Biomedical subjects

Chiara Mussi

Publications and source records attributed to Chiara Mussi.

At least 19 recordsLinked to original sources

PubMed2006

Advanced extremity soft tissue sarcoma: prognostic effect of isolated limb perfusion in a series of 88 patients treated at a single institution.

PURPOSE: To explore the prognostic impact of isolated limb perfusion (ILP) in locally advanced extremity soft tissue sarcomas (ESTS). METHODS: From August 1982 to April 2005, 1,119 patients affected by ESTS (girdle excluded) were observed and treated at our institution. Eighty-eight (7.9%) were judged non-resectable or locally advanced and underwent ILP. Thirty-seven patients received antiblastic alone (non-TNF-ILP) while 51 had anti-blastic + recombinant-tumor necrosis factor alpha (TNF-ILP). Local disease-free survival (LDFS) was calculated by the Kaplan-Maier method and was reported separately in the two subgroups. RESULTS: Limb salvage was achieved in 83% (73/88) of the patients. The observed overall (complete + partial) response rate was 59%. In the TNF-ILP group a complete response (CR) was achieved in 21 (41%) patients, while in the non-TNF ILP group a CR was obtained in seven (19%) cases (P < 0.05). Patients with in-transit metastases (epithelioid sarcomas and clear cell sarcomas) had a significantly worse long-term outcome (LDFS at 5 years was 40.9 vs 67.3%, P < 0.05). A trend towards a better LDFS at 5 years could be observed in the patients receiving TNF (63.6 vs 57.1%) and post-operative radiation therapy (RT) (79.3 vs 55.4%). CONCLUSIONS: Isolated limb perfusion is an active treatment. By adding TNF a better local control seems to be obtained, possibly due to a higher rate of CR. It should therefore be considered as a valid option for patients affected by limb-threatening STS, save for in-transit metastases from epithelioid and clear cell sarcoma. Post-operative RT should always be considered.

Adolescent↗

PubMed2006

Malignant peripheral nerve sheath tumors: prognostic factors and survival in a series of patients treated at a single institution.

BACKGROUND: The authors explored the prognostic factors and clinical outcomes of patients who had malignant peripheral nerve sheath tumors (MPNST) with and without neurofibromatosis type 1 (NF-1). METHODS: Two hundred five patients with localized MPNST who underwent surgery at the Istituto Nazionale per lo Studio e la Cura dei Tumori (Milan, Italy) over 25 years were reviewed. Forty-six patients had concomitant NF-1 syndrome, and 159 patients did not. Local recurrence, distant metastases, and survival rates were studied. RESULTS: One hundred thirty patients presented with primary disease, and 75 patients had locally recurrent tumors. The disease-specific mortality rate was 43% at 10 years, with a continuously disease-free survival rate of no greater than 40%. Presentation with either primary or recurrent disease, tumor size, and tumor site (trunk vs. extremity) were the strongest independent predictors of survival. Margin status and radiation therapy also played a role, mostly related to their effect on local outcome. Pathologic grade influenced distant metastases, but only a trend for survival could be observed. No significant independent differences between patients with and without NF-1 were observed. CONCLUSIONS: To the authors' knowledge, this was among the largest single-institution series to date. The results confirmed that patients with MPNST share similar prognostic factors with patients who have other soft tissue sarcomas and have some of the worst clinical outcomes. The presence of NF-1 syndrome per se did not affect survival, but patients with NF-1 were more likely to have larger tumors. Therefore, such patients should be followed carefully to detect disease as early as possible.

Adolescent↗

PubMed2006

Prognostic effect of re-excision in adult soft tissue sarcoma of the extremity.

