Biomedical subjects

Mario Taffurelli

Publications and source records attributed to Mario Taffurelli.

15 recordsLinked to original sources

PubMed2006

p66Shc/Notch-3 interplay controls self-renewal and hypoxia survival in human stem/progenitor cells of the mammary gland expanded in vitro as mammospheres.

The comprehension of the basic biology of stem cells is expected to provide a useful insight into the pathogenesis of cancer. In particular, there is evidence that hypoxia promotes stem cell renewal in vitro as well as in vivo. It therefore seems reasonable that stem cell survival and hypoxia response are strictly connected at molecular level. We here report that the 66-kDa isoform of the SHC gene (p66Shc) is induced in a breast cancer cell line by the exposure to hypoxic environment and that it controls the expression of the stem cell regulatory gene Notch-3. Then, we show that p66Shc/Notch-3 interplay modulates self-renewal (by inducing the Notch-ligand Jagged-1) and hypoxia survival (by inducing the hypoxia-survival gene carbonic anhydrase IX) in mammary gland stem/progenitor cells, expanded in vitro as multicellular spheroids (mammospheres). We conclude that mechanisms that regulate stem cell renewal and hypoxia survival are integrated at the level of the p66Shc/Notch3 interplay. Because Notch-3, Jagged-1, and carbonic anhydrase IX are dysregulated in breast cancer, and because p66Shc is an aging-regulating gene, we envision that these data may help in understanding the relationship among aging, cancer, and stem cells.

Adaptor Proteins, Signal Transducing↗

PubMed2006

Microarray-based identification and RT-PCR test screening for epithelial-specific mRNAs in peripheral blood of patients with colon cancer.

BACKGROUND: The efficacy of screening for colorectal cancer using a simple blood-based assay for the detection of tumor cells disseminated in the circulation at an early stage of the disease is gaining positive feedback from several lines of research. This method seems able to reduce colorectal cancer mortality and may replace colonoscopy as the most effective means of detecting colonic lesions. METHODS: In this work, we present a new microarray-based high-throughput screening method to identifying candidate marker mRNAs for the early detection of epithelial cells diluted in peripheral blood cells. This method includes 1. direct comparison of different samples of colonic mucosa and of blood cells to identify consistent epithelial-specific mRNAs from among 20,000 cDNA assayed by microarray slides; 2. identification of candidate marker mRNAs by data analysis, which allowed selection of only 10 putative differentially expressed genes; 3. Selection of some of the most suitable mRNAs (TMEM69, RANBP3 and PRSS22) that were assayed in blood samples from normal subjects and patients with colon cancer as possible markers for the presence of epithelial cells in the blood, using reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Our present results seem to provide an indication, for the first time obtained by genome-scale screening, that a suitable and consistent colon epithelium mRNA marker may be difficult to identify. CONCLUSION: The design of new approaches to identify such markers is warranted.

Adult↗

PubMed2006

Cell proliferation in breast cancer is a major determinant of clinical outcome in node-positive but not in node-negative patients.

The growth rate of a tumor cell population depends on two major factors: the percentage of proliferating cells (cell growth fraction) and the rapidity of their duplication (cell proliferation rate). The authors evaluated the prognostic and predictive value of both kinetics parameters in a large series of breast cancer patients (n=504). The cell growth fraction was determined by MIB-1 immunostaining, the cell proliferation rate by AgNOR analysis. Ki-67 LI (labeling index) and AgNOR area were significantly associated with histotype, histologic grade, tumor size, estrogen/progesterone receptor status, patient age, and lymph node involvement (P<0.005). In the entire series of patients, both kinetics variables were significantly and independently associated with the clinical outcome, but their prognostic relevance was quite different when node-negative and node-positive patients were considered separately. Although in node-positive patients Ki-67 LI and AgNOR area were the unique independent predictors of disease-free and overall survival, they were excluded by the multivariate Cox model in node-negative patients, where only tumor size and estrogen receptor status retained a significant P-value. These results show that in breast carcinoma the cell growth fraction and the cell proliferation rate have a different prognostic impact with respect to the lymph node status and are major determinants of clinical outcome in node-positive patients only. Within this subgroup, the rapidity of cell proliferation as assessed by AgNOR analysis also served as a sensitive predictor of the response to adjuvant treatments.

Adult↗

PubMed2006

Skin angiosarcoma arising in an irradiated breast: case-report and literature review.

