Biomedical subjects
Publications and source records attributed to A G Tsiotou.
With the possible exception of pulmonary artery catheters, central venous catheters (CVCs) have the highest rates of infection of all intravascular catheters, accounting for up to 90% of all vascular catheter-related bloodstream infections. The frequency of CVC-related infections is between 10-30%.
It is not at all uncommon for surgeons dealing with breast disease to be confronted with the issue of prophylactic mastectomy. Recent advances in understanding the genetic basis of susceptibility to breast cancer and a better identification of the histological factors affecting a woman's lifetime risk of developing breast cancer have contributed to placing prophylactic mastectomy in a proper clinical perspective. Existing data suggest that prophylactic total mastectomy significantly reduces, but does not totally eliminate, the risk of subsequent development of cancer. However, the benefit of prophylactic mastectomy over alternative strategies (surveillance and chemoprevention) remains to be proven. Currently, prophylactic mastectomy may be considered in a few, carefully selected patients. The decision to perform a prophylactic mastectomy should be a multidisciplinary one. Detailed patient' counselling is very important; the patient should understand the limitations of prophylactic mastectomy and the need for postoperative follow-up. Furthermore, she should be well informed about the alternative strategies.
BACKGROUND: Molecular alterations in proto-oncogenes, tumour suppressor genes, and genes that function in DNA damage recognition and repair are considered to be hallmarks of a carcinogenic process, including breast carcinogenesis. METHODS: A computer-assisted search of the English literature (Medline database, 1990-1999) was performed, followed by a manual search of the reference list of pertinent articles retrieved. RESULTS: Hereditary breast cancer accounts for 5-10 per cent of all breast cancer cases. About 90 per cent of hereditary breast cancers involve mutation of the BRCA1 and/or BRCA2 genes. Other cancer-related genes (including myc, c-erbB2, Tsg101 and Mdgi) are involved in breast carcinogenesis, but they do not give rise to familial breast cancer syndromes. Risk estimation is the most important clinical implication. Management options for the high-risk mutation carriers include cancer surveillance and preventive strategies (prophylactic surgery or chemoprevention). CONCLUSION: Despite inadequate knowledge about the genetic predisposition to breast cancer and its clinical implications, the demand for genetic testing is likely to expand rapidly. In addition to risk estimation, cancer surveillance and preventive strategies, gene therapy offers a new and theoretically attractive approach to breast cancer management.
Pancreatic cancer represents the fourth leading cause of cancer death in men and the fifth in women. Prognosis remains dismal, mainly because the diagnosis is made late in the clinical course of the disease. The need to improve the diagnosis, detection, and treatment of pancreatic cancer is great. It is in this type of cancer, in which the mortality is so great and the clinical detection so difficult that the recent advances of molecular biology may have a significant impact. Genetic alterations can be detected at different levels. These alterations include oncogene mutations (most commonly, K-ras mutations, which occur in 75% to more than 95% of pancreatic cancer tissues), tumour suppressor genes alterations (mainly, p53, p16, DCC, etc.), overexpression of growth factors (such as EGF, TGF alpha, TGF beta 1-3, aFGF, bTGF, etc.) and their receptors (i.e., EGF receptor, TGF beta receptor I-III, etc.). Insights into the molecular genetics of pancreatic carcinogenesis are beginning to form a genetic model for pancreatic cancer and its precursors. These improvements in our understanding of the molecular biology of pancreatic cancer are not simply of research interest, but may have clinical implications, such as risk assessment, early diagnosis, treatment, and prognosis evaluation.
Ductal carcinoma in situ (DCIS) of the breast is an early, localized stage of carcinoma in the process of multistep breast carcinogenesis. The incidence of DCIS is increasing, mainly due to screening mammography, which results in diagnosing the disease in an increasing proportion of asymptomatic patients. Consequently, clinicians are being confronted with growing numbers of women who present with DCIS of the breast; thus, the concepts of managing such patients are assuming greater importance. The most common presentation is calcifications on mammography. DCIS is a biologically and morphologically heterogeneous disease. If left untreated, a significant proportion of these tumours will evolve into invasive cancer. However, when appropriately treated, the prognosis of DCIS is excellent. Optimal management of DCIS remains controversial. The goal in the treatment of patients with DCIS is to control local disease and prevent subsequent development of invasive cancer. For several decades, total mastectomy was the treatment of choice for DCIS and it should still be considered the standard of care, to which more conservative forms of treatment must be compared. Mastectomy is associated with a risk for chest wall recurrence of approximately 1%. Axillary lymph node dissection is not routinely recommended in the management of DCIS. However, mastectomy probably represents overtreatment in a substantial number of patients, especially those with small, mammographically detected lesions. Local excision alone has been suggested in carefully selected patients, whilst the rest of the patients undergoing breast-conservation surgery should be treated with breast irradiation. There is evidence that breast-conservation therapy is an effective option in the management of selected patients with DCIS. The use of radiotherapy after lumpectomy significantly decreases the rate of recurrence. Nuclear grade, presence of comedo necrosis, and margin involvement are the most commonly used predictors of the likelihood of recurrence. There is no role for adjuvant chemotherapy in the management of this disease. The role of tamoxifen in the treatment of DCIS is not clearly defined; tamoxifen should be given only in patients enrolled in clinical trials. Following breast-conservation therapy, about 50% of the tumours recur as invasive cancer. Most patients with recurrent disease can be treated effectively, usually by salvage mastectomy, but also in selected cases by breast-conservation therapy.
