Annals of Coloproctology

Volume 19(2); April 2003

Original Articles

Effect of Lactacystin on the Sulindac-Induced Apoptosis Mechanisms in HT-29 Cells.: Kim, Jung Min , Park, Ki Jae , Kim, Sung Heun , Choi, Hong Jo; J Korean Soc Coloproctol. 2003;19(2):61-66.

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Abstract PDF: PURPOSE
One of possible mechanisms of the antineoplastic effect by nonsteroidal anti-inflammatory drugs (NSAIDs) is an induction of apoptosis. The NSAIDs-induced apoptosis appears to be caspase- and mitochondria-dependent. The ubiquitin-proteasome system, which is a fundamental non- lysosomal tool that cells use to process or degrade a variety of short-lived proteins, is known to be involved in apoptosis and to be located upstream of mitochondrial changes and caspase activation. The present study was conducted to explore the potential role of proteasome pathway in NSAIDs-induced apoptosis.
METHODS
We employed sulindac as a NSAID, and the lactacystin as a proteasome inhibitor to investigate the extent of the apoptosis in colon cancer cell line, HT-29 cells. The proteasome activity and the amount of apoptosis were quantified after cells were treated with 1 mM sulindac, 1micrometer lactacystin or both.
RESULTS
Sulindac treatment caused apoptosis of the HT-29 cells in a time-dependent manner with resultant changes in nuclear morphology. Western blots also showed caspase-3 activation and PARP cleavage after sulindac treatment. Not only single treatment with lactacystin decreased proteasome activity, but co-treatment with sulindac enhanced decrease in proteasome activity further (P<0.01). Treatment with lactacystin only did not induce apoptosis. However, lactacystin augmented the induction of sulindac-induced apoptosis (P<0.01). This synergistic effect was also proven by Western blot analyses, where co-treatment augmented the caspase-3 activation and PARP degradation.
CONCLUSIONS
The combination treatment of sulindac with a proteasome inhibitor lactacystin is suggested to be a very effective strategy for the induction of cancer cell apoptosis. Elucidation of the mechanism underlying the regression of colon cancers by combination of sulindac and lactacystin seems to be an immediate challenge in the near future.

Relationship between Expression of Thy- midylate Synthase mRNA and Resistance of Colon and Gastric Cancer Cells to 5-FU.: Cho, Sang Hyuk , Min, Young Don , Lee, Tae Bum , Choi, Seok Min , Byun, Ik Gun , Choi, Cheol Hee , Kim, Kyung Jong; J Korean Soc Coloproctol. 2003;19(2):67-73.

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Abstract PDF: PURPOSE
Thymidylate synthase (TS) is an important target for chemotherapeutic drugs such as 5-fluorouracil (5-FU). Overexpression of TS has been linked to chemotherapy resistance, but their relationship was not completely understood. We compared the expression level of TS with resistance of colon and gastric cancer cell lines to 5-FU.
METHODS
Expression of TS mRNA was determined by RT-PCR assay in 9 colon and 10 gastric cancer cell lines. Cytotoxicity of 5-FU was determined by MTT assay. Apoptosis was determined using propidium iodide staining by flow cytometry.
RESULTS
All cancer cell lines tested showed differential levels of TS mRNA expression. Colon cancer cell Colo320 (the highest expression of TS) was more resistant to 5-FU than SNU-C1 (the lowest expression of TS) was. Flow cytometry also showed that 5-FU induced apoptosis less in Colo320 than SNU-C1. But in gastric cancer cells SNU-1 (the highest expression of TS) was not resistant to 5-FU than SNU-16 (the lowest expression of TS) was.
CONCLUSIONS
The high level of expression of TS was correlated with resistance of colon cancer cells to 5-FU, but not in gastric cancer cells. Thus, TS may be differently involved in the resistance of gastric and colon cancer cells to 5-FU, which may depend on the origin of cancer cells and status of apoptosis related genes.

Outcome and Prognostic Factors Associated with Poor Outcome of Biofeedback Therapy for Constipated Patients with Non- relaxing Puborectalis Syndrome.: Baek, Soon Mann , Kim, Nam Hyuk , Hwang, Yong Hee , Kim, Kyong Rae , Choi, Kun Pil; J Korean Soc Coloproctol. 2003;19(2):74-81.