BACKGROUND: Angiosarcoma (AS) is a rare, invasive malignancy originating from endothelial cells caused by many different clinical situations. AS following radiotherapy for breast cancer after conservative surgery is a rare but well-known association. OBJECTIVE: The aim of this article is to describe a case of AS after breast conserving surgery and to review the literature to date. RESULTS: We report the case of an 84-year-old woman who developed AS four years after she was subjected to quadrantectomy for invasive ductal cancer, followed by 30 tangent field radiotherapy sessions. She presented with a one-month history or red papular skin eruptions on the operated breast. Skin lesions were submitted for biopsy, and they were positive for AS. The patients was subjected to surgical excision of the remaining breast including all AS lesions. She is alive with no evidence of disease after 10 months follow-up. CONCLUSION: Post-radiotherapy AS is rare neoplasm, but it should be considered in the case of patients with red lesions after breast conserving surgery and adjuvant radiotherapy.

Aged, 80 and over↗

PubMed2005

Postoperative Delirium after elective and emergency surgery: analysis and checking of risk factors. A study protocol.

BACKGROUND: Delirum is common in hospitalized elderly patients and may be associated with increased morbidity, length of stay and patient care costs. Delirium (acute confusional state) is defined as an acute disorder of attention and cognition. In elderly patients, delirium is often an early indicator of patho-physiological disturbances. Despite landmark studies dating back to the 1940s, the pathogenesis of Delirium remains poorly understood. Early investigators noted that Delirium was characterized by global cortical dysfunction that was associated predominantly with specific electroencephalographic changes. It's important to understand the risk factors and incidence of Delirium. Some of the risk factors are already identified in literature and can be summarized in the word "VINDICATE" which stands for: Vascular, Infections, Nutrition, Drugs, Injury, Cardiac, Autoimmune, Tumors, Endocrine. Aims of this study are: to re-evaluate the above mentioned clinical risk factors, adding some others selected from literature, and to test, as risk factors, a pattern of some genes associated to cognitive dysfunction and inflammation possibly related to postoperative Delirium. DESIGN: All patients admitted to our Emergency Unit who are meet our inclusion/exclusion criteria will be recruited. The arising of postoperative Delirium will select incidentally two groups (Delirium/non Delirium) and the forward analysis of correlate risk factors will be performed. As in a typical observational case/control study we will consider all the exposure factors to which our population are submitted towards the outcome (presence of Delirium). Our exposures are the following: ASA, Pain (SVS; VAS), Blood gas analysis (pH; Hb; pO2; pCO2), Residence pharmacological therapy (BDZ; hypnotics; narcotic drugs; alcohol; nitrous derivates), Body temperature, Arterial pressure, Heart frequency, Breath frequency, Na, K, Creatinin, Glicemia, Albumin, Hct, White blood cells, Glasgow Coma Scale (GCS), Cognitive state (SPMSQ), Functional state (ADL and IADL), Psychological Distress (HADS), Cumulative Illness Rating Scale (CIRS), Hypotension (classified in: light; moderate and severe and duration), Blood loss (classified in: < 2 lt and > 2 lt), Blood transfusions (< 2 lt and > 2 lt), Quantity of red cells and plasma transfusions, Visual VAS / SVS (timing: I-II-III post-operative day), Red cells and Plasma transfusions, Blood count evaluation and Saturation (O2%), Postoperative analgesia (Emilia-Romagna protocol), Presence of malignant tumoral disease, APACHE Score II. Moreover the presence of some relevant genetic polymorphisms will be studied in different genes such as IL-6, IL-10, TNF-alpha, and IL-1 cluster.

Aged↗

PubMed2005

Small bowel tumours in emergency surgery: specificity of clinical presentation.

BACKGROUND: Despite advances in diagnostic modalities, small bowel tumours are notoriously difficult to diagnose and are often advanced at the time of definitive treatment. These malignancies can cause insidious abdominal pain and weight loss, or create surgical emergencies including haemorrhage, obstruction or perforation. The aim of the present study was to describe the clinical presentation, diagnostic work-up, surgical therapy and short-term outcome of 34 patients with primary and secondary small bowel tumours submitted for surgical procedures in an emergency setting and to look for a correlation between clinical presentation and the type of tumours. METHODS: From 1995 to 2005, 34 consecutive surgical cases of small bowel tumours were treated at the Department of Emergency Surgery of St Orsola-Malpighi University Hospital, Bologna, Italy. Clinical and radiological charts of these patients were reviewed retrospectively from the department database. RESULTS: All patients presented as surgical emergencies: intestinal obstruction was the most common clinical presentation (15 cases), followed by perforation (11 cases) and gastrointestinal bleeding (eight cases). Lymphoma was the most frequent histologic type (nine patients), followed by stromal tumours (eight patients), carcinoids (seven patients), adenocarcinoma (seven patients) and metastasis (three patients). Of the nine patients with lymphoma, eight were perforated, all patients with stromal tumours had bleeding, and all carcinoids patients had bowel obstruction. There were two patients with melanoma metastasis, both had bowel intussusception. Resection of the neoplasm was carried out in 32 patients and two patients were deemed unresectable and received a palliative procedure. CONCLUSIONS: The present study shows that there is a correlation between small bowel tumours and clinical emergency presentation: gastrointestinal stromal tumours (GIST) mostly bleed; carcinoids make an obstruction; lymphomas cause a perforation; and melanoma metastasis causes intussusception.

