Randomized study of zorubicin versus zorubicin-cisplatin in undifferentiated carcinoma of the nasopharynx (UCNT)

BACKGROUND: The most active chemotherapy regimens in UCNT were those combining anthracyclines (doxorubicin or epirubicin) and cisplatin. Our previous pilot study on 37 patients treated with the zorubicin-cisplatin combination with a RR of 67% and literature data about other anthracyclines such as epirubicin achieving a response rate of over 50% were the basis of this randomized study comparing efficacy and toxicity of the combination vs. zorubicin as monotherapy. PATIENTS AND METHODS: A total of 80 patients entered the study. The diagnosis of UCNT was confirmed by two independent pathologists. All patients had their primary tumors in the nasopharynx. The patients were randomized in two groups: group A (zorubicin 325 mg/m2, day 1), and group B (zorubicin 250 mg/m2, day 1 and cisplatin 30 mg/m2, days 2-5). The inter-cycle interval was four weeks. The two groups were well balanced according to sex, age, stage Ho and TNM stage. RESULTS: Group A: 40 patients included, 34/40 evaluable for activity. Activity on evaluable patient basis: CR 4/34 (11.75%), PR 4/34, SD 14/34, PD 12/34, response rate 8/34 (23.5%); response rate on intent to treat basis 8/40 (20%). TOXICITY: granulocytopenia grade 3-4 6/40, thrombocytopenia grade 3-4 2/40, no febrile neutropenias, nausea/vomiting any grade 3/40, cardiac toxicity any grade (rhythm) 3/40 other toxicities minor or absent. Group B: 40 patients included, 36/40 evaluable for activity. Activity on evaluable patient basis: CR 10/36 (27.78%), PR 17/36, SD 3/36, PD 6/36, response rate 27/36 (75%); response rate on intent to treat basis 27/40 (67.5%). TOXICITY: granulocytopenia grade 3-4 10/40, thrombocytopenia grade 3-4 8/40, two febrile neutropenias, nausea/vomiting any grade 13/40, other toxicities mild or absent. Of the group of patients achieving a CR, four relapsed following 7, 11, 22 and 23 months, one was lost to follow-up, one died after six months from fulminant hepatitis B and eight are in complete remission lasting for 30+ to 66+ months. Following CR achievement none received any consolidation radiotherapy, and the projected five years of freedom from relapse for complete responders is about 60%. CONCLUSION: Zorubicin is an effective drug in UCNT and its combination with cisplatin has a significant activity and an acceptable toxicity.

A controversial issue: could a watch-and-wait policy for patients with non-Hodgkin's lymphoma clinical stage I or IE with no lymphoma left following diagnostic surgery be justified? Results of a single centre study.

BACKGROUND: A subset of patients with non-Hodgkin's lymphoma (NHL) with clinical stage I or IE at presentation is left without other NHL localizations following surgery performed for diagnostic histology, and thus without any target lesion to judge the immediate effectiveness of immediately applied additional treatment modalities. MATERIAL AND METHODS: Since 1988 we have adopted in this single centre, prospective non-randomized study, a watch-and-wait policy for such patients, who in addition had to have non-bulky disease, normal LDH levels, no 'B' symptoms and no Burkitt, lymphoblastic and cutaneous T-cell histology. Up to 1993 we have observed 50 consecutive cases. Patients were regularly followed with the endpoint to determine the relapse-free interval and overall survival. NHL relapses were treated, either with locoregional radiotherapy, or with chemotherapy, or both. RESULTS: The median observation time is at the moment 53.5+ months (range 6-106+). The initial NHL localizations were: a solitary cervical or auxillary lymph node in 18 patients, inguinal or scarpal lymph node in eight, tonsil in 12 and skin/subcutis in 12 (B-cell NHL only for skin/subcutis). Nine patients had low, 15 intermediate, and 26 high-grade histology. Within the observation period NHL relapses occurred in 10/50 patients (20 per cent). At the moment 46/50 patients (92 per cent) are alive and NHL free. The estimated 9-year freedom from relapse is 79 per cent and overall survival 92 per cent, and for 41 patients with intermediate/high-grade histologies 80 per cent and 95 per cent respectively. CONCLUSION: It seems that a proportion of the very selected subgroup of patients with stage I of IE NHL and absolutely no NHL left following diagnostic surgery, with additional criteria as described in this study can achieve a substantial freedom from relapse and overall survival rate without immediate additional therapeutic procedures following diagnosis of NHL, but no prognostic factors predicting this outcome seem yet available.

