Cisplatin and etoposide as first-line chemotherapy for metastatic breast carcinoma: a prospective randomized trial of the Italian Oncology Group for Clinical Research.

In this prospective randomized study, first-line treatment with the combination of cisplatin (P) and etoposide (E) was compared with the standard cyclophosphamide, methotrexate, and fluorouracil (CMF) combination in 140 patients. Complete remissions were obtained in 11% of 65 assessable patients on CMF and in 12% of 65 assessable patients on PE. Complete plus partial remission rates were 48% on CMF and 63% on PE (P = .08). Time to progression (median, 32 v 31 weeks), duration of response (48 v 39 weeks), and survival (75 v 76 weeks) were not different. Hematologic toxicity was significantly higher with PE, and gastrointestinal side effects were frequent with this treatment. This study demonstrated that the PE combination is effective as front-line chemotherapy. As far as response rate is concerned, a trend of superiority over CMF was observed, which was of borderline significance. Due to the lack of survival advantage and to toxicity, this combination is not recommended for routine clinical use. However, its high level of activity should be taken into account for further research.

Low-dose aminoglutethimide with and without hydrocortisone replacement as a first-line endocrine treatment in advanced breast cancer: a prospective randomized trial of the Italian Oncology Group for Clinical Research.

PURPOSE: A randomized study comparing low-dose aminoglutethimide (AG) with and without hydrocortisone (HC) was performed to investigate whether corticosteroid replacement contributes to the therapeutic effects of the drug administered as a front-line endocrine therapy in postmenopausal advanced breast cancer. PATIENTS AND METHODS: Postmenopausal patients who had not had prior endocrine therapy for advanced disease and with estrogen receptor (ER) or progesterone receptor (PgR) status positive or unknown were eligible. AG was administered at a dose of 250 mg twice a day orally (125 mg twice a day during the first month) with or without HC (20 mg twice a day orally). Seventy-nine and 74 patients were assessable for response on the AG plus HC arm and on the AG arm, respectively. The two treatment groups were well balanced and patients were largely untreated. Approximately 60% had not received any adjuvant treatment, and approximately 75% had not received any medical treatment after relapse. RESULTS: The overall responses (complete response [CR] plus partial response [PR]) were 44% and 41% for the AG plus HC and the AG arm, respectively, showing no significant difference. Time to progression (median, 8.1 and 6.3 months), duration of response (median, 15.8 and 13.7 months), and duration of survival (median, 34.2 and 36.3 months) were not significantly different between the two treatment arms. Side effects were infrequent and mild in both arms, with no significant differences. CONCLUSION: We conclude that half of the conventional daily dose of AG has optimal therapeutic activity as a front-line endocrine treatment of postmenopausal advanced breast cancer and that HC does not significantly contribute to the therapeutic effects.

First isolated locoregional recurrence following mastectomy for breast cancer: results of a phase III multicenter study comparing systemic treatment with observation after excision and radiation. Swiss Group for Clinical Cancer Research.

PURPOSE: We performed a randomized phase III multicenter study to compare systemic treatment versus no treatment after complete excision and radiotherapy for isolated first locoregional recurrence in patients with breast cancer. PATIENTS AND METHODS: One hundred sixty-seven good-risk patients with an estrogen receptor (ER+) positive recurrence or, in case of unknown receptor status, a disease-free interval (DFI) of greater than 12 months and < or = three recurrent tumor nodules each < or = 3 cm in diameter were entered onto the study. They were randomized to observation subsequent to local treatment or to receive tamoxifen (TAM) until disease progression. Seventy-nine percent of the patients were postmenopausal. RESULTS: The median observation period for the entire study population was 6.3 years. The median disease-free survival (DFS) duration was 26 months for observation and 82 months for TAM patients (P = .007). This was mainly due to the reduction of further local recurrences, whereas the occurrence of early distant metastases was delayed. A multivariate analysis identified DFI and treatment with TAM as significant prognostic factors for DFS. The 5-year overall survival (OS) rates were 76% and 74%, respectively (P = .77). DFI was also a prognostic factor for OS. CONCLUSION: Systemic therapy with TAM after isolated locoregional recurrence of breast cancer significantly increased 5-year DFS rates from 36% to 59% compared with observation alone and prolonged median DFS by more than 4.5 years in patients with ER+ tumors or in the case of unknown ER status with a DFI of greater than 12 months and minimal tumor burden. Treatment with TAM currently has no significant impact on OS, but the median survival duration of the study population has not yet been reached.