Adenocarcinoma↗

PubMed2004

Emergency surgery for recurrent intraabdominal cancer.

BACKGROUND: Recurrent abdominal cancer can manifest in many ways but there are certain situations that are a great challenge to clinicians. Emergency presentation is one such situation. Surgeons are faced with a therapeutic dilemma that on the one hand most of these patients have a limited life expectancy, and on the other surgical procedures are unavoidable. We reviewed our experience of recurrent abdominal cancers presenting with acute abdominal symptoms requiring emergency. PATIENTS AND METHODS: Over the last 10 years, 81 patients with recurrent abdominal cancer presented with an abdominal emergency. Case records, operative notes and histology were reviewed. Frequency distributions were prepared for clinical, hematological, biochemical parameters, treatment and complications. Surgical analysis was carried out by the Kaplan Meier method and groups were compared using a log-rank test. RESULTS: The mean age of the patients was 70.1 years with a female to male ratio of 1.25. An overall postoperative mortality of 11.1% and morbidity of 27.1% was observed. Postoperative infections and respiratory complications were the most common causes of morbidity and mortality. Emergency resections carried the same risk of mortality and morbidity as the other surgical procedures (p > 0.05). Patients who underwent radical or palliative resections had a better survival than patients undergoing other procedures (p < 0.05). Preoperative Apache II score was found to be single most important predictor of postoperative mortality and morbidity. CONCLUSIONS: We conclude that surgical resection offers the best chance for improvement in survival after emergency surgery for recurrent abdominal cancer. If resection is not feasible, the possibility of creating a bypass or enterostomies should be considered to improve the patients' quality of life.

Journal Article↗

PubMed2004

Stapled versus hand-sewn anastomoses in emergency intestinal surgery: results of a prospective randomized study.

PURPOSE: Sutured and stapled intestinal anastomoses are perceived to be equally safe in elective intestinal surgery. However, our search of the literature failed to find any studies comparing hand-sewn and mechanical anastomoses in emergency intestinal surgery. Thus, we compared the short-term outcomes of patients with sutured as opposed to stapled anastomoses in emergency intestinal surgery. METHODS: Between 1995 and 2001, 201 patients underwent emergency intestinal operations at the Department of Emergency Surgery of Sant'Orsola-Malpighi University Hospital. The outcomes of patients with sutured and stapled anastomoses were compared in a prospective analysis. Patients were randomly divided into a stapled group (106 anastomoses) with anastomoses made using linear and circular staplers, and a hand-sewn group (95 anastomoses) with anastomoses made by double-layer suturing. RESULTS: There were no significant differences between the groups in operative indications or other parameters. The operation times in the stapled group were significantly shorter than those in the hand-sewn group (P < 0.05), but there were no significant differences in anastomotic leak rates, morbidity, or postoperative mortality between the two groups. CONCLUSIONS: In emergency intestinal surgery comparable results can be achieved using mechanical and manual anastomoses.

Aged↗

PubMed2004

Necrotizing fasciitis: a dramatic surgical emergency.

OBJECTIVES: Necrotizing fasciitis is a challenging and potentially lethal disease; early diagnosis is of paramount importance and aggressive multidisciplinary treatment is mandatory. Overall mortality rates of 33-73% have been reported. The aim of this study was to report the experience with necrotizing fasciitis of an emergency surgery department. METHODS: From October 1995 to December 2001 we observed 11 cases of necrotizing fasciitis. The patients were five men and six women, with ages ranging from 33 to 80 years. RESULTS: Triggering aetiological factors were found in eight cases. In all patients a multidisciplinary approach was utilized. Every patient had a daily surgical debridement of the necrotic areas in the operating room. Polyantibiotic therapy was performed, and was changed according to culture results. After surgery, nine patients were submitted to hyperbaric oxygen therapy. Seven deaths (63.6%) were observed: two cases of pulmonary embolism and five cases of septic shock. Four patients survived; three had a complete recovery with progressive healing of the wounds, whereas one patient had severe impairment of the motility of the affected hand. The mean interval between the onset of symptoms and hospital admission was 5.4 days; for patients who ultimately died it was 7.3 days, whereas for patients who ultimately survived it was 2 days (P<0.05); moreover these patients were significantly younger than those who died (P<0.05). CONCLUSION: The treatment for necrotizing fasciitis is a combination of surgical debridement, appropriate antibiotics and optimal oxygenation of the infected tissues. However, the mortality for this disease is quite high, and is related to late diagnosis and advanced age. Necrotizing fasciitis must be considered a true dramatic surgical emergency.