BACKGROUND: We explored the outcome of patients with primary adult soft tissue sarcoma (STS) of the extremities undergoing re-excision after previous unplanned surgery. METHODS: A total of 597 consecutive adult patients with primary extremity STS were treated with conservative surgery at our institution over a 20-year time span. A total of 318 patients were referred after unplanned excisions, and the remaining 279 underwent primary resection at our center. The two groups significantly differed in tumor size and depth. The assessed end points were sarcoma-specific mortality, local recurrence, and distant metastasis. Univariable and multivariable analyses, adjusted for other prognostic factors, were performed in the competing risks framework. RESULTS: The adjusted 10-year cumulative incidences in re-excised and primarily operated patients were, respectively, 18.7% and 16.4% (P = .535) for local relapse, 17.6% and 20.2% (P = .541) for metastasis, and 20.4% and 22.4% (P = .645) for mortality. Among patients who underwent re-excision, evidence of microscopic residual disease on pathologic examination had a significant prognostic effect on multivariable analysis for distant metastases (P = .002). A trend for survival was detected as well. CONCLUSIONS: At a referral center with a liberal policy of re-excisions in adult primary STS of the extremities, the outcome of patients who underwent re-excision was similar to that of patients who had primary resections. Evidence of microscopic residual disease at re-excision was a marker of clinical aggressiveness.

Adult↗

PubMed2006

Surgical treatment of metastatic tumors to the pancreas: a single center experience and review of the literature.

BACKGROUND: Unlike primary pancreatic carcinoma, metastases to the pancreas are rare, and their resection may be performed as palliative treatment. The aim of this study was to review our experience with the operative management of pancreatic metastases. MATERIALS AND METHODS: Between January 1994 and December 2004 13 patients (nine women and four men; median age: 59 years; range: 36-79 years) were admitted to our institution with metastatic lesion to the pancreas. The clinical features of the treatment and results were examined. RESULTS: Primary tumors were renal cell carcinoma (n=5), lobular carcinoma of the breast (n=3), endometrioid carcinoma of the ovary (n=1), colonic adenocarcinoma (n=1), jejunal leiomyosarcoma (n=1), melanoma (n=1), and non-small-cell lung cancer (n=1). The median interval between primary tumor and pancreatic metastases was 36 months (range: 5-192 months). Six patients (46%) were asymptomatic, while the other seven patients presented with jaundice, pain, and duodenal obstruction. Two patients with extrapancreatic disease underwent palliative surgery, and the remaining 11 patients underwent operative procedures that included seven pancreaticoduodenectomy and four distal pancreatectomies with splenectomy. Postoperative mortality was nil, and the morbidity rate was 30%. The two patients who underwent palliative surgery died after 7 and 9 months, respectively. The median survival of the resected patients was 26 months (range: 13-95 months). Five patients died of disease, eight are alive at the time of this report. CONCLUSION: A trend towards improved survival, even if not statistically significant, was observed in the renal carcinoma patients reported here. Surgical resection can be performed safely in selected patients with isolated metastases to the pancreas, achieving long-term survival as well as good palliation.

Adult↗

PubMed2006

Standardized-care pathway vs. usual management of syncope patients presenting as emergencies at general hospitals.

AIMS: The study hypothesis was that a decision-making approach improves diagnostic yield and reduces resource consumption for patients with syncope who present as emergencies at general hospitals. METHODS AND RESULTS: This was a prospective, controlled, multi-centre study. Patients referred from 5 November to 7 December 2001 were managed according to usual practice, whereas those referred from 4 October to 5 November 2004 were managed according to a standardized-care pathway in strict adherence to the recommendations of the guidelines of the European Society of Cardiology. In order to maximize its application, a decision-making guideline-based software was used and trained core medical personnel were designated-both locally in each hospital and centrally-to verify adherence to the diagnostic pathway and give advice on its correct application. The 'usual-care' group comprised 929 patients and the 'standardized-care' group 745 patients. The baseline characteristics of the two study populations were similar. At the end of the evaluation, the standardized-care group was seen to have a lower hospitalization rate (39 vs. 47%, P=0.001), shorter in-hospital stay (7.2+/-5.7 vs. 8.1+/-5.9 days, P=0.04), and fewer tests performed per patient (median 2.6 vs. 3.4, P=0.001) than the usual-care group. More standardized-care patients had a diagnosis of neurally mediated (65 vs. 46%, P=0.001) and orthostatic syncope (10 vs. 6%, P=0.002), whereas fewer had a diagnosis of pseudo-syncope (6 vs. 13%, P=0.001) or unexplained syncope (5 vs. 20%, P=0.001). The mean cost per patient and the mean cost per diagnosis were 19 and 29% lower in the standardized-care group (P=0.001). CONCLUSION: A standardized-care pathway significantly improved diagnostic yield and reduced hospital admissions, resource consumption, and overall costs.

