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Biomedical subjects

A Ruol

Publications and source records attributed to A Ruol.

At least 37 records · Page 2Linked to original sources
PubMed1997

First-line chemotherapy improves the resection rate and long-term survival of locally advanced (T4, any N, M0) squamous cell carcinoma of the thoracic esophagus: final report on 163 consecutive patients with 5-year follow-up.

OBJECTIVE: The objective of this prospective, nonrandomized study was to evaluate the immediate and long-term results of first-line chemotherapy and possible surgery in locally advanced, presumably T4 squamous cell esophageal cancer. SUMMARY BACKGROUND DATA: Locally advanced esophageal cancer is rarely operable and has a dismal prognosis. For this reason, neoadjuvant cytoreductive treatments are more and more frequently used with the aim of downstaging the tumor, increasing the resection rate, and possibly improving survival. METHODS: From January 1983 to December 1991, 163 consecutive patients with a presumedly T4 squamous cell carcinoma of the thoracic esophagus (group A) received on average 2.5 cycles (range, 1-6) of first-line chemotherapy with cisplatin (100 mg/m2 on day 1) and 5-fluorouracil (1000 mg/m2 per day, in continuous infusion from day 1 through day 5). Chemotherapy was followed by surgery when adequate downstaging of the tumor was obtained. RESULTS: Chemotherapy toxicity was WHO grade 0 to 2 in 80% of cases, but 3 toxic deaths (1.9%) occurred. Restaging suggested a downstaging of the tumor in 101 of 163 patients (62%), but only 85 patients (52%) underwent resection surgery; it was complete or R0 in 52 (32%) and incomplete or R1-2 in 33. Overall postoperative mortality was 11.7% (10 of 85), morbidity 41% (35 of 85). Complete pathologic response was documented in 6 patients, and significant downstaging to pStage I, IIA, or IIB occurred in 25 more patients. The overall 5-year survival was 11 % (median, 11 months). After resection surgery, the 5-year survival was 20% (median, 16 months); none of the nonresponders survived 4 years after palliative treatments without resection (median survival, 5 months). The 5-year survival rate of the 52 patients undergoing an R0 resection was 29% (median, 23 months). Stratifying patients according to the R, pT, pN, and pStage classifications, the survival curves were comparable to the corresponding data obtained in the 587 group B patients with "potentially resectable" esophageal cancer who underwent surgery alone during the same period. Furthermore, the results were improved in comparison with 136 previous or subsequent patients with a locally advanced tumor who did not undergo neoadjuvant treatments (group C). In these patients, the R0 resection rate was 7%, and the overall 5-year survival was 3% (median, 5 months). CONCLUSION: Although nonrandomized, these results suggest that in locally advanced esophageal carcinoma, first-line chemotherapy increases the resection rate and improves the overall long-term survival. In responding patients who undergo R0 resection surgery, the prognosis depends on the final pathologic stage and not on the initial pretreatment stage.

Adult↗
PubMed1997

p53 alterations but no human papillomavirus infection in preinvasive and advanced squamous esophageal cancer in Italy.

Geographic differences in exposure to suspected carcinogens have been identified in esophageal carcinogenesis, and both p53 alterations and human papillomavirus (HPV) infection have been reported in esophageal squamous carcinoma (ESC) from high-risk areas, including China and South Africa. The status of p53 alterations and HPV infection in ESC has not been determined in northern Italy, where the incidence of ESC is low. Formalin-fixed paraffin-embedded esophageal samples containing normal, dysplastic, and carcinomatous tissue from 18 patients were examined for p53 protein accumulation with immunohistochemistry, p53 mutation (exons 5-8) with PCR-single-strand conformation polymorphism analysis and DNA sequencing, and HPV infection with PCR using general primers to amplify the L1 gene. Accumulation of p53 protein was observed in both precancerous and carcinomatous lesions. p53 mutations were rare in dysplastic lesions but were detected in 9 of 18 carcinomas, a finding consistent with reports from other geographic areas. Examination of the p53 mutation spectrum revealed no hot spot mutation. In contrast, HPV was not found in any of these 18 cases. This is consistent with the findings from other low ESC risk areas in which HPV infection may not play a crucial role in esophageal oncogenesis, whereas the high risk of ESC in China and South Africa may be attributed to frequent HPV infection.