Follow-up after primary treatment for breast cancer is a routine practice aiming at early detection and management of local recurrences and/or distant metastases of the disease or of new primaries. Breast self-examination and periodic physical examination, mammography, and pelvic examination are the most important methods in following-up these patients. The, at one time, more popular intensive routine diagnostic evaluation (including head, chest, abdominal, and pelvic computerized tomography and/or magnetic resonance imaging, liver ultrasonography, bone scans, tumor markers, etc.) is not currently considered appropriate and cost-effective. However, flexibility, based on clinical judgement, is required on the part of medical staff involved in the follow-up in order appropriately to adapt the general guidelines and meet the specific needs of the individual patients. Non-specialist or non-physician models of follow-up care have been proposed as interesting and cost-effective alternatives in the follow-up of breast cancer patients.
Axillary lymph node dissection (ALND) has traditionally been considered as a standard procedure in the surgical management of patients with breast cancer. The goals of ALND in breast cancer surgery are: (a) to provide accurate prognostic information, (b) to maintain local control of the disease in the axilla and (c) to provide a rational basis for decisions about adjuvant therapy. Although controversial, ALND may also be associated with a small therapeutic benefit. Recently, the question of whether ALND is needed for every patient with invasive breast cancer has been the subject of ongoing debate in the literature. This is mainly due to the widespread use of adjuvant systemic therapy for patients with node-negative breast cancer and to the increasingly frequent detection of small invasive cancers by mammographic screening; the majority of these patients have negative axillae. Sentinel lymph node (SLN) biopsy is a new, promising, minimally invasive procedure, which accurately predicts nodal status with minimal morbidity, and reserves ALND for patients with positive SLN biopsies. However, this method is still investigational. Partial (levels I and II) ALND remains the gold standard in the surgical management of patients with breast cancer.
Breast conservation, comprising limited excision of the breast and axillary lymphadenectomy followed by irradiation, yields survival equal to mastectomy with the advantage of preservation of the breast for properly selected patients. When breast conservation therapy is competently done it achieves highly satisfactory cosmetic results and acceptably low rates of local recurrence. However, numerous controversies surround the selection criteria, the relative importance of some of them, and the treatment. Four critical elements in selecting patients for breast conservation therapy are: history and physical examination, careful mammographic evaluation, histological assessment of the resected specimen, and assessment of the patient's needs and expectations. Today, it is estimated that breast conservation can be recommended to 50%-75% of all women with operable breast cancer. However, this treatment is not widely used. In this article we review the generally accepted principles and controversies about the selection of patients for breast conservation.
Acute pancreatitis is a disorder that has numerous causes and an obscure pathogenesis. Bile duct stones and alcohol abuse together account for about 80% of acute pancreatitis. Most episodes of biliary pancreatitis are associated with transient impaction of the stone in the ampulla (that causes obstruction of the pancreatic duct, with ductal hypertension) or passage of the stone though and into the duodenum. Other causes of acute pancreatitis are various toxins, drugs, other obstructive causes (such as malignancy or fibrotic sphincter of Oddi), metabolic abnormalities, trauma, ischemia, infection, autoimmune diseases, etc. In 10% of cases of acute pancreatitis, no underlying cause can be identified; this is idiopathic pancreatitis. Occult biliary microlithiasis may be the cause of two thirds of the cases of "idiopathic" acute pancreatitis. Intra-acinar activation of trypsinogen plays a central role in the pathogenesis of acute pancreatitis, resulting in subsequent activation of other proteases causing the subsequent cell damage. Ischemia/reperfusion injury is increasingly recognized as a common and important mechanism in the pathogenesis of acute pancreatitis and especially in the progression from mild edematous to severe necrotizing form. Increased intracellular calcium concentration also mediates acinar cell damage. Oxygen-derived free radicals and many cytokines (e.g., interleukin [IL]-1, IL-6, IL-8, tumor necrosis factor-alpha, platelet activating factor) are considered to be principal mediators in the transformation of acute pancreatitis from a local inflammatory process into a multiorgan illness.
