Occurrence of indoleamine 2,3-dioxygenase in human cutaneous malignant melanoma.
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Humans↗
Biomedical subjects
M Lise
Publications and source records attributed to M Lise.
p53 gene alterations and protein accumulation in colorectal cancer.
Aim-To correlate immunohistochemical staining with single strand conformation polymorphism (SSCP) analysis of the p53 gene in colorectal cancer in order to understand how the findings provided by the two techniques complement each other in defining p53 functional status.Methods-Frozen tumour tissue from 94 patients with colorectal cancer was studied for p53 protein accumulation and gene mutations. Accumulation of p53 protein was detected by immunohistochemistry using PAb1801 and BP53-12-1 monoclonal antibodies. The findings were then compared with SSCP analysis of exons 5 to 8 of the p53 gene. All cases with a positive result by SSCP analysis were confirmed by sequencing.Results-Nuclear staining was observed in 51 (54.2%) cases. SSCP analysis of the DNA amplified by PCR revealed that the electrophoretic pattern had shifted in 30 cases; sequence analysis confirmed the occurrence of a mutation in 29 cases and of a polymorphism in one. In 27 cases both assays gave a positive result, and in 40 both were negative; therefore, concordance between PCR-SSCP and immunohistochemistry was seen in 72% of cases.Conclusion-The data indicate that positive immunostaining corresponds with the presence of a mutation in most, but not all, cases studied; other mechanisms could be responsible for stabilisation and accumulation of p53 protein in the nucleus. Nonsense mutations which do not confer stability on the protein will not be detected by immunohistochemistry and false negative results can also occur with SSCP analysis.
Journal Article↗
Eating pattern in the first year following adjustable silicone gastric banding (ASGB) for morbid obesity.
OBJECTIVE: To analyse the relationships between eating pattern, vomiting frequency, weight loss and the rate of band related complications in morbidly obese patients undergoing Adjustable Silicone Gastric Banding (ASGB). SUBJECTS: 80 morbidly obese patients (57 females and 23 males) consecutively operated by ASGB were evaluated both before and 3, 6 and 12 months after ASGB. Ten patients (12.5%) had binge eating disorder and were analysed separately. MEASUREMENTS: (1) weight loss expressed as percentage of overweight, (2) total daily energy intake, (3) percentage of energy as lipids, carbohydrates and proteins, (4) percent as liquid, soft or solid foods and (5) vomiting frequency. RESULTS: ASGB induced a highly significant reduction of total daily energy intake and percent as solid foods, without significant changes in macronutrient distribution. There was an inverse relationship between vomiting frequency and the intake of solid foods. Non-binge eaters with more vomiting ate less solid food and lost more weight than patients without vomiting. The frequency of neostoma stenosis was higher in patients with high vomiting frequency than in patients with no vomiting. Patients with binge eating disorder had a significantly higher vomiting frequency and a five-fold higher frequency of neostoma stenosis than patients without binge eating disorder. However, the percentage of overweight lost did not differ between patients with and without binge eating. CONCLUSIONS: Vomiting is a major determinant of global outcome after ASGB. The vomiting frequency in the first months after ASGB was associated with eating pattern, the frequency of neostoma stenosis and possibly the rate of weight loss during the first year of follow-up.
Adolescent↗
Does surgery resolve outlet obstruction from rectocele?
In order to ascertain whether plastic surgery for rectocele is of value in the treatment of outlet obstruction, a retrospective study was made of 21 women complaining of difficulty in expelling faeces: 13 patients (group A) underwent surgery with transanal longitudinal plication of the anterior rectal wall (Block's technique), and 8 patients (group B) had colpoperineoplasty which, in 2, was associated with bladder-neck suspension following the Raz-Peyrera technique for urinary incontinence. The mean follow-up was 24.2 +/- 18.7 and 36.8 +/- 17.8 months respectively. In 11 group A patients (80.9%) and 6 group B patients (75%) cure, or an improvement, was achieved. Of the remaining 4 patients (19%), recurrent rectocele was found in 2 (one group A and one group B) and intestinal transit time tests detected colonic constipation in one group A and in one group B patient. It is concluded that surgery can resolve outlet obstruction from rectocele, but Block's technique is preferable because it is more straight-forward and easier.