Aged↗

PubMed2006

Thymic output and functionality of the IL-7/IL-7 receptor system in centenarians: implications for the neolymphogenesis at the limit of human life.

During aging, the thymus undergoes a marked involution that is responsible for profound changes in the T-cell compartment. To investigate the capacity of the thymus to produce new cells at the limit of human lifespan, we analyzed some basic mechanisms responsible for the renewal and maintenance of peripheral T lymphocytes in 44 centenarians. Thymic functionality was analyzed by the quantification of cells presenting the T-cell receptor rearrangement excision circles (TREC). A new method based upon real-time PCR was used, and we found that most centenarians (84%) had undetectable levels of TREC+ cells. Six-color cytofluorimetric analysis revealed that centenarians had an extremely low number of naïve T cells; central memory and effector memory T cells were greatly increased, while terminally differentiated cells were as numerous as in young (aged 20-45) or middle-aged (aged 58-62) donors. Interleukin (IL)-7 and IL-7 receptor alpha-chain (CD127) levels were the same at all ages, as shown by ELISA, flow cytometry and real-time PCR. However, IL-7 plasma levels were higher in centenarian females than males. The presence of TREC+ cells and of very few naïve T lymphocytes suggests that in centenarians such cells could either derive from residues of thymic lymphopoietic islets, or even represent long-living lymphocytes that have not yet encountered their antigen. IL-7 could be one of the components responsible, among others, for the higher probability of reaching extreme ages typical of females.

Adult↗

PubMed2006

Diagnosis and characteristics of syncope in older patients referred to geriatric departments.

OBJECTIVES: To test the applicability and safety of a standardized diagnostic algorithm in geriatric departments and to define the prevalence of different causes of syncope in older patients. DESIGN: Multicenter cross-sectional observational study. SETTING: In-hospital geriatric acute care departments and outpatient clinics. PARTICIPANTS: Two hundred forty-two patients (aged>or=65, mean+/-standard deviation=79+/-7, range 65-98) consecutively referred for evaluation of transient loss of consciousness to any of six clinical centers participating in the study. Of these, 11 had a syncope-like condition (5 transient ischemic attack; 6 seizures), and 231 had syncope (aged 65-74, n=71; aged>or=75, n=160). MEASUREMENTS: Protocol designed to define etiology and clinical characteristics of syncope derived from European Society of Cardiology Guidelines on syncope. RESULTS: No major complication occurred with use of the protocol. Neurally mediated was the more prevalent form of syncope in this population (66.6%). Cardiac causes accounted for 14.7% of all cases. The neuroreflex form of syncope (vasovagal, situational, and carotid sinus syndrome) was more common in younger than in older patients (62.3% vs 36.2%; P=.001), whereas orthostatic syncope was more frequent in the older than in the younger group (30.5% vs 4.2%; P<.001). In only 10.4% of cases, syncope remained of unexplained origin. After initial evaluation, a definite diagnosis was possible in 40.1% of the cases, and a suspected diagnosis was obtained in 57.9%. Syncope of suspected cardiac origin after initial evaluation was confirmed in 43.7% of cases, and neuromediated causes were confirmed in 83.5% of the cases. CONCLUSION: The protocol is applicable even beyond the age of 90 in geriatric departments. The standardized protocol is associated with a reduction in the frequency of unexplained syncope to about 10%.

Age Factors↗

PubMed2006

[Role of renal failure in the pathogenesis of adverse drug reactions in the elderly].

The high prevalence of multiple chronic disorders and polypharmacotherapy expose elderly patient to an increased risk of adverse drug reactions. Aging is associated with relevant morphological and functional changes in the kidney, with consequent changes in the pharmacokinetics of hydrosoluble drugs. Changes in renal function are not always clinically evident, and a concealed renal failure can lead to an increased risk of adverse drug reactions to hydrosoluble drugs. Targeting these at-risk patients could contribute to reduce the risk of adverse drug reactions with relevant cost saving.

