Annals of Coloproctology

Volume 18(6); December 2002

Original Articles

Genetic Instability and Mutations of Mismatch Repair (MMR) and p53 Gene in Colorectal Cancers with Multiple Polyps and Sporadic Colorectal Cancers.: Chun, Sung Won , Chang, Suk Kyun; J Korean Soc Coloproctol. 2002;18(6):353-362.

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Abstract PDF: PURPOSE
General conceptions of carcinogenic mechanisms by recent reports are ras-p53 gene pathway in sporadic colorectal cancers (SCC), MMR gene pathway in hereditary nonpolyposis colorectal cancer (HNPCC) and APC gene in familial adenomatous polyposis (FAP). But in the colorectal cancer with multiple polyps (CCMP), the carcinogenic pathway is not still defined exactly. In order to find out the which carcinogenic pathway control the CCMP and SCC, genetic instability were studied in CCMP and SCC.
METHODS
In this study, genetic instability on D2S123, D3S1029, D5S107, D6S87 and AP delta3 foci and gene mutations of hMLH1 (exon 2, 16, 19), hMSH2 (exon 11, 12, 13, 14) gene of MMR gene, p53 gene (exon 5, 6, 7, 8, 9) were studied on the 60 DNA samples of CCMP (30 cases) and SCC (30 cases).
RESULTS
1. Observed positive genetic instability was higher in CCMP (30%) than SCC (20%), and was higher in right colon cancers (33%) than left colon cancers (23%) or rectal cancers (17%), but not significant statisitically. And observed positive genetic instability was lower in moderate differentiated cancers (16%) than well (67%) or poorly (60%) differentiated cancers (P=0.005). 2. Any mutations of hMLH1 and hMSH2 gene of MMR gene were not observed in both of CCMP and SCC, but 3 cases (2 CCMPs and 1 SCC) point mutations of intron of hMSH2 gene, which were higher in positive genetic instability than negative (P=0.002). 3. This 3 cases point mutations were C for T which were on 6th bases upstream from codon 669. 4. From the results of SSCP for nucleotide sequencing of p53 gene, the abnormal bands were observed in 30% (9 of 30) of CCMP and SCC. Also the abnormal bands were observed in both of positive or negative genetic instability without differences.
CONCLUSIONS
With above results the authors suggested that the mechanism of genetic instability and mutations of p53 gene strongly affect the mechanism of carcinogenesis in SCC and CCMP. And there are relationship between genetic instability and point mutation at intron region of hMSH2 gene. However further evaluation and research is needed to establish relation between APC gene and other different kind of MMR gene.

Treatment of Chronic Anal Fissure with Topical Nitroglycerin.: Kim, Ji Yeon , Kim, Young Eil , Kim, Taek Kyu , Yoon, Chang Sik , Lee, Ho , Yoon, Wan Hee; J Korean Soc Coloproctol. 2002;18(6):364-368.

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Abstract PDF: PURPOSE
Lateral partial internal sphincterotomy is considered as the best surgical procedure of the idiopathic chronic anal fissure. Because the aim of surgery is to relieve sphincter spasm, and occasional minor incontinence following surgery has been reported, alternative chemical means of spasmolysis could be considered. Nitric oxide (NO) is known to be a major inhibitory neurotransmitter of the internal anal sphincter, so we investigated the effect of topical nitroglycerin for chronic anal fissure.
METHODS
Twenty nine patients (19 women, mean age 36 years) with chronic anal fissure were treated with 0.2% nitroglycerin ointment. Pain score was quantitated with Visual Analog Scale (VAS) in regular time interval. Manometry was performed in five patients and maximum anal resting pressure (MARP) was measured before and 30 minutes after topical application of nitroglycerin ointment. All patients were re-examined and questioned regarding pain relief and side effects 2 years after cessation of treatment.
RESULTS
All had appearances of chronicity and pain. There were 25 posterior and 12 anterior fissures. Pain was significantly abolished within 5 minutes after application of nitroglycerin ointment. Mean pain score (VAS) was 6.03 before, 0.69 30 min after, 0.58 1 week after, and 0.53 3 weeks after application of nitroglycerin ointment (P<0.001). MARP was markedly reduced 30 minutes after application of nitroglycerin from 166.2 15.1 cmH2O to 108.8 20.9 cmH2O (P<0.05). The 57% of patients (13/23) were effective for 2 years and 22% of patients (5/23) had recurred their symptom after cessation of nitroglycerin ointment. Two patients (9%), whose fissures had not healed completely within 3 weeks were requested for surgery and the other 2 patients (9%) had been operate due to the side effect of the ointment. Mild headache (7%) and dizziness (10%) were occured, but well tolerated when the dose was reduced.
CONCLUSIONS
Topical application of nitroglycerin ointment seems to be an effective and safe alternative in the treatment of chronic anal fissure.

