Israel Medical Association Journal

Objectives: To analyze our 8 year experience using TEM[1] for the management of rectal cancer.

Methods: Local resection by TEM was performed in patients with benign tumors and early rectal cancer. In addition, selected patients with T2 and T3 rectal cancers who were either medically unfit or unwilling to undergo radical surgery were also treated with this modality. Radical surgery was offered to all patients with incomplete tumor excision by TEM.

Results: Overall, 116 TEM operations for rectal tumors were carried out between 1995 and 2003, including 74 patients with rectal adenomas and 42 patients with rectal carcinomas. Twenty-five patients had T1 tumors that were all successfully removed, with clear tumor margins, by TEM. Fourteen patients had T2 cancer and 3 of them (21%) required additional radical surgery due to incomplete excision. Local recurrence was observed in one patient with T2 cancer. There was no mortality. Major surgery, or radiotherapy-related complications requiring additional surgical intervention was needed in five patients with T2 cancer.

Conclusions: Local excision by TEM is a safe surgical procedure and should be offered to highly selected patients with early rectal cancer.

Objective: To investigate the effectiveness of preoperative chemoradiation in increasing the resectability rates of rectal cancer and increasing the anal sphincter preservation rate.

Methods: The study group included 66 patients aged 33–84 years with T₂–T₃ rectal carcinoma who were treated in our institute from 1997 to 2002 with preoperative chemoradiation followed by surgery 6 weeks later. All patients underwent preoperative transrectal endoscopic ultrasound for tumor staging and localization. The duration of follow-up was 25 months.

Results: Chemoradiation led to tumor downstaging in 61 patients (92.4%), all of whom underwent low anterior resection. Only 11.4% of this group needed a temporary (6 weeks) loop colostomy/ileostomy. None of the 16 patients with post-treatment T₀ tumors had evidence of malignant cells on pathologic study. Five patients (7.6%) failed to respond to chemoradiation and underwent APR[1]. There were no major complications, such as leakage, and no deaths.

Conclusions: Neoadjuvant chemoradiation is an effective modality to downstage advanced rectal cancer, improving patient quality of life by significantly reducing the need for a terminal permanent colostomy, or even a temporary one.

Objectives: To evaluate operative procedures, complications, early and late results and long-term functional outcome in FAP[1] patients operated in our department.

Methods: The study group included all patients with FAP who were operated between 1988 and 2003. Demographic data, length of follow‑up, complications, colorectal cancer, pouch function and extracolonic manifestations were recorded.

Results: Median age at surgery was 33 years (range 13–61 years). The final operative breakdown was: 48 proctocolectomies, 41 ileal pouch-anal anastomoses, 2 Kock’s pouch, 5 permanent ileostomies, and 2 colectomies with ileorectal anastomosis. There was no perioperative mortality. Early and late complications occurred in 20 and 9 patients, respectively. Twelve patients required re‑operation. Colorectal carcinoma was diagnosed in eight patients, three of whom were in an advanced stage. The mean follow‑up was 74 months (range 3–288 months). Four patients were lost to follow‑up. Extracolonic manifestations developed in 38 patients, including desmoid tumors (in 12), duodenal adenomas (in 9), pouch adenomas (in 5), and rectal stump adenomas (in 3). Two patients died (4%) because of desmoid tumor and malignant fibrous histiocytoma. At last follow‑up, 37 IPAA[2] patients have (median) six bowel movements/24 hours and good fecal control.

Conclusions: Restorative proctocolectomy can be performed with low mortality, acceptable morbidity, and good functional results. Patients should be closely followed after surgery for development of other manifestations of the syndrome. Relatives of the affected patients should be referred to a specialist multidisciplinary clinic.

____________________________

[1] FAP = familial adenomatous polyposis

[2] IPAA = ileal pouch-anal anastomosis

Background: Restorative proctocolectomy eliminates the risk of colorectal cancer in patients with familial adenomatous polyposis. Complications and extra‑intestinal manifestations are inherent to the procedure.

Objectives: To evaluate operative procedures, complications, early and late results and long-term functional outcome in FAP[1] patients operated in our department.

