Objective: To improve early diagnosis of primary gallbladder carcinoma (PGC) and the understanding of its pathogenesis, pathological stages and prognosis. Methods: The data from 679 patients with PGC treated in our hospital from 1956 to 1998 were analyzed retrospectively. Results: The incidence of PGC has been increasing in recent years, and the treatment is not satisfactory. Upon diagnosis, most patients with PGC were at advanced stage. PGC was usually found in elderly women. The ratio of man to woman was 1:3. The gallstone, closely related to PGC, was found in 60% of the patients with PGC. The diagnostic accordance rate before and after operation was low. In most patients, PGC was found unexpectedly during operation for gallstone or acute cholecystitis. Many patients with PGC missed the opportunity of diagnosis and therapy because doctor only noticed the diagnosis of gallstone. Pathological classification revealed that PGC in most patients (84.4%) were adenocarcinoma. Imaging helped to find early-stage cases and improve prognosis. Conclusions: Understanding of pathogenesis, pathological stages and prognosis of PGC and proper use of various examinations are essential to the early diagnosis and treatment of the disease.

Am J Clin Pathol. 2002 Jun;117 Suppl:S104-8.
Prostate-specific antigen and the early diagnosis of prostate cancer.
Caplan A, Kratz A.
Division of Laboratory Medicine, Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, USA.

With digital rectal examination (DRE), prostate-specific antigen (PSA) is a major screening tool for prostate cancer. PSA is specific for the prostate, but not for prostate cancer. Multiple factors influence PSA value. Determination of PSA levels is not 100% sensitive for prostate cancer, as PSA levels may be normal despite presence of prostate cancer. The cutoff value for PSA of 4.0 ng/mL gives the highest sensitivity and highest specificity. Several modifications of PSA testing have been developed and may be beneficial for select populations. Uncertainty about the natural progression of prostate cancer and inherent limitations of PSA testing make it unclear whether universal screening is beneficial, and the recommendations of various organizations conflict. Randomized studies are in progress to address the role of PSA testing and of modifications of this test in the early detection of prostate cancer.

Korean J Gastroenterol. 2003 Sep;42(3):183-9.
Measurement of telomerase activity and telomerase reverse transcriptase expression in gastric fluid and tissue for early diagnosis of stomach cancer
Lee HJ, Myung SJ, Park YH, Cho YK, Jung HY, Lee GH, Hong WS, Yang SK, Kim JH, Min YI.
University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.

BACKGROUND/AIMS: Telomerase activity and telomerase reverse transcriptase (TERT) expression have been proposed as a marker for malignancy. However, little is known about those markers in intestinal metaplasia (IM). This study was performed to evaluate the usefulness of telomerase activity in gastric washing fluid and TERT expression in tissue as a marker for early diagnosis of stomach cancer. METHODS: Gastric washing fluid and biopsies were taken endoscopically. We examined the telomerase activity by telomeric repeat amplification protocol (TRAP) and the TERT expression by semiquantitative reverse transcription-polymerase chain reaction in 26, 21 and 15 cases of cancer, IM, and normal mucosa respectively. RESULTS: The telomerase activity was positive in 65% of cancer, 44% of incomplete IM, and 33% of complete IM. The TERT was expressed in 89% of cancer, 81% of IM, but not in normal mucosa. The TERT expression level was higher in cancer and incomplete IM than in complete IM and normal mucosa (p<0.05). CONCLUSIONS: Telomerase activity in gastric washing fluid and TERT expression in tissue may have limited usefulness as a marker for the early diagnosis of stomach cancer. However, the increased levels of TERT expression in IM and cancer suggest that TERT expression may be associated with carcinogenesis in stomach cancer.

An Sist Sanit Navar. 2002 Sep;25(3):305-315
FICTION as a new tool to early lung cancer diagnosis
Zudaire I, Pio R, Martin-Subero I, Lozano M, Blanco D, Garcia Lopez J, Odero De Dios M, Rey N, Zulueta J, Siebert R, Calazanz M, Montuenga L.
Departamento de Genetica, Universidad de Navarra, Pamplona.

