHODS: A retrospective chart review was performed on patients diagnosed with benign anal diseases, combined with HIV disease, between 1996 and 2001. Their clinical aspects were compared with HIV patients registered with the National Institute of Health in Korea between 1985 and 2001. RESULTS: A total of 1,613 patients were registered, with the National Institute of Health in Korea, as having HIV disease. The ratio of sex was 7.2:1, with a male predominance. The disease was most common in the 3rd & 4th decades, with 64.2%, of the patients in this age range. As for the routes of transmission, sexual contact was the most common (96.9%), followed by blood transfusion (including blood products) (2.8%), vertical transmission (0.1%) and drug injection (0.1%). With regard to the sexual contact routes, homosexuality accounted for 28.0%. Of the cases of HIV disease presenting with a benign anal disease, 32 patients, with a sex ratio of 31:1, with an overwhelming male predominance, were selected. Twenty-six cases had been newly diagnosed at our hospital. As for the routes of the transmission, the disease had been transmitted by sexual contact in all cases. In 43.8% of these cases, the disease had been transmitted by homosexual contact, which showed a marked difference to that of the National database (P<0.05). For those associated with an anal diseases, there were 10 cases of anal fistula, 9 of perianal abscess, 7 of condyloma acuminata, 7 of anal fissure, 5 of hemorrhoids and 2 of ulceration on the lower rectum, noted. CONCLUSIONS: Nowadays, the numbers of anorectal-disease patients with HIV are increasing in Korea. Since HIV is common in the area of benign proctology, all proctologists must consider the possibility of HIV when managing patients.

Association between Helicobacter pylori and Colorectal Neoplasm

PURPOSE: Helicobacter pylori infection has been reported as a major factor of chronic gastritis, peptic ulcer, gastric lymphoma, and stomach cancer. In some uncontrolled studies, a high seroprevalence of H. pylori infection unexpectedly has been found in patients with colorectal cancer. The purpose of this study was to investigate the prevalence of H. pylori infection in patients with colorectal neoplasm. METHODS: 93 colonic tissue samples were collected during the colonoscopic biopsy. The specimens included polyp, cancer, and normal colonic mucosa. The CLO testTM kit (Delta West Ltd., Bentley, Western Australia) was used for detection of H. pylori. The SAS program (USA) was used for the Fisher's exact test. RESULTS: H. pylori infection was detected 11 (11.8%) of total 93 specimens, 7 (25.7%) of 27 in cancers and 3 (6.9%) of 43 in polyps. Significantly higher H. pylori infection was detected in the colorectal cancers than non-cancer lesions (p=0.012) and polyps (p=0.038). CONCLUSIONS: These results suggest a statistically significant association between H. pylori and colorectal neoplasm. The mechanism underlying this association needs to be investigated.

Clinical Significance of Cyclooxygenase-2 Expression in Colorectal Adenoma and Carcinoma

PURPOSE: Interest is mounting in developing prevention strategies for patients at high risk of developing colorectal cancer. Recent epidemiological investigations indicate an inverse relationship between the intake of NSAIDs and colorectal cancer risk. Cyclooxygenase (COX) enzyme may be involved in the initiation and/or the promotion of carcinogenesis. A major action of NSAIDs is the inhibition of COX. We have studied the clinical significance of COX-2 expression in colorectal adenoma and carcinoma. METHODS: We studied 19 patients with colorectal adenomas (15 males and 4 females: ages 30~73 years) and 20 patients with colorectal carcinoma (12 males and 8 females: ages 35~80 years). COX-2 status were determined by immunohistochemical methods using the mouse monocolnal antibody for COX-2 (Transduction Lab, USA) on paraffin sections. RESULTS: Immunoreactive COX-2 were expressed in 9 patients (47%) of colorectal adenoma and 9 patients (45%) of colorectal carcinoma. 57% of villous adenoma and 42% of tubular adenoma were positive for COX-2 in colorectal adenoma (p=0.650). COX-2 were expressed in 12.5% of stage B and 73% of stage C of colorectal cancer (p=0.006). COX-2 expression did not relate with the size of adenoma and carcinoma. CONCLUSIONS: The data suggest that COX-2 may be more expressed in villous adenoma and advanced carcinoma. Therefore, enhanced expression of COX-2 may play a role in the carcinogenesis of colorectal cancer.

Sufficiency of Preoperative CT Staging of Colorectal Cancer?