Aged↗

PubMed2005

A new management of syncope: prospective systematic guideline-based evaluation of patients referred urgently to general hospitals.

AIMS: The guidelines of the European Society of Cardiology (ESC) define the current standard for the management of syncope, but are still incompletely applied in the clinical setting. METHODS AND RESULTS: Prospective systematic evaluation, on strict adherence to the guidelines, of consecutive patients referred for syncope to the emergency departments of 11 general hospitals. In order to maximize the application, a decision-making guideline-based software was used and trained core medical personnel were designated-both locally in each hospital and centrally-to verify adherence to the diagnostic pathway and give advice on its correction. A diagnostic work-up consistent with the guidelines was completed in 465/541 patients (86%). A definite diagnosis was established in 98% (unexplained in 2%): neurally mediated syncope accounted for 66% of diagnosis, orthostatic hypotension 10%, primary arrhythmias 11%, structural cardiac or cardiopulmonary disease 5%, and non-syncopal attacks 6%, respectively. The initial evaluation (consisting of history, physical examination, and standard electrocardiogram) established a diagnosis in 50% of cases. Hospitalization for the management of syncope was appropriate in 25% and was required for other reasons in a further 13% of cases. The median in-hospital stay was 5.5 days (interquartile range, 3-9). Apart from the initial evaluation, a mean of 1.9+/-1.1 appropriate tests per patient was performed in 193 patients and led to a final diagnosis in 182 of these (94%). CONCLUSION: The results of this study assess the current standard for the management of syncope on the basis of a rigorous adherence to guidelines of the ESC and provide a frame of reference for daily activity when dealing with syncope.

Aged↗

PubMed2005

Dermatofibrosarcoma protuberans treated at a single institution: a surgical disease with a high cure rate.

PURPOSE: Dermatofibrosarcoma protuberans (DFSP) is a rare, low-grade, cutaneous sarcoma with autocrine overproduction of the platelet-derived growth factor (PDGF) beta-chain from gene rearrangement as a key pathogenetic factor, now susceptible of molecular-targeted therapy. The aim of this retrospective analysis was to explore the outcome of patients with primary or recurrent DFSP. PATIENTS AND METHODS: Two hundred eighteen patients surgically treated at the Istituto Nazionale per lo studio e la cura dei Tumori (Milan, Italy) over 20 years were reviewed. Local relapse, distant metastasis, and survival were studied. RESULTS: One hundred thirty-six patients (62.4%) presented with a primary DFSP, while 82 patients (37.6%) had a recurrent disease. In the primary group, margins were microscopically positive in 11.8%, while in the recurrent group they were positive in 14.6% (P =.613). In the primary group, patients undergoing re-excision after inadequate previous surgery had residual disease in 62% of cases. Reconstructive surgery was needed in 30%, significantly more frequently in patients with a recurrence or a head and neck tumor. The crude cumulative incidence of local relapses was 4% at 10 years, and 2% at 10 years for distant metastases. No significant difference was found between primary and recurrent patients, as well as between positive and negative margins. CONCLUSION: This being one of the largest mono-institutional series of DFSP, we confirm that long-term outcome is excellent, in terms of both local and distant control, after a wide excision with negative margins. Reconstructive surgery is often needed. Novel medical therapies will be of use in a limited subgroup of patients.

Adolescent↗

PubMed2005

Palliative management strategies of advanced gastrointestinal carcinoid neoplasms.