Aged↗
PubMed1997

Prognosis of early squamous cell carcinoma of the esophagus after surgical therapy.

Between 1980 and 1995, 91 (13.7%) out of 666 patients were determined by pathologic staging to have a superficial squamous-cell esophageal carcinoma of the thoracic esophagus. The male to female ratio was 3.3:1, and the mean age 60 years. Postoperative mortality was 4.3%. The median follow-up was 48 months (range 3-179). Survival was significantly decreased with increased depth of tumour invasion and presence of nodal metastases (P=0.03). Recurrent disease was prevalent in patients with submucosal tumours compared to those with mucosal tumours (P < 0.05). Only intra-epithelial and intramucosal carcinomas deserve the definition of 'early' tumours. Given the relative inaccuracy of current staging modalities and the low morbidity and mortality rates associated with surgical resection, surgery appears to be the mainstay of treatment of superficial squamous-cell esophageal cancer.

Adult↗
PubMed1996

Serum procollagen type III peptide in chronic hepatitis B. Relationship to disease activity and response to interferon-alpha therapy.

The clinical significance of serum procollagen type III peptide, a marker of active fibrogenesis, was evaluated in 110 hepatitis B surface antigen positive patients with chronic hepatitis (32 chronic persistent hepatitis, 60 chronic active hepatitis, and 18 active cirrhosis), selected on the basis of active viral replication and biochemical activity, including 54 cases treated with interferon-alpha. At presentation the procollagen type III peptide level serum was above normal in 48 (44%) of the 110 patients and the median value was significantly higher than that of healthy carriers with normal transaminases and histology (P < 0.000005). Semiquantitative histological evaluation showed a significant correlation between serum procollagen type III peptide levels and necrosis/inflammation in the subgroup of patients with chronic active hepatitis, but no relationship with the score of fibrosis. Among patients treated with interferon-alpha and with increased fibrogenic activity (indicated by high pretreatment serum levels of procollagen type III peptide), peptide levels were significantly decreased when pretreatment levels were compared with those at 12 months after therapy withdrawal, both in responders to interferon (P = 0.022) and non-responders (P = 0.012). However, serum procollagen type III peptide levels normalized in 75% of responders to interferon with sustained serological and histological remission of liver disease, but in only 21% of non-responders (P = 0.02). These results obtained in a well-defined population suggest that serum procollagen type III peptide is a better marker of active fibrogenesis and inflammation than an indicator of the extent of fibrosis, and that interferon may reduce active liver fibrogenesis in chronic hepatitis B independently of its effect on viral replication. However, a consistent proportion (56%) of our chronic hepatitis B patients had normal serum procollagen type III peptide levels at presentation, thus precluding the clinical use of this marker both for diagnosis of liver injury and for monitoring the therapeutic response to interferon.

Adult↗
PubMed1996

A survey of adverse events in 11,241 patients with chronic viral hepatitis treated with alfa interferon.