Axl expression is associated with adverse prognosis and with expression of Bcl-2 and CD34 in de novo acute myeloid leukemia (AML): results from a multicenter trial of the Swiss Group for Clinical Cancer Research (SAKK).

Receptor tyrosine kinases (RTK) play a significant role in the signal transduction of normal, and malignant hematopoietic cells. We have previously shown that Axl, a novel RTK, is mainly expressed in leukemias of myeloid origin, and that its expression may be associated with cells of monocytic origin. Since expression of certain RTKs in cancer may be associated with different biology and survival, we investigated whether the expression of Axl is associated with clinical characteristics and survival in acute myeloid leukemia (AML). RNA from 54 patients with AML treated in a cooperative group trial was analyzed in a retrospective and blinded manner using a semi-quantitative reverse transcriptase polymerase chain reaction-based assay with primers specific for the Axl gene. Axl expression was found in 19 out of the 54 cases (35%). Axl expression was not detected more frequently in patients of older age, specific FAB categories, or cases with extramedullary disease. However, there existed a correlation between Axl and bcl-2 expression levels. AML cells with high bcl-2 expression showed higher Axl expression (r = 0.32; P = 0.02), and furthermore, Axl transcript numbers were also higher in AML with high CD34 expression (n = 38, r = 0.42; P = 0.008). No significant difference between leukemias expressing and not expressing Axl was found with regard to complete remission rate. However, quantitative Axl expression was associated with worse progression-free and overall survival. Higher Axl levels had worse prognosis for progression-free (beta: 0.68, s.e.: 0.28, P = 0.015) and overall survival (beta: 0.61, s.e.: 0.31, P = 0.05) using multivariate Cox models adjusted for age, Auer rods and leukocyte counts. In conclusion, in this retrospective analysis, no difference with regard to clinical characteristics at diagnosis was found between AML patients whose leukemia cells show Axl expression vs patients whose cells are Axl negative. The association between Axl and bcl-2 and Axl and CD34 expression in de novo AML needs further investigation. Similarly, the negative impact of Axl levels on outcome should be confirmed in a larger cohort.

Exercise during pregnancy attenuates prenatal depression: a randomized controlled trial.

Recent studies have estimated the prevalence of depression during pregnancy to be between 10% and 30%, which is higher than that in the postpartum period. Pharmacological treatment during pregnancy is difficult because of the possible side effects of antidepressants on the mother and the fetus. The aim of this study was to examine whether a supervised exercise program (EP) reduces depressive symptoms in pregnant women. A randomized controlled trial was designed. One hundred eighty four healthy pregnant women from Fuenlabrada Hospital were included (31.37 ± 3.62 years). Women from the exercise group (EG) participated in a supervised EP consisting of three, 55- to 60-min sessions per week throughout pregnancy. The main outcome measure was the patients' depression level assessed by means of the Center for Epidemiologic Studies Depression Scale (CES-D). A total of 167 pregnant women were analyzed; 90 were allocated to the EG and 77 to the control group (CG). Significant differences were found between groups at the end of the study in CES-D scores (EG: 7.67 ± 6.30 vs. CG: 11.34 ± 9.74, p = .005) and in percentages of pregnant women depressed (EG: n = 11/12.2% vs. CG: n = 19/24.7%, p = .04). Our results show that supervised physical exercise during pregnancy reduces the level of depression and its incidence in pregnant women.