Analysis of Factors Influencing Secondary Bleeding after Hemorrhoidectomy.: Hwang, Do Yeon , Kim, Yoo Jin , Chung, Ji Eun , Lee, Jong Ho , Chang, Hee Chul , Rhu, Jae Hyun , Kim, Hyun Shig , Lee, Jong Kyun; J Korean Soc Coloproctol. 2002;18(6):369-372.

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Abstract PDF: PURPOSE
Secondary bleeding is an inevitable and a troublesome complication of hemorrhoidectomy. This study analyzed the factors related to secondary bleeding after hemorrhoidectomy.
METHODS
A total of 14,062 patients received a hemorrhoidectomy from Apr. 1999 to Apr. 2001. A retrospective study of 83 patients with secondary bleeding was done. At first, the doctors were divided into two groups. In one group, each doctor had performed more than 500 hemorrhoidectomies; in the other groups, each doctor had performed less than 500 hemorrhoidectomies. The incidence of secondary bleeding of the two groups was compared. Then, 155 patients without secondary bleeding were randomly selected as a control group. Clinical aspects and laboratory data were compared with those of the bleeding group.
RESULTS
The total incidence of secondary bleeding was 0.6%. The incidence for the group with experienced doctors was 0.5%, that for the other group was 1.3%. When bleeding patients were compared with the control group, the proportion of patients who received a blood transfusion within 1 week before operation was 12.1% in the bleeding group and 2.6% in the control group. The postoperative WBC count was increased more in the bleeding group. The percentage treated with metronidazole was 12% compared with 25.3% in the control group. The incidences of bleeding according to operation sites were 19.6% in the right anterior, 12.2% in the left lateral, 10.9% in the right posterior, and 8.4% in the posterior portion.
CONCLUSIONS
Secondary bleeding after a hemorrhoidectomy is more prevalent with less experienced doctors, recent history of blood transfusion, less use of metronidazole, and specific location of the hemorrhoid, such as the right anterior and the left lateral site of the hemorrhoid pile.

The Clinical Features and Charateristics of anal Cancer Arising from Chronic Fistula-in-ano.: Son, Byung Ho , Han, Won Kon , Kim, Heung Dae , Kim, Kwang Yun; J Korean Soc Coloproctol. 2002;18(6):373-378.

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Abstract PDF: PURPOSE
The incidence of unhealed chronic fistula is about 7% and the cancer can occur in the longstanding unhealed fistula. The most of the cancer is mucinous adenocarcinoma. The report is diverse about treatment, adjuvant chemotherapy and prognosis. The purpose of this study is review of the clinical characteristics and survival of the anal cancer arising from chronic fistula-in-ano.
METHODS
The number of patients was 10. The diagnosis is made under pathological examination at the Kanbuk Samsung Hospital from 1983 to 2000. The retrograde study was done with patients' records and telephone questionnaire. The survival rate was calculated with Kaplan-Meier method.
RESULTS
All patients were male. The patients had symptoms of anal discharge and anal swelling suggesting the anal fistula. The patients had history of anal surgery. The external openings were multiple. Seven patients had mucinous adenocarcinoma. The prognosis was poor. Among 8 patients' follow-up data, except one patient, 7 patients died within 43 months.
CONCLUSIONS
The anal cancer can occur in longstanding unhealed fistula. In our series, all patients were male, and they had multiple opening fistula. The patient who had small size tumor have only survived. Through meticulous exploring and deep biopsy of the fistula, early detection is best method to treat the anal cancer arising from chronic fistula-in-ano.