AIMS: The aim of this study was to assess the incidence of fatal, life-threatening side effects and the de novo appearance of non-hepatic morbidity during interferon alfa therapy for chronic viral hepatitis. The relationship of these adverse events to actual total dose and duration of interferon was also evaluated. METHODS: We conducted a retrospective study at 73 Italian centers of 11,241 consecutive patients with chronic viral hepatitis who underwent interferon alfa treatment. RESULTS: Five patients died during interferon therapy due to liver failure (n = 4) or complications arising from sepsis. Life-threatening side effects were observed in eight patients: two cases where depression developed and led to a suicide attempt and six patients with bone marrow suppression (granulocytes < 500/mm3 or platelets < 25,000/mm3). These symptoms and signs completely disappeared after interferon withdrawal. During interferon treatment, 131 patients developed the following de novo non-hepatic disorders: symptomatic thyroid disease (n = 71), impotence (n = 5), systemic autoimmune disease (n = 5), immune-mediated dermatologic disease (n = 14), diabetes mellitus (n = 10), cardiovascular disease (n = 7), psychosis n = 10), seizures (n = 4), peripheral neuropathy (n = 3) and hemolytic anemia (n = 2). Most of these complications are reversible or can be ameliorated. Fatal or life-threatening side effects were not related to actual total dose or duration of interferon alfa, while the majority of patients with de novo non-hepatic morbidity received medium/high doses (> 200 million units) of interferon alfa or were treated for periods longer than 16 weeks (68% and 80%, respectively). CONCLUSIONS: Treatment with interferon alfa may have fatal or life-threatening side effects, their incidence in this study being low (0.04% and 0.07%, respectively) and perhaps no different than in untreated patients with chronic viral hepatitis. Moreover de novo non-hepatic morbidity occurred in 1.2% of patients, and the dose and duration of interferon therapy seem important in determining the frequency of this complication. The development of clinically-overt thyroid disease was most common.

Adolescent↗
PubMed1996

Serum levels of soluble CD30 in chronic hepatitis B virus infection.

There is evidence that both cellular and humoral components of the immune response are required for viral clearance to occur in chronic hepatitis B. Recent studies demonstrated that CD30 molecule, a member of the tumour necrosis factor superfamily of membrane cytokine receptors, is expressed on, and released as a soluble molecule (sCD30) by activated T cells producing T helper 2 (Th2) cytokines, which modulate antibody responses. To better characterize the immunoregulatory mechanisms in chronic hepatitis B virus (HBV) infection, sCD30 values were evaluated by an ELISA in 90 hepatitis B surface (HBsAg)-positive patients with chronic hepatitis, selected on the basis of active viral replication and biochemical activity. At presentation abnormal levels (> 20 U/ml) of sCD30 were detected in 57 (63%) out of 90 patients with chronic hepatitis B, and median value was significantly higher in this group of patients compared with that of healthy HBsAg carriers (26.7 versus 10.5 U/ml, P < 0.000 05) and with normal controls (26.7 versus 3 U/ml P < 0.000 01). Sequential studies of chronic hepatitis B did confirm the association of raised sCD30 levels with the active phase of the illness. On the other hand, a significant decrease was noted when sCD30 levels at diagnosis and after termination of HBV replication and biochemical remission of hepatitis were compared in 10 untreated patients (median, 28 U/ml at entry versus 8 U/ml at remission, P < 0.01) and in six patients responding to interferon-alpha therapy (median, 29.5 U/ml at entry versus 6 U/ml at remission, P < 0.05). The high serum sCD30 levels reported during the active phase of HBsAg-positive chronic hepatitis suggest a certain degree of immune competence of these patients, at least with respect to a Th2-type response. These data are in agreement with recent serologic surveys showing that most chronic hepatitis B patients do demonstrate ongoing humoral immune response to HBV antigens, using novel immunoassays designed to detect antibody in the presence of excess serum viral antigen. Th2 functions that mainly promote humoral immunity to HBV antigens may be critical, in association with a competent virus-specific cytotoxicity, for efficient termination of HBV replication in chronic hepatitis B.

Adolescent↗
PubMed1995

p53 overexpression in the multistep process of esophageal carcinogenesis.

The timing of p53 mutation in the multistep process of esophageal carcinogenesis is still under debate. We tested p53 expression in 16 samples of low-grade and 29 samples of high-grade esophageal dysplasia (ED) coexisting with esophageal squamous cancer (ESC) in 31 patients who underwent total esophagectomy. In normal mucosa, a positive immunoreaction was detected in 10 of 31 cases, always restricted to the lower half of the epithelial thickness. We detected p53-positive nuclei in 11 of 16, 23 of 29, and 23 of 31 samples of low-grade ED, high-grade ED, and ESC, respectively. Cases exhibiting positive staining in dysplastic samples also demonstrated positive immunoreaction in the carcinomatous tissue. Immunoreactivity in cancer cells was never found in the absence of positive dysplastic nuclei. A significantly higher score of immunoreactive nuclei was detected in high-grade versus low-grade and in low-grade compared with normal mucosa. These data suggest that p53 mutation may represent an early event in esophageal oncogenesis.

