Israel Medical Association Journal

The laparoscopic approach to the treatment of colon and rectal cancer was controversial long after it was accepted for benign conditions. Laparoscopic cancer resection should meet appropriate oncologic standards and achieve a long-term oncologic outcome at least equivalent to that of open resection. Several international randomized controlled trials have provided adequate data to ascertain the oncologic quality of laparoscopic colon resection, showing a benefit in short-term outcome over open resection. The use of laparoscopic resection for rectal cancer is awaiting further investigation.

Background: HER2 is an important prognostic and predictive marker in invasive breast cancer. It is currently assessed by immunohistochemistry for protein over-expression and by fluorescence in situ hybridization for gene amplification. The immunohistochemistry-equivocal cases (2+) are currently retested by FISH[1] to determine eligibility for trastuzumab treatment. Retesting by FISH significantly raises the cost of patient management and sometimes delays treatment. The 4B5 is a new, FDA-approved, rabbit monoclonal antibody for HER2 testing.

Objectives: To examine the reliability of 4B5 IHC[2] HER2 testing in cases found to be HER2 status equivocal by CB11 IHC.

Methods: Twenty-eight invasive breast cancer cases, with an equivocal HER2 status by CB11 IHC, were retested by the 4B5 antibody as well as by FISH analysis. The scoring was performed using the same guidelines as HercepTest and was correlated with the FISH ratio. Results: Of the original 28 CB11 clone designated equivocal cases, 14 (50%) showed negative HER2 staining using the 4B5 clone (HercepTest score 0 and 1+). Five cases (18%) proved to be positive (HercepTest score 3+) and 9 cases (32%) remained equivocal (HercepTest score 2+). The corresponding FISH ratio results showed that all 4B5 negative cases were negative by FISH testing, with a negative predictive value of 100% 4 of 5 of the 4B5-positive cases were positive by FISH testing, with a positive predictive value of 80%. One 4B5-positive case was borderline-high (2.2 ratio) by FISH. The correlation between 4B5 IHC and FISH was statistically significant (P = 0.0013) by chi-square test.

Conclusions: Sequential testing by 4B5 IHC could greatly reduce the need for FISH testing in cases considered HER2 equivocal by CB11 IHC.
 

 
[1] FISH = fluorescence in situ hybridization

[2] IHC = immunohistochemistry

Background: An accurate preoperative definition of tumor and lymph node status is needed for reaching the correct decision regarding rectal cancer treatment. Transrectal ultrasonography is the most commonly used diagnostic modality for the local staging of rectal cancer.

Objectives: To determine the accuracy of TRUS[1] in the staging of rectal cancer.

Methods: We conducted a retrospective study on 95 patients evaluated by TRUS. The rectum was subdivided into two parts (lower and upper).

Results: Sixty patients underwent radical surgery. Of these, 34 received no preoperative chemo-irradiation owing to µT1, µT2 tumor or the patient’s choice (neo-adjuvant treatment was suggested to patients with adenocarcinoma that proved to be µT3). The overall accuracy rate was 80% for T stage. Overstaging was found in 13.3% and understaging in 6.7%.The N-stage was correctly assessed in 70%. The overall accuracy rate for tumors was 73.9% in the lower part and 90.9% in the upper. A trend towards a lower accuracy rate for low-lying tumors compared to high-located rectal tumors was found (P = 0.532), which did not reach statistical significance.

Conclusions: TRUS gave better results for T1 and T3 stage rectal tumors but was inaccurate for stage T2, indicating the possible need for local excision in order to base the final treatment for T2 tumors on pathologic staging.
[1] TRUS = transrectal ultrasonography
 

Background: Cancer is a leading cause of mortality worldwide. The most effective way to combat cancer is by prevention and early detection.

Objectives: To evaluate the outcome of screening an asymptomatic population for the presence of benign and neoplastic lesions.

Methods: Routine screening tests for prevention and/or early detection of 11 common cancers were conducted in 300 consecutive asymptomatic, apparently healthy adults, aged 25–77 years. Other tests were performed as indicated.

Results: Malignant and benign lesions were found in 3.3% and 5% of the screenees, respectively, compared to 1.7% in the general population. The most common lesions were in the gastrointestinal tract followed by skin, urogenital tract and breast. Advanced age and a family history of a malignancy were associated with increased risk for cancer with an odds ratio of 9 and 3.5, respectively (95% confidence interval 1.1–71 and 0.9–13, respectively). Moreover, high serum C-reactive protein levels and polymorphisms in the APC and CD24 genes indicated high cancer risk. When two of the polymorphisms existed in an individual, the risk for a malignant lesion was extremely high (23.1%; OR[1] 14, 95% CI[2] 2.5–78).

Conclusions: Screening asymptomatic subjects identifies a significant number of neoplastic lesions at an early stage. Incorporating data on genetic polymorphisms in the APC and CD24 genes can further identify individuals who are at increased risk for cancer. Cancer can be prevented and/or diagnosed at an early stage using the screening facilities of a multidisciplinary outpatient clinic.

