Lyubica Dabich

Gastroesophageal Reflux in Esophageal Scleroderma: Diagnosis and Implications

Fifty-three patients with scleroderma were evaluated by history, barium swallow, and esophageal function tests. The most common esophageal symptoms were heartburn and dysphagia. Abnormal motility was seen radiologically in 43 patients, gastroesophageal reflux in only 9. Esophageal function tests demonstrated: (1) abnormal motility in 51 patients and lack of a distal esophageal high-pressure zone in 18; (2) moderate to severe gastroesophageal reflux in 38; and (3) abnormal acid-clearing ability in 50. Eleven patients, including 8 with peptic stricture, underwent the combined Collis-Belsey operation. Symptomatically, reflux was abolished in all and dysphagia in 10. Roentgenograms showed that regression of strictures was complete in 5 and partial in 3. Postoperative esophageal function tests in 9 patients demonstrated a competent distal esophageal valvular mechanism in 7. Gastroesophageal reflux, not impaired motility, is the major cause of esophageal symptoms in scleroderma. Its effecitve operative control is not contraindicated by systemic disease in these patients.

Scleroderma in the child

Twelve children with scleroderma are presented. All had characteristic cutaneous abnormalities and manifestations of visceral involvement. Raynauds phenomenon and joint symptoms frequently prompted medical consultation. The presence of visceral disease may be overlooked unless specific diagnostic procedures such as pulmonary function testing, gastrointestinal radiographs, esophageal motility studies, and plethysmography are routinely employed since the patients may be asymptomatic.

Retrospective studies in scleroderma: Effect of potassium para-aminobenzoate on survival

Demographic and survival data are presented for 390 patients with scleroderma. For the entire group an estimated 81.4% survived 5 years from diagnosis and 69.4% survived 10 years. Life-table analyses revealed that adequate treatment with potassium para-aminobenzoate (Potaba KPAB) was associated with improved survival (p less than 0.01); 88.5% 5 year survival rate and 76.6% 10 year survival rate for adequately treated patients. Five and ten year survival rates for patients never treated with KPAB were 69.8 and 56.6%, respectively. Similar findings were obtained by comparing observed to expected mortality for these patients; again, KPAB therapy showed prolongation of survival. The Cox proportional hazards model was also applied to this retrospective study adjusting for baseline clinical involvement, demographics and KPAB treatment. There were some interesting results including a high significance for skin involvement per se as a prognostic indicator: the greater the extent of skin involvement the poorer prognosis. Time from first diagnosis to first University Hospital visit or admission when included as a covariate did not influence survival.

Barrett's esophagus complicating scleroderma

Two patients with scleroderma whose esophageal involvement was associated with longstanding reflux esophagitis were found to also have Barretts esophagus. Since Barretts esophagus is a premalignant condition, these patients with scleroderma should be considered at high risk for the development of adenocarcinoma of the esophagus.

Retrospective Studies in Scleroderma: Pulmonary Findings and Effect of Potassium p-Aminobenzoate on Vital Capacity

The principal clinical pulmonary findings were extracted from University of Michigan Hospital records of 390 patients with scleroderma. Dyspnea was the most frequent symptom and strongly correlated with pulmonary fibrosis and with decreased vital capacity (FVC) and CO diffusing capacity (DLCO). The mean value for FVC was 84% of the predicted normal for 326 patients, and that of the initial DLCO 56.8% of the predicted normal (323 patients). Pulmonary fibrosis was diagnosed on first chest X-ray in 80 of 382 patients. An additional 48 patients developed fibrosis detected on subsequent X-rays. Analyses were performed to determine whether the deterioration of pulmonary function over time was less for scleroderma patients who were adequately treated with potassium p-aminobenzoate (KPAB) than for those inadequately or never treated with KPAB, The average decrease for both FVC and DLCO was found to be less for KPAB-treated patients. However, only in the case of vital capacity was the difference significant. In the presence of radiological evidence of pulmonary fibrosis FVC decreased more rapidly (p = 0.002), but the decline in DLCO was not affected. When adjusting for the presence or absence of fibrosis the average slopes of the logarithm of vital capacity were significantly less negative (p = 0.003) for patients on KPAB.