Lung cancer is one of the most frequent causes of cancer death in Western countries. Overall 5-year survival rate is lower than 15% mainly due to the late diagnosis of the disease. Primary prevention (reduction of tobacco consumption) and more effective methods for early detection are needed. Some studies have recently shown that low-dose spiral computed tomography (CT) is a useful technique to the detection of pulmonary malignant nodules in early stages. Studies are developing to evaluate its efficacy in series of high-risk patients. A new cytogenetic technique has been developed: the FICTION technique (Fluorescence Immunophenotyping and Interphase Cytogenetics as a Tool for the Investigation of Neoplasms). This technique allows the simultaneous study of immunophenotypic markers and genetic abnormalities present in tumour cells. The goal of our project is optimise this technique in sputum and bronchoalveolar lavage specimens from lung cancer patients. The overall goal of this project is evaluate the usefulness of this technique, together with the new radiological techniques, in early detection programs of lung cancer in high-risk patients. In the present study we review the cytogenetic studies on lung cancer carried out in the recent years. We also introduce the basic methodological aspects that will be developed in our project.

Harefuah. 2003 Apr;142(4):281-6, 317.
Screening mammography for early diagnosis of breast cancer: facts, controversies, and the implementation in Israel
Allweis TM, Nissan A, Spira RM, Sklair-Levy M, Freund HR, Peretz T.
Department of Surgery, Roentgen Institute, Department of Oncology, University Hospitals, Hadassah Har-Hatsofim, Jerusalem, Israel.

BACKGROUND: Breast cancer is the leading cancer among Israeli women. Mammography is the most widely used tool for early diagnosis of breast cancer. Eight published randomized controlled trials followed nearly 500,000 women over 7 to 18 years. Most trials found that screening mammography decreases breast cancer mortality by 20 to 40%. A recent study examined the methodology of the randomized clinical trials and found that most trials were flawed in the methodology of data collection and analysis in a way that might have influenced the results of those trials. PURPOSE: To review the studies, clarify the issues, and reach a conclusion regarding the utility of screening mammography in reducing breast cancer-related mortality in Israel. METHODS: A review of the world literature, and analyses of the Israeli data. RESULTS: Seven out of eight published randomized controlled trials found a significant decrease in breast cancer mortality among women who underwent screening mammography. A meta-analysis of the trials also supports the utility of screening mammography in decreasing breast cancer mortality. The criticism over the methodology of these trials does not necessarily invalidate their conclusions. CONCLUSIONS: The data indicate that screening mammography does indeed assist in early diagnosis, and most published studies show a significant reduction in breast cancer-related mortality in the screened population. Due to the high incidence of breast cancer in the Israel, especially among young women, the national screening program should continue. Moreover, consideration should be given to expanding it to women starting at age 45, instead of 50, as is practiced today.

Refuat Hapeh Vehashinayim. 2002 Jul;19(3):38-48, 89.
Update review on prevention and early diagnosis in oral cancer
Hirshberg A, Calderon S, Kaplan I.
Dept. of Oral Pathology and Oral Medicine, Maurice and Gabriela Goldschleger School of Dental Medicine, Tel-Aviv University.