Pancreatic cancer is not a common malignancy in Israel, but it is the third most common cause of cancer mortality, attributable to a lack of screening tests, inaccessibility of the pancreas, and late cancer stage at diagnosis. We reviewed the epidemiology, known risk factors and screening methods available in Israel and describe the Israeli national consortium that was established to identify persons at risk and decide on screening methods to detect and treat their early-stage pancreatic cancer. In collaboration with the Israel National Cancer Registry, we evaluated the incidence and trends of the disease in the Jewish and non-Jewish populations. The consortium reviewed known lifestyle risk habits and genetic causes, screening methodologies used and available in Israel. Overall, there are about 600 new patients per year, with the highest incidence occurring in Jewish men of European birth (age-standardized rate 8.11/10⁵ for 2003–06). The 5 year survival is about 5%. The consortium concluded that screening will be based on endoscopic ultrasonography. Pancreatic cancer patients and families at risk will be enrolled, demographic and lifestyle data collected and a cancer pedigree generated. Risk factors will be identified and genetic tests performed as required. This concerted national program to identify persons at risk, recommend which environmental risk factors to avoid and treat, and perform endoscopic ultrasound and genetic screening where appropriate, might reduce their incidence of invasive pancreatic cancer and/or improve its prognosis

Head and neck cancer is the sixth most common cancer worldwide. HNCs[1] can originate in the skin or soft tissue, in the upper aerodigestive tracts (oral cavity, oropharynx, hypopharynx, larynx, nasopharynx, paranasal sinuses, salivary glands), or in the thyroid. In each of these sites, tumors vary not only by the primary site but also by pathophysiology, biological behavior and sensitivity to radiotherapy or chemotherapy. Management should be planned according to the tumor's characteristics, patient factors and expertise of the medical team. The main goals of therapy are ablation of the cancer while minimizing morbidity and preserving function and cosmesis. A multidisciplinary team is needed to achieve these goals. Early-stage HNC (stage I and II) should be managed with a single modality, and advanced tumors (stage III and IV) with multimodality therapy. Treatment should be directed to the primary tumor and the area of its lymphatic drainage – the neck lymph nodes. Evidence of metastases in the neck necessitates comprehensive clearance of regional lymphatic basins. However, even if there is no evidence of lymph nodes metastases, when the risk for positive neck lymph nodes exceeds 15–20% elective neck dissection is indicated. Advances in minimally invasive techniques now enable reliable microscopic and endoscopic procedures that mimic the open approaches. Development of contemporary surgical techniques and reconstructive means will help improve the quality of life of patients and prolong survival.

Background: The role of endoscopic ultrasound in evaluating the response of esophageal cancer to neoadjuvant chemotherapy is controversial.

Objectives: To evaluate the accuracy of EUS[1] in restaging patients who underwent NAC[2].

Methods: The disease stage of patients with esophageal cancer was established by means of the TNM classification system. The initial staging was determined by chest and abdominal computed tomography and EUS. Patients who needed NAC underwent a preoperative regimen consisting of cisplatin and fluouracil. Upon completion of the chemotherapy, patients were restaged and then underwent esophagectomy. The results of the EUS staging were compared with the results of the surgical pathology staging. This comparison was done in two groups of patients: the study group (all patients who received NAC) and the control group (all patients who underwent primary esophagectomy without NAC).

Results: NAC was conducted in 20 patients with initial stage IIB and III carcinoma of the esophagus (study group). Post-chemotherapy EUS accurately predicted the surgical pathology stage in 6 patients (30%). Pathological down-staging was noted in 8 patients (40%). However, the EUS was able to observe it in only 2 patients (25%). The accuracy of EUS in determining the T status alone was 80%. The accuracy for N status alone was 35%. In 65% of examinations the EUS either overestimated (35%) or underestimated (30%) the N status. Thirteen patients with initial stage I-IIA underwent primary esophagectomy after the initial staging (control group). EUS accurately predicted the surgical pathology disease stage in 11 patients (85%).

Conclusions: EUS is an accurate modality for initial staging of esophageal carcinoma. However, it is not a reliable tool for restaging esophageal cancer after NAC and it cannot predict response to chemotherapy.

Background: Gastrointestinal stromal tumors are the most common mesenchymal neoplasms of the human gastrointestinal tract.

Objectives: To review our accumulated experience using surgery to treat gastrointestinal stromal tumors.

Methods: We reviewed all patient charts and histological diagnoses of leiomyomas, leiomyosarcomas, leiomyoblastomas and schwannomas. Only tumors that displayed c-kit (CD117) immunopositivity were defined as GISTs[1].

Results: The study group comprised 40 female and 53 male patients (age 26–89 years); 40.9% of the tumors were classified as malignant, 39.8% as benign, and 19.4% as of uncertain malignancy. Fifty-six GISTs were located in the stomach (60.2%), 29 in the small bowel (31.2%), 4 in the duodenum (4.3%), 2 in the colon (2.1%) and 2 in the rectum (2.1%). Incidental GISTs were found in 23.7% of our patients. Mean overall survival time for malignant gastric GISTs was 102.6 months (95% confidence interval 74.2–131.1) as compared to 61.4 months mean overall survival for malignant small bowel GISTs (95% CI[2] 35.7–87) (P = 0.262). The mean disease-free survival period for patients with malignant gastric GISTs was 97.5 months (95% CI 69.7–125.2) as compared to only 49.6 months (95% CI 27.4–71.7) for patients with small bowel malignant GISTs (P = 0.041).

Conclusions: We found a high percentage of incidental GISTs. Gastric GISTs are more common than small bowel GISTs. Patients with malignant gastric GISTs have a significantly better prognosis than patients with malignant small bowel GISTs. A statistically significant correlation was found between age and malignant potential of the GIST.