Methods: The study group included all patients with FAP who were operated between 1988 and 2003. Demographic data, length of follow‑up, complications, colorectal cancer, pouch function and extracolonic manifestations were recorded.

Results: Median age at surgery was 33 years (range 13–61 years). The final operative breakdown was: 48 proctocolectomies, 41 ileal pouch-anal anastomoses, 2 Kock’s pouch, 5 permanent ileostomies, and 2 colectomies with ileorectal anastomosis. There was no perioperative mortality. Early and late complications occurred in 20 and 9 patients, respectively. Twelve patients required re‑operation. Colorectal carcinoma was diagnosed in eight patients, three of whom were in an advanced stage. The mean follow‑up was 74 months (range 3–288 months). Four patients were lost to follow‑up. Extracolonic manifestations developed in 38 patients, including desmoid tumors (in 12), duodenal adenomas (in 9), pouch adenomas (in 5), and rectal stump adenomas (in 3). Two patients died (4%) because of desmoid tumor and malignant fibrous histiocytoma. At last follow‑up, 37 IPAA[2] patients have (median) six bowel movements/24 hours and good fecal control.

Conclusions: Restorative proctocolectomy can be performed with low mortality, acceptable morbidity, and good functional results. Patients should be closely followed after surgery for development of other manifestations of the syndrome. Relatives of the affected patients should be referred to a specialist multidisciplinary clinic.

Background: Preoperative radiotherapy is standard treatment for rectal cancer and is often combined with 5-fluorouracil-based chemotherapy. UFT, a new oral 5FU[1] derivative, given daily during a course of radiotherapy mimics the effect of continuous-infusion 5FU.

Objectives: To determine the maximum tolerated dose of oral UFT and leucovorin with preoperative pelvic irradiation for rectal cancer, and assess tumor response.

Methods: In this phase 1 trial, 16 patients aged 42–79 years with tumors within 12 cm of the anal verge received radiotherapy, 45 Gy over 5 weeks, an escalating dose of oral UFT, and a fixed dose of 30 mg/day leucovorin. UFT and leucovorin were given for 28 consecutive days concomitant with the first 4 weeks of radiotherapy. Surgery was scheduled for 4–6 weeks after completion of radiotherapy. The surgical procedure was determined by the surgeon at the time of surgery.

Results: No grade III toxicity was seen at 200 mg/m²/day UFT. Of eight patients who received 240 mg/m²/day UFT, one developed grade IV diarrhea; of four patients who received 270 mg/m²/day UFT, one was hospitalized with grade IV diarrhea and leukopenic fever and died during hospitalization. Of the 15 evaluable patients, 9 had pathologic tumor down-staging including 4 patients with complete response. Only one patient required a colostomy.
Conclusions: The MTD[2] of UFT together with leucovorin and preoperative radiotherapy for rectal cancer is 240 mg/m². The major toxicity was diarrhea. Down-staging was noted in 60% of patients, allowing sphincter-preserving surgery even in patients with low tumors.

Background: Mid- and lower rectum cancer is a technical challenge to the surgeon aiming to preserve the anal sphincter. The choice between abdominoperineal resection and anterior resection is often related to surgical skills.

Objectives: To evaluate the role of a specialized colorectal unit in preserving the anal sphincter mechanism in the treatment of rectal cancer.

Methods: Between 1991 and 1996, 75 patients with rectal cancer up to 12 cm from the anal verge were operated at the Sheba Medical Center. Among them, 21 patients (group 1) underwent surgery in the colorectal unit and 54 patients (group 2) in the other two surgical departments. All patients had a complete preoperative investigation and were followed for 12–90 months.

Results: Background and tumor parameters were similar for both groups. In group 1, 20 patients (95%) had low anterior resection and 1 patient (5%) had abdominoperineal resection as compared to 20 patients (37%) and 34 patients (63%), respectively, in group 2 (P < 0.005). There was no statistical difference in the systemic recurrence rate. Local recurrence was more frequent in group 2 (P < 0.05).