PURPOSE: Establishing the preoperative stage of colorectal cancer is of primary importance in determining the management and the operative procedure. A comparative study of preoperative evaluation of colorectal cancer is necessary for proper management. METHODS: This study reports a 7 years' experience using another two species of CT for preoperative staging. One species of CT (1989, Delta 2060, Technicare, USA) was used from January 1990 to December 1992; the other species of CT (1992, Highlight Advantage, General Electric Company, USA) was used from January 1993 to December 1997. This study included retrospective analysis of 237 cases of colorectal cancer from January 1990 to December 1997. In first group, the preoperative stage evaluation was done with a much older species of CT from January 1990 to December 1992; in the other group, the preoperative stage evaluation was done with a newer species of CT from January 1993 to December 1997. RESULT: The accuracy & sensitivity of preoperative staging between the two groups showed no significant differences. CONCLUSION: CT is recommended in the preoperative staging of rectal cancer and as an aid in choosing the appropriate therapy. In addition to CT, transrectal ultrasonography and MRI are recommend for improving the accuracy of preoperative staging in assessing local invasion by cancer.

Comparative Study of Anatomic and Physiologic Measurement of the Anal Sphincter in Adult Women

PURPOSE: This study has carried out to clarify the relationship between changes in the anal sphincter muscle thickness and pressure. Also, this study shows the effect of vaginal delivery and benign anal disease on the function and structure of the anal sphincter. METHODS: Women (n=42; mean age: 33.2 +/- 9.6 years old) without defecation problems or history of anal surgery, who came to Ewha Womans University Hospital between July 1999 and October 1999, were chosen. We measured the resting and the squeezing pressure with anal manometry and the thickness of the internal anal sphincter (IAS) and external anal sphincter (EAS) by endoanal sonography. RESULTS: The mean squeezing and resting pressures were 98.3 +/- 38.2 and 53.9 +/-17.4 cmH2O, and the mean EAS and IAS thicknesses were 4.9+/-0.9 and 1.9+/-0.3 mm, respectively. The thickness of the EAS and squeezing pressure did not correlate. Neither did the IAS thickness and the resting pressure. In cases with a history of vaginal delivery (n=15), the squeezing and the resting pressures were 94.0+/-43.0 and 57.1+/-22.2 cmH2O, and the thicknesses of the EAS and the IAS, 4.6+/-0.9 and 2.0+/-0.4 mm, respectively. The number of deliveries had no correlation with the thickness or the pressure of the anal sphincter. In patients with benign anal lesions (n=11), the squeezing and the resting pressure was 113.0+/-42.9 and 57.0+/-14.0 cmH2O, and the thicknesses of the EAS and the IAS were 5.0+/-1.3 and 2.1+/-0.4 mm, respectively. CONCLUSION: Our data suggest that the function and the structure of the anal sphincter are independent. In adult women, the thickness of the anal sphincter, the history of vaginal delivery, and the existence of benign anal lesions had no effect on anal sphincter function.

Preoperative CT Diagnosed Transomental Internal Hernia with Intestinal Obstruction: A case report

We report a case of an incarcerated internal hernia which was diagnosed preoperatively by using an abdominal CT scan. An-84-year-old female patient suddenly developed cramping upper abdominal pain after a meal, followed by nausea and vomiting associated with slight abdominal distension. This patient's initial abdominal plain X-ray was interpreted as indicating abdominal free gas. A dilated small bowel loop was revealed based on a late abdominal CT scan, and an internal hernia was suspected. On operation, herniation through defects in the gastrocolic omentum and gastrohepatic ligament was found and was successfully reduced. A jejunal loop internal herniation of this nature is extremely rare, and closed-loop obstructions result to incarceration or strangulation. When abnormal gas is detected at the right upper or the epigastric area in a simple abdominal X-ray. An unusual internal hernia must be a concern, and an abdominal CT scan can be useful for preoperative diagnosis.

A Case of a Metastatic Papillary Thyroid Carcinoma Presenting as a Lateral Neck Cyst

A case of a papillary thyroid carcinoma presenting as a cystic lateral neck mass is reported. A 73-year-old woman presented with a painless swelling of the right side of the neck which had been noticed for 60 years. The soft tissue mass was clinically and sonographically thought to be branchial cleft cyst. However, excisional biopsy showed it to be a cystic lymph-node metastasis from a papillary thyroid carcinoma. Two weeks later, a total thyroidectomy was performed, but no malignant lesion was found in the thyroid. This case of a metastatic papillary thyroid carcinoma to the lateral neck node mimiced a branchial cleft cyst. In old age, a lateral neck cyst being a cystic metastasis, as well as a benign cyst, should be considered so a careful preoperative evaluation is neccessary.