Outcome and Predictors of Biofeedback Therapy for Patients with Internal Rectal Intussusception.: Kwon, Soon Ho , Hwang, Yong Hee , Choi, Kun Pil; J Korean Soc Coloproctol. 2002;18(6):379-385.

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Abstract PDF: PURPOSE
The aim of this study was to determine the outcome and identify predictors of success of biofeedback therapy for patients with internal rectal intussusception.
METHODS
Twenty-one patients (median age. 54 years, 15 female, 6 male) diagnosed with internal rectal intussusception by using cinedefecography were evaluated by standardized questionnaire, before, immediately after treatment, and at follow-up. Clinical bowel symptoms and anorectal physiological studies were also analyzed.
RESULTS
Follow up (median: 15, range 2~24 months) results were evaluated by an independent observer in 20 patients. At post-biofeedback, 20 (95%) patients felt improvement in symptoms, including 7 (33%) with complete symptom relief. At follow-up, 17 (85%) patients felt improvement in symptoms, including 7 (35%) with complete symptom relief. There was a significant reduction in difficult defecation (from 90 to 29, 10 percent, from pre-biofeedback to post-biofeedback, and at follow up respectively; P<0.001), sensation of incomplete defecation (from 90 to 24, 35 percent; P<0.001), enema use (from 29 to 0, 0 percent; P<0.01), and anal pain (from 19 to 0, 0 percent; P<0.05). Digitation (from 19 to 0 percent, from pre- biofeedback to at follow up; P<0.05) and laxative use (from 29 to 5 percent; P<0.05) were also decreased. Normal spontaneous bowel movement was increased from 52 percent, at pre-biofeedback to 86 percent, at post- biofeedback (P<0.05), 95 percent at follow up (P<0.005). Low bowel frequency, at pre-biofeedback (P<0.01), and hard stool (P<0.05) predicted poor outcome. Long puborectalis length during push (P<0.05) and dynamic descent (P<0.05) on defecography also predicted poor outcome. Low electrical activities of puborectalis and anal sphincter muscle during rest (P<0.001), squeeze (P<0.01) and push (P<0.005) on pre-biofeedback electromyography were related to poor outcome. No patient developed full rectal prolapse during follow up.
CONCLUSIONS
Biofeedback is an effective option and should be considered as the first line therapy especially for patients that don't have low bowel frequency, long puborectalis during push, and dynamic descent before treatment.

The Significance of Diverting Ileostomy during Restorative Proctocolectomy.: Hong, Dong Hyun , Yu, Chang Sik , NamGung, Hwan , Cho, Young Kyu , Kim, Hee Cheol , Kim, Jin Cheon; J Korean Soc Coloproctol. 2002;18(6):386-389.

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Abstract PDF: PURPOSE
Restorative proctocolectomy (RP) is a standard surgery in patients with ulcerative colitis and familial adenomatous polyposis. Usually, diverting ileostomy is performed to protect an ileoanal anastomosis with RP. However, there are many controversies whether diverting ileostomy might urgently be needed. This study was performed to compare postoperative complications after RP with or without diverting ileostomy.
METHODS
Between July 1994 and June 2001, 77 (M : F= 45 : 32) patients underwent RP. The indication criteria for diverting ileostomy included tension at the anastomosis, positive leakage test, compromised blood flow in the ileal pouch, long-term and high-dose steroid use, and severe rectal inflammation in ulcerative colitis patients.
RESULTS
Histopathologic diagnoses revealed 45 ulcerative colitis, 23 familial adenomatous polyposis, 5 rectal cancer, and 4 hereditary nonpolyposis colorectal cancer. Diverting ileostomies were performed in 40 patients (51.9%) and closed approximately 4 months later. Fourty eight complications were present in 32 patients. There was no perioperative death. There was no difference in perioperative outcome, morbidity or functional status between patients with and without ileostomy. However, in ulcerative colitis patients, anastomosis leakage was more frequent in patients without ileostomy.
CONCLUSIONS
Restorative proctocolectomy can be safely performed without diverting ileostomy in most cases of RP. However, diverting ileostomy may reduce anastomosis leakage in patients with ulcerative colitis.