Possible deleterious effect of tamoxifen in premenopausal women with locoregional recurrence of breast cancer.

Tamoxifen (TAM) treatment following isolated locoregional recurrence of breast cancer significantly increases 5-year disease-free survival rates compared with observation alone in potentially hormone-responsive patients [J Clin Oncol 1994, 12, 2071-2077]. The treatment outcome was re-analysed by menopausal status (stratification factor) in 35 premenopausal and in 132 postmenopausal patients. Disease progression was highly reduced by tamoxifen in the postmenopausal group and was similar to control in the premenopausal group. However, the 5-year cumulative incidence analysis of the type of first failure showed TAM to be associated with increased incidence of distant metastases (P = 0.01) in premenopausal patients. TAM reduced local progression (P = 0.40) in premenopausal and both types of failure (P = 0.16 and P = 0.001, respectively) in postmenopausal patients. Administration of TAM was associated with a decrease of 5-year overall survival from 90 +/- 7% to 60 +/- 14% in premenopausal patients. Although cautious interpretation of these results is highly recommended due to the small patient numbers and the retrospective subset analyses, these findings might be worthy of further investigation in larger trials. Prospective randomised studies to test hormonal treatment outcome by menopausal status should be encouraged in breast cancer.

Cisplatin, doxorubicin and etoposide (PAV) in advanced gastric carcinoma: the SAKK experience. Swiss Group for Clinical Cancer Research (SAKK).

EAP (etoposide, doxorubicin, cisplatin), a chemotherapeutic combination given over 8 days, proposed by German investigators in cancer of the stomach, has been considered to be too toxic by others. A positive experience with a similar regimen (PAV) developed by the SAKK given over 3 days in small cell lung cancer led us to test it in gastric adenocarcinoma. 41 patients with metastatic gastric cancer were enrolled in the study and 38 were evaluable for response and toxicity. One complete response and 12 partial responses were recorded, giving a response rate of 34% (95% confidence interval (CI) 20-51%). Median progression-free and overall survival were 3.4 and 6.3 months, respectively. Haematotoxicity was the leading toxicity with 34 (90%) and 17 (45%) grade III-IV neutropenia and thrombocytopenia, respectively. Despite this high rate of granulocytopenia, only six episodes of non-fatal febrile neutropenia were observed. Other toxicities were relatively easy to manage with infrequent grade III-IV occurrences. We conclude that PAV is active in gastric cancer and seems to be better tolerated than EAP.

Adenoid cystic carcinoma of trachea metastatic to the placenta.

This is the first case described of an adenoid cystic carcinoma of trachea metastatic to the placenta. An immunohistochemical study is reported as well as a brief review of the literature.

Deletion of Epstein-Barr virus latent membrane protein 1 gene in United States and Brazilian Hodgkin's disease and reactive lymphoid tissue: high frequency of a 30-bp deletion.

A 30-basepair (bp) deletion in the Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) gene has been reported in nasopharyngeal carcinoma and EBV-associated malignant lymphomas. Prior studies have found the deletion in about 10% to 28% of cases of Hodgkin's disease (HD), particularly in cases with aggressive histology. We studied the prevalence of 30-bp LMP1 gene deletion in EBV-positive HD in the United States (US) (12 cases) and Brazil (26 cases) with comparison to reactive lymphoid tissues (21 cases) and HD without EBV-positive Reed-Sternberg cells (15 cases). We studied the status of the LMP1 gene by Southern blot hybridization of polymerase chain reaction (PCR) products obtained after amplification with primers spanning the site of the deletion. We also performed EBV typing, EBER1 in situ hybridization, and LMP1 protein immunohistochemistry. EBV was detected in 12/26 (46%) cases of HD from the US and 26/27 (96%) cases of Brazilian HD. The 30-bp LMP1 gene deletion was observed in 4/12 (33%) cases of EBV-positive HD from US, and 12/26 (46%) cases of Brazilian EBV-positive HD, including 3 cases of type B EBV, as compared with 12/21 (57%) reactive lymphoid tissues and 9/15 (60%) cases of EBV-negative HD. US and Brazilian HD showed a higher prevalence of the 30-bp LMP1 gene deletion, compared with studies of others. The unexpected finding of high incidence of 30-bp deletion in LMP1 gene in reactive lymphoid tissue and HD without EBV-positive Reed-Sternberg cells suggests that this deletion may not be relevant to HD pathogenesis in most cases.