BACKGROUND/AIMS: Optimal management of gastrointestinal carcinoid neoplasms that metastasize to the liver is controversial. Although operative resection seems to be the most effective approach to metastatic disease, hepatic metastases are usually multicentric and often non-resectable. We investigated the effectiveness of several forms of palliative tumor cytoreduction followed by administration of somatostatin analogues in advanced carcinoid neoplasms. METHODS: We reviewed our experience with 34 patients with gastrointestinal carcinoid neoplasms. Eighteen patients had metastases and 14 had hormonal symptoms. Twenty-two patients underwent radical surgery, ten with multiple liver metastases were treated with a combination of debulking (resection, radiofrequency ablation, chemoembolization), followed by medical treatment with long-acting octreotide and eventually by radiolabelled somatostatin analogues, and two patients with intractable disease received only biotherapies. RESULTS: The six patients with metastatic disease who underwent radical curative liver resection had a median survival of 52 months, compared with a median survival of 48 months in the ten patients who underwent palliative debulking. Symptomatic improvement was observed in all the patients after debulking procedures. The two patients who underwent only medical treatment died after 9 and 18 months. CONCLUSIONS: Aggressive tumor debulking should be performed in patients with liver metastases already at diagnosis even when complete resection is not feasible because the combination of cytoreductive procedures followed by biotherapies may provide good long-term survival and achieves symptom control in most patients with advanced disease.

Adult↗

PubMed2005

Concealed renal insufficiency and adverse drug reactions in elderly hospitalized patients.

BACKGROUND: Adverse drug reactions (ADRs) are common causes of in-hospital complications for elderly people. The purpose of the present study is to verify whether concealed renal insufficiency, that is, reduction of the estimated glomerular filtration rate (GFR) in people with normal serum creatinine levels, is a risk factor for ADRs in elderly hospitalized patients. METHODS: We used data on 11,687 hospitalized patients enrolled in the Gruppo Italiano di Farmacovigilanza nell'Anziano study. The outcomes of the study were any ADR, ADR to hydrosoluble drugs, and ADR to any other drug during the hospital stay. We compared 3 groups: normal renal function (normal serum creatinine levels and normal estimated GFRs), concealed (normal serum creatinine levels and reduced estimated GFRs), or overt (increased creatinine levels and reduced estimated GFRs) renal insufficiency. The relationship between renal function and ADR was evaluated using contingency tables and multiple regression analysis including potential confounders. RESULTS: Concealed renal insufficiency was detected in 1631 (13.9%) patients and was frequently associated with male sex and poor nutritional status. Hydrosoluble drugs were responsible for 301 of the 941 recorded ADRs. After adjusting for potential confounders, both concealed (odds ratio [OR], 1.61; 95% confidence interval [CI], 1.15-1.25) and overt (OR, 2.02; 95% CI, 1.54-2.65) renal failure were associated with ADR to hydrosoluble drugs, but not with ADR to other drugs (OR, 0.83 [95% CI, 0.65-1.08], and OR, 1.01 [95%CI, 0.83-1.23], respectively). CONCLUSION: Older hospitalized patients frequently have impaired renal function despite normal serum creatinine levels and are exposed to an increased risk of ADRs to hydrosoluble drugs.

Age Factors↗

PubMed2004

Balanced regulation of mRNA production for Fas and Fas ligand in lymphocytes from centenarians: how the immune system starts its second century.

BACKGROUND: The functionality of the immune system during aging is crucial for protection against the most common age-related diseases. Apoptosis plays a central role in the senescence of the immune system, as evidenced by the increased plasma membrane expression of a key molecule like Fas protein. We analyzed the mRNA levels of different forms of Fas (total [tFas] and membrane [mFas]) and of its ligand (FasL) in peripheral blood lymphocytes from centenarians, the best example of successful aging, who were compared with young and middle-aged donors. METHODS AND RESULTS: Using real-time polymerase chain reaction, we quantified mRNA for different forms of Fas and for FasL. In resting lymphocytes, mRNA for tFas, but not for mFas, significantly increases with age, whereas FasL mRNA significantly decreases. In vitro production of Fas/FasL mRNA after different stimuli was similar in cells from the 3 groups. Even if the percentage of Fas+ cells was higher than in the other groups, peripheral blood lymphocytes from centenarians had normal Fas-induced apoptosis, as revealed by flow cytometry. By ELISA, we observed that cells from centenarians showed normal in vitro production of the soluble form of Fas (sFas) and that plasma levels of such molecule were significantly higher in centenarians than in the other groups. CONCLUSIONS: Lymphocytes from centenarians are able to balance the production of proapoptotic (mFas and FasL) and antiapoptotic (sFas) molecules, whose proportions are likely crucial for the well-preserved immune functionality at the extreme limits of human life.