The Clinical Analysis of Colonic Diverticulitis Accompanying Acute Abdomen.: Song, Joon Ho , Paik, Chong Dae , Lee, Sang Hee , Kim, Han Sun; J Korean Soc Coloproctol. 2002;18(6):390-396.

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Abstract PDF: PURPOSE
With the gradual changes in diet pattern, the incidence of diverticular disease have progressively increased. The diverticular disease including diverticulitis is difficult to diagnose prior to the operation as it mimics common acute abdominal conditions like acute appendicitis. Also, controversies abound as regards the optimal treatment, ranging from conservative treatment to colon resection. The aim of the present paper was to review diagnosis and treatment strategy followed by a clinical appraisal.
METHODS
We studied retrospectively 101 patients who were diagnosed as colonic diverticulitis for 10 years period between January, 1991 and December, 2000 at Seoul Red Cross Hospital, Dept. of Surgery.
RESULTS
There were 59 males and 42 females. The male to female ratio was 1.4 : 1. During admission, everyone complained abdominal pain as an initial symptom, especially on the right lower quadrant. The right colon was the most common site with single diverticulitis. The diagnosis of diverticulitis was performed by ultrasonography, CT scan, and colon study, barium enema, colonofiberscopy except in 17 cases which were diagnosed preoperatively having appendicitis. Two treatment groups were identified. Group I (n=48) received conservative treatment with or without appendectomy, while group II (n=53) underwent definitive surgery. Overall, there was no difference in clinical outcome except for the duration of antibiotics between two groups.
CONCLUSIONS
In treating uncomplicated diverticulitis, the conservative treatment should be considered at first. Conservative treatment with systemic antibiotics have resulted in a comparable outcome to that of the surgical group with low morbidity and low recurrence rate. Therefore, without serious complications such as hemorrhage, fistula, septic condition, inability to exclude carcinoma, clinical deterioration, young age, right colon diverticulitis, chronic stricture or the use of steroid, we propose that a conservative approach be adopted.

Oncological Safety of Flexible Rectal Stent Insertion in Obstructive Colorectal Cancer: Short Term Result.: Kim, Jong Hyun , Lee, Doo Seok , Choi, Sung Il , Lee, Woo Yong , Choo, Sung Wook , Do, Young Soo , Chun, Ho Kyung; J Korean Soc Coloproctol. 2002;18(6):397-401.

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Abstract PDF: PURPOSE
Flexible rectal stent for obstructive colorectal cancer has an advantage of elective one stage operation after decompression. But, forceful expansion of stent may increase the possibility of tumor cell dissemination through lymph nodes and blood vessels. We studied the oncological safety of stent insertion in obstructive colorectal cancer.
METHODS
From June 1996 to August 2001, the patients with stent insertion for obstructive colorectal cancer at Samsung Medical Center were retrospectively evaluated. Seventy- one patients had stent insertion for palliation or curative resection. Among these patients 15 patients underwent curative surgery after stent insertion (stent group). During the same period 25 patients underwent multi-staged operation after the decompressing colostomy or Hartman operation. (staged operation group). Statistical methods such as Fisher's exact test, 2-test, Kaplan-Meier method were used.
RESULTS
There was no significant difference between two groups in terms of age, gender, tumor location, and stage. The median follow-up period was 21 months in stent insertion group and 29 months in staged operation group. Overall recurrence rate was 33.3% in stent insertion group and 32.0% in staged operation group. The 5-year survival rate in stent insertion group was higher than in staged operation group (75.8% vs. 48.3%). But there was no statistical significance (P>0.05 ). Disease free survival was 22.4 (6~51) months in stent insertion group and 27.8 (5~71) months in staged operation group. There was no significant difference either.
CONCLUSIONS
There was no significant difference between two groups in survival rate, recurrence rate in short term result. Flexible rectal stent insertion can be considered as oncologically safe and useful treatment of obstructive colorectal cancer. But we think long term follow up and much more cases will be necessary to make a conclusion more definitively.