Adult↗
PubMed1995

Therapeutic options for cancer of the hypopharynx and cervical oesophagus.

Between 1980 and 1990, 291 patients with a cancer in the cervical area of the oesophagus were admitted to our Department: in 187 the cancer was located mainly in the cervical region, 76 in the hypopharynx and 28 had a tumour that had spread to the cervical oesophageal region following laryngectomy. Most tumours of the hypopharynx involved the cervical oesophagus when it was often difficult to define the site of origin. 153 patients (53%) underwent surgical resection which included a modified neck dissection followed by different kinds of reconstruction. 96 patients underwent pharyngogastric anastomosis. Twenty anastomotic leaks (23%) were recorded including both those clinically evident and asymptomatic ones detected radiologically. Moreover, segmental proximal necrosis was seen in ten patients. Hospital mortality rate after pharyngogastric anastomosis was 14.7% (14/95). Colon interposition was used in 11 patients. Two anastomotic leaks and two partial necroses were observed. Hospital mortality was 18% (2/11). Eighteen patients underwent laryngopharyngectomy and cervical oesophagectomy with reconstruction performed by means of revascularized jejunal loop. One anastomotic leak was observed and hospital mortality was nil in these cases. Twenty-four patients underwent total oesophagectomy with larynx preservation when the cancer was located at least 2 cm below the upper oesophageal sphincter. Five anastomotic leaks and two partial necroses occurred and hospital mortality was 8.3% (2/24) in these patients. The remaining five patients operated on underwent miscellaneous surgical procedures with one postoperative death. Overall survival for resections considered curative was 21%:37% for hypopharyngeal and 18% for cervical cancers respectively, while it was nil at three years after palliative resection and total oesophagectomy with larynx preservation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Relationship between serum HCV markers and response to interferon therapy in chronic hepatitis C. Evaluation of HCV genotypes during and after long-term follow-up.

Hepatitis C virus is the most frequent cause of chronic non-A, non-B hepatitis, and the antibodies to structural and nonstructural proteins encoded by viral genome have been suggested to be markers of ongoing HCV infection. We studied the behavior of these antibodies during interferon therapy in 18 patients with chronic hepatitis C and also during a follow-up period of at least four years. A significant decrease of anti-HCV titer was found only in patients who had shown positive response to therapy and all of them were anti-HCV negative at the end of follow-up. Analysis by recombinant immunoblotting assay showed that only anti-c100 were affected by interferon therapy, whereas anti-c22 and anti-c33 were not modified. Using polymerase chain reaction to detect small amounts of HCV genome in serum, we could confirm that the behavior of HCV-RNA during and after interferon therapy is similar to that of anti-HCV and the loss of anti-c100 seems to be closely related to HCV-RNA disappearance from serum. Our patients with chronic hepatitis C were found to be of type 1b and 2, according to the recent score of Simmonds, and the clearance of serum HCV-RNA during treatment and its sustained negative status are closely related to genotype 2 and to long-term positive response to interferon.

Chronic Disease↗
PubMed1994

Single-layered cervical esophageal anastomoses: a prospective study of two suturing techniques.

We carried out a prospective, randomized study over a 1-year period to compare the efficacy of a single layer of continuous absorbable monofilament (Maxon) with that of a single layer of interrupted Polyglactin sutures (Vicryl) in the performance of cervical esophagogastric anastomoses. Forty-two consecutive patients with carcinoma of the esophagus or cardia, in whom the stomach was transposed through the mediastinal route after esophagectomy, were enrolled in the study. There were 21 patients in each group. There was no hospital mortality. One asymptomatic anastomotic leak and two early anastomotic strictures requiring dilation occurred in patients in whom an interrupted technique was employed. The continuous technique required significantly less operative time (p < 0.0001), and the cost of the suture material was reduced markedly. We conclude that either a continuous or an interrupted monolayer esophagogastric anastomosis can give satisfactory results after esophagectomy for cancer, provided that the vascular supply to the gastric fundus is maintained adequately. The continuous technique has the advantages of being time-saving, cheaper, and easier to perform and to teach.

