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עמוד בית
Thu, 26.12.24

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November 2005
Galinsky, D. Kisselgoff, T. Sella, T. Peretz, E. Libson and M. Sklair-Levy
 Background: Mammography is the principal breast cancer imaging technique; however, sensitivity is reduced, especially in dense breast tissue. Magnetic resonance imaging is increasingly used in the detection and characterization of breast cancers. The high sensitivity (95–100%) of MRI is consistently observed, and in many situations, MRI is proving superior to classical forms of imaging. Assessment of its impact on management and outcome is vital if MRI is to become standard in the management of breast cancers.

Objectives: To establish the impact of breast MRI on women undergoing testing in our institution.

Methods: We analyzed 82 cases that underwent MRI between January 2001 and April 2003. Analysis appraised the clinical impact of MRI testing in cases where medical summaries were available.

Results: Studies were categorized into five indications: a) screening in high risk women (n=7), b) search for primary disease in the presence of disease (n=5), c) monitoring of chemotherapy (n=2), d) postoperative assessment of tumor bed (n=9), and e) diagnostic/characterization of primary or recurrent breast cancer (n=59). Results were defined as negative, positive or no impact on clinical management. MRI testing had a positive impact in 62 cases, affecting measurable change in 9 cases. Benefit was seen in screening, diagnosis and postoperative cases. In 15 cases, MRI stimulated investigations.

Conclusion: MRI is a valuable tool in breast imaging and affects management. Further trials are necessary to define clearly the role of MRI and to ascertain whether in cases where beneficial impact on management is noted, there is ultimate impact on outcome. 

August 2005
Y. Niv
 Colorectal cancers develop as a consequence of genomic instability. Microsatellite instability is involved in the genesis of about 15% of sporadic colorectal cancers and in most hereditary non-polyposis cancers. High frequency MSI[1] has been associated with a favorable prognosis, however it is not clear whether this is because MSI-H[2] tumors are inherently less aggressive or because they are more sensitive to chemotherapy. Chemotherapy with a combination of 5-fluorouracil and leukovorin or levamizole has been the standard of care for high risk stage II and stage III CRC[3]; it is also used in stage IV CRC. Several in vitro studies have shown that colon cancer cell lines displaying MSI-H are less responsive to fluorouracil than microsatellite-stable cell lines. Human studies, all of them retrospective, yielded conflicting results. The selection of patients with CRC for 5-FU[4] treatment has been based so far on the stage of tumor rather than the biology of the tumor. Although surgical staging is highly predictive of survival, there are indications that the form of genomic instability within a patient’s colorectal tumor has clinical implications, with and without 5-FU treatment. This review suggests that patients with MSI-H colorectal tumors may not benefit from 5-FU-based chemotherapy and can avoid its potential side effects (nausea, diarrhea, stomatitis, dermatitis, alopecia, and neurologic symptoms) that occur in half the treated patients. If confirmed by future prospective randomized controlled studies, these findings would indicate that microsatellite-instability testing should be conducted routinely and the results used to direct rational adjuvant chemotherapy in colon cancer.


 


[1] MSI = microsatellite instability

[2] MSI-H - high frequency MSI

[3] CRC = colorectal cancer

[4] 5-FU = 5-fluorouracil


July 2005
S.D. Duek, M.M. Krausz and D.D. Hershko
Background: Transanal endoscopic microsurgery has recently gained acceptance as an alternative minimally invasive surgical technique for the curative management of large rectal adenomas and selected early rectal carcinomas.

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.


 


[1] TEM = transanal endoscopic microsurgery


E. Evron, L. Barzily, E. Rakowsky, N. Ben-Baruch, J. Sulkes, S. Rizel and E. Fenig
Background: Post-mastectomy loco-regional radiation to the chest wall and draining lymphatics, combined with adjuvant chemotherapy and hormonal therapy, significantly improve survival in patients with node-positive breast cancer. However, the actual benefit of post-mastectomy radiotherapy and the desired extent of treatment are still debatable.

Objectives: To examine the effect of postoperative loco-regional radiotherapy on local and regional recurrence and survival in breast cancer patients with four or more involved lymph nodes or extracapsular tumor extension.

Methods: This controlled clinical trial included 258 breast cancer patients with four or more involved nodes or ECE[1]. Eighty-nine patients in the control group had modified radical mastectomy and received adjuvant chemotherapy with melphalan and 5FU, but no radiation therapy. The 169 patients in the study group (87 with MRM[2] and 82 with lumpectomy and axillary dissection) received various adjuvant chemotherapy regimes and radiation therapy to the chest wall/breast, supraclavicular region and full axilla.

Results: With an average follow-up of more than 5 years, loco-regional radiation significantly reduced local and regional disease recurrence. The median disease-free survival was significantly longer in radiated patients (59.2 months and 63.3 months in the MRM and L+AXLND[3] groups, respectively, vs. 28.4 months in the control group; P < 0.01). There was no difference in the rate of systemic recurrence and overall survival. The median overall survival was 71.2 and 67.5 months in the study groups (MRM and L+AXLND, respectively) and 70.5 months in the control group (P = 0.856).