Constipation↗
Striated anal sphincter electromyography in idiopathic fecal incontinence.
PURPOSE: This study was designed to determine the importance of innervation of striated anal sphincters, one of the most important structures in idiopathic fecal incontinence. METHODS: Forty-three idiopathic, fecally incontinent patients (40 women and 3 men; mean age, 57.2 +/- 11 (range, 33-77) years) underwent anorectal manometry and sphincteric electromyography. On the basis of electromyographic findings, patients were subdivided into three groups: Group A consisted of 21 patients with normal electromyography; Group B consisted of 14 patients with moderate denervation; Group C consisted of 8 patients with severe denervation. Manometric results from the patients were compared with those from 15 healthy subjects (8 women and 7 men; mean age, 35 +/- 12 (range, 15-55) years). RESULTS: Incontinent patients had a shorter anal canal (P = 0.005), and anal canal pressure was lower at rest (P < 0.001), at contraction (P < 0.001), and at coughing (P < 0.001); rectal distention and rectal compliance were reduced (maximum tolerated volume, P < 0.003; compliance at 200 ml, P = 0.03; at 250, P < 0.005; at 300 ml, P = 0.03). No statistically significant differences were found between the manometric results of the three different groups of patients. A statistically significant linear correlation was reached by comparing the clinical severity of fecal incontinence with age (P = 0.02) and some other manometric parameters: the pressure of the anal canal at rest (P < 0.001) and at contraction (P < 0.01); rectal compliance at 50 ml (P = 0.03), 100 ml (P = 0.004), and 150 ml (P = 0.004). CONCLUSION: Clinical severity of fecal incontinence is correlated with some manometric parameters. Severity of denervation of the anal striated sphincters does not appear to influence severity of fecal incontinence.
Adult↗
Nitric oxide synthase and VIP distribution in enteric nervous system in idiopathic chronic constipation.
Idiopathic chronic constipation has been correlated to neural abnormalities that consist of a reduced number of myenteric plexus neurons and a decreased concentration of VIP-positive nerve fibers within the circular muscle. Recent studies hypothesized the involvement of nitric oxide in motility disorders of the human gut. To date, no information is available on nitric oxide involvement in idiopathic chronic constipation. The density of VIP- and nitric oxide-producing neurons was evaluated by immunocytochemistry using anti-VIP and anti-nitric oxide synthase antibodies in five patients with idiopathic chronic constipation. A low total neuron density was found at the myenteric plexus. The density of VIP-positive neurons was low while that of nitric oxide synthase-positive neurons was high at both plexuses. Our data confirm that idiopathic slow-transit chronic constipation is due to abnormal neurogenic factors. The presence of numerous nitric oxide synthase-positive neurons, all along the colon and at both plexuses, supports the hypothesis that an excessive production of nitric oxide may cause the persistent inhibition of contractions.
Adult↗
Prognostic factors in resectable gastric cancer: results of EORTC study no. 40813 on FAM adjuvant chemotherapy.
BACKGROUND: The high incidence of locoregional recurrences and distant metastases after curative surgery for gastric cancer calls for improved locoregional control and systemic adjuvant treatment. METHODS: In a randomized clinical trial on adjuvant FAM2 chemotherapy, quality of surgery was evaluated by comparing surgical and pathology data. Univariate and multivariate analysis was made to evaluate the effect of prognostic factors on survival and time of recurrence in relation to patients, tumor, and therapy. RESULTS: Of 314 patients randomized from 28 European institutions, 159 comprised the control and 155 the FAM2 group. After a median follow-up of 80 months, no statistically significant difference was found between survivals. However, for recurrence time, treated patients had a significant advantage over controls (p = 0.02). At univariate analysis, statistically significant differences in survival and time to progression emerged for T, N, disease stage and "adequacy" of surgery. The multivariate analysis retained preoperative Hb level, T, N, and "adequacy" of surgery for time of survival; and T, N, "adequacy" of surgery and adjuvant chemotherapy for recurrence time. CONCLUSIONS: Disease stage is the most important prognostic factor. "Adequate" surgery has an important effect. Adjuvant FAM2 delayed time of recurrence, but did not influence overall survival.
