Whole chromosome 17 loss in ovarian cancer

Chromosomal deletions, associated with the loss of normal function of tumour suppressor genes, have been identified in a variety of both familial and sporadic human cancers. Although the molecular pathology of ovarian cancer is not understood, several studies have reported deletions in chromosome 17 in ovarian tumours. We have used 13 restriction site polymorphic, microsatellite, and variable number tandem repeat markers to make a detailed analysis of chromosome 17 deletions in 12 benign and 19 malignant ovarian tumours. Two benign and 11 malignant tumours were informative for at least one marker on each arm of the chromosome. Loss of heterozygosity (LOH) was detected in both arms (by all informative markers) in 5 malignant tumours from four women (three with the disease at FIGO stage la). In a further bilateral ovarian tumour a partial LOH affecting 17q22-q25 was present in one ovary only. By contrast to a number of previous studies, none of the 19 malignant and 12 benign tumours showed ERBB2 (17q12ndash;22) amplification. The data presented show that the loss of a whole copy of chromosome 17 is a frequent and relatively early event in the development of some ovarian cancers. This suggests the possible involvement of multiple chromosome 17 loci in the pathogenesis of ovarian cancer. Equally plausible is that the loss of a whole chromosome copy could be the product of chromosomal instabilities induced by loss of the normal allele of tumour suppressors, such as TP53, located on this chromosome. © 1993 Wiley-Liss, Inc.     

Optimal Future Liver Remnant in Patients Treated with Extensive Preoperative Chemotherapy for Colorectal Liver Metastases

Background

Patients with colorectal liver metastases (CLM) are increasingly treated with preoperative chemotherapy. Chemotherapy associated liver injury is associated with postoperative hepatic insufficiency (PHI) and mortality. The adequate minimum future liver remnant (FLR) volume in patients treated with extensive chemotherapy remains unknown.

Methods

All patients with standardized FLR > 20 %, who underwent extended right hepatectomy for CLM from 1993-2011, were divided into three cohorts by chemotherapy duration: no chemotherapy (NC, n = 30), short duration (SD, ≤12 weeks, n = 78), long duration (LD, >12 weeks, n = 86). PHI and mortality were compared by using uni-/multivariate analyses. Optimal FLR for LD chemotherapy was determined using a minimum p-value approach.

Results

A total of 194 patients met inclusion criteria. LD chemotherapy was significantly associated with PHI (NC + SD 3.7 vs. LD 16.3%, p = 0.006). Ninety-day mortality rates were 0 % in NC, 1.3 % in SD, and 2.3% in LD patients, respectively (p = 0.95). In patients with FLR > 30 %, PHI occurred in only two patients (both LD, 2/20, 10 %), but all patients with FLR > 30 % survived. The best cutoff of FLR for preventing PHI after chemotherapy >12 weeks was estimated as >30 %. Both LD chemotherapy (odds ratio [OR] 5.4, p = 0.004) and FLR ≤ 30 % (OR 6.3, p = 0.019) were independent predictors of PHI.

Conclusions

Preoperative chemotherapy >12 weeks increases the risk of PHI after extended right hepatectomy. In patients treated with long-duration chemotherapy, FLR > 30 % reduces the rate of PHI and may provide enough functional reserve for clinical rescue if PHI develops.     

Eradication of Missing Liver Metastases After Fiducial Placement

Background

The risk of colorectal liver metastases (CLM) disappearing on cross-sectional imaging has increased with advances in preoperative chemotherapy, but <50 % of disappearing CLM demonstrate complete pathological response.

Objective

The aim of this study was to evaluate the role of fiducial marker placement before potentially curative treatment of CLM at risk of disappearing with chemotherapy.

Methods

All consecutive patients who underwent fiducial placement for tracking of CLM at a tertiary center were reviewed.

Results

Among 1377 patients undergoing CLM resection between 2005 and 2015, 35 patients underwent fiducial placement. Three patients were excluded due to disease progression. The study population comprised 32 patients who underwent fiducial placement in 41 CLM. Among the 41 marked CLM, 34 (83 %) were located >10 mm deep in the liver parenchyma, 25 (61 %) were in the right liver, and median size was 12 mm (range, 6–20 mm). No complication occurred after fiducial placement. After chemotherapy, 19 (46 %) of the 41 marked metastases disappeared on cross-sectional imaging. All fiducial-tracked CLM were treated with resection (n?=?31) or ablation (n?=?10). After median follow-up of 14 months (range, 0–64 months), no local recurrences were observed.

Conclusion

Fiducial placement represents a safe procedure that facilitates accurate localization for resection or ablation of small CLM at risk of disappearing with chemotherapy.

     

How can oral health care providers determine if patients have dry mouth?