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Abstract PDF: PURPOSE
Biofeedback is a major treatment method for constipated patients with non-relaxing puborectalis syndrome. However a significant percent of patients still showed poor outcome, and little has been known about the predictors associated with outcome of biofeedback. The aim of this study was to determine the outcome and identify predictors associated with poor outcome of biofeedback therapy for constipated patients with non- relaxing puborectalis syndrome.
METHODS
Fifty-two constipated patients with non-relaxing puborectalis syndrome (median age, 47 years) who had more than one biofeedback session after defecography were evaluated by standardized questionnaire, before, immediately after treatment, and at follow-up. Clinical bowel symptoms and anorectal physiological studies were analyzed. Any differences in demographics, clinical symptoms, and parameters of anorectal physiological study were evaluated between success group (patients felt improvement in symptoms at follow-up) and failure group (patients felt no improvement).
RESULTS
Follow up (mean follow-up; 17 months) results were evaluated by an independent observer in 45 patients. At post-biofeedback, 42 (81 percents) patients felt improvement in symptoms, including 7 (13 percents) with complete symptom relief. At follow-up, 25 (56 percents) patients felt improvement in symptoms, including 1 (2 percents) with complete symptom relief. There was a significant reduction in difficult defecation (from 81 to 44, 53 percent, from pre-biofeedback to post-biofeedback, and at follow up respectively; P<0.005, P<0.01), sensation of incomplete defecation (from 90 to 50, 40 percent; P< 0.00001, P<0.000005), laxative use (from 25 to 10, 11 percent; P<0.05), and enema use (from 13 to 0, 2 percent; P<0.01, P<0.05). Normal spontaneous bowel movement was increased from 42 percent pre-biofeedback to 81 percent post-biofeedback (P<0.0001), 80 percent at follow up (P<0.0005). Pre-biofeedback presence of symptoms of bowel habit change predict poor outcome (15 vs. 0 percent; failure vs. success, P<0.05). High pressure zone in prebiofeedback manometry was longer in failure group than in success group (2.80 vs 2.01 cm, P<0.05). In the success group, 11 (44 percent) had a rectocele, 1 (4 percent) had a rectal intussussception, 18 (72 percent) had a descending perineal syndrome, and 3 (12 percent) had a sigmoidocele. In the failure group, 4 (20 percent) had a rectocele, and 1 (5 percent) had a rectal intussusception, 14 (70 percent) had a descending perineal syndrome, and a sigmoidocele was not accompanied (P<0.05). Accompanied rectocele, rectal intussusception, descending perineal syndrome, and sigmoidocele did not influence outcome.
CONCLUSIONS
Biofeedback is an effective option and should be considered as the first line therapy. Bowel habit change and long high pressure zone in pre-biofeedback manometry were predictors associated with poor outcome of biofeedback therapy for constipated patients with non-relaxing puborectalis syndrome.

Ileostomy Related Complications.: Song, Gi Won , Yu, Chang Sik , Lee, Hae Ok , Kim, Mi Sook , Namgung, Hwan , Lee, Gang Hong , Kim, Hee Cheol , Kim, Jin Cheon; J Korean Soc Coloproctol. 2003;19(2):82-89.

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Abstract PDF: PURPOSE
Ileostomy may affect various aspects of life style of the patient. Moreover the complication after ileostomy formation or closure may lower the life quality of the patient. The purpose of this study is to investigate ileostomy related complications and elucidate associated factors.
METHODS
We recruited 103 patients who underwent ileostomy in Asan Medical Center between July 1989 and June 2000. All ileostomies are constructed through the rectus muscle at the right lower quadrant of the abdomen. To mnimize peristomal skin irritation, at least two to three centimeters of the ileum lies above the skin level. We analyzed complications after ileostomy formation in relation to underlying diseases, types and purpose of ileostomy. Also, we analyzed complication after ileostomy closure in relation to underlying diseases, time interval and method of take-down.
Results
are compared using chi-square test. Statistical significance was assigned to a P value of<0.05.
RESULTS
Complications of ileostomy formation were developed in 17 (16.5%) cases; 8 peristomal dermatitis, 3 wound infection, 2 prolapse, 1 stenosis, 1 perforation, 1 bleeding, 1 high output ileostomy. There was no significant difference of complication rate in relation to underlying diseases, types and purpose of ileostomy. Ileostomy take-down was performed in 55 (53.4%) cases of 103 patients. Complications related with ileostomy take-down were developed in 18 (32.7%) cases; 7 wound infection, 5 intestinal obstruction, 2 incisional hernia, 2 enterocutaneous fistula, 1 anastomosis leakage, 1 bleeding. There was no significant difference of complication rate in relation to time interval or method of take-down. However, complication rate of ileostomy take-down was significantly increased in patient with inflammatory bowel disease.
CONCLUSIONS
Ileostomy formation is simple and safe surgical procedure. We couldn't find any factor affecting the morbidity of ileostomy formation or closure. However, complication rate after ileostomy closure, especially in patient with inflammatory bowel disease, is relatively high.

