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M H Tattersall

Publications and source records attributed to M H Tattersall.

At least 19 recordsLinked to original sources
PubMed1992

Prevalence and distribution of human papillomavirus type-16 DNA in pelvic lymph nodes of patients with cervical cancer and in women with no history of cervical abnormality.

The polymerase chain reaction (PCR) was used to investigate the prevalence and distribution of human papillomavirus (HPV)-16 DNA in paraffin sections of all pelvic lymph nodes removed from 14 patients with Stage Ib-cervical cancer at the time of resection of their primary tumours. The results were compared with those obtained from 8 women with no known history of cervical abnormality. In all, 22 cervical biopsies and 40 I lymph nodes (296 paraffin blocks) were examined. Nine of the 14 cervical cancer patients had primary tumours that were positive for HPV-16 DNA: only 3 of these had lymph nodes with histological evidence of metastasis, and HPV 16 DNA was detected in each of the corresponding paraffin blocks. HPV 16 DNA was also detected in varying proportions (8%-92%) of the histologically-negative lymph nodes from these women. There was no correlation between the HPV DNA-positive lymph nodes and their proximity to the primary tumour. HPV-16 DNA was not identified in any of the lymph nodes from the 5 women whose cancers were not HPV-16-related, or in those of women with no evidence of cervical abnormality. This preliminary survey suggests that HPV DNA is frequently transported from HPV-16-related cervical tumours to regional lymph nodes. However, its practical significance will not be clear until sufficient time has elapsed for correlation of the results with the clinical outcome.

Adult↗
PubMed1992

Long-term survival with advanced ovarian cancer: an analysis of 5-year survivors in the Australian trial comparing combination versus sequential chlorambucil and cisplatin therapy.

Of 369 patients with apparent advanced ovarian cancer entered on a randomized trial between September 1979 and June 1983, 56 survived more than 5 years. Central pathology review confirmed the diagnosis in 318 cases (15 cases not ovarian primary, 36 slides did not reach central review). Two hundred ninety-eight were invasive cancer and 34 of these (11.4%) patients were alive at 5 years. The remaining 20 cases were tumors of low malignant potential and 17 (85%) were alive at 5 years. The clinical, pathological, and treatment characteristics of these long-term survivors has been ascertained. No significant difference in survival has emerged between the two treatment arms being compared--combination chlorambucil and cisplatin versus sequential chlorambucil followed by cisplatin on treatment failure. Of 298 cases of invasive cancer there were 133 with residuum less than 2 cm after initial surgery and 20 of these (15%) survived 5 years compared with 14/165 (8.5%) of those with more tumor residuum. Clinical response was a poor indicator of survival. Only 7 of 46 (15%) patients with complete clinical response survived 5 years; however, of 44 patients with complete surgical response, 29 (65.9%) were alive at 5 years. These results highlight the improved survival prospects of women with low-potential malignancy, even in advanced stage, compared to those with invasive tumors and make a strong case for central pathology review of all cases of apparent ovarian cancer entered on randomized trials.

Adult↗
PubMed1992

A randomized trial of adjuvant chemotherapy after radical hysterectomy in stage Ib-IIa cervical cancer patients with pelvic lymph node metastases.

Seventy-one patients with Stage Ib-IIa cervical cancer treated by radical hysterectomy and found to have pelvic lymph node metastases were entered on a randomized trial comparing standard pelvic radiotherapy versus three cycles of combination chemotherapy with cisplatin, vinblastine, and bleomycin followed by pelvic radiotherapy. After a median follow-up of 2.5 years, 24 patients have relapsed. In 12 patients, the first evidence of relapse was in the pelvis, in 11 patients the first relapse was evident at a distant site, and in 1 patient the local recurrence and distant metastases were documented simultaneously. No difference in disease-free or overall survival has emerged between the two treatment groups. Relapse was more common in patients with non-squamous tumors (44%) and in those with metastases in several pelvic lymph nodes. We conclude that patients with pelvic lymph node metastases have a rather poor prognosis, but it remains to be determined how they should best be treated after radical surgery.

Adult↗
PubMed1992

Dual sequential non-cross-resistant chemotherapy for advanced stage squamous cell carcinoma of the cervix.

Forty-three patients with recurrent and metastatic squamous cell carcinoma of the cervix received a program of sequential combination chemotherapy incorporating induction with cisplatin, vinblastine, and bleomycin (PVB) and subsequent consolidation with 5-fluorouracil, doxorubicin, cyclophosphamide, and vincristine (FACV). The overall response rate was 62% and 10 patients (23%) achieved complete remission. Response status was improved in 11 patients at the completion of FACV after initial PVB therapy, including 9 complete remissions. The median survival for all patients in the study was 38 weeks and 50 weeks for the responding patients. Myelosuppression was the principal toxicity encountered and 10 episodes of neutropenic sepsis occurred, including one septic death. However, the only cumulative toxicity was peripheral neuropathy, although this was only moderate to severe in 2 patients. These results are encouraging, but will require confirmation in randomized comparison to cisplatin, presently accepted as standard single-agent therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

DNA fragmentation, dATP pool elevation and potentiation of antifolate cytotoxicity in L1210 cells by hypoxanthine.

