Israel Medical Association Journal

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.

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.

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[1] FAP = familial adenomatous polyposis

[2] IPAA = ileal pouch-anal anastomosis

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.

Israel has a National Screening Program for early detection of breast cancer. The need to continue and even expand this program was recently stressed in light of the high risk in the population. However, the optimal modalities for breast cancer screening are controversial, especially for women at risk. Mammography, the established screening method, is critically examined, and molecular imaging techniques, such as magnetic resonance spectroscopy and spectroscopic imaging are explored, especially for primary breast cancer detection. MRS[1] and MRSI[2] are currently limited by their reliance on the conventional framework for data analysis in biomedical imaging, i.e., the fast Fourier transform. Recent mathematical advances in signal processing via the fast Pade transform can extract diagnostically important information, which until now has been unavailable with in vivo MRS. A clinical MRS signal illustrates the rapid and stable convergence provided by FPT[3], yielding accurate information about key metabolites and their concentrations at short acquisition times. We suggest that the next step would be to apply the FPT to in vivo MRS/MRSI signals from patients with breast cancer and to compare these to findings for normal breast tissue. The potential implications of such an optimized MRS/MRSI for breast cancer screening strategies are discussed, especially for younger women at high risk.

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: Hyperthermia combined with radiation therapy was shown to be more effective in local recurrent breast cancer than radiotherapy alone, but it use is limited due to technical difficulties, stringent reimbursement policies and because it is time consuming.

Objectives: To report our experience with a simple and convenient XRT+HT[1] delivery system.

Methods: XRT was delivered through either electron or photon beams (total dose 30–40 Gy in previously irradiated fields or 50–70 Gy in non-irradiated fields). Hyperthermia was delivered by a dedicated HT device operating at 915 MHz. The heating session lasted 45 minutes. The maximal tumor surface temperature was set at 45°C and modified according to patient comfort. No intratumoral (invasive) thermometry was used. At least two HT sessions were scheduled to each HT field during the entire XRT treatment period. Tumor response was evaluated every 3 months after completion of treatment. The overall survival was measured from XRT+HT initiation until the last follow‑up.

Results: Fifteen women underwent 114 HT treatments delivered through 28 HT fields. Twenty-four HT fields (15 patients) were previously irradiated. There was complete infield response in 10 fields (6 patients), partial response in 8 fields (4 patients), no response or progressive disease in 4 fields (3 patients), and no parameters in 6 fields (5 patients). Eighteen (64%) fields had complete or partial response. Seven patients had outfield recurrence despite wide XRT+HT fields. Ulceration was the only major side effect (three patients, three fields).

Conclusions: The combined HT+XRT delivery system, with no invasive thermometry, is a simple and effective method for treating local recurrent breast cancer.

Background: Major efforts are being directed at the early diagnosis of breast cancer. The diagnosis rate of non-palpable tumors is steadily growing as a result of increased screening by mammography. In most patients with non-palpable lesions, percutaneous image-guided biopsies have replaced wire localization with surgical excision for obtaining tissue diagnosis. In recent years the Israel Ministry of Health initiated a mammograpy screening program. Percutaneous image-guided biopsies have also become widely available.

Objective: To assess the impact of these changes on breast cancer surgical treatment in our hospital.

Methods: The charts of 483 patients operated on in our department for primary breast carcinoma during the years 1997 to mid-2001 were reviewed. Data on the mode of diagnosis, tumor stage, resection margins, and number and types of operations were recorded and analyzed. The term non-palpable tumors relates to tumors necessitating wire localization for surgical excision.

Results: The percentage of patients diagnosed with non-palpable tumors rose from 16.2% in 1997 to 47.4% in 2001, with an average size of 2.6 cm for palpable and 1.7 cm for non-palpable tumors. The rate of preoperative diagnosis for non-palpable tumors rose from 6.2% in 1997 to 96.4% in 2001. The rate of involved or very close margins was reduced by 73% in the patient group diagnosed preoperatively as compared to those without a preoperative diagnosis (10.6% vs. 39.4%). Finally, the percentage of patients who had two operations fell from 56.2% in 1997 to 11.1% in 2001.

Conclusions: The mammography screening program in Jerusalem in 1997–2001 was effective in increasing the relative percentage of non-palpable breast cancers with reduced tumor size at diagnosis. The improved availability of preoperative tissue diagnosis in these patients reduced the number of surgical procedures needed.

Background: The World Health Organization considers a country's morphine consumption to be an important indicator of progress in pain relief. Despite the strong consensus favoring the use of opioids in many types of pain, limited data are available for gauging the trends in opioid usage in specific medical institutions, such as hospitals

Objectives: To assess the possibility that monitoring opioid consumption can shed light on directions and trends in the treatment of pain in a hospital setting.