Adenocarcinoma↗
Multimodality treatment of extra-visceral soft tissue sarcomas M0: state of the art and trends.
We here outline principles and trends in the treatment of soft tissue sarcomas without distant metastases (M0). Over the last 15 years significant advances have been made in the diagnostic imaging and histological classification of these tumors as well as in their treatment. Magnetic resonance imaging (MRI) has essentially replaced computerized tomography (CT) for the evaluation of the local growth pattern, although the latter is still preferred for the detection of pulmonary metastases. Immunohistochemistry techniques and electron microscopy have improved the histological diagnosis, although the results obtained should always be interpreted in the context of routine light microscopy. Adequate surgical resection and radiotherapy can reduce the incidence of local recurrence, which is still high for head-neck and retroperitoneal sarcomas. Limb-sparing surgery in combination with irradiation and/or intra-arterial or perfusion chemotherapy is considered the treatment of choice in 90% of limb sarcomas, with a local recurrence rate of less than 20%. New radiotherapeutical techniques and anti-neoplastic agents are now under investigation in an attempt to improve local control. There is also a need for a more effective adjuvant chemotherapy. Randomized clinical trials using doxorubicin/ifosfamide and growth factors are now underway.
Animals↗
Tumour-infiltrating lymphocytes bear the 75 kDa tumour necrosis factor receptor.
Tumour necrosis factor alpha (TNF-alpha) is a cytokine with a variety of immunological properties. The identification of two receptors for this molecule, i.e. the 75 kDa and the 55 kDa TNF receptors (TNF-R), recently clarified the mechanisms through which this cytokine provides its wide range of immunomodulatory activities. In this study we have investigated the expression and the functional properties of these receptors on tumour-infiltrating lymphocytes (TILs) recovered from 17 patients with solid cancers (melanoma, colorectal carcinoma and lung cancer). To this end, TIL lines and freshly isolated TILs were evaluated for (a) the expression and the functional role of TNF receptors following culture in the presence of interleukin 2 (IL-2) and (b) the production of TNF-alpha following culture with IL-2 and the role of this cytokine in IL-2-driven TIL proliferation. Flow cytometry analysis demonstrated that TILs bear the 75 kDa TNF-R. Moreover, TIL lines express detectable messages for TNF-alpha and release this cytokine. Functional in vitro studies have shown that anti-TNF-alpha, as well as anti-75 kDa TNF-R antibodies, are able to inhibit the IL-2-induced TIL proliferation. These data demonstrate that TILs are equipped with a fully functional TNF-R system and suggest a putative role for this receptor and its ligand in the activation and expression of TILs following immunotherapy with IL-2.
Antibodies, Monoclonal↗
Association of p53 gene and protein alterations with metastases in colorectal cancer.
Using monoclonal antibody PAb 1801, p53 protein was detected in the neoplastic cells of 39 (46.9%) of 83 colorectal carcinomas studied. Patients with p53+ tumors showed a higher incidence of lymph node and liver metastases (p = 0.035); in patients whose tumors were located in the rectosigmoid, p53 expression also correlated with a more advanced stage according to Dukes' classification (p = 0.015) as well as nodal (p = 0.006) and liver (p = 0.019) metastases. Following amplification of exons 5 to 8 of the p53 gene by means of the polymerase chain reaction technique, single-strand conformation polymorphism analysis disclosed an anomalous migration pattern in 23 of the 39 p53+ tumors and in four of the 35 p53- tumors analyzed. Sequence analysis showed G:C-->A:T transitions in 63.6%, G:C-->T:A and G:C-->C:G transversions in 18.2%, deletions and insertions in 13.6%, and A:T-->G:C transitions in 4.6% of the cases. Loss of heterozygosity was studied in the DNA of 79 patients; allelic loss was found in 29 (49.1%) of the 59 informative patients. Loss of heterozygosity was correlated with p53 overexpression (p = 0.0002) as well as with the presence of mutations as detected by single strand conformation polymorphism analysis (p = 0.0024).