Conclusions: Special training in colorectal surgery enables the surgeon, in keeping with the principles of oncologic surgery, to preserve the anal sphincter mechanism in most patients with adenocarcinoma located in the mid- and lower third of the rectum.

Background: First-degree relatives of colorectal cancer patients are the largest groups of individuals at increased risk for colorectal cancer.

Objective: To assess the knowledge, attitudes and behavior to disease prevention and colorectal cancer screening among first-degree relatives of colon cancer patients.

Methods: A descriptive, point-prevalence epidemiological study was conducted among 215 first-degree relatives of survivors of colorectal cancer in the southern (Negev) region of Israel. Variables included perceived health status, knowledge about cancer screening, compliance rates with colorectal cancer screening, and interest in participation in early detection programs in the future.

Results: The mean age of the respondents was 47.9111.2 years, and 54% were males. Only 58 (27%) remembered having been encouraged to undergo an early detection test. In the previous year only 15% underwent fecal occult blood tests, while 9% had a barium enema and 14% an endoscopic examination of the colon by sigmoidoscopy or colonoscopy. A total of 49% of the asymptomatic respondents were unaware of recommendations for screening, and only 38.3% expressed any interest in participating in early detection programs in the future. Only 19% of respondents over the age of 50 and 8% of respondents over age 60 were interested in participating compared with 49% under the age of 50 (P0.0001).

Conclusion: A minority of first-degree relatives of colorectal cancer patients reported having been counseled to undergo screening, although most had seen their family physician in the previous 3 years. Primary care physicians should be more active in informing at-risk patients and encouraging them to undergo periodic screening.

There is increasing evidence to suggest that aspirin and other non-steroidal anti-inflammatory drugs reduce the risk of colorectal cancer. This observation is supported by animal studies that show fewer tumors per animal and fewer animals with tumors after administration of several different NSAIDs. Intervention data in familial adenomatous polyposis have established that the effect is exerted on the process of human colonic adenoma formation. Supportive evidence in sporadic colorectal neoplasia, derived from 22 of 24 studies (both case-control and cohort), found a reduced risk in men and women for cancers of the colon and the rectum and for both aspirin and the other NSAIDs. Earlier detection of lesions as a result of drug-induced bleeding does not seem to account for these findings. Although the molecular mechanism responsible for the chemopreventive action of this class of drugs is not yet completely understood, the protection may affect several pathways including both cell cycle arrest and induction of apoptosis.

In the third millennium the question is not if but how. Based on the consistency of epidemiological, clinical and experimental data, the association between regular long-term aspirin or NSAIDs intake and a decreased death rate from colorectal cancer is sound and there is no need for further placebo trials. At the same time, despite this consistency there is no clear data on the dose, duration or frequency of use for cancer-preventive activity.

Background: Previous studies have published controversial results regarding a connection between Helicobacter pylori infection and colorectal cancer. One possible mechanism is increased gastrin secretion in subjects infected with H. pylori, insofar as gastrin is known to be a trophic factor for the colonic mucosa.

Objectives: To investigate a possible role of gastrin secretion in H. pylori infection associated with colorectal cancer, and determine whether H. pylori infection is a factor in this disease.

Methods: The serum gastrin levels and the presence of H. pylori IgG antibodies were measured in 51 colorectal cancer patients and 51 control subjects. The cancer patients were also tested for carcinoembryonic antigen and CA 19-9.

Results: H. pylori IgG antibodies were found in the serum of 41 (80.4%) of the cancer patients compared to 32 (62.7%) of the control subjects (P=0.05). A significant correlation was found between CA 19-9 (γ=0.3432, n=49, P=0.01) and seropositive H. pylori IgG antibodies in the serum of the cancer patients (odds ratio 2.43, and 95% confidence limit 0.99-5.95), but none between CEA and H. pylori IgG antibodies nor between the serum gastrin level and the presence of colorectal cancer.

Conclusions: The results of this study indicate a significant association between seropositive H. pylori IgG antibodies and elevated CA 19-9 in colorectal cancer patients, but no correlation between the serum gastrin level and the presence of this cancer. H. pylori seropositivity is more prevalent in patients with colorectal cancer.