BACKGROUND: Dentists recognize the importance of saliva in maintaining oral health and often are familiar with the clinical effects an insufficient salivary flow can have on oral tissues. A variety of medical conditions and medications can alter salivary secretion and composition. Typically, diagnosis of hyposalivation is made only after damage has occurred to the oral tissues. OVERVIEW: The author describes a series of clinical steps that, if followed properly, may help in the early detection of salivary gland hypofunction and prevention of its severe complications. This four-step approach includes identifying a patient's chief complaint and the symptoms and duration of illness that brought the patient to the dentist, as well as any approaches the patient took to relieve symptoms; obtaining a medical history that includes a review of the body systems; performing a clinical evaluation that notes the patient's overall condition in addition to the health and functioning of the salivary glands and oral soft and hard tissues; and, when needed, conducting further diagnostic evaluations. CONCLUSIONS AND CLINICAL IMPLICATIONS: Oral health care providers will continue to face the challenges of treating new and recurrent carious lesions if the profession's approach to salivary hypofunction remains reactive rather than proactive. The recommendations in this article may enhance clinicians' awareness of the objective methods used to identify patients with salivary gland hypofunction or those at risk of developing it. It is hoped that early identification of asymptomatic patients at risk of developing hyposalivation, as well as symptomatic patients will lower the incidence and prevalence of dental caries and fungal infection in this population and ultimately enhance their quality of life.     

Inhibition of insulin-like growth factor-1 receptor signaling enhances growth-inhibitory and proapoptotic effects of gefitinib (Iressa) in human breast cancer cells

Introduction  

Gefitinib (Iressa, ZD 1839, AstraZeneca) blocks the tyrosine kinase activity of the epidermal growth factor receptor (EGFR) and inhibits proliferation of several human cancer cell types including breast cancer. Phase II clinical trials with gefitinib monotherapy showed an objective response of 9 to 19% in non-small-cell lung cancer patients and less than 10% for breast cancer, and phase III results have indicated no benefit of gefitinib in combination with chemotherapy over chemotherapy alone. In order to improve the antineoplastic activity of gefitinib, we investigated the effects of blocking the signalling of the insulin-like growth factor 1 receptor (IGF-1R), a tyrosine kinase with a crucial role in malignancy that is coexpressed with EGFR in most human primary breast carcinomas.     

Diffuse FDG shoulder uptake on PET is associated with clinical findings of osteoarthritis

OBJECTIVE: Our objective was to examine the degree and pattern of (18)F-FDG uptake within the shoulder as a potential marker of joint inflammation or injury. SUBJECTS AND METHODS: Twenty-four patients undergoing (18)F-FDG PET for clinical oncologic assessment completed questionnaires regarding history of shoulder disease, trauma, pain, and/or functional impairment. Thorough physical examination of the shoulder was performed. A clinical diagnosis of specific shoulder derangement or normal was established for each patient. PET scans were evaluated blindly by a nuclear medicine physician and a musculoskeletal radiologist qualitatively for location, distribution, and intensity of shoulder uptake. Standardized uptake values (SUV) were measured. RESULTS: Twenty-one patients had shoulder PET findings. Fourteen had clinical findings consistent with a specific diagnosis in the PET-positive shoulder. The remaining seven PET-positive patients were clinically normal. Three recognizable patterns of uptake were appreciable. Eight of 10 patients with diffuse uptake had findings of osteoarthritis (n = 7) or bursitis (n = 1). Two of four patients with focal greater tuberosity uptake had findings of rotator cuff injury. Two of four patients with focal glenoid uptake had findings of frozen shoulder. SUV showed a positive correlation with subject age (p < 0.01), but no association with clinical findings was identified. CONCLUSION: The pattern of FDG uptake within the shoulder may point to specific clinical entities. While focal uptake is less reliably related to clinical findings, diffuse uptake is associated with signs and symptoms of osteoarthritis or bursitis.     

Non-contrast MR imaging of the glenohumeral joint. Part II. Glenohumeral instability and labrum tears

MR imaging of the shoulder without contrast is frequently used for evaluation of glenohumeral instability in spite of the popularity of MR arthrography. With proper imaging technique, familiarity with normal anatomy and variants as well as knowledge of the expected pathologic findings high diagnostic accuracy may be achieved.Part I of this Review Article Non-contrast MR imaging of the glenohumeral joint: Normal anatomy appeared in the previous issue (Number 10/Oct. 2004). See also:     

Saliva: a fountain of opportunity

Saliva continues to demonstrate that it is more complex than generally perceived and has more diagnostic value than is generally appreciated. This article will review some of the components and functions of saliva; discuss its promise as a diagnostic aid; review some of the problems associated with inadequate salivary function; and, it is hoped, enhance oral health care providers' appreciation of the importance of saliva in everyday clinical practice.