Adenocarcinoma↗
Final results of a phase III clinical trial of adjuvant chemotherapy with the modified fluorouracil, doxorubicin, and mitomycin regimen in resectable gastric cancer.
PURPOSE: In a randomized clinical trial (European Organization for the Research and Treatment of Cancer [EORTC] no. 40813) on adjuvant chemotherapy in gastric cancer, results obtained after administration of the FAM2 regimen (fluorouracil [5-FU], doxorubicin, and mitomycin) were compared with results obtained after surgery alone to assess the effect of this regimen on overall survival, time to progression, and disease-free interval. PATIENTS AND METHODS: Three hundred fourteen patients who had undergone curative resection for stage II or stage III (International Union Against Cancer [UICC] 1978) gastric adenocarcinoma were randomized to receive chemotherapy (treatment arm) or no further treatment (control arm). The chemotherapy schedule was repeated every 43 days for seven cycles. The log-rank test and the Cox model were used for statistical analysis. RESULTS: Of 314 patients, 159 comprised the control group and 155 the FAM2 group. Nineteen FAM2 patients never received chemotherapy. The median number of cycles was five. Of the patients started on adjuvant treatment, severe hematologic and nonhematologic toxicity (grades 3 or 4, World Health Organization [WHO] scale) occurred, respectively, in 6% to 9% and in 1% to 29% of cases. The overall 5-year survival rate was 70% for stage II and 32% for stage III patients. No statistically significant difference was found between overall survival of the two treatment arms (P = .295). However, time to progression was significantly delayed in the FAM2 arm (P = .020) and disease-free survival showed borderline significance (P = .068). CONCLUSION: FAM2, in view of its high toxicity, cannot be advocated as standard adjuvant treatment for gastric cancer. Large-scale clinical trials using more active, less toxic regimens are required to demonstrate whether adjuvant chemotherapy provides any real benefit.
Adenocarcinoma↗
Laparoscopic Adjustable Silicone Gastric Banding: Technique and Results.
BACKGROUND: Kuzmak's Adjustable Silicone Gastric Banding (ASGB) is the least invasive operation available for morbid obesity, and it is one of the more effective. Based on the know-how gained from performing more than 250 'open' procedures, we have developed an original laparoscopic technique, whose main steps are pouch measurement, limited dissection along the lesser and the greater curvature and the application of the retention sutures. METHODS: From September 1993 through October 1994, 30 morbidly obese patients underwent laparoscopic ASGB. RESULTS: Mean operative time was 2 h and the postoperative stay 2-3 days. Only one major perioperative complication (stomach slippage) was observed. The weight loss achieved, reported as a variation of Body Weight, Body Mass Index, per cent Ideal Body Weight and per cent Excess Weight Loss was similar to that obtained with the open procedure. CONCLUSION: This new approach is a major achievement in bariatric surgery, because it combines the minimal invasiveness of laparoscopy with the reversibility and adjustability of ASGB.
Journal Article↗
Laparoscopic Placement of Adjustable Silicone Gastric Banding: Early Experience.