Adult↗

PubMed2004

Search for epithelial-specific mRNAs in peripheral blood of patients with colon cancer by RT-PCR.

Research has widely supported the efficacy of screening for colorectal cancer in reducing mortality. A blood-based assay potentially represents a more accessible early detection tool for the identification of solid tumor cells originating from a primary tumor site in the body. We demonstrate a relatively easy and highly reproducible technique for the detection of mRNA expression of genes as markers of malignancy in blood samples of patients with colon cancer. The present study aims to identify a set of specific mRNAs expressed in epithelial cells but not in blood cells, which may be useful as markers for early detection of circulating colon cancer cells by a simple, qualitative RT-PCR assay following semi-automated RNA extraction from peripheral blood samples. Our approach includes a systematic search for candidate markers using digital differential display, search on UniGene colon EST libraries and analysis of published data on colon cancer gene expression. A final list included the following genes: bone morphogenetic protein 4 (BMP4), cyclin D (CycD), family with sequence similarity 3, member D (FAM3D), gastrin (GAS), glycoprotein A33 transmembrane (GPA33), glutathione peroxidase 2 gastrointestinal (GPX2), galactoside-binding, soluble, 4 (galectin 4) (LGALS4), non-SMC, structural maintenance of chromosomes, element 1 protein (NSE1), tumor-associated calcium signal transducer 1 (TACSTD1), telomerase reverse transcriptase (hTERT), trefoil factor 3 intestinal (TFF3), transmembrane 4 superfamily member 3 (TM4SF3), UDP glycosyltransferase 1 family, polypeptide A9 (UGT1A9), villin 1 (VIL1), and the novel gene FLJ20127. The mRNA expression of these genes was evaluated in a pool of 16 samples from subjects diagnosed with colon cancer and from 16 normal-controls. We observed expression in 13 of the 15 investigated genes from the blood samples of the vast majority of patients considered, but also in a certain percentage of the controls (from 14.3 to 100%). This finding confirms that the extreme sensitivity of RT-PCR is able to detect minimal amounts of mRNA expressed in a non tissue-specific manner ('illegitimate transcription'). On the contrary, NSE1 and GAS mRNAs were not detected either in patient or in control blood samples; however, they were abundantly expressed in normal and cancerous colon mucosa, encouraging further search for useful markers able to detect epithelial cells in peripheral blood.

Aged↗

PubMed2003

Retention of the p53 codon 72 arginine allele is associated with a reduction of disease-free and overall survival in arginine/proline heterozygous breast cancer patients.

PURPOSE: The arginine to proline substitution at codon 72 represents a common aminoacidic polymorphism of the p53 protein. Recent data suggest that p53 codon 72 may modulate the response to cancer therapy. The aim of this study was to test the hypothesis that the p53 codon 72 genotype, evaluated in the tumor tissue and in the disease-free lymph node, is related to differences in disease-free and overall survival among breast cancer-affected patients. EXPERIMENTAL DESIGN: We assessed the p53 codon 72 genotype in DNA from disease-free lymph nodes and neoplastic tissues obtained from 67 women affected by breast cancer who underwent surgical resection at the Bologna Breast Cancer Surgical Unit from 1993 to 1995. RESULTS: We found that the retention of the p53 codon 72 arginine allele in the tumor tissue of proline/arginine heterozygous breast cancer patients is associated with statistically significant reduced disease-free and overall survivals. CONCLUSIONS: Our findings suggest that the genotyping for p53 codon 72 locus in both the tumor tissue and in the lymph node of breast cancer patients could contribute to identify a subset of arginine/proline heterozygous patients who have a reduced survival that is associated with the specific retention of the arginine allele in the tumor tissue.

Adult↗

PubMed2003

Ogilvie's syndrome treatment.