Labelling of breast carcinoma, thyroid carcinoma and melanoma with manno- and galacto-specific lectins from marine invertebrates.

Three marine invertebrate FITC-labelled lectins, CNL, GCL, and GSL, isolated respectively, from the sponges Chondrilla nucula, Geodia cydonium, and the hexacoral Gerardia savaglia, were used as potential diagnostic tools for different breast tumors. The lectins vary in their carbohydrate binding properties: GSL is D-mannose specific, GCL and CNL D-galactose specific. GSL labels most investigated types of malignant tissues distinctively, while the results with CNL and GCL are less consistent. The well known D-mannose specific lectin, concanavalin A, also binds to tumor tissues, but with much lower intensity than GSL.

Primary gastric non-Hodgkin's lymphoma localized to the gastric wall: no adjuvant treatment following radical surgery.

The paper presents the experience with watch-and-wait policy following radical surgery in 25 patients with primary gastric non-Hodgkin's (NH) lymphoma localized to the gastric wall. The median follow-up is at the moment 40 months (range 18-85). Only 3/25 patients have relapsed (during the first year of the follow-up) and achieved a complete response following chemotherapy. The median disease-free interval following surgery is at the moment 40+ months, and the median survival 40+ months. Primary gastric NH lymphoma localized to the gastric wall, regardless of the histological grade, probably does not need any adjuvant treatment following radical surgery. In occasional patients with lymphoma relapse, the disease can be controlled by additional chemotherapy.

Non-IPSID small intestinal lymphoma: evidence for disseminated disease at presentation.

During the period 1984-1989 the authors have observed 20 patients with non-IPSID small intestinal lymphomas, 11 males and 9 females. In 11 patients the first symptoms were abdominal cramps requiring laparotomy, in 4 ileus, and in 5 perforation with peritonitis. Resection of the involved part of the intestine was performed in 17 patients. Lymphoma tissue was present in 4 of 5 retrogradely examined resection lines on macroscopically normal small intestine. According to Working Formulation, 3 patients had low grade, 3 intermediate grade and 14 high grade histology. Affection of extra intestinal/mesenteric structures was found in 18 of 20 patients, with a total of 36 other lymphoma localizations. 8 of 20 had affection of the nasopharynx and/or Waldeyer's ring. According to the Crowther's classification 55% of patients were in Stage IV, 35% in Stage III and 10% in Stage Ib. All patients were treated with chemotherapy, 13 with ProMACE regimen and 7 with CHOP-type regimens. Ten of twenty patients are alive and in complete remission for over 5 years (7 of 11 of Stage IV and 3 of 9 of Stage Ib/III; 8 of 14 with high grade and 2 of 6 with intermediate/low grade histology). Our results point to the fact that in non-IPSID lymphoma of the small intestine, lymphoma involvement of the intestinal wall might be present beyond obvious lymphoma lesions. Most patients with apparently primary small intestinal lymphoma have a widespread disease. Thus, local forms of treatment such as surgery, and/or radiotherapy can not be expected to be curative in the majority of patients. Data from this study suggest that following initial surgery the chemotherapy is the treatment of choice for these patients.

Acute aseptic panophthalmitis caused by a copper foreign body.

Enucleation was performed on a 10-year-old boy after an eye injury from the explosion of a dynamite cartridge. Amaurosis was noted 48 h after the injury upon admission to our clinic. The clinical picture of panophthalmitis comprised bulbus protrusion with limited movement and hypopion; total retinal detachment was demonstrated by ultrasonography. Intensive pain was present. A histochemical investigation was performed, showing purulent exudation in the anterior chamber, choroid, and retina. Copper stained with rubeanic acid was positive. Electrogravimetrically, the foreign body was found to be 94% copper and approximately 40 mm2 in size.

Local immunodeficiency of the intestinal mucosa--a contribution to etiopathogenesis of recurrent urticaria and diarrhoea.

The case of a 10 month-old girl with a history of recurrent urticaria and diarrhoea is presented. Immunological study was carried out and secretory component in sputum, duodenal juice and stool was not found, while IgA was detected. Peroral biopsy of intestinum was also carried out and histology revealed partial villous atrophy. Immunofluorescent staining showed only a few IgA and IgG producing cells scattered within the villous stroma, while the IgM producing cells were increased in number. Serum concentration of IgA, IgM and particularly IgG was increased. Both parents had measurable IgA in the serum, however, the secretory component was not detectable neither in mother nor in father. The deficiency of secretory component and deficiency of IgA producing cells in the jejunal villous stroma led to local immunodeficiency of the intestinal mucosa and that caused recurrent urticaria and diarrhoea in the girl presented.