Treatment of Paradoxical Puborectalis Contraction (PPC) Using Botulinum Toxin-A.: Lee, Tae Soon , Lee, Han Il , Kim, Mi Kyoung , Park, Ki Hyuk , Choi, Dong Rack , Joo, Dae Hyun , Park, Sung Hwan , Yoo, Yong Oon , Park, Ki Ho , Kim, Jin Cheon; J Korean Soc Coloproctol. 2003;19(2):90-93.

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Abstract PDF: PURPOSE
Paradoxical puborectalis contraction (PPC) or Anismus is known to have a pathogenesis of abnormal contraction of puborectalis at defecation and its managements are not satisfactory. Recently, therapy of PPC and its associated symptoms using Botulinum toxin-A (BTX-A) has been introduced. we evaluate the effect of BTX-A injection to the puborectalis for the patients with PPC.
METHODS
Fourteen patients were diagnosed as paradoxical puborectalis contraction on defecography and/or anorectal manometry and electromyography (EMG) during September 1998 to January 2001 in Daegu Catholic Medical Centre, Catholic University of Daegu. All patients were underwent 30 (15 15) units of BTX-A injection on each side of puborectalis guided by EMG. Among them, five patients needed further injection of 20 (10 10) units because the expected results were not satisfied. Follow-up were conducted on one month and one year after BTX-A injection and the patients were assessed for the constipation score and anorectal manometry.
RESULTS
After injection of BTX-A, constipation score was significantly decreased from 15.5 +/- 3.5 (mean SD) to 5.7 +/- 4.3. Maximal resting and squeezing pressure also decreased from 48.4 +/- 22 mmHg, 96.9 +/- 39.8 to 41.2 +/- 17, 68.3 +/- 38.2, respectively. Twelve patients who were followed up more than one year after injection, the constipation score (n=12) increased up to 7.7 +/- 2.9 (mean SD). Among them, three patients have had stool softeners or laxatives to evacuate and the remained nine patients did not have any kinds of drug or food for defecation. There was no complication for the injection BTX-A.
CONCLUSIONS
BTX-A injection seems to be effective for the treatment of PPC and the long term therapeutic effect can be defined through double blind placebo-controlled trials.

Characteristic Findings and Their Clinical Appraisal of Proctography and Cinedefecography in Patients with Pelvic Outlet Obstructive Disease.: Kim, Kyong Rae , Kim, Young Sok , Chung, Soon Sup , Lee, Chang Hee , Chae, Gi Bong , Roh, Hye Rin , Choi, Won Jin , Park, Ung Chae; J Korean Soc Coloproctol. 2003;19(2):94-100.