AIDS-related lymphoma in Brazil. Histopathology, immunophenotype, and association with Epstein-Barr virus.

The occurrence of malignant lymphoma is an increasingly important cause of morbidity and mortality in AIDS patients. The incidence of AIDS-related lymphoma in some developing countries such as Brazil is increasing as the survival of HIV infection has improved. Although there is a clear association between several types of immunodeficiency-related lymphomas and Epstein-Barr virus (EBV), the association of EBV infection in AIDS-related lymphoma in Brazil, where the incidence of AIDS is high, is unknown. Formalin-fixed, paraffin-embedded tissue from 24 cases of AIDS-related lymphoma in Brazil were analyzed for morphologic classification, immunophenotype, and EBV association using in situ hybridization studies with an EBV-EBER1 biotinylated probe. Twenty cases of AIDS-related lymphoma were classified as non-Hodgkin's lymphoma and four cases were Hodgkin's disease. Eleven non-Hodgkin's lymphomas were classified as diffuse large cell type, five cases were small non-cleaved cell, Burkitt-type, and four cases were large cell immunoblastic non-Hodgkin's lymphoma. Eighteen cases were of B-cell phenotype; one was a T-cell lymphoma, and one was classified as null. Epstein-Barr virus (EBV) was demonstrated in the majority of tumor cells of 11 of 20 (55%) of the cases non-Hodgkin's lymphomas and in 3 of 4 (75%) cases of Hodgkin's disease. AIDS-related lymphomas in Brazil are usually of large cell/immunoblastic type, but Hodgkin's disease is also seen. Both non-Hodgkin's lymphoma and Hodgkin's disease are often associated with EBV infection. The non-Hodgkin's lymphoma is predominantly of B-cell phenotype.

PIP: While there is a clear association between several types of immunodeficiency-related lymphomas and Epstein-Barr virus (EBV), the association of EBV infection in AIDS-related lymphoma in Brazil, where the incidence of AIDS is high, has remained unknown. The authors report their findings from an analysis of tissue samples from 24 cases of AIDS-related lymphoma in Brazil. The samples were analyzed for morphologic classification, immunophenotype, and EBV association. 20 cases were classified as non-Hodgkin's lymphoma, while 4 were Hodgkin's disease. 11 non-Hodgkin's lymphomas were classified as diffuse large cell type, 5 as small, non-cleaved cell, Burkitt-type, and 4 as large cell immunoblastic non-Hodgkin's lymphoma. 18 cases were of B-cell phenotype; one was a T-cell lymphoma and one was classified as null. EBV was demonstrated in the tumor cells of 11 of the 20 non-Hodgkin's lymphoma cases and in 3 of the 4 cases of non-Hodgkin's disease.

Support of Paracoccidioides brasiliensis multiplication by human monocytes or macrophages: inhibition by activated phagocytes.

