Biomedical subjects
R A Audisio
Publications and source records attributed to R A Audisio.
Oesophageal cancer treatment: studies, strategies and facts.
Esophageal cancer is among the ten most frequent cancers in the world. Once diagnosis is established prognosis is poor with five-year survival rates below 10%. Over the last few years, the evidence--base for treatment of oesophageal cancer has changed with the publication of several important articles in this field. This article reviews these and other relevant publications with focus on current evidence which holds potential for an improvement in survival in oesophageal cancer patients. Prevention and early detection represent the mainstay in the ongoing struggle to improve prognosis, which is most stringently linked to tumor stage. Other efforts have been dedicated to optimise surgical treatment, radiotherapy and chemotherapy and to discover the most efficient combinations of these treatment modalities. Strong but not unanimous evidence in favour of a multimodality approach with chemoradiotherapy followed by surgery has accumulated in recent years, and confirmatory trials are presently ongoing. A pathological complete response to chemoradiotherapy has been identified to significantly enhance survival. Among the strategies to achieve higher response rates, variations in the administration of the most commonly used drugs rather than higher drug and radiation dosages seem promising. Occult lymphatic spread has been recognized as a major source of recurrence and has been successfully targeted by three field surgical dissection and extended field radiotherapy. In search of the optimal treatment for patients with oesophageal cancer, a variety of different tracks are being pursued. This review outlines and analyses current treatment approaches and investigates how recent advances may impact on patient management.
Psycho-social aspects of breast cancer susceptibility testing: a literature review.
An important demand for breast cancer susceptibility (BRCA) testing is anticipated not only in women at high risk of breast cancer but also in the general population. However, the benefits of this new technology may be substantially counterbalanced by the risks and limitations associated with it. BRCA testing offers the potential for early detection of breast cancer; however, it may lead to psycho-socially harmful consequences. Both carriers and non-carriers of a BRCA mutation may face tremendous emotional upheaval which may adversely impact on subsequent attitudes towards health care. This paper points to the need for empirical studies examining the psycho-social aspects of BRCA testing. These studies should be undertaken cross-culturally in order to take into account the variations due to different health care systems and cultural background on psycho-social correlates of cancer genetic testing.
Practical considerations in the treatment of hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) represents one of the most common neoplasms worldwide. To date, curative treatment options include liver transplantation or resection. Unfortunately, most patients are detected with nonresectable or -transplantable HCC due to disease extension or comorbid factors, and are therefore candidates only for palliative treatments. Palliative medical treatments, including systemic chemotherapy, immunotherapy or hormonal manipulation, have a borderline activity on HCC and cannot be recommended outside clinical trials. A high response rate has been reported with local therapies such as transcatheter arterial embolisation, intra-arterial chemotherapy or percutaneous alcohol (ethanol) injection, but as there is no clear evidence of a survival advantage for these treatment modalities, further investigations are required. Multidisciplinary treatment, including preoperative cytoreduction or postoperative adjuvant therapy, is currently under investigation, with encouraging survival results. HCC patients should be evaluated within clinical trials, possibly randomised and with homogeneous prognostic factors, in order that we may find the answer to all these important questions.
Personalized surgery for rectal tumours: the patient's opinion counts.
In recent times there have been many important changes in the surgical management of rectal cancer. The general thrust of these changes has been towards a less invasive approach with preservation of intestinal continuity and avoidance of the psychological sequelae of a stoma. It is also becoming increasingly apparent that profound sexual and autonomic dysfunction can be associated with abdominoperineal resection. This paper highlights these issues and the conflict between performing an adequate oncological procedure and reducing the incidence of postoperative psychological morbidity. It outlines the great changes there have been in surgical technique and their relevance to psychological problems after surgery for rectal cancer. The need for auditing psychological morbidity when assessing the outcome of surgical series is emphasised, as is the importance of involving the patient in the medical decision making.
Elective surgery for gastrointestinal tumours in the elderly.
The geriatric population is expanding and clinical decision-making is often complicated by the effects of ageing. Age should not be the only parameter considered when addressing medical problems. Elderly subjects have been denied surgery because of their presumed higher mortality and morbidity. The present review summarises the physiology of the aged and discusses operative risks, mortality and morbidity rates as well as therapeutic results for the different gastrointestinal sites when affected by cancer. Reports on surgical treatments are revisited and compared to the same procedures delivered to younger patients in the context of the ethical issue of offering the best care to every patient. Elective operations by surgical oncologists are found to be safe with the exception of major liver resections. Complication rates and mean hospital stay do not differ between the two age groups provided the procedure is conducted with the best-known technique in expert hands. A drop in operative morbidity has occurred in the past three decades. Several investigators have emphasised the marked increase in morbidity and mortality experienced by elderly patients when undergoing emergency procedures. Associated diseases have to be properly assessed, as the elderly have a frail physiological balance with a reduced capacity for recovery from traumatic events including major surgical procedures. Careful preoperative evaluation, intraoperative conduct and postoperative care are presently achieved in almost every major hospital. Good clinical practice is based on the balance between probability of cure and toxic effects. Treatment of the elderly should no longer be based on untested beliefs and personal opinions. The elderly should be accrued for prospective clinical evaluation and should not be denied optimal surgical treatment.