A Case of a Metastatic Papillary Thyroid Carcinoma Presenting as a Lateral Neck Cyst

A case of a papillary thyroid carcinoma presenting as a cystic lateral neck mass is reported. A 73-year-old woman presented with a painless swelling of the right side of the neck which had been noticed for 60 years. The soft tissue mass was clinically and sonographically thought to be branchial cleft cyst. However, excisional biopsy showed it to be a cystic lymph-node metastasis from a papillary thyroid carcinoma. Two weeks later, a total thyroidectomy was performed, but no malignant lesion was found in the thyroid. This case of a metastatic papillary thyroid carcinoma to the lateral neck node mimiced a branchial cleft cyst. In old age, a lateral neck cyst being a cystic metastasis, as well as a benign cyst, should be considered so a careful preoperative evaluation is neccessary.

Chemoembolization in the Treatment of Multiple or Unresectable Hepatic Metastases from Colorectal Cancer

BACKGROUND: Hepatic artery chemoembolization represents an alternative treatment for patients of metastasis or primary hepatic malignant lesions. The aims of this study was confirm the usefulness, the complications and the survival benefits of chemoembolization for patients with colorectal carcinoma metastasis to the liver. METHODS: During 3 years, 23 patients with multiple or bulky unresectable liver metastasis from colorectal cancer were treated with chemoembolization using adriamycin, cisplatin or mitomycin with lipiodol . Repeated treatments were perform at 6- to 8-week intervals. RESULTS: Hepatic metastases were detected at the initial diagnosis of colorectal cancer in 15 patients. The metastatic lesions included 7 cases of a single bulky lesion and 16 cases of multiple lesions. A decrease of at least 25% of the baseline CEA level occurred transiently in 43% of the cases. The median survival for all 23 patients was 10 months after initiation of chemoembolization, and the 1-year survival rate was 36%. Complications were liver abscesses with cholecystitis, thrombocytopenia, and ascites. CONCLUSION: Chemoembolization is feasible treatment modality for patients with multiple or un resectable hepatic metastases from colorectal cancer.

Modified Hanley's Operation in the Treatment

PURPOSE: Horseshoe type-ischiorectal fistula is originating initially from infected anal gland that connect with an anal crypt usually situated in the posterior midline of the anal canal. In the modified Hanley's operation, a prove inserted into the primary opening in directed into the posterior anal space. A straight incision from the primary opening toward the tip of the coccyx is made to unroof the posterior anal spcae and the anal portion of the fistulous tract. The secondary external fistula openings are incisied to permit better external drainage. The tracts are curratted but their entire lengths are not unroofed. This study presents the clinical features and the results obtained with modified Hanley's operation in the surgical management of horseshoe fistula. METHODS: This report is based on the clinical analysis of 22 cases of horseshoe type among 329 cases of fistula in ano, which were treated at the Department of General Surgery of Ewha Womans University Hospital from October 1993 to May 1998. RESULTS: The male to female ratio was 3.7:1 and the age was range from 19 years-old to 61 years-old. The symptom were anal discharge and pain. The previous or combined anal disease were anal abscess and hemorrhoids. The internal openings were located at the dentate line in 18 cases and anterior portion in 5 cases. Horseshoe ischorectal fistula included 17 cases of semi-horseshoe fistula and 1 case of horseshoe fistulous sinus. The spinal anesthesia and lithotomy position was used for operations. The cutting seton was applied in the 4 cases for preservation of sphincter function. The average hospital stay was 7.6 days and average wound healing time was 5.4 weeks. The postoperative complication of urinary retensio was found in the 2 cases. Recurrence, fecal incontinence, anal deformity and anal anterior diaplacement was not developed during following periods. CONCLUSIONS: We confirm that the modified Hanley's operation is a effective and conservative surgical procedure that minimizes the disadvantages of complete unroofing method & useful method for preservation of sphincter function.