BACKGROUND: the authors describe a laparoscopic technique for the positioning of stoma adjustable silicone gastric banding (SASGB), which respects the main steps of the open procedure. METHODS: (1) patient position: supine with thighs abducted and 30 degrees reverse Trendelenburg; (2) Four 10 mm trocars (supra-umbilical, sub-xiphoid, right upper quadrant, left upper quadrant) and an 18 mm trocar (left subcostal); (3) exposure of the subcardial area; (4) measurement of the pouch; (5) dissection of the lesser and greater curvatures; (6) retrogastric tunnel; (7) introduction and placement of the band; (8) band closure and stoma calibration; (9) retention sutures. RESULTS: results obtained in a first (1992) series of five patients who underwent the laparoscopic application of the regular SASGB and results of a second series (1993-1994) of seven patients in whom the new LAP-ASGB was utilized are reported. CONCLUSION: this new approach can represent a major achievement in bariatric surgery, as it combines the minimal invasiveness of the laparoscopic approach with the reversibility of SASGB.
Journal Article↗
Phase II study on neoadjuvant hyperthermic-antiblastic perfusion with doxorubicin in patients with intermediate or high grade limb sarcomas.
BACKGROUND: Locoregional control of soft tissue sarcomas of the limbs is achieved generally using a multidisciplinary approach consisting of conservative surgery combined with radiation therapy, intraarterial chemotherapy, or hyperthermic antiblastic perfusion (HAP). Before surgery, HAP seems to be the more suitable tool in decreasing tumor mass and allowing limb-sparing surgery. The authors' aim was to ascertain the activity of HAP with doxorubicin against intermediate or high grade limb tumors. METHODS: In 23 patients with limb sarcomas (2 patients International Union Against Cancer Stage IIA, 4 stage IIB, 1 stage IIIA, 11 stage IIIB, and 5 stage IVB) doxorubicin was administered via HAP 4-6 weeks before surgery. The drug (bolus, 0.7-1.4 mg/kg) was perfused for 60 minutes with a tumor temperature of at least 40.5 degrees C (range, 40.5-42.6 degrees). Tumor necrosis was then assessed radiologically and pathologically. RESULTS: Systemic toxicity was hematologic grade (G) 2 in 2 patients, gastrointestinal (hepatic) in 6, G1 in 2, G2 in 3, and G3 in 1; 2 patients had alopecia; locoregional toxicity (graded according to Wieberdink) was G1 or G2 in 18, G3 in 4, and G4 in 1. Tumor necrosis was more than 50% in 17 patients (74%). Limb-sparing surgery was feasible in 20 patients (91%). At present, 14 patients are alive. Six had local recurrences, and eight had distant metastases. CONCLUSIONS: Our findings show that HAP with doxorubicin is an active and well-tolerated procedure within a multidisciplinary approach to treatment of limb sarcomas.
Adult↗
Efficacy of dilatations for anastomotic colorectal stenoses: prognostic factors.
The authors report their experience of 30 patients with colorectal anastomotic stenosis treated by 62 dilatation sessions in order to evaluate which anastomotic characteristics could influence the success of dilatation therapy. Patients were subdivided into group A (dilatation successful) and group B (dilatation unsuccessful). Overall, dilatation was successful in 73.3% of cases, with only one important complication. The prognostic factors considered were anastomotic dehiscence, adjuvant radiotherapy, presence of colostomy at dilatation, site, morphology and length of the stenosis, presence of neoplastic recurrence, type of anastomosis and type of dilatation. Radiotherapy, local neoplastic recurrence and large anastomotic dehiscence were the more important independent prognostic factors. If present together, they were associated with an almost 100% probability of failure and, vice versa, if they were absent this probability was 5%.
Adult↗
Femoral nerve damage after abdominal rectopexy.