The interaction of human monocytes or monocyte-derived macrophages and yeast-form Paracoccidioides brasiliensis was studied in vitro. Yeast cells were readily ingested by adherent monocytes or macrophages. Multiplication of P. brasiliensis, measured by growth as colony forming units (cfu) on a supplemented medium with good plating efficiency, was greater in monocyte co-cultures compared to the number of cfu obtained from complete tissue-culture medium (CTCM). Multiplication increased with time in macrophage co-cultures, e.g., from two-six-fold in 24 h to nine-fold in 72 h. Microscopic observations indicated that ingested yeast cells multiplied inside macrophages. When monocytes were treated with supernate cytokines (CK) from concanavalin-A-stimulated mononuclear cells, then co-cultured with P. brasiliensis, multiplication was significantly inhibited compared with control monocyte co-cultures. Treatment of macrophages--derived from monocytes by culture in vitro for 3 days--for a further 3 days with CK resulted in maximal inhibition of multiplication over the subsequent 72 h. Similarly, when monocyte-derived macrophages (after culture for 7 days) were treated for 3 days with recombinant human gamma-interferon (IFN; 300 U/ml) or CK they restricted multiplication of P. brasiliensis by 65% and 95%, respectively, compared with control macrophages. Antibody to IFN abrogated the effect of IFN or CK treatment. These findings show that ingested P. brasiliensis can multiply in human monocytes or macrophages and that this multiplication can be restricted by activated monocytes or macrophages.

Indirect fluorescent test for detection of anti-Paracoccidioides brasiliensis antibodies using coated bentonite particles as antigen.

An indirect fluorescent test was developed for detecting antibodies to Paracoccidioides brasiliensis using bentonite particles as antigen (Bent-IF). The bentonite particles were coated with P. brasiliensis polysaccharide antigen and tested with sera from paracoccidioidomycosis patients (36 sera), normal blood donors (32 sera) and patients with non-mycotic diseases (29 sera). The titres given by the positive sera were compared with those of complement fixation (CF), immunodiffusion (ID) and immunofluorescent test using yeast forms of the fungus as antigen (conventional-IF). All normal blood donors' sera gave a negative Bent-IF, conventional-IF, ID and CF tests. All paracoccidioidomycosis sera were reactive in conventional-IF and gave concordant results in Bent-IF. There was no correlation between CF and Bent-IF titres. 27.6% of sera from patients with non-mycotic diseases gave weak titres in both IF-tests. The present data indicate that the Bent-IF is a sensitive and simple serodiagnostic technique comparable with the conventional P. brasiliensis antibody test.

Cerebral venous oxygen saturation studied with bilateral samples in the internal jugular veins.

The current literature reports many measurements (arteriovenous oxygen content difference and cerebral metabolic rate of oxygen, etc.) with samples from the internal jugular veins (IJs), obtained from either side of the neck, based on the assumption that a reliable sample of mixed venous blood can be drawn. We compared oxygen saturation in both IJs in 32 patients with head injuries to establish the similarities or discrepancies in the two veins. Both IJs were cannulated with 20-G catheters; in five patients, a fiberoptic catheter was used to obtain a continuous recording of the hemoglobin saturation. Blood samples were taken simultaneously from the two IJs and immediately processed; the total number of samples processed was 342, with an average of 5.34 paired samples from each patient. The mean and the standard deviation of the differences between the saturation of the two IJs were, respectively, 5.32 and 5.15. Fifteen patients showed differences greater than 15% in hemoglobin saturation; three more patients showed differences greater than 10% at some point during the investigation. Ultimately, only eight patients had differences of less than 5%. No relationship was found among the computed tomographic scan data and the pattern of hemoglobin saturation detected. Therefore, we were not able to identify the side more appropriate for monitoring in patients with bilateral, predominantly monolateral, cortical, or deeply located lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of metastatic malignant melanoma with dacarbazine plus tamoxifen, or vindesine plus tamoxifen: a prospective randomized study.