Methods: Data on opioid consumption, number of inpatient days, and number of operations performed each year during the period 1990–1999 were obtained from records kept in the hospital’s pharmacy and archives.

Results: During that decade the overall opioid consumption in the hospital increased from the equivalent of 3.7 mg of oral morphine per inpatient day to 7.3 mg, and from 56 mg per surgical procedure to 100 mg. In 1990, injected opioids accounted for 93% of the overall consumption, whereas in 1999 they accounted for only 44%. Yet, the proportion of injected meperidine to injected morphine increased only from 43% to 51%.

Conclusions: These results suggest that the ongoing monitoring of opioid consumption can highlight trends and directions and possibly emphasize strengths and weaknesses in the treatment of pain in hospitals.

Background: The precise genes involved in conferring prostate cancer risk in sporadic and familial cases are not fully known.

Objectives: To evlauate the genetic profile within several candidate genes of unselected prostate cancer cases and to correlate this profile with disease parameters.

Methods: Jewish Israeli prostate cancer patients (n=224) were genotyped for polymorphisms within candidate genes: p53, ER, VDR, GSTT1, CYP1A1, GSTP1, GSTM1, EPHX and HPC2/ELAC2, followed by analysis of the genotype with relevant clinical and pathologic parameters.

Results: The EPHX gene His113 allele was detected in 21.4% (33/154) of patients in whom disease was diagnosed above 61 years, compared with 5.7% (4/70) in earlier onset disease (P < 0.001). Within the group of late-onset disease, the same allele was noted in 5.5% (2/36) with grade I tumors compared with 18% (34/188) with grade II and up (P = 0.004). All other tested polymorphisms were not associated with a distinct clinical or pathologic feature in a statistically significant manner.

Conclusions: In Israeli prostate cancer patients, the EPHX His113 allele is seemingly associated with a more advanced, late-onset disease. These preliminary data need to be confirmed by a larger and more ethnically diverse study.

Background: Drains are inserted in the dissected axilla of most patients during surgery for breast cancer.

Objective: To evaluate the presence and prognostic value of MUC1 and Met-HGF/SF in the axillary drainage of these patients.

Methods: The study group included 40 consecutive patients with invasive ductal carcinoma of the breast who were suitable for breast-conserving treatment; 20 malignant melanoma patients found to have negative axillary sentinel lymph node served as the control group. The output of the drains, which had been placed in the axilla during operation, was collected, and the presence of MUC1, Met-hepatocyte growth factor/scatter factor and b-actin were assessed in the lymphatic fluid by reverse transcription-polymerase chain reaction assays. The data were compared to the pathologic features of the tumor and the axillary lymph nodes, and to the estrogen and progesterone receptors status.

Results: RT-PCR[1] assays of the axillary lymphatic drainage were positive for MUC1 and Met-HGF/SF[2] in 15 (37.5%) and 26 (65%) of the patients, respectively. Patients in whom MUC1 and Met-HGF/SF were not found in the axillary fluid had smaller tumors and less capillary and lymphatic invasion, compared to patients with positive assays (P < 0.02 for all these comparisons). The lymph nodes were negative for metastases in all patients with negative assays (P < 0.001). The presence of MUC1 and Met-HGF/SF showed negative correlations with the estrogen and progesterone receptors (P < 0.05).

Conclusion: MUC1 and Met-HGF/SF can be detected in the axillary fluids of patients with breast cancer. The expression of both tumor markers in the axillary drainage is strongly associated with unfavorable tumor features and can be used as a prognostic factor.

Background: The histologic status of axillary lymph nodes is one of the most important prognostic factors in breast cancer, influencing the management of these patients. Axillary lymph node dissection was traditionally performed in all patients to obtain this information but this procedure carries a considerable rate of complications. Recently, sentinel lymph node biopsy has emerged as an accurate and minimally invasive tool for predicting the axillary nodal status and has become the standard of care in selected patients with breast cancer.

Objective: To examine the accuracy of SLN[1] biopsies performed by surgical residents during surgical resident training.

Methods: This prospective, randomized controlled study included 100 consecutive patients with clinically early breast cancer (T1-T2, N0, M0) study. Lymphatic mapping was performed using radiotracers, blue dye, or both. Formal axillary lymph node dissection completed the operations in all patients. All operations were performed by surgical residents under the supervision of senior surgeons.

Results: The overall rate of identification of sentinel lymph nodes was 92%. The accuracy of SLN biopsy in reflecting the axillary nodal status was 96% with a false negative rate of 5.7%.

Conclusions: Sentinel lymph node biopsy is an accurate method for the evaluation and staging of regional lymph nodes in breast cancer patients. A dedicated instruction program for surgical residents may increase the standard of care and lead to highly trained surgeons in the management of early breast cancer.

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