Surgical relevance of diagnostic imaging techniques in pretherapeutic staging of carcinoma of the esophagus, stomach, colon and rectum

Summary. The increasing spectrum of therapeutic options for tumors of the gastrointestinal tract has resulted in a refinement of the pretherapeutic diagnostic strategies. The diagnostic approach in surgical institutions that are focused on primary surgical resection will therefore be much less sophisticated than in institutions who propose a selective therapeutic approach based on the pretherapeutic tumor stage and prognostic parameters. Pretherapeutic assessment of the depth of tumor infiltration, i. e. the T-category, is essential because most further diagnostic and therapeutic decisions are based on this information. This can today be achieved with a high degree of accuracy by endoscopy and endoscopic ultrasonography. Early T-stages (T1–2) are usually an indication for primary surgical resection and, after exclusion of distant metastases, no further diagnostic studies are required. In patients with locally advanced esophageal, gastric or rectum tumors (T3–4) multimodal therapeutic concepts should be considered. This usually requires additional diagnostic studies. None of the available diagnostic imaging modalities today allows satisfactory pretherapeutic assessment of lymph node metastases. The assumed nodular status should therefore currently not influence therapeutic decisions. Essential is, however, the assessment of distant metastases, since the documentation of distant tumor spread will change the therapeutic approach to a palliative situation. Detailed histologic and molecular-biologic assessment of tumor characteristics is growing in importance. This not only provides therapeutically relevant information regarding tumor grading, but opens the door towards a modern molecular diagnostic approach. It can be expected that in the near future a vast amount of relevant prognostic information can be obtained from endoscopic tumor biopsies, which may soon alter our therapeutic concepts.      

Breast Cancer Genes

Abstract: The identification of familial breast cancer genes heralds an era of directed breast cancer treatment. Currently, two hereditary breast cancer genes have been identified, BRCA-1 and BRCA-2 . Although accounting for only approximately 5% of all breast cancers, they are being used to identify women with germ-line alterations that are at high risk of developing breast or ovarian cancer. With the identification of such genes comes a need for consideration of the ethical issues associated with testing. These genes are also being examined from a biochemical standpoint encompassing both their biological roles and biochemical pathways in which they reside. Such studies are likely to lead to novel breast cancer therapies.     

Expression of CD44V2 in transitional cell carcinoma of the urinary bladder and in urine

CD44 is the principal cell surface receptor for hyaluronate. Variant forms of the receptor, produced by alternative splicing, have been found to be associated with tumor progression in a variety of cancers. Based on investigations at the RNA level, it has recently been proposed that expression of CD44 variant V2 was present in urothelial cancer but not in normal urothelium. Since a distinctive marker for urothelial cancer would be extremely useful, frozen sections of normal urothelium and urothelial cancer were examined for expression of standard CD44 and CD44V2. Frozen sections of specimens of 35 patients with transitional cell carcinoma of the bladder, 16 specimens of normal bladder and 5 ureters were examined. Immunohistochemical staining was performed using a polyclonal antibody to CD44V2 (PAB CD44V2), a monoclonal antibody to CD44V2 (MAB CD44V2) and a monoclonal antibody to CD44S (MAB CD44S). CD44V2 and CD44S were also measured in lysates of urine sediments from 21 patients by enzyme-linked immunoabsorbent assay (ELISA). All investigated transitional cell carcinomas expressed CD44V2. There was no differentiation between invasive and noninvasive carcinoma. CD44V2 was also expressed in normal urothelium. Standard CD44 was expressed by the transitional cell carcinoma, normal urothelium, musculature and interstitial tissue. The amount of CD44V2 and CD44S in lysates of urine sediments is not correlated to diagnosis. In contrast to investigations at the RNA level, CD44V2 on the protein level seems not to be a distinctive marker for urothelial cancer. Therefore, CD44V2 will not be a useful diagnostic marker for detection of transitional cell carcinoma.     

Hypothesis: association of the critical region of trisomy 18 and 18q2—syndrome with dermatoglyphic findings and a growth suppressor (deleted in colon cancer) locus

Evidence from the literature is reviewed to suggest that when fingertip dermal ridge patterns in chromosomal deletion syndromes are characteristic of the opposite spectrum of the developmental scale from patterns found in cases trisomic for the same chromosomal region, the association may be a consequence of loci with growth regulatory functions. Evidence is presented that DNA markers at 18q21 should be the first candidate sequences to be used to test this hypothesis in families with fingertip arches segregating in an apparent autosomal dominant fashion.     