Aclacinomycin A in the treatment of multiple myeloma: A Southwest Oncology Group study

SummaryFifty-two patients with progressive resistant multiple myeloma were entered in this Southwest Oncology Group Phase II study, using weekly intravenous Aclacinomycin A. Of forty-three evaluable patients for response, there was one partial remission of 2 years duration and two sustained clinical improvements with 25% reduction in paraprotein. Major toxicity seen was severe myelosuppression and significant nausea and vomiting requiring dose reduction and delay of the scheduled treatment. Cardiac arrhythmia was seen in one patient. Chronic daily schedule or continuous IV infusion is recommended for future study.

Potassium para-aminobenzoate and liver function test findings

Risk of hepatotoxicity has been raised with respect to potassium para-aminobenzoate (Potaba) therapy. In this regard relevant clinical and laboratory hepatic findings in the hospital records of 390 scleroderma patients were analyzed. There were 274 patients who had received potassium para-aminobenzoate at some time and 116 who never received it. No instance was found in which potassium para-aminobenzoate was the cause of an acute hepatic hypersensitivity reaction. There were random or intercurrent abnormalities in hepatic test findings over time, but these actually occurred more often in the group of patients never treated with potassium para-aminobenzoate. Further, there was no evidence that long-term potassium para-aminobenzoate therapy is hepatotoxic. These findings suggest that acute hepatic reaction to potassium para-aminobenzoate is at least uncommon if not rare.

Adult Acute Nonlymphocytic Leukemias

For the first two decades, leukemic chemotherapy had little impact on survival. In the past 10 years, however, remission induction therapy has generated complete remissions which last approximately one year in about half to three fourths of those treated, with a seventh in some series alive at 5 years.

Alternated Versus Syncopated CHOP-PVB: Two Studies for the Treatment of Non-Hodgkin's Lymphoma by the Southwest Oncology Group

Based on a preliminary trial that suggested that CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), and PVB (cisplatinum, vinblastine, bleomycin), are at least partially non-cross-resistant, the Southwest Oncology Group treated patients with unfavorable histology, non-Hodgkins lymphoma with CHOP and PVB. In the first study, 76 eligible patients were given three courses of CHOP, with complete or partial responders receiving three courses of PVB followed by three further courses of CHOP. Nonresponders after the initial three cycles of CHOP, received six courses of PVB. In the second study, 154 eligible patients were treated with alternating cycles of the two drug regimens. The overall objective antitumor response (CR + PR) was 77% for the first study and 58% for the second. The complete remission rates were 48% and 38%, respectively. The overall survival for both studies is similar. These results are interpreted in terms of the Goldie-Coldman hypothesis.

Cisplatin, VP-16-213 and MGBG (Methylglyoxal bis guanylhydrazone) combination chemotherapy in refractory lymphoma, a phase II study

SummaryIn an effort to improve the treatment of patients with refractory or recurrent lymphoma, we developed a protocol using cis-platinum combined with two other agents of known efficacy in these disorders but with differing side effects: VP-16 and MGBG. Twenty-six eligible patients were treated with this regimen. There were 15 men and 11 women with a median age of 54 years (22–73), and performance status of 1 (0–3). Their diagnoses were Hodgkins disease 5 and non-Hodgkins lymphoma [NHL] 21 which included 11 with diffuse histocytic lymphoma [DHL]. The median number of chemotherapy regimens was 2 (1–5); 12 also received radiotherapy. Twenty patients are evaluable for response: 15 NHL and 5 Hodgkins disease. Three patients, all of whom had DHL entered complete remission (20%) with a median time to treatment failure of 7 1/2 months. Six NHL (40%) and one Hodgkins disease (20%) patients entered a partial remission. There were three early deaths: one due to progressive disease, one to acute respiratory failure, and one with disease status undocumented. Toxicity included leukopenia, thrombocytopenia, anorexia, nausea, vomiting, stomatitis, alopecia, renal failure, profound peripheral neuropathy, and hypersensitivity vasculitis. Treatment was stopped because of the latter two. These agents are non-crossresistant with doxorubicin-containing regimens. The drugs are possibly synergistic and modestly active with moderate to severe toxicity.