Iatrogenic femoral nerve damage has already been described after hysterectomy, but never after abdominal rectopexy. We report the occurrence of femoral nerve injury in six of twenty-four patients operated on for complete rectal prolapse (n = 21) or rectorectal intussusception (n = 3). Four patients had unilateral and two bilateral lesions. All six patients had clinical and electromyographic (EMG) assessment. EMG findings were given a score from 0 (complete denervation) to 5 (normal findings). During the immediate postoperative period all patients complained of reduced cutaneous sensation of the anterior surface of the thigh and knee, and quadriceps weakness. EMG showed complete denervation in one patient, marked denervation in three, and slight or moderate denervation in the remaining two. In five patients there was complete clinical resolution at 3 to 12 months postoperatively, while one showed an improvement only. EMG control performed in four patients showed a full recovery in three. Two patients refused this examination. We believe femoral nerve damage was caused by the large-bladed self-retaining retractors used, which directly or indirectly compressed the femoral nerve.
Abdomen↗
Proliferating cell nuclear antigen (PCNA) and recurrence in patients with cutaneous melanoma.
A positive correlation between PCNA and the most important histoprognostic factors of cutaneous melanoma has been demonstrated. The aim of our work was to evaluate the efficacy of PCNA in predicting melanoma recurrence and to compare it with that of Breslow thickness. One-hundred and fifteen patients (75 women, 40 men; mean age 50 years) with primary cutaneous melanoma were retrieved. pTNM stages were as follows: stage I, 54 patients; stage II, 31 patients; stage III, 26 patients; and stage IV, four patients. The mean follow-up period was 55 months (range 2-260). Six patients developed lymph node metastases and 28 developed distant metastases; 27 patients died within 2-202 months from diagnosis. Tumour thickness was re-evaluated for each case. PCNA immunostaining was performed using the avidin-biotin complex method and the percentage of PCNA-positive tumour cells was indicated as the PCNA index. In order to evaluate and compare the PCNA index and Breslow thickness as predictors of recurrence, the receiver-operating characteristic (ROC) curve method, based on true-positive and false-positive rates was used. The PCNA index showed the highest true-positive rates and the lowest false-positive rates in the 5-30 interval. The PCNA index optimal cut-off is 20, characterized by 70% sensitivity and 80% specificity; Breslow thickness optimal cut-off is 3.5 mm, with 40% sensitivity and 90% specificity. Our results indicate that the PCNA index has a higher efficacy in predicting locoregional and distant recurrences in patients presenting primary cutaneous melanoma.
Adult↗
Stoma Adjustable Silicone Gastric Banding: Results in 111 Consecutive Patients.
From April 1990 through December 1992, 111 patients (80 females, 31 males, mean age 38 years, range 16-60) underwent stoma adjustable silicone gastric banding (SASGB) at the Department of Surgery, University Hospital, Padua, Italy. Patients' characteristics were: mean height 166 +/- 8 cm; mean body weight (BW) 129.1 +/- 21.6 kg; mean body mass index (BMI) 46.4 +/- 6.3 kg/m(2); mean percentage of ideal body weight (%IBW) 206.2 +/- 27. Eighty-eight patients were morbidly obese and 23 superobese. All patients were available for follow-up. Median follow-up was 18.8 months (range 12-44). At I year (I 03 patients), mean postoperative BW, BMI, %IBW and excess weight lost (%EWL) were 101.5 +/- 20 kg, 36.5 +/- 6 kg/m(2), 164 +/- 30 and 40.8 +/- 19 respectively; at 2 years (58 patients) 92.3 +/- 19 kg, 33.1 +/- 6 kg/m(2), 148.8 +/- 28, 52 +/- 23, respectively, and at 3 years (26 patients) 86.9 +/- 14 kg, 31.4 +/- 5 kg/m(2), 141.5 +/- 25 and 63.6 +/- 20 respectively. The overall postoperative mortality rate was zero and the early morbidity rate 9%. Late complications were band slippage (two patients), stoma stenosis with pouch dilatation (seven patients), band erosion (one patient), reservoir leakage (three patients) and reservoir infection (two patients). Surgical revision was performed in ten (9%) patients, two of whom required band removal. Most complications occurred in patients who underwent SASGB during our initial experience. Our findings confirm that SASGB is a safe and effective surgical means of achieving weight reduction.
Journal Article↗