Adenocarcinoma↗
PubMed1994

A randomized controlled trial of thymopentin therapy in patients with chronic hepatitis B.

Strategies of treatment of chronic hepatitis type B are currently based on the use of either antiviral or immunomodulatory agents. A randomized, controlled trial was performed to assess the safety and efficacy of 6-month thymopentin therapy in 30 patients with chronic hepatitis B. Inclusion criteria were biopsy-proven chronic hepatitis, elevated alanine aminotransferase and serum HBsAg and HBV-DNA positivity for at least 12 months. At the conclusion of the study (1 year), HBV-DNA was negative and alanine aminotransferase had normalized in 13% and 20% of treated cases and in 20% and 27% of controls. None of the ten treated and one of the nine control patients who were initially HBeAg positive subsequently cleared HBeAg. None became HBsAg negative. A histologic improvement was noted in 27% of the treated patients compared with 18% of controls. These results indicate that this regimen of thymopentin therapy is not effective in treating chronic hepatitis B.

Adult↗
PubMed1994

Interferon antibodies in patients with chronic hepatitic C virus infection treated with recombinant interferon alpha-2 alpha.

Patients treated with alpha-2a interferon for chronic hepatitis C may produce anti-interferon antibodies whose effect, if any, on the individual response to therapy has not been fully clarified. The prevalence and kinetics of anti-interferon, including those of neutralizing type, have been studied in 60 patients with chronic hepatitis C enrolled in a randomized controlled trial of recombinant alpha-2a interferon. Thirty patients received interferon while 30 were untreated controls. Two different methods, an enzyme immunoassay and an antiviral neutralization bioassay, were used and serial serum samples from each patient were analyzed. Enzyme immunoassay-positive anti-interferon appeared in 60.7% of treated patients within 6 months of therapy; antiviral neutralization bioassay-positive anti-interferon appeared in 52.9% of these enzyme immunoassay-positive patients, and was associated with high enzyme immunoassay reactivity and long-term persistence. Anti-interferon was detected in 75% of patients showing no response to interferon. Antibodies were also detected in three out of six patients who showed alanine aminotransferase normalization persisting up to the end of treatment and in 8 out of 14 patients who showed an initial marked reduction or even normalization of alanine aminotransferase, followed by reactivation of liver damage during treatment. Interestingly, patients who became anti-interferon positive before complete alanine aminotransferase normalization later showed reactivation of liver damage independently of interferon dose reduction, while patients who became positive for anti-interferon after complete alanine aminotransferase normalization either did not reactivate or did so only after interferon dose reduction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Juxtaglomerular cell tumor of the kidney.

A juxtaglomerular cell tumor (JGCT) was found in a 40 year old woman. For 5 years she had mild hypertension, responding to classical anti-hypertensive treatment, then she became severely hypertensive. Two renal angiographies and a CT scan were reported as normal. A second CT scan and third selective renal angiography were diagnostic, associated with lateralization of renin in renal vein measurement. Light, electron microscopy and immunohistochemistry of the resected tumor confirmed the diagnosis of renin-secreting juxtaglomerular cell tumor of the kidney.

Adult↗
PubMed1994

[Adenocarcinoma in Barrett's esophagus: long-term results of curative resection].

Between 1980 and 1993, out of 635 patients presenting with an adenocarcinoma of the esophagogastric junction, 74 (11.7%) had a neoplasm arising from a columnar specialized epithelium lining the distal esophagus. Fifty of these patients (68%) underwent a curative (R0) resection. 36 patients (72%) were in stage 0, I or II, and the 5-year actuarial survival rate was 44%. The survival rate dropped to 13% when nodal metastases were present. We conclude that the long-lasting symptoms during the pre-neoplastic phase, and a closer endoscopic surveillance allow a early diagnosis of Barrett adenocarcinoma. Surgical therapy must be radical in these patients in order to improve prognosis.