Clinical Trial of Oxaliplatin, 5-Fluorocuracil, and Leucovorin in Advanced Colorectal Cancer: 48 Cases.: Lee, Seung Hyun , Ahn, Byung Kwon , Baek, Sung Uhn; J Korean Soc Coloproctol. 2002;18(6):402-407.

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Abstract PDF: PURPOSE
Although 5-fluorouracil (5-FU) has been used as the basis of chemotherapy regimen for colorectal cancer for more than 40 years, 5-FU as single agent treatment has rarely achieved objective response rates higher than 15% in advanced colorectal cancers. The modulation of 5-FU with biologic modifiers has resulted in higher response rates, but survival advantages was not meaningful. Oxaliplatin is one of the newly developed drugs with proven activity against colorectal cancer. To evaluate the therapeutic efficacy and safety profile of oxaliplatin, we reviewed patients who received oxaliplatin chemotherapy.
METHODS
We reviewed 48 patients who received combination chemotherapy with oxaliplatin, 5-FU, and leucovorin (LV) from Jan. 2000 to Dec. 2001. The combination chemotherapy consisted of oxaliplatin (85 mg/m2 on day 1) as a 2~6 hour infusion followed by continuous infusion of 5-FU (1,500 mg/m2 on day 1, 2), concurrently with LV (45 mg on day 1, 2) as a 2 hour infusion. The combination chemotherapy interval was 2 weeks.
RESULTS
Of the 48 patients who received the combination chemotherapy with oxaliplatin, 5-FU, and LV, 25 cases were male, 23 cases were female. The median age was 51.4 years. The primary tumor sites were colon in 22 cases, and rectum in 26. According to TNM stage at diagnosis, 1 case was stage I, 5 cases were stage II, 21 cases were stage III, and 21 cases were stage IV. The metastatic sites were liver in 29 cases, lung in 10, pelvis in 7, peritoneum in 5, bone in 1, lymph node in 1, and spleen in 2. Previous chemotherapy were Mayo regimen in 43 patients, irrinotecan in 1 patient. Four patients had not received previous chemotherapy. Previously of the 48 patients, we could assess the chemotherapy response for 25 cases. Complete response was not observed. Partial response was 3 cases (12%), stable disease in 12 cases (48%), progressive disease in 10 cases (40%). From 227 cycles analyzed, the main toxicity was gastrointestinal one. Peripheral neuropathy was identifed in 5 cases.
CONCLUSIONS
We reviewed 48 patients with advanced colorectal cancer who received combination chemotherapy with oxaliplatin, 5-FU and LV. Of the 25 evaluable patients, the objective response rate was 12%. In our study, the combination chemotherapy with oxaliplatin, 5-FU, LV has not resulted in improved response rate, but overall toxicity was acceptable.

Age Factor in the Prognosis of the Colorectal Cancer.: Kang, Won Kyung , Chae, Byung Joo , Cho, Hyun Min , Park, Jong Kyung , Kim, Ji Yeon , An, Chang Hyeok , Oh, Seong Taek , Kim, Se Kyung; J Korean Soc Coloproctol. 2002;18(6):408-414.

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Abstract PDF: PURPOSE
Prognostic factors for patients who underwent colorectal cancer surgery, are such as clinical staging, possibility for curative surgery, and pathologic findings. But the age as a prognostic factor is still controversial. Therefore, we investigated the significance of age factor in colorectal cancer between young and older patients.
METHODS
The study subjects included 755 patients who underwent surgery for colorectal adenocarcinoma from January 1, 1990 to March 31, 1999 in Kangnam St. Mary's Hospital, Seoul, Korea. Average follow-up period was 24.8 24.4 months. The patients were divided into younger than 40 and older than 74 year-old groups and compared with control group including the age from 40 to 74. The prognosis of each group was evaluated according to the sex, staging, characteristics of tumor, family history, recurrence rate and patterns, pathologic findings, possibility for curative surgery, and survival rate.
RESULTS
Younger than 40 year-old group included 65 patients (8.6%) and older than 74 year-old group included 77 patients (10.2%). Their control groups included 613 patients (81.2%). There were no significant differences in tumor location, sex ratio, stage distribution, recurrence rate and patterns between the study and the control groups. However, there was significant higher incidence of family history in younger than 40 year-old group (7.7% vs 0.3%, P<0.05). Although there was no statistical significance, it is noteworthy that the ratio of undifferentiated or mucinous type were higher in younger than 40 year-old group than control group. Comparing the survival rates for each stage, the advanced stage of older than 74 year-old group had lower survival rate than control group (P<0.05).
CONCLUSIONS
Low survival rate in the older group can be explained by poor general condition and the high ratio of palliative surgery. The prognosis of cancer in the young age can not be poor just because it is discovered at the young age itself and it can be improved by careful follow-up in patients with familial history and early diagnosis and radical surgery in patients without familial history. However, it must be noted that younger patients have higher risk for undifferentiated or mucinous type.