Elective surgery for colorectal cancer in the aged: a clinical-economical evaluation.
A series of 56 consecutive patients, referred for surgery to a specialized institute, had elective laparotomies with various surgical procedures aimed at curing locoregional colorectal cancer. Data defining patient and tumour-related preoperative, operative and postoperative variables, including costs, were collected. The study group was divided into two age groups (< 65 vs > or = 65 years), which were similar in terms of patient- and tumour-related variables. Differences were not statistically significant (Pounds 440; 95% exact CI; Pounds -50; 1800). There is no evidence to suggest that there are any total charge differences in treating the two age groups, as confirmed by the cost analysis.
Follow-up in colorectal cancer patients: a cost-benefit analysis.
BACKGROUND: No conclusive evidence exists concerning the effectiveness of follow-up programs after curative surgery for colorectal cancer, and presently cost-benefit analyses have not indicated that follow-up strategies increase survival or quality of life. METHODS: Five hundred five patients who survived curative surgery for stage I-III colorectal adenocarcinoma were closely followed for at least 4 years. RESULTS: One hundred forty-one (28%) patients had recurrence. Of these, 32 underwent one or more surgical procedures for cure, whereas 109 could only benefit from palliation. Eighteen were cured. The mean survival of all recurrent cases was 44.4 months. Of those operated on with curative intent, the mean survival was 69.3 months compared with 37.1 months in those operated on with palliative intent. Of those 18 patients who were cured by reoperative surgery, the average survival was 81.4 months. The overall follow-up cost was $1,914,900 (U.S.) for the 505 patients; $13,580 (U.S.) for each recurrence, $59,841 (U.S.) for each case treated for cure, and $136,779 (U.S.) for those effectively cured. CONCLUSIONS: Careful postoperative monitoring is expensive yet effective when one considers that one-quarter of the detected recurrences were suitable for potentially curative second surgery; however, only 3.6% of the original group were effectively cured. Follow-up programs should be tailored according to the stage and site of the primary to reduce costs.
Clinical relevance of serological markers in the detection and follow-up of pancreatic adenocarcinoma.
Pancreatic adenocarcinoma is a relatively common malignancy and its incidence is increasing. Prognosis in these patients is poor, and surgery, the only effective treatment, saves only a minority of patients. The number in this small group of patients might be increased by early detection of pancreatic tumours. This review examines the current status of pancreatic tumour associated proteins in the detection of pancreatic cancer. As well as existing markers, the review also reports on newer markers that may offer advantages over existing ones in the detection of pancreatic adenocarcinoma. This is particularly important because recent studies have identified high-risk groups susceptible to pancreatic cancer. Future research in pancreatic cancer should be directed at earlier detection, and tumour markers may play an important role in this process.
Total rectal resection and colo-anal anastomosis for low rectal tumours: comparative results in a group of young and old patients.
Rectal cancer incidence is increasing among the elderly who are more often considered for palliation rather than for surgical cure. Moreover, sphincter-sparing surgery is often avoided when treating the elderly. We report our experience on a consecutive series of 38 subjects, suffering from a lower third rectal tumour with a median distance of 5.6 cm from the anal verge (7 Dukes' A, 6 Dukes' B, 17 Dukes' C, 3 Dukes' D, 3 anastomotic recurrences and 2 large villous adenomas). All subjects were prospectively collected in a 2-year period and treated with total resection and colo-anal hand-sewn anastomosis on a J colic reservoir. 20 patients younger than 65 years and 18 over 65 years were matched for surgical complications, late morbidity, oncological and functional results but no statistical difference was found. Our hope is that a conservative approach in treating the low rectal tumours will progressively be accepted for elderly patients.
Prevalence of sexual dysfunction in male cancer patients treated with rectal excision and coloanal anastomosis.
Impotency due to parasympathetic nerve injury is one of the most feared consequences of rectal cancer surgery. Sexual relationships make a significant contribution to the quality of life for almost everybody. Rectal excision and coloanal anastomosis (CAA) is a new surgical procedure for low rectal tumor with little data regarding the prevalence of sexual impairment as yet. We have examined the sexual life of 21 male patients who have undergone CAA by means a self-administered questionnaire. Only two patients reported reactive impotency. On the other hand 17 out of 21 patients had no ejaculation after undergoing surgery. According to our data it appears that CAA results in surgery a low degree of sexual impairment (impotency). Both sexual dysfunction and quality of life investigations should be integrated with oncological results when reporting data about colorectal surgery.
Role of surgery in patients with primary non-Hodgkin's lymphoma of the stomach: an old problem revisited.