Adult↗

PubMed2004

Pancreaticoduodenectomy for pancreatic metastases from breast carcinoma.

CONTEXT: Unlike primary pancreatic carcinoma, metastases to the pancreas are rare events and their resection may be performed as a palliative treatment. The aim of this study was to review our experience with the operative management of pancreatic metastases from breast carcinoma. CASE REPORT: Three patients underwent pancreaticoduodenectomy for pancreatic metastases from breast carcinoma between 1990 and 2002. The clinical features of and the results after resection were examined. The presenting clinical symptoms were jaundice, pain and weight loss. In all cases, the pancreatic metastases were solitary lesions located in the head of the pancreas and the intervals between the primary breast carcinoma and the pancreatic metastases were 3, 5 and 7 years. The primary tumor was lobular carcinoma. Metastases were initially misdiagnosed as primary cancers. All patients underwent pancreaticoduodenectomy. One patient died from disseminated metastatic disease 26 months after surgery. The other two patients are alive 37 and 21 months after pancreaticoduodenectomy; the second one has had recurrence of the disease. CONCLUSION: In rare cases, the pancreas may be the presenting site for breast metastases, typically years after treating the primary tumor. Pancreaticoduodenectomy can be performed in the absence of extreme metastatic disease; it can provide worthwhile palliation and improve survival.

Adult↗

PubMed2004

Melanoma metastatic to the gallbladder and small bowel: report of a case and review of the literature.

From post-mortem case records, the small bowel is the most frequent site of metastatic melanoma in the gastrointestinal (GI) tract, with gallbladder involvement occurring in 15% of cases. However, few cases have been documented in living patients and, when found, are associated with a poor prognosis. We report a case of a Caucasian man with metastatic gallbladder and small bowel melanoma from an unknown primary. He presented with diffuse abdominal pain, vomiting and progressive asthenia; subsequently, intestinal obstruction occurred. He had no past history of malignant melanoma and the primary lesion was not found. The multiple lesions, together with the absence of mucosal involvement in both the gallbladder and small bowel, led us to believe that the lesions were metastatic deposits from a probably regressed primary melanoma. It should be emphasized that surgical resection for melanoma metastatic to the GI tract is recommended for palliative reasons and can be performed safely. The clinical presentation, diagnosis, treatment and prognosis of previously reported cases of melanoma metastatic to the gallbladder and small bowel are reviewed. The differences between primary and secondary GI tract melanomas are also discussed.

Gallbladder Neoplasms↗

PubMed2004

The "nondipper" elderly: a clinical entity or a bias?

OBJECTIVES: To determine the prevalence of nondipper (ND) blood pressure profile in the elderly and to ascertain whether the ND pattern of ambulatory blood pressure in the elderly is an artifact or represents a specific clinical entity. DESIGN: Cross-sectional, observational study. SETTING: Cardiovascular diagnostic center, division of geriatrics, secondary care, institutional practice. PARTICIPANTS: Sixty-five consecutive community-dwelling elderly hypertensive patients referred to the cardiovascular center. MEASUREMENTS: The patients underwent actigraphy and ambulatory blood pressure monitoring and completed a sleep assessment questionnaire. Patients were divided based on the night-time decrease in blood pressure (>10%: "dippers" (n=19); <10%: "NDs" (n=46)). RESULTS: Nondippers displayed poorer quality of sleep, as demonstrated objectively by actigraphic data; they obtained a higher mean score+/-standard deviation on the sleep questionnaire (4.6+/-2.9 vs 3.0+/-1.1, P=.030) and were taking more benzodiazepines (33.1% vs 10.7%, P=.035), indicating that their usual sleep quality was worse than that of dippers. Multivariate analysis showed a strong correlation between nondipper profile and quality of sleep and also with comorbidity, total number of drugs being taken, and pulse pressure. CONCLUSION: Actigraphy demonstrates impaired sleep in the nondipper elderly. Nevertheless, the nondipping pattern seems independent of the discomfort of cuff-inflation during the night and occurs in association with higher comorbidity and polypharmacy; therefore, it cannot be considered a "bias," but is related to detrimental clinical conditions that should be studied in depth.