Exogenous purines (greater than or equal to 10(-5)M) can modulate the cytotoxicity of methotrexate (MTX) in cultured cells, protecting cells at low MTX concentrations (less than or equal to 8 x 10(-8) M) and markedly potentiating its effect at higher concentrations. The ability of hypoxanthine (HX) to modulate the effects of two antifolates-ICI 198583 (an inhibitor of thymidylate synthetase) and piritrexim (PTX, a lipophilic inhibitor of DHFR)-was investigated using cultured mouse leukaemic cells, L1210. HX (10(-4) M) was found to potentiate only the cytotoxicity of DHFR inhibitors (MTS and PTX), increasing cell kill by 20-70 fold to the level achieved by an equivalent concentration (10(-5) M) of ICI 198583 alone. Agarose gel electrophoresis of DNA extracted from cells exposed to antifolates for 24 h demonstrated that the chromatin was cleaved into multimers of 200 base pairs. This pattern of DNA cleavage indicates cell death via apoptosis. The degree of DNA fragmentation was found to be closely linked to cytotoxicity. DNA fragmentation increased from 50% in cells treated with 10(-5) M MTX or PTX to 70% when HX was added with the drugs, a level achieved by 10(-5)M ICI 198583 alone. HX potentiation of cytotoxicity was correlated with a substantial increase in dATP in conjunction with low dTTP pools. The specific potentiation of DHFR inhibitors by HX may be due to their inhibition of purine synthesis with a concurrent rise in PRPP levels. Addition of HX with MTX substantially raised intracellular purine levels via the salvage pathway as indicated by ribonucleotide pool measurements. ICI 198583, on the other hand, stimulated de novo purine synthesis with or without added HX. Treatment with MTX plus HX or ICI 198583 (with or without HX) caused a reduction of dTTP pools to 8% of untreated control and excess dATP accumulation. The subsequent elevation (to 300% of control) of the dATP pool may provide a signal for endonucleolytic fragmentation of DNA and subsequent cell death.

Animals↗
PubMed1991

Letters to patients: improving communication in cancer care.

Numerous studies have shown that patients are usually dissatisfied with the information they receive during clinical consultations with medical specialists. Therefore, a randomised study design has been used to assess the role of personal letters to patients outlining their cancer consultation. Compared with the control group, patients receiving letters were more satisfied with the amount of information given, and tended to have greater and more accurate recall of the consultation. A survey of referring doctors revealed general support for the idea of sending to cancer patients letters that outline the substance of their consultations. The study shows that letters to patients are a useful method of improving patient satisfaction and recall in clinical consultations. They also provide a permanent record of the consultation, which can be kept for future reference, and encourage greater patient involvement in their care.

Communication↗
PubMed1991

Endocrine therapy for desmoid tumors.

Two female patients with desmoid tumors (aggressive fibromatosis) showed tumor regression after endocrine therapy. In one patient, tumor response to tamoxifen has been maintained over several years of treatment. In the second patient, who had inoperable mesenteric fibromatosis, the tumor progressed on tamoxifen but regressed after treatment with Zoladex (goserelin acetate, ICI, Melbourne, Australia) and medroxyprogesterone acetate (MPA). To the authors' knowledge this is the first report of the use of Zoladex in the treatment of desmoid tumors. This review of the literature reveals that the biology of this disease is related to the endogenous hormonal environment and that estrogen receptors have been documented in desmoid tumors. Thirty-five cases are identified where endocrine agents have been employed, with a response rate of 51%. Furthermore, tumors may respond to second-line hormonal therapy after failing to respond to initial endocrine treatment. Endocrine treatments have also been used in other disorders of fibroblastic origin. The authors recommend that endocrine treatment be employed in inoperable desmoid tumors or where there has been postsurgical recurrence. In addition, the role for endocrine therapy in other soft tissue neoplasms should be determined.

Adult↗
PubMed1991

Inhibition of 2-desamino-2-methyl-10-propagyl-5,8-dideazafolic acid cytotoxicity by 5,10-dideazatetrahydrofolate in L1210 cells with decrease in DNA fragmentation and deoxyadenosine triphosphate pools.

5,10-Dideazatetrahydrofolate (DDATHF) is an antifolate drug, the cytotoxic effects of which can be fully reversed by hypoxanthine, suggesting that DDATHF exerts its effects by inhibiting de novo purine biosynthesis. ICI198583 is a quinazoline based inhibitor of thymidylate synthase. In this study we examine the interaction between treatment of mouse leukaemic L1210 cells with these drugs. The addition of DDATHF with ICI198583 was correlated with a decrease in ICI198583 cytotoxicity in a dose dependent manner. This protection was associated with a decrease in DNA fragmentation, and a drop in intracellular dATP pools. These results support the hypothesis that inhibitory effects on de novo purine biosynthesis by inhibitors of dihydrofolate reductase may limit cytotoxicity, and indicate that a rise in dATP pools may be an important cytotoxic signal.