The literature after 1980 dealing with the treatment of primary gastric non-Hodgkin's lymphoma (stages I and II) is reviewed. Gastrectomy is recommended for patients with acute symptoms at presentation or with complications of chemotherapy or radiotherapy. In elective cases, patients with stage I disease may be candidates for gastrectomy as a single therapy, provided that tumour-free resection margins are achieved. There is no evidence of substantial benefit from adding postoperative chemotherapy or radiotherapy after an apparently radical resection. In stage II disease, the best results are achieved with ablative surgery plus adjuvant therapy. The resection volume should be limited to macroscopically involved structures, in principle avoiding total gastrectomy and extensive lymph node dissection, since residual disease may be optimally controlled with radiotherapy or chemotherapy. Primary chemotherapy, with or without radiotherapy, represents an experimental approach; the advantages of sparing the stomach must be balanced against the toxicity of an aggressive chemotherapy regimen and the risk of emergency operation for iatrogenic complications.
Importance of orthotopic implantation for human tumors as model systems: relevance to metastasis and invasion.
Transplantation of human tumors into immunodeficient athymic nude mice has become an important experimental approach to study the biology and the treatment of human cancer. Most human tumor xenograft experiments have employed subcutaneous injection procedures, but the main limit of this technique is the lack of metastasis from the subcutaneous site. The possibility of producing experimental metastasis by intravenous injection of cells in the animals has been known for a long time, and it has been recently reported that tumorigenic properties and metastatic ability of human cancer can be altered by transplantation of the tumor into its organ or tissue of origin in the recipient animals (orthotopic transplantation). In this paper we review (1) the principal techniques of orthotopic injection of most solid tumors, (2) the most recent techniques to achieve experimental metastases, and (3) the methods for preparing tumor cell suspensions from human surgical specimens suitable for transplantation into animals. These animal models should be used for a more appropriate evaluation of new antitumor treatments including the ones targeted to inhibit metastatic spread.
Phase II trial of mitomycin C (MMC) in advanced gallbladder and biliary tree carcinoma. An EORTC Gastrointestinal Tract Cancer Cooperative Group Study.
BACKGROUND: Based on a recent pharmacokinetic study suggesting that high biliary levels of mitomycin C (MMC) may be achieved as a result of an entero-hepatic recycling mechanism, we conducted a Phase II EORTC trial which involved MMC administration to patients with non-resectable biliary tract carcinoma. PATIENTS AND METHODS: Of the 34 patients entered in the study, 30 were eligible (11m + 19f, median age 58 yrs). I.V. bolus injections of 15 mg/m2 MMC were administered at six-week intervals. The tumors were confined to the liver in 17 patients and 13 had extra-hepatic localizations. RESULTS: All 30 eligible patients were evaluable for toxicity and response. Mild thrombocytopenia was the main toxic side effect. Severe, WHO grade III/IV thrombocytopenia was limited to 4 patients. The haemolytic uraemic syndrome was not observed and there were no toxic deaths. Of 30 patients, 3 had partial remissions (overall response 10%, 95% confidence interval 2%-27%). CONCLUSIONS: This study, the largest such ongoing phase II trial, shows no significant activity of single-agent MMC in patients with advanced biliary tract carcinoma.
The outcome of cholangitis after percutaneous biliary drainage in neoplastic jaundice.
The purpose of this paper is to evaluate factors affecting the outcome of cholangitis after PTBD in jaundiced cancer patients. Twenty nine patients with neoplastic jaundice (male/female ratio 13/16, median age 55 years) with full clinical data, were treated by PTBD and developed cholangitis at a median of 9 days later. Four patients (14%) died of biliary sepsis a median of one month after PTBD while the other 25 survived a median of 6 months, with one week median duration of cholangitis. The probability of the cholangitis resolving was analyzed by time to resolution and it was found that 50% and 100% of the recoveries occurred 5 and 9 months respectively from the onset of the complication. The series was analyzed to determine the role of several variables (disease/patient/treatment related) in the resolution of cholangitis. Only a low stricture site, a large initial drainage catheter (10F) and a temperature increase exceeding 39 degrees C were correlated with a positive outcome. We conclude that PTBD-related cholangitis has, in our experience, a good chance of cure, low mortality rate and satisfactory 6 months median survival.
Primary mucoepidermoid carcinoma of the liver. A case report.
The authors report a case of primary mucoepidermoid carcinoma of the liver in a 66-year-old woman. Electron microscopy findings suggest an origin from the biliary epithelium as well as cholangiocarcinoma, which clinical and prognostic features are similar to those of mucoepidermoid carcinoma.
Differential efficacy of flavone acetic against liver versus lung metastases in a human tumour xenograft.
A human ovarian carcinoma, IGROV-1, was xenografted into different sites (i.p., s.c., i.v., and intrasplenically) in nude athymic female mice to investigate the pattern of antitumour efficacy of FAA and compare it to that of doxorubicin and cisplatin, two established cytotoxic drugs. Ascitic and lung-growing tumours totally failed to respond to FAA, whereas s.c. and liver-growing tumours were significantly growth inhibited. This pattern of activity differs from that achieved by the two conventional cytotoxic drugs, which were active against the IGROV-1 tumour growing in all of the tested sites. These studies indicate that cytotoxicity is not the major determinant of FAA antitumour efficacy even against human tumour xenografts. Moreover, the dramatic difference between the sensitivity of lung and liver tumour colonies demonstrates the great importance of the site of tumour growth for FAA efficacy.