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Abstract PDF: PURPOSE
We were assessed the characteristic findings of defecography and cinedefecography in patients with pelvic outlet obstructive disease, and compared the characteristic physiologic findings between proctography and cinedefecography.
METHODS
Physiologic findings of 196 patients who were performed at least two items of physiologic tests were retrospectively evaluated. Patients were categorized as rectocele (Group I: n=119), nonrelaxing puborectalis syndrome (Group II: n=58), rectoanal intussusception (Group III: n=16), significant sigmoidocele (Group IV: n=3). The proctographic and cinedefecographic features were analyzed according to disease categories. The sensitivity, specificity, accuracy, false positive rate, false negative rate, diagnostic rate, and reproducibility were calculated, and we analyzed the difference between proctography and cinedefecography according to the disease groups.
RESULTS
On the proctographic examinations; 1) 112 patients were confirmed as a clinically significant rectocele (n=128, sensitivity; 94%, specificity; 79%, accuracy; 88%, false positive rate; 21%, false negative rate; 6%, kappa; 0.749). 2) A clinically significant nonrelaxing puborectalis were 36 patients (n=73, sensitivity; 62%, specificity; 73%, accuracy; 70%, false positive rate; 27%, false negative rate; 38%, kappa; 0.328). 3) 12 patients were confirmed as significant rectoanal intussusception (n=31, sensitivity; 75%, specificity; 89%, accuracy; 88%, false positive rate; 11%, false negative rate; 25%, kappa; 0.425). 4) 3 patients were confirmed as clinically significant sigmoidocele (n=15, sensitivity; 100%, specificity; 94%, accuracy; 94%, false positive rate; 6%, false negative rate; 0%, kappa; 0.316). On the combination of proctography and cinedefecography; 1) 117 patients were confirmed as a clinically significant rectocele (n=122, sensitivity; 98%, specificity; 94%, accuracy; 96%, false positive rate; 6%, false negative rate; 2%, kappa; 0.925). 2) A clinically significant nonrelaxing puborectalis were 50 patients (n=64, sensitivity; 86%, specificity; 90%, accuracy; 88%, false positive rate; 10%, false negative rate; 14%, kappa; 0.738). 3) 16 patients were confirmed as significant rectoanal intussusception (n=22, sensitivity; 100%, specificity; 97%, accuracy; 97%, false positive rate; 3%, false negative rate; 0%, kappa; 0.826). 4) 3 patients were confirmed as clinically significant sigmoidocele (n=9, sensitivity; 100%, specificity; 97%, accuracy; 97%, false positive rate; 3%, false negative rate; 0%, kappa; 0.488). As compared with combined study (proctography plus cinedefecography), the proctography show decreased diagnostic rates in the evaluation of rectocele (P<0.05), nonrelaxing puborectalis (P<0.01), and rectoanal intussusception (P<0.05). And, the proctography also show increased false positive rate in the evaluation of rectocele (P<0.01), nonrelaxing puborectalis (P<0.01), and rectoanal intussusception (P<0.05).
CONCLUSIONS
In our study, proctography showed a tendency to overdiagnosis. Therefore, the combined study of proctography and cinedefecography should be taken as a diagnostic tools for pelvic outlet obstructive disease. Adhering to these findings, other anorectal physiologic studies should be added for the clinically significant diagnosis.

Randomized Controlled Trial

Clinical and Physiologic Anorectal Function after Low Anterior Resection in Patients with Rectal Cancer: A Prospective Randomized Comparison of Straight and Colonic J-Pouch Anastomoses.: Choi, Hong Jo , Kim, Sung Heun , Park, Ki Jae; J Korean Soc Coloproctol. 2003;19(2):101-107.