Aged↗

PubMed2003

Development of real time PCR assays for the quantification of Fas and FasL mRNA levels in lymphocytes: studies on centenarians.

Apoptosis plays a central role in the homeostasis of the immune system. During aging, there is an altered regulation of pivotal molecules that are responsible for the regulation of this type of cell death, such as those of the Fas/FasL system. Understanding the regulation of these genes can help to clarify, at least in part, the age-related changes that occur in immune cells. We have developed an original real time PCR assay for quantification of mRNA for Fas and FasL, and have studied a group of young donors, middle aged subjects and centenarians. We have found that the production of Fas mRNA is greatly increased in resting lymphocytes from centenarians; such an increase follows an age-related trend. On the contrary, the production of mRNA for the molecule, which is the natural ligand of Fas, i.e. FasL, is consistently reduced. Our preliminary results suggest that during aging a subtle balance in the production of molecules that cause apoptosis could exist, and that, in order to avoid an excessive death of immune cells, a still unknown mechanism could compensate the increase of Fas with the reduction of FasL.

Aged↗

PubMed2003

Alteration of hypothalamus-pituitary-adrenal glands axis in colorectal cancer patients.

BACKGROUND/AIMS: in advanced cancer patients a cell-mediated immunological impairment, both at baseline and during postoperative period (surgical trauma response) is often found and is associated with poor prognosis. Furthermore it is well known that cortisol is strictly involved in the response to major surgical stress, has an important immunosuppression activity and causes a redistribution of immunological population cells in different tissues. The aim of the study was to verify serum levels and circadian rhythm of cortisol and ACTH in patients with colorectal cancer at baseline before surgery and in the postoperative period, and relate it to the immune status. METHODOLOGY: 40 patients (22 female, 18 male with a median age of 66 yrs) with histologically proven colorectal cancer undergoing to surgery were enrolled in the study. Assessment of total lymphocyte, CD4+, cortisol level, circadian rhythm of cortisol (11 pm and 8 am) was performed at baseline and in 3rd and 7th postoperative days. ACTH levels (11 pm and 8 am) were studied in 18 patients. RESULTS: increase of cortisol serum level in the post-operative period vs baseline was statistically significant both in 3rd and 7th days. A significant decrease of total and CD4+ lymphocytes count was found on both 3rd and 7th postoperative days compared to baseline and to normal values. The rate of patients with an altered circadian rhythm was 68% and 53% at 3rd and 7th postoperative days respectively. At baseline 28% of patients had an altered cortisol circadian rhythm and it was significantly more frequent in patients with nodal involvement (P<0.005) and with metastatic spread (P<0.004). 44% of 18 patients evaluated for ACTH circadian rhythm displayed an alteration and it was significantly higher in patients with nodal involvement and metastatic disease (P<0.05). No relations between lymphocytopenia and alteration of night-cortisolemy, day-cortisolemy and cortisol and ACTH circadian rhythm were found, neither at baseline, 3rd and 7th postoperative days. CONCLUSIONS: it is known that lymphocytopenia, both at baseline and in the postoperative period, is associated with a poor prognosis in cancer patients and that cortisol plays an important role in the immune response. Our data show that lymphocytopenia often present in cancer patients, poor prognostic factor, seems not to be associated with ACTH and cortisol level and circadian rhythm alteration, both at baseline and after surgical stress. Otherwise even if paraneoplastic syndromes seems not to be related to colorectal cancer and no patient showed adrenocortical metastasis, an impairment of circadian rhythm of cortisol and ACTH was found at baseline in 28% and 44% respectively. It was significantly associated with the presence of metastatic disease. These preliminary results suggest further investigations on relation between cancer and endocrine system.

Adrenocorticotropic Hormone↗