One of the most important prognostic indicators in patients with breast cancer is axillary lymph node status. Sentinel lymph node (SLN) biopsy has emerged as a potential alternative to routine axillary dissection in clinically node-negative early breast cancer. This procedure requires a specialized but multidisciplinary approach utilizing the surgeon, nuclear radiologist and pathologist. SLN biopsy allows adequate assessment of the axillary nodal status in patients with early breast cancer, with minimal-if any-morbidity. Blue dye and lymphoscintigraphy are complementary techniques, and the success rate is maximized when the two methods are used together. Focused histopathologic examination on one or two lymph nodes most likely to contain metastases [SLN(s)], using serial sectioning and immunohistochemical techniques, allows an improved staging to be performed. Detection of metastases on SLN(s) is not only a prognostic indicator, but it also dictates whether the patient should receive further surgery and adjuvant chemotherapy. Until data regarding the long-term results of the SLN biopsy are available, this method should be considered investigational and be performed by surgeons experienced in this technique to achieve a failure rate of less than 2 per cent.
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Patients with occult breast cancer pose a challenging diagnostic and therapeutic problem. High-quality mammography is required to decrease the false-negative rates. A number of other imaging methods have been proposed in the diagnostic evaluation of these women, including breast ultrasonography, color Doppler ultrasonography, breast magnetic resonance imaging (MRI), positron emission tomography (PET), and scintimammography. Among them, MRI may be particularly helpful, since it has a high sensitivity and may enable preoperative localization of the primary, thus allowing the surgeon to perform a breast conserving procedure. Treatment options include surgery, radiotherapy and watchful waiting (followed by mastectomy when a breast tumor is detected). Systemic therapy is usually required in the management of these patients.
Chronic pancreatitis (CP) is generally considered as a risk factor for pancreatic adenocarcinoma (PAC). However, the cumulative risk differs among the epidemiological studies. In the individual patient, the differential diagnosis between PAC and CP cannot be always resolved preoperatively and even intraoperatively. In those cases, the uncertainty can only be answered with histological studies of the resected specimen after a radical resection, provided that this type of surgery can be performed with a reasonable risk in a surgically fit patient. The type of resection depends on the location of the suspicious mass. For masses in the tail of the pancreas, a distal pancreatectomy is the procedure of choice. For suspicious lesions in the head of the pancreas, a pancreatoduodenectomy (PD) should be performed. The surgeon and the patient should also acknowledge that a radical resection will occasionally be performed for a suspected malignancy only to find that another etiology (i.e. CP) accounts for the suspicious pancreatic mass. In the presence of a strong suspicion for an underlying malignancy in a patient with head dominant CP, PD should probably be preferred over the newer organ-preserving Beger and Frey procedures, since it is an adequate procedure for both CP and PAC.
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The poor prognosis of pancreatic cancer relates mainly to its delayed diagnosis. It has been repeatedly shown that earlier diagnosis of pancreatic cancer is associated with a better outcome. Molecular diagnostic methods (mainly detection of K-ras mutations in pure pancreatic or duodenal juice, on specimens obtained by percutaneous fine-needle aspirations or in stool specimens) can achieve earlier diagnosis in selected subgroups of patients, such as patients with chronic pancreatitis (especially hereditary), adults with recent onset of non-insulin-dependent diabetes mellitus and patients with some inherited disorders that predispose to the development of pancreatic cancer. There is increasing evidence that pancreatic carcinogenesis is a multi-step phenomenon. Screening procedures for precursor lesions in these selected subgroups of patients may reduce the incidence and mortality from pancreatic cancer.
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In the present study we have compared the incidence and degree of hypoxemia during the early postoperative period and for the first 3 nights after operation occurring after the administration of total intravenous anesthesia with propofol versus inhalation anesthesia with nitrous oxide and isoflurane. We studied 50 consecutive non-obese patients, ages 25-65, ASA I-II, who were scheduled for elective cholecystectomy. Patients received randomly either total intravenous anesthesia with propofol (24 patients) or inhalation anesthesia with nitrous oxide and isoflurane (26 patients). Oxygen saturation was continuously recorded on the night before surgery, for 8 hours after extubation (early postoperative period) and during the first, second and third nights after operation. In the early postoperative period we found statistically significant higher values of mean (P<0.05) and minimum (P<0.01) SpO2 in patients who received total intravenous anesthesia compared to patients in whom inhalation anesthesia was used. Moreover, in the early postoperative period, 4 (16.7%) patients of the intravenous anesthesia group versus 11 (42.3%) patients of the inhalation anesthesia group had at least 1 hypoxemic event (P<0.05). We conclude that the incidence and degree of hypoxemia in the early postoperative period is significantly less when total intravenous anesthesia with propofol is used.