Intraoperative Detection of Liver Metastasis after Preoperative Radiotherapy in Rectal Cancer.: Lee, Seung Hyun , Ahn, Byung Kwon , Baek, Sung Uhn; J Korean Soc Coloproctol. 2002;18(6):415-418.

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Abstract PDF: PURPOSE
Preoperatvie radiotherapy has many theoretical advantages in contrast to postoperative one such as preventing dissemination of cancer cells during surgery and increasing resectability rate by down-staging, thus more feasibility of preserving anus and improving survival. But there are several adverse effects, too. Distant metastasis can be detected after preoperative radiotherapy. Postoperative complication rate is high. Pathologic stage is changed after preoperative radiationtherapy so that there is difficulty in prediction of prognosis. We reviewed distant metastasis after preoperative radiotherapy and evaluated detection rate of metastasis with computed tomography in rectal cancer.
METHODS
Fifty patients with histologically proven rectal cancer and locally advanced lesions, as determined by physical examination and with no distant metastasis on preoperative computed tomography, entered the trial from 1990 to 1999. Surgery followed 2 to 6 weeks after completion of hyperthermia-chemoradiotherapy (HTCRT). Preoperative stages were determined with computed tomography. Postoperatve stage were determined by pathologic study.
RESULTS
Thirty cases were male. Twenty cases were female. Distance from anal verge to tumor were under 7 cm of 36 cases, over of 14 cases. The median tumor size was 3.3 cm in diameter. The conservation rate of anal sphincter function were 48.0%. In preoperative staging with computed tomography, the number of stage I, II, and III were 4, 11 and 35 cases. none were stage IV. The overall resectability rate was 90.0% (45 of 50 patients). In postoperative staging with pathologic study, the number of stage 0, I, II, and III were 4, 5, 19, and 13 cases. stage IV were 9 cases. Anastomotic leakage were noticed in 2 cases. In stage IV cases, liver metastases were noticed in all cases.
CONCLUSIONS
The preoperative radiotherapy was applied to the 50 patients with rectal cancer. The liver metastases which were detected after preoperative radiotherapy were 9 cases. The false negative value of computed tomography for liver metastasis in rectal cancer was 18.0%. We need more sensitive study for detecting liver metastasis of rectal cancer, especially in scheduled preoperative radiotherapy.

Case Report

Papillary Serous Carcinoma in Rectum-a Case of Complete Remission of Bulky Pelvic Disease after Platinum-paclitaxel Combination Chemotherapy.: Choi, Jung Hun , Yoon, Suk Hyun , Yoon, Wan Hee; J Korean Soc Coloproctol. 2002;18(6):419-422.

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Abstract PDF: Papillary serous carcinoma of the peritoneum (PSCP) is a primary tumor of peritoneal lining (mesothelioma) of the abdomen and is histologically difficult to differentiate from papillary serous carcinoma of the ovary. It is very rare tumor that involves the surface of the pelvic and/or abdominal peritoneum. Most patients with this tumor have been treated with optimally surgical cytoreduction and postoperative chemotherapy. However, long term survival has not been achieved in many studies. In recent years, platinum-paclitaxel combination therapy was reported as a effective initial therapy for recurrent PSCP. We have experienced one case of recurrent PSCP which was successfully treated with heptaplatin and paclitaxel. We report the toxicity and long term result of the patient.

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