Significance of p53 Expression in Colorectal Cancer in Young Patients

BACKGROUND: In Korea, the incidence rate of colorectal cancer is increasing, even in patients under 40 years of age. In most young adult patients with colorectal cancer, the tumors are already in advanced stages at initiation of treatment, and they are more aggressive, so the prognosis is considered unfavorable. In addition, alteration of the p53 gene may be associated with poor prognosis for colorectal cancer. METHODS: We evaluated the p53 expression in a young adult group and an adult group with colorectal cancer who had been operated at the Department of Surgery, Doungdaemoon Hospital, Medical Center of Ewha Womans University, from 1991 to 1996. We retrospectively reviewed the medical records of a randomized sampling of patients, 17 in the young adult group under 40 years of age and 20 in the adult group over 41 years of age. Pathologic slides were prepared for immunohistochemical staining of the p53 protein. The staining results were divided into positive and negative. The chi-square test, Fisher's exact test, and student t-test were perforemd with SAS program. RESULTS: There was no difference in the sex ratio, the tumor stage, the preoperative CEA level, the size of the tumor, the location of the tumor and the histologic differentiation between the two groups (p>0.05). In the young adult group, p53 was expressed in 41% of the cases (7/17), and in the adult group, p53 was expressed in 10% of the cases (2/20); thus p53 was expressed more frequently in the young adult group (p<0.05). CONCLUSION: The p53 expression tended to be associated with age and with more aggressive colorectal cancer, p53 expression may be a useful factor in determining a poor prognosis for patients with colorectal cancer.

Establishment of Canine Partial Liver Autotransplantation Model and Protective Effect of Prostaglandin I2 on the Ischemia-Reperfusion Injury / 대한이식학회지

BACKGROUND: The pathogenesis of primary non function or delayed graft function after liver transplantation is not yet clearly defined. However it is presumed that these unhappy events most likely attributes to the Kupffer cell-mediated, reperfusion injury aggravating the sinusoidal endothelial cell damage following preformed ischemic insults. Prostaglandin (PG) I2 and its analogues were reported to protect the liver against ischemic injury thereby be efficacious for the use during the preservation of harvested liver. Prevention of platelet aggregation, vasodilation, stabilization of lysosomal membranes, and inhibition of thromboxane generated by platelets may be the attributable biological activities of PGI2. PURPOSES: We designed this experimental study to assess the effect of continuous PGI2 infusion during in situ liver splitting on the bile flow from liver segment during resection and after reimplantation, and to establish our unique autotransplantation model in mongrel dogs before warming-up of living donor partial liver transplantation in the clinic. METHODS: Mongrel dogs weighing 15-25 kg were used after fasting for 12 hours. After endotracheal intubation under monitoring, abdomen was opened through the Chevron incision extending to xiphoid process. Initially, the right hepatic duct was ligated and divided. The common bile duct was divided, the end being cannulated proximally and drained. Basal bile flow was measured for 1 hour as a reference value. The left partial graft including the right medial, quadrate, left medial, left lateral lobe, and the papillary process of caudate lobe was resected en bloc. After cold flushing ex vivo, the harvested segment was immediately reimplanted orthotopically. In PGI2 group, PGI2 50 microgram was slowly infused through splenic venous cannulation. After closing the abdomen, the bile flow was measured continuously. RESULTS: Eleven out of 24 dogs were alive 12 hours after surgery; 5 in PGI2 and 6 in control group. Basal mean bile flow (BF) rate were 2.9 ml/hr/100 gm of liver tissue in control vs. 2.5 ml/hr/100 gm in PGI2 group. This difference did not reach the statistical significance. However, postoperative BF increased significantly in PGI2 group; 0.45 ml/hr/100 gm in contro vs. 1.71 ml/hr/100 gm in PGI2 group (p=0.04). CONCLUSION: Continuous infusion of PGI2 through the splenic vein during the harvest of the liver could mitigate the manipulation injury. The BF reflecting the quality of resected liver segment was relatively well preserved in PGI2 group after canine autotransplantation model. This model is not complicated, and will be useful for the mastery of surgical techniques for the living donor partial liver transplantation in the clinic.

Double Primary Cancer Patient with Sigmoid Colon Adenocarcinoma and Anal Squamous Cell Carcinoma with Rectal Mucosal Metastasis A case report

Synchronous neoplams are uncommon condition but the incidence is now being increased. The situation is rare when these tumors comes from different origin. We experienced the case with synchronous sigmoid colon cancer and anal squamous cell carcinoma with rectal mucosal metastasis. The patient was 61 years old male. He complained of intermittent hematochezia since 3~4 months ago. The patient underwent anterior resection for colon cancer and wide excision for anal squamous cell carcinoma. After surgical operation, postoperative adjuvant chemotherapy (5-FU + Leucovorin) and radiotherapy were done. In this case, we could preserve the anal sphincter using combined therapy. We think that this type of management may be useful treatment in patients with colon cancer and anal squamous cell cancer simultaneously.