Adenocarcinoma↗
PubMed1994

[Limited surgery in cancer of the hypopharynx and cervical esophagus: role of autotransplants of the intestinal loop and skin flaps].

The cervical esophageal region can be involved by several cancer types as primary malignancies of the hypopharynx and cervical esophagus, locally advanced tumors of the larynx and thyroid, and neoplastic recurrence after laryngectomy for cancer. These situations often require complex surgical procedures, and the integrated use of multiple surgical techniques or multistage operations. It is often a limit-type surgery that requires free loop intestinal autotransplants, local and regional skin flaps, and peduncle myocutaneous flaps, and therefore requires specific skill not only in general and thoracic surgery but also in head and neck surgery, plastic surgery and microsurgery. This paper summarizes the experience in the field of cervical esophagus replacement with jejunal free loop autotransplant (23 cases) and cutaneous or myocutaneous flaps (23 cases) at the "Centro Regionale Veneto per le Malattie dell'Esofago" from 1980 to 1993.

Esophageal Neoplasms↗
PubMed1993

Flow cytometric DNA analysis does not predict the radiochemoresponsiveness of esophageal cancer.

The relationship between the DNA pattern and the responsiveness to chemotherapy or chemoradiotherapy has been evaluated in 30 patients with squamous cell carcinoma of the esophagus. In 24 patients polychemotherapy with cisplatin (100 mg/m2 on day 1) and 5-fluorouracil (1,000 mg/m2/24 h, continuous infusion of 120 h) every 3 weeks, was performed. Six other patients received chemoradiotherapy with cisplatin 80 mg/m2 on day 1 and 18.5 Gy (split course). Before treatment, at least three endoscopic biopsies were taken from each tumor and frozen at -85 degrees C. Five patients were excluded from the evaluation, three because of interrupted treatment and two due to unsuitable biopsy material obtained endoscopically. The response rate to the cytoreductive treatment was 40% (10/25). DNA content was analyzed with flow cytometry. Out of 25 evaluable patients, a diploid and aneuploid tumor was present in 8 (32.0%) and 17 (68.0%) patients, respectively. According to the DNA pattern, a major response was observed in 4 of 8 patients with a diploid tumor and in 6 of 17 patients with an aneuploid tumor (P = 0.5). No relationship between the percentage of cells in the S-phase and the response to the cytoreductive treatment was evident. Although a slightly higher percentage of major responses was found in euploid tumors, there is no evidence that flow-cytometric DNA analysis can be helpful in the selection of patients for chemotherapy or chemoradiotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Correlation of p53 mutations with epidermal growth factor receptor overexpression and absence of mdm2 amplification in human esophageal carcinomas.

Esophageal carcinomas from 24 patients, most of whom were smokers and consumed alcoholic beverages daily, were analyzed for mutations in exons 5-8 of the p53 tumor suppressor gene. Mutations were identified by polymerase chain reaction amplification and direct sequencing in 12 of 24 (50%) of the samples; almost half of the mutations were at A:T base pairs. Nuclear accumulation of p53 protein, determined by immunohistochemistry with the CM-1 polyclonal antibody, was observed in all cases in which a missense mutation in the p53 gene was detected. None of the 24 carcinomas had amplification of the mdm2 gene, an alternate pathway to p53 loss of function. Alterations involving three other cancer-related genes associated with human esophageal carcinogenesis, c-erbB-1/epidermal growth factor receptor (EGFR), c-myc, and retinoblastoma (Rb), were examined by Southern blot or immunohistochemical analysis in the same sample set to explore the possibility of a link between oncogene activation and loss of tumor suppressor function. While no associations were observed between amplification of the c-myc or EGFR genes and p53 abnormalities, a significant correlation (P < 0.01) was seen between the presence of p53 mutation and EGFR overexpression. Absence of Rb protein, measured immunohistochemically, was observed in four tumors, none of which had aberrations of the p53 gene.

Carcinoma, Squamous Cell↗