INTRODUCTION: Ogilvie's Syndrome (OS) is a rare condition caused by parasympathetic dysfunction of large bowel characterized by acute and massive colon distension without mechanical obstruction. Rarely this disease has to be treated by the surgeon but operations may be indicated in case of medical treatment failure. METHODS: A retrospective analysis was carried out at the Emergency Surgery DPT of St Orsola-Malpighi University Hospital Bologna Italy. From 1995 to 2002 11 patients were treated for severe OS: they were 8 males and 3 females and the mean age was 68 yrs. All these subjects had large bowel distension with caecum diameter more than 8 cm without any evidence of mechanical obstruction. RESULTS: In 4 patients (36%) OS was caused by trauma or surgical procedures whereas in 7 cases (64%) was produced by other conditions. Only in 3 cases (27%) conservative treatment was successful; the remaining 8 patients were submitted to surgical therapy. 6 patients were submitted to decompressive caecostomy and in 2 cases a subtotal colectomy was done. Mortality was 36%. DISCUSSION AND CONCLUSIONS: Surgical treatment of OS is indicated when there is a conservative treatment failure. The high mortality is related to diagnostic and therapeutic delays, advanced age and comorbidities.

Aged↗

PubMed2002

Immunocytochemical expression of epidermal growth factor receptor in myoepithelial cells of the breast.

The immunohistochemical expression and distribution of epidermal growth factor receptor (EGFr) in mammary myoepithelial cells (MECs) in normal tissue, benign epithelial proliferative lesions, and in situ carcinoma was performed. Results of the current study demonstrated that MECs stained constantly and strongly for EGFr, creating an outer continuous ring surrounding the epithelium of ducts and acini in healthy, in proliferative epithelial lesions, and in in situ carcinoma, both of ductal and lobular type. Foci of microinvasion were easily appreciated for the complete loss of EGFr immunostaining. Epidermal growth factor receptor expression in normal epithelia ranged from negative to weakly positive; it was positive in hyperplasia, whereas it was not constantly negative in in situ carcinoma. In conclusion, immunohistochemical staining for EGFr is diagnostically useful for MEC identification. The specific EGFr in MECs leads the authors to suggest that its expression may be related to the recently recognized high-specialized paracrine function by which the MECs exert the natural mechanical and functional role in the juxtaposition between epithelium and stoma.

Breast↗

PubMedDate not supplied

Audit system on Quality of breast cancer diagnosis and Treatment (QT): results from the survey on screen-detected lesions in Italy, 2003-2004.

Within the Italian Breast Screening Network, individual data are collected yearly on about 50% of all screen-detected operated lesions. In 2003 results showed a good overall quality of diagnosis and treatment, and an improving trend over time. Critical issues were identified in the number of cancers diagnosed pre-operatively, which is still below standards, and in the waiting times for surgery. Compliance with recommendations as to not performing frozen section on small lesions and unnecessary axillary dissection for ductal carcinoma in situ still have not reached the target. The sentinel lymph node technique was performed on the axilla in more than 60% of screen-detected invasive cancers, avoiding a large number of potentially harmful dissections. Preliminary data for 2004 show further progress towards better quality, particularly in pre-operative diagnosis and in the avoidance of frozen section. The detailed results of this survey have been distributed to local and regional screening programmes in order to allow multidisciplinary discussion and the identification of appropriate solutions to any problems documented by the data. Specialist Breast Units with adequate case volume would provide the best setting for making audit effective in producing quality improvement.

Aged↗

PubMedDate not supplied

[Determinants of clinical priority and of actual waiting times for surgical interventions].

OBJECTIVES: To explore determinants of clinical priority and of actual waiting times for elective surgical interventions. DESIGN, SETTING PARTECIPANTS: 405 patients cared for at two general surgery wards, receiving an explicit judgement of clinical priority and whose actual waiting times to surgery were assessed. Clinicalpriority was assessed through 0 (no priority) to 10 (maximum priority). MAIN OUTCOME MEASURE: Identification through multivariate regression techniques of the clinical characteristics associated with high clinical priority (score 28) and with shorter actual waiting times. RESULTS: Patients with cancer, severe pain, relevant impairment in functional status and relevant expert improvement on quality and duration of survival were more frequently attributed a high clinical priority. As for waiting times, presence of cancer was the only factor associated with shorter waitings. Only for cancer patients high priority judgement was associated with shorter waiting times (median 21 vs. 69 days; p < 0.008). CONCLUSIONS: These findings suggest that actual waiting times are not influenced by the same clinical characteristics that clinicians value when assigning clinical priority. That may have some relevant implications on how waiting lists are managed, if consideration of relevant aspects of patients' needs are missed.

Aged↗