This study aimed to verify whether the advantage in terms of response rate and survival of dacarbazine plus tamoxifen over dacarbazine alone in metastatic malignant melanoma reported in a previous randomized trial was due to a specific interaction of dacarbazine with tamoxifen. A total of 125 patients with locoregional or disseminated malignant melanoma were randomized to receive dacarbazine (250 mg/m(2) days 1-5 every 3 weeks) plus tamoxifen (arm A) or vindesine (3 mg/m(2) every week for 6 weeks, then every 2 weeks) plus tamoxifen (arm B). Of the 125 randomized patients, 57 and 59 were evaluable in arm A and B, respectively. The complete response rates were the same (2% versus 2%) and the complete plus partial response rates were similar (11% versus 14%) in the two groups. There was no significant difference in survival. Neither response or survival correlated with gender. In conclusion, when combined with tamoxifen, dacarbazine does not have a specific effect on response or survival compared with vindesine. The lower response rate to dacarbazine plus tamoxifen (11%) than that reported in the previous trial (28%) might be explained by actual differences in patient and/or participating centre accrual characteristics in the presence of apparently identical eligibility criteria.

Genetic heterogeneity of hypertrophic cardiomyopathy.

We studied the pattern of inheritance of hypertrophic cardiomyopathy among 111 first-degree relatives of 30 patients with the disease. Results of segregation analysis suggest a genetic heterogeneity for hypertrophic cardiomyopathy in that both autosomal dominant and autosomal recessive mode of inheritance can occur.

Chemotherapy with cis-platin, doxorubicin, and cyclophosphamide (CAP) in patients with metastatic breast cancer.

Thirty-three evaluable patients with metastatic breast cancer (12 previously treated with adjuvant chemotherapy) were treated with a combination of cis-platin, doxorubicin, and cyclophosphamide (CAP). cis-Platin was given intravenously, 20 mg/m2, on days 1-3, doxorubicin, 40 mg/m2 i.v., on day 1, and cyclophosphamide, 200 mg/m2 i.v., on days 1-3. Cycles were repeated every 3 weeks. A complete response (CR) was obtained in 3 patients (9%) and a partial response (PR) in 18 (54%). The highest response rate was observed in soft tissue and in liver metastases. Median response duration was 48 weeks and median survival 93 weeks. Toxicity was moderate and consisted of alopecia (100%), gastrointestinal toxicity (86%), and myelosuppression (60%). We conclude that this regimen is active in the treatment of advanced breast carcinoma, with a generally acceptable tolerance, but further evaluations in Phase III studies are required.

Mature results of a prospective randomized trial comparing a three-weekly with an accelerated weekly schedule of cisplatin in advanced ovarian carcinoma.

In a retrospective analysis of a series of clinical trials by Levin and Hryniuk in 1987, the average relative dose intensity of first-line chemotherapy for advanced ovarian cancer correlated significantly with clinical response and survival, and cisplatin was the only drug for which the outcome correlated with the individual drug relative dose intensity. There was a need to test whether and to what extent this evidence would be confirmed in a prospective evaluation. In this study 101 patients with advanced ovarian carcinoma were randomized to receive the same total dose of cisplatin but at the conventional 3-weekly schedule (CTWS) (100 mg/m2 every 3 weeks for six cycles) (51 patients) or at an experimental accelerated weekly schedule (AWS) (100 mg/m2 every week for two triplets of three cycles separated by a 5-week interval) (50 patients). To benefit from a multidrug regimen at the same extent, patients in both arms sequentially received four cycles of doxorubicin and cyclophosphamide. The median follow-up period of this study is 9.7 years. In 42 and 40 patients of the two arms having evaluable response, the clinical complete response rates to cisplatin were 14% and 22% and the complete plus partial response rates were 48% and 55% in the CTWS and in the AWS arm, respectively. These differences were not statistically significant. However, the survival curves were similar during the first 2 years but clearly diverged thereafter in favor of the AWS arm (p = 0.07). At 5 years, 12% and 30% of the patients were still alive in the CTWS and in the AWS arm, respectively. Hematologic toxicity was not relevant in either arm of the study. Nonhematologic toxicity, especially ototoxicity, was substantial and significantly higher in the AWS arm. Although statistically nonsignificant, this AWS regimen of cisplatin is associated with long-term better survival compared to the CTWS regimen in advanced ovarian carcinoma. This accelerated approach administering cisplatin should be further investigated, especially in patients with low residual disease after primary surgery.