Animals↗
PubMed1991

Pericardiocentesis for symptomatic malignant pericardial effusion: a study of 36 patients.

We reviewed 36 cases of symptomatic malignant pericardial effusion managed with pericardiocentesis at our institution from 1982 to 1989. There were 13 men and 23 women, aged 49 +/- 12 years (range, 33-76 years). The commonest underlying tumours were lung cancer (12 cases, 33%) and breast cancer (11 cases, 30%). Pericardiocentesis was successful as the initial management in 34 of 36 patients (94%); one patient died as a result of the procedure and another required subxiphoid incision and tube drainage of the effusion. When intrapericardial sclerotherapy was performed, only three of 28 patients required repeat pericardiocentesis, and when sclerotherapy was not performed initially, four of seven patients had recurrent symptomatic effusions. Median survival following pericardiocentesis in breast cancer patients was 10 months (range, 0-36 months) and in all other malignancies was four months (range, 0-12 months). We conclude that pericardiocentesis with intrapericardial sclerotherapy provides good local control for symptomatic malignant pericardial effusion in the majority of patients. In spite of this, the median survival of such patients is poor, especially in patients with malignancies other than breast cancer, with few patients surviving more than a few months.

Adult↗
PubMed1991

Detection of human papillomavirus type 16 E6/E7 transcripts in fixed paraffin-embedded cervical cancers by the polymerase chain reaction.

A simple, and sensitive method for the detection of human papillomavirus (HPV) 16 E6/E7 transcripts in RNA purified from formalin acetic alcohol (FAA)-fixed, paraffin embedded cervical cancer (CaCx) tissue is described. The entire procedure, including polymerase chain reaction (PCR) amplification of cDNA obtained from mRNA by reverse transcription, can be completed within a day. The results obtained compare favourably with those using total nucleic acids extracted from the same fixed material, and are consistent with results using RNA purified from corresponding fresh tumour tissue. Although developed for investigating the expression of HPV in tumours, this method should find general application in studies of gene expression and viral detection.

DNA, Single-Stranded↗
PubMed1991

Undergraduate education about cancer.

The quality, quantity and balance of undergraduate cancer teaching in Australian Medical Schools were investigated by a survey, using a self-administered questionnaire, of recent graduates from all Australian medical schools. Stratified random cluster sampling was used and a response rate of 84% (389 respondents) was achieved. The results revealed substantial differences in knowledge, experience in, and rating of teaching between the medical, surgical, radiotherapeutic and palliative components of cancer management. The proportions of graduates who had never attended radiotherapy and palliative care clinics or units (42.3% and 49.9%, respectively) were more than double the proportion who had never attended medical and surgical cancer clinics or units (17.5% and 10.9%, respectively). More than twice as many graduates rated their instruction in the palliative management of cancer as poor or very poor (29.4%) compared with those rating their instruction as poor or very poor in both cancer prevention (8.4%) and treatment for cure (14.6%). The respondents displayed a considerable lack of knowledge about radiotherapy treatment options, and reported a lack of perceived competence in doing cervical smears. Their answers to questions about 5-year survival of selected cancers, about the existence of screening tests validly shown to reduce mortality, and the ages at which breast and cervical cancers are likely to develop all revealed worrying levels of incorrect knowledge. There was some important disturbing variation in levels of knowledge, experience and rating of cancer instruction between states and between universities.

Australia↗
PubMed1991

Inflammatory pseudotumor of the liver causing biliary obstruction. Treatment by biliary stenting with 5-year follow-up.

Inflammatory pseudotumors of the liver are rare lesions that are becoming increasingly recognized, possibly because of frequent use of abdominal computed tomography (CT) and ultrasonography. Most previously reported cases have been treated by hepatic resection. For this reason, we describe a patient with obstructive jaundice secondary to an inflammatory hepatic pseudotumor in the porta hepatis. Bilateral internal biliary stents were inserted, and the patient remains well 5 years later. The clinicopathologic features of inflammatory pseudotumors of the liver are described, as are the implications of accurate diagnosis. There have been no previous reports of biliary stenting in management of inflammatory hepatic pseudotumors.

Adult↗
PubMed1990

Analysis of inferred cytogenetic clonal evolution in a metastatic human ovarian carcinoma.

Cytogenetic analyses of solid tumors are hampered both by the difficulties in preparing high-quality banded metaphases and the high degree of karyotypic heterogeneity. Three specimens were obtained from a single patient with serous carcinoma for karyotyping and compared to determine whether the tumor was multifocal or metastatic. All three specimens were hypodiploid, sharing marker chromosomes, thus indicating metastasis. To simplify comparison between the specimens, a diagram of the inferred cytogenetic evolution of the