Oral cancer is a major health problem in some parts of the world, especially in developing countries. Worldwide, the annual incidence exceeds 3,000,000 new cases. The main risk factors are tobacco and alcohol. However, dietary factors, viruses and possibly genetic predisposition have also been associated with oral cancer. Several oral lesions such as leukoplakia, erythroplakia and lichen planus carry an increased risk for malignant transformation in the oral cavity. Prognosis of oral cancer differs significantly between specific oral locations, with cancer of the lip for example having a much better prognosis than at the base of tongue or on the gingiva. Prognosis of intra-oral cancer is generally poor, with a five-year survival less than 50 percent. Local recurrences as well as lymph node metastases occur in a significant percentage of patients, while distant metastases are less frequent. Prognosis correlates mainly with the size of the lesion and the nodal status at the time of diagnosis, therefore early detection of small, stage-1 oral cancer can reduce mortality and morbidity. Oral lesions can be easily observed by direct visualization, however, knowledge of the differential diagnosis of oral lesions is mandatory for early diagnosis of malignant and pre-malignant lesions in the oral cavity. Use of screening and detection aids such as vital stains and Oral CDX can increase the number of cases diagnosed at an early stage, or even in the pre-malignant stage. Development of molecular markers can improve the early diagnosis and can help in predicting treatment response. New treatment modalities including tumor specific antibodies and gene therapy are emerging, giving more hope for patients with oral cancer. There is an important role for the dentist in both early diagnosis of pre-malignant and malignant lesions, and in prevention by educating the patients of the risks associated with tobacco, alcohol and dietary factors.

Magy Onkol. 2000 Dec 1;44(4):275-283.
Early diagnosis of testicular cancer
Geczi L, Horvath Z, Beczassy E, Kisbenedek L, Bak M, Bodrogi I.
Kemoterapia B.osztaly, Orszagos Onkologiai Intezet, Budapest, H1122, Hungary.

PURPOSE: The authors analyze their 3-year results of the "educational and early detection program for testicular cancer". The goals of the program are to reduce the duration of symptoms and to improve early detection. METHODS: Advertisements were placed in the media describing the early signs of testicular cancer, the risks factors, the correct method of self-investigation and the importance of early detection. Between 1 April, 1995 and 1 April, 1998 5056 volunteers were examined. They underwent physical and ultrasound examination of the testicles, and in case of suspicious findings, tumor markers (alpha-fetoprotein, human choriogonadotropin) were checked. RESULTS: Testicular tumors were found in 1.28% of patients with symptoms (testicular enlargement or nodules). No tumor was found in the population that was symptom-free, or in patients with pain, sensitivity to palpation, or unrelated complaints. Of the patients with a palpable lump and swollen testicles, 4.5 and 3.9% were found to have tumors respectively. In total 32 testicular tumors were detected in 30 patients: 15 (2 bilateral) seminomas, 13 non-seminomas and 4 benign tumors. The occurrence of malignant testicular tumors was most frequent, 1.6% in the age group between 15 and 40 years. The stages were as follows: 9 I/A, 9 I/B, 1 I/S, 3 II/A, 1 II/B and 2 III/B. One patient was lost to follow-up after castration. All the other patients achieved complete remission. CONCLUSION: Despite the increasing incidence of testicular cancer screening of asymptomatic men does not lead to detection of tumors. The awareness of the early signs associated with cancer, self-examination, ultrasound examination of the testicle help in establishing an early diagnosis, nevertheless a widescale program for the early detection of testicular cancer is not justifiable. Effective early detection should be based on an educational program for the population at risk, the appropriate training of doctors and staff engaged in the health care of the young, and the initiation and facilitation of early ultrasound examination at the first symptoms. Serum markers play a limited role in early diagnosis.

Eur J Med Res. 2000 Dec 29;5(12):512-6.
The sign of Leser-Trelat: a paraneoplastic cutaneous syndrome that facilitates early diagnosis of occult cancer.
Vielhauer V, Herzinger T, Korting HC.
Medizinische Poliklinik, Ludwig-Maximilians-Universitat Munchen, Pettenkoferstr 8a, D-80336 Munchen, Germany.

The sign of Leser-Trelat has been described as a rare cutaneous marker of internal malignancy. We report a patient presenting with the sign of Leser-Trelat, in whom a limited diagnostic workup for an associated malignancy lead to the early diagnosis of asymptomatic renal cell carcinoma and curative tumor nephrectomy. A review on this and other cutaneous paraneoplastic syndromes is given. Since they may be the only presenting sign of an occult cancer, patients with these syndromes should undergo a diagnostic screening program for malignant disease.