Conclusions: Radiotherapy to the breast/chest wall and to the draining lymphatics, in addition to surgery and adjuvant therapy, significantly reduced the risk of local and regional recurrence in high risk breast cancer patients with four or more involved lymph nodes or ECE.


 


[1] ECE = extracapsular tumor extension

[2] MRM = modified radical mastectomy

[3] L+AXLND = lumpectomy and axillary dissection


June 2005
I.L. Nudelman, V. Fuko, A. Geller, E. Fenig and S. Lelchuk
 Background: Abdominoperineal resection entails the need for a permanent colostomy, which significantly reduces patient self-image and quality of life.

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.


 





[1] APR = abdominoperineal resection


April 2005
H. Geva, G. Bar-Sela, Z. Dashkowsky, T. Mashiach and E. Robinson
Background: The use of complementary and alternative medicine has increased over the last decade in the western world.

Objectives: To evaluate the extent and characteristics of CAM[1] use among cancer patients in northern Israel.

Methods: Telephone interviews were conducted with 2,176 newly registered cancer patients or their family members, at least 1 year following referral.

Results: The rates of CAM use varied significantly according to demographic characteristics and chemotherapy treatment, from 3% in the basically educated elderly group up to 69% of educated Israeli-born Jews younger than 70 years receiving chemotherapy. The overall rate of CAM use was 17%. The most influential factors determining CAM use were academic or high school education, chemotherapy treatment, Israel as country of birth, and age 41–50 years. All patients used CAM in addition to conventional therapies. Less than half of them reported it to their physicians. The most frequently used treatments were various chemical, biological, botanic and homeopathy remedies. Friends and relatives were the main recommenders of CAM. Most CAM users reported that they used CAM because they believed it “strengthens the immune system,” alleviates side effects of chemotherapy, improves quality of life and helps to overcome pain and stress, and 62% of them reported subjective beneficial effects.

Conclusions: A predicting module of CAM user patients was built, which may help physicians initiate conversations with their patients on CAM use. Expanding physicians' knowledge on CAM methods will encourage them to provide additional advice, promote the use of beneficial therapies, and inform patients about potentially harmful methods.

___________________

[1] CAM = complementary and alternative medicine

L. Saidel-Odes and H. Shmuel Odes
 Colorectal cancer is a leading cause of cancer death in Israel. Our current understanding of the colorectal adenoma-carcinoma sequence has led to the use of screening for timely detection of polyps and cancer. Digital examination of the rectum is a test that can be performed by all doctors. Fecal occult blood testing, flexible sigmoidoscopy and colonoscopy are the standard screening techniques for patients. Computerized tomography colonography is now entering this field. This review discusses the merits and uncertainties of these strategies as related to the risk of colorectal cancer in selected populations.

February 2005
H. Tulchinsky, A. Keidar, G. Goldman, J.M. Klausner and M. Rabau
 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.

____________________________

[1] FAP = familial adenomatous polyposis

[2] IPAA = ileal pouch-anal anastomosis

H. Tulchinsky, A. Keidar, G. Goldman, J.M. Klausner and M. Rabau

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.

 






[1] FAP = familial adenomatous polyposis



[2] IPAA = ileal pouch-anal anastomosis


December 2004
T. Raveh Tilleman, M.M. Tilleman and M.H.A. Neumann

Background: The physical properties of cancerous skin tissue have rarely been measured in either fresh or frozen skin specimens. Of interest are the elastic properties associated with the skin's ability to deform, i.e., to stretch and compress. Two constants – Young’s modulus and Poisson’s ratio – represent the basic elastic behavior pattern of any elastic material, including skin. The former relates the applied stress on a specimen to its deformation via Hooke’s law, while the latter is the ratio between the axial and lateral strains.

Objectives: To investigate the elastic properties of cancerous skin tissue. For this purpose 23 consecutive cancerous tissue specimens prepared during Mohs micrographic surgery were analyzed.

Methods: From these specimens we calculated the change in radial length (defined as the radial strain) and the change in tissue thickness (defined as axial strain).

Results: Based on the above two strains we determined a Poisson ratio of 0.43 ± 0.12 and an average Young modulus of 52 KPa.

Conclusions: Defining the elastic properties of cancerous skin may become the first step in turning elasticity into a clinical tool. Correlating these constants with the histopathologic features of a cancerous tissue can contribute an additional non-invasive, in vivo and in vitro diagnostic tool.

October 2004
M.R. Pfeffer, Y. Kundel, M. Zehavi, R. Catane, M. Koller, O. Zmora, R. Elkayam and Z. Symon

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.







[1] 5FU = 5-fluorouracil

[2] MTD = maximum tolerated dose


K. Belkic

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.






[1] MRS = magnetic resonance spectroscopy

[2] MRSI = magnetic resonance spectroscopic imaging

[3] FPT = fast Padé transform


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