Detection of infectious disease agents in tissue by immunocytochemistry.

1. Immunocytochemical procedures have played an increasingly larger role in the identification of infectious disease agents in tissue sections owing to the increased availability and specificity of antibody reagents, the great sensitivity of the methods, and the relative facility with which the studies are performed. 2. Immunocytochemical methods can be applied to routine formalin-fixed tissue for the detection of infectious agents such as viruses, bacteria, fungi, and protozoa among other microorganisms for diagnostic and research purposes.

Epstein-Barr virus infection and gastric carcinoma in São Paulo State, Brazil.

Epstein-Barr virus (EBV) is a ubiquitous herpesvirus, and most people have serological evidence of previous viral infection at adult age. EBV is associated with infectious mononucleosis and human cancers, including some lymphomas and gastric carcinomas. Although EBV was first reported in lymphoepithelioma-like gastric carcinoma, the virus was also found in conventional adenocarcinomas. In the present study, 53 gastric carcinomas diagnosed in São Paulo State, Brazil, were evaluated for EBV infection by non-isotopic in situ hybridization with a biotinylated probe (Biotin-AGACACCGTCCTCACCACCC GGGACTTGTA) directed to the viral transcript EBER-I, which is actively expressed in EBV latently infected cells. EBV infection was found in 6 of 53 (11.32%) gastric carcinomas, mostly from male patients (66.7%), with a mean age of 59 years old. Most EBV-positive tumors were in gastric antrum. Two EBV-positive tumors (33.3%) were conventional adenocarcinomas, whereas four (66.7%) were classified as lymphoepithelioma-like carcinomas. EBV infection in gastric carcinomas was reported elsewhere in frequencies that range from 5.6% (Korea) up to 18% (Germany). In Brazil, a previous work found EBV infection in 4 of 80 (5%) gastric carcinomas, whereas another study found 4.7 and 11.2% of EBV-positive gastric carcinomas of Brazilians of Japanese origin or not, respectively. In the present study, the frequency of EBV-positive gastric carcinomas is similar to that reported in other series, and the clinicopathologic characteristics of these EBV-positive tumors are in agreement with the data in the literature.

Duodenogastric and non acid gastro-oesophageal reflux in patients with reflux oesophagitis.

BACKGROUND/AIM: The role and the identification criteria of non acid gastro-oesophageal reflux (GOR) are still debated. Moreover, the relationship between nonacid GOR and gastric alkalinizations, particularly if secondary to duodeno-gastric reflux is yet to be defined. MATERIALS AND METHODS: One hundred and forty one patients affected by GORD symptoms and oesophagitis entered the study. Oesophagitis was divided into four categories, according to a modified Savary and Miller classification. Acid (pH<4), alkalacid (47), alkaline (pH>7) GOR and duodenogastric reflux were measured by means of ambulatory three channel esophago-gastric pH monitoring with a combined analysis of the pH traces recorded in the oesophagus fundus and antrum. RESULTS: Total time percentage (T%) of acid GOR was significantly greater in patients than in healthy volunteers (HV) and between groups of patients in direct relation with the severity of the oesophagitis. Alkaline GOR was hardly detectable in every class of esophagitis. Alkalacid GOR increased with the grade of severeness of oesophagitis. Alkalacid GOR occurred prevalently in the postprandial period; it was only 8% of the time in patients with mild reflux oesophagitis and even less in patients with moderate or severe oesophagitis. The 24 hr total time percentage of duodenogastric reflux was similar in the patients and healthy volunteer groups. The frequency distribution in 0.1 intervals of fundic and antral pH samples showed a greater number of them in the acid range (0.8-1.2) in the patients than in healthy volunteer group (0.00067) samples was similar in patients and in healthy volunteers. CONCLUSIONS: Our findings demonstrate that alkaline GOR is rare in GORD patients and that non acid GOR has a minor role in the pathophysiology of reflux esophagitis.