Expression of pS2, c-erbB-2, and cathepsin D during the menstrual cycle in human breast cancers

Background: Many studies have addressed the effect of the timing of surgery for breast cancer relative to menstrual cycle phase, with conflicting results. Explanations for the possibility that survival could be altered by the appropriate timing of breast cancer surgery in humans remain speculative. Methods: We examined the expression of three estrogen related proteins (c-erbB-2, cathepsin D, pS2) in the breast tumors from 69 premenopausal women sampled in different phases of the menstrual cycle. Data on S-phase fraction and hormone receptor expression were also analyzed. Immunohistochemical assays were used to measure the proteins of interest. S-phase fraction was determined by flow cytometry. Analyses were performed based on fraction of cells staining positive for the protein, density of stain, and a histoscore that combined both fraction of positive cells and density. Results: We found no differences in c-erbB-2, cathepsin D, hormone receptor, or S-phase levels in tumors sampled in the follicular versus luteal phase, or perimenstrual versus periovulatory phase. The exception was pS2, which was expressed at greater levels during the luteal than during the follicular phase of the cycle (p<0.01); but there was no difference in pS2 expression when the patients were classified as periovulatory versus perimenstrual. Conclusions: Our findings do not support a variation in c-erbB-2, cathepsin D, S-phase fraction, or receptor expression as an explanation for the differences in breast cancer prognosis when surgery is timed by menstrual cycle phase. The finding that pS2 (an indicator of hormone sensitivity, and possibly better prognosis) is expressed at higher levels in tumor samples during the luteal phase suggests that the biologic profile of breast tumors may vary with the menstrual cycle and that these variations deserve further study.     

Assessment of SPECT ventilation-perfusion imaging in patients with lung cancer

Ventilation and perfusion SPECT images during tidal breathing were studied in 15 cases of lung cancer using ^81mKr gas and ^99mTc-microspheres. Furthermore, functional images of V/Q ratio and Q/V ratio were prepared, and their clinical significance is descussed with reference to general lung function. There was a decreas in %VC and %FEV _1.0in 7 of 15 cases, and an increase of AaDo₂ in the blood gas analysis in 12 of 15 cases. Both planar and SPECT images showed ventilation and perfusion abnormalities in all 15 cases. Of these, 12 patients showed matched ventilation and perfusion defects, 2 patients a dead-space effect and 1 patient a shunt effect. In comparing planar and SPECT images, depiction of ventilation and perfusion impairments were equally clear in 11 cases, but in 3, showing a lobar or segmental defect with a shunt effect, the SPECT images were superior. In a patient with markedly impaired function of the affected lung, the remaining function could not be depicted by SPECT. From the above, it seems that better information can be obtained for understanding the ventilation and perfusion states of lung cancer by adding the SPECT images to the planar image.     

The pros and cons of fecal occult blood testing for colorectal neoplasms

Testing feces for occult blood is widely recommended as a means of detecting subclinical colorectal tumors. Guaiac tests such as Hemoccult^® are the most widely used, but chemical sensitivity is relatively low and the tests are affected by dietary peroxidases, the state of fecal hydration, and certain drugs. The newly devised HemoQuant^® and immunologic techniques appear more sensitive and specific, but they require further evaluation before widespread clinical usage can be recommended.Occult blood screening has both merits and weaknesses. Testing does uncover subclinical colorectal cancer, often at a relatively early stage, but whether this actually improves the prognosis remains to be proven. Benign neoplastic polyps are also detected, although it is debatable whether this is a valid rationale for screening. Test sensitivity for malignancy varies from good to moderate, but is poor for benign polyps. Specificity is usually around 97%–98%, yet the predictive value of a positive test for cancer is only about 10%: hence most test-positive individuals are needlessly subjected to invasive colonic investigations. Reported figures on public compliance with occult blood testing vary widely from excellent to poor. Published costs of screening are usually quite low, but these overlook important indirect and hidden expenses and are therefore misleading.On balance, the problems of occult blood testing currently appear to outweight the merits. This could change, however, with the newer testing techniques and with awaited mortality data from controlled clinical trials now underway.     

Bone Density in Survivors of Childhood Cancer

Advances in combination chemotherapy, radiation therapy, surgery, and bone marrow transplantation have resulted in markedly improved survival rates for many children with cancer. Advancements in therapy, however, have led to new concerns, namely long-term consequences of effective treatments. Young adult and adult survivors of childhood cancer are at risk for a number of disorders related to therapy. Specifically, the young adult who has survived cancer, attendant treatments, and their complications is at risk for factors that can lead to suboptimal acquisition of peak bone mass. These factors include chronic illness, nutritional deficiencies, limited physical activity, and treatment with glucocorticoids, multiagent chemotherapy, and radiation. The long-term adverse effects of these therapies on endocrine systems, especially sex steroid and growth hormone deficiencies, are additional risk factors for some patients. After a brief review of the processes associated with acquisition of peak bone mass in the young adult, this article examines the impact of cancer and cancer therapy on bone mineral density in survivors of childhood cancer.     

Symptomatic renal metastasis 5 years after the management of a squamous cell carcinoma of the lung

A case of solitary renal metastasis five years after the management of a primary squamous cell carcinoma of the lung is presented.