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Abstract PDF: PURPOSE
The aim of this prospective study was to analyze anorectal physiologic and clinical outcomes of the colonic J-pouch-anal anastomosis compared with the traditional straight colorectal anastomosis after ultra-low anterior resection in patients with rectal cancer, thus to define if this method of modified reconstruction has a functional superiority.
METHODS
After total mesorectal excision for mid or low rectal cancers, patients were randomized to either a straight (n=23) or a colonic J-pouch anastomosis (n=24) to the lowermost rectum or anal canal. Functional outcomes were compared between two groups using an anorectal manometry performed before and 1 year after surgery and a bowel function questionnaire administered 6 months and 1 year postoperatively.
RESULTS
Except the arithmetic level of anastomosis which was significantly higher in straight group than in pouch group (5.1 +/- 1.2 cm vs. 3.8 +/- 0.9 cm; P=0.0001), the two groups were well matched for demographic distribution, pathologic stage, colonic segment used for neorectum and use of adjuvant therapies. Patients with colonic J-pouch anastomosis showed functional superiority in terms of frequency of bowel movements, degree of urgency at 6 months (P<0.0001 and =0.03, respectively) and 1 year postoperatively (P<0.0001 and <0.05, respectively). Functional parameters, including incontinence to liquid stool and impaired discrimination between gas and stool were more pronounced in straight group after 6 months (P=0.04, and <0.05, respectively), but the differences were not statistically significant after 1 year. Sensation of incomplete evacuation was not different statistically between groups at 6 months, but more common in J-pouch group at 1 year (39.1% vs. 8.3%; P=0.04). As well as the length of high pressure zone and presence of rectoanal inhibitory reflex, there was no difference in sphincter pressure parameters between groups either before or 1 year after surgery. Maximal tolerable volume of the neorectum in J-pouch group was 110.2 +/- 16.7 ml, which was significantly larger than that of 74.1 +/- 14.9 ml in straight group (P<0.0001), and the neorectum in J-pouch group was significantly more compliant than that in straight group (6.1 +/- 1.9 vs. 3.3 +/- 2.1; P<0.0001) in 1 year after surgery.
CONCLUSIONS
Construction of a colonic J-pouch as a substitute for the rectum restores neorectal volume and compliance. Clinically it offers patients superior anorectal function compared with straight anastomosis. To minimize evacuation difficulty associated with the pouch, optimal size of the pouch should be defined, thus to achieve an ideal balance between stool frequency/urgency and evacuation problems through larger prospective studies.

Case Reports

A Case of Appendiceal Carcinoid Tumor.: Bae, Jong Dae , Bae, Jung Min , Jung, Ki Hoon , Jung, Byung Ook , Bae, Sung Han; J Korean Soc Coloproctol. 2003;19(2):108-111.

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Abstract PDF: Carcinoid is the most common tumor in the appendix and most often occurs in young patient. A case of mesoappendiceal invasion of carcinoid of appendix in presented and the literature review for indications for right hemicolectomy. A 38-year-old man was admitted to hospital after 3 day with right lower quadrant pain. The appendectomy was performed. At gross pathologic examination the appendix measured 7.5 cm in length and 1.6 cm in diameter. The serosal surface is congested and covered with yellow white fibrinoid material. The cut surface revealed a focal thickening of wall, measured 0.7 x 0.5 cm at 2 cm from tip of the appendix. Light microscopy revealed a typical carcinoid tumors infiltrating periappendiceal fat tissue. The patient was readmitted 4 weeks postoperatively for an elective right hemicolectomy. At exploratory laparotomy, there were no palpable lymph nodes. Exploration of the distal ileum, small bowel, and remaining abdomen did reveal any other carcinoid tumors.

Pseudomyxoma Peritonei Originated from Colon Cancer: Reports of Two Cases.: Kim, Kyung Rae , Min, Byung Wook , Um, Jun Won , Moon, Hong Young; J Korean Soc Coloproctol. 2003;19(2):112-118.

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Abstract PDF: Pseudomyxoma peritonei in which gelatinoid material deposits onto the peritoneum, accompanied by large amounts of mucinous ascites is a relatively infrequent disease, occurring with a 2 to 3-fold incidence in females. Among diverse benign and malignant tumors causing this condition, appendiceal and ovarian tumors are proved to be the most common. Yet on debate is whether these two tumors are simultaneously primary, while recent studies endorse the theory that the latter is secondary to the former. Removal of every inspected lesion should be performed in the treatment of pseudomyxoma peritonei. Laser photodynamic therapy after surgery is offered but still needs more clinical studies before utilization. Intraperitoneal or intravenous chemotherapy as intra- or postoperative adjuvant therapy is actively being studied for improvement of survival. The modality for treatment spotlighted recently is heated intraoperative intraperitoneal chemotherapy, based on the fact that chemoagents are more cytotoxic at a higher temperature of about 44 degrees C than at the usual body temperature and that pseudomyxoma peritonei rarely metastasizes via blood or lymph circulations. Many different clinical studies report many different results as to recurrence and survival rates. Tendency is that patients with pseudomyxoma peritonei which has originated from highly malignant tumors yield higher rate of operative complications and disease recurrence, and low survival rate on the other hand, which warrants ample studies and proper determination before any surgical procedure. We report with reviews of relavant literature two cases of pseudomyxoma peritonei we have experienced.

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