[An analysis of complications and bacteriological and histological studies following extraction of an intrauterine contraceptive device (Beospir) which was inserted several years ago]. / Analiza komplikacija, bakterioloska i histoloska ispitivanja nakon ekstrakcije kontracekcijskog uterinog uloska (Beospir) postavljenog pre vise godina.

Ninety-nine women with the average IUCD (Beospir type) insertion length of 45.2 months were investigated. Pathological changes were clinically evidenced in 9 women (9.09%). Causes of the IUCD removal were bleeding in 4 women (4.04%) and pregnancy during the IUCD use in situ in 3 women (3.03%). The IUCD and endometrium were bacteriologically and the endometrium also histologically analysed. In 58 women (58.58%) the endometrium and in 29 women (29.29%) the IUCD remained sterile. The dominant findings were facultatively pathogenic bacteria commonly present in the cervix. The infection, i.e. when the same kind of bacteria was found in the whole material, was evidenced in 6 women (6.06%), and this was also histologically confirmed. The same kind of bacteria were found in the IUCD and the endometrium. The histological analysis has shown that at the moment of the IUCD removal the endometrium was in physiological phases in 86 women (86.86%). There was glandular hyperplasia in 4 (4,04%) women whose bacteriological vaginal flora was positive. By the Papanicolau test all the women belonged to group II. The IUCD produces no pathologic effect most probably because there is a cyclic renewal (regeneration) of the endometrium.

[Cystic lymphangioma of the liver]. / Cisticni limfangiom jetre.

The authors presented a rare condition of cystic lymphangion of the liver in a female child of 14 months, comprising the whole left lobe leading to compression of the surrounding intestinal organs and partly of some chest organs. By a transversal supraumbilical laparotomy, the cystic tumor of the left liver lobe was identified, and a left lobectomy of the liver was made by removing all cystic formations. It was hystologically acknowledged that it was about a cystic lymphangiom of the liver. Postoperatively the course ran regularly and with no complications. The control examinations showed that the function of the liver was not damaged. The cystic changes of the liver are most frequently in the framework of the polycystic diseases when even other organs are invaded. All cysts of the liver can be divided into congenital cysts or acquired. The presented case was most probably about a congenital anomaly, which was getting augmented gradually and resulted to a compression of the surrounding organs.

[Focal nodular hyperplasia of the liver]. / Foklana nodularna hiperplazija jetre.

Two cases of focal nodular hyperplasia of the liver were presented. The first case involved a 9 year old girl in whom palpable findings were made in the left lobe of the liver. The second case was incidentally discovered during a cholecystectomy. In both cases the laboratory results were within normal limits. The changes were found in the left portion of the liver. They were well delineated from the surrounding parenchyme and appeared septated. Central fibrotic contraction was also noted. The hepatocytes showed no changes. The biliary network was proliferated and the fibrous septae were of various thicknesses being in some places invaded by inflammatory infiltrate and irregular stretching. These alterations must be differentiated from hepatic adenoma because of the latter's malignant potential. Focal nodular hyperplastic lesions of the liver on the other hand are benign. The postoperative laboratory findings were also within normal limits. A lobectomy was performed in the first case and a partial resection and tumerectomy was carried out in the second case.

[Intracavitary use of highly radioactive foci in the treatment of uterine carcinoma (author's transl)]. / Intrakavitarna primena visokoradioaktivnih fokusa u tretmanu karcinoma uterusa.

The report relates to the survival period of 24--44 months after the end of treatment and has a preliminary character. In 213 patients the radiological treatment was applied, either alone or combined with surgery. A total of 174 patients (81.6%) are alive, without any sign of malignity. In the observed period 29 patients sorders. In addition to protecting medied of carcinoma or intercurrent didical staff from radiation, the method described has also other advantages: 1. Radiation is of short duration, it last only a few minutes, 2. Subjective complaints in the course and after treatment are negligible, 3. Owing to its possible non-hospital application, patients are free of "cancer psychosis" which developes in respective hospitals, 4. Complications in the course and after treatment are fewer than with classical radiation methods, 5. Disappearance of malignant cells from the vaginal swab and regression of the tumour are twice as fast as with classical methods. 6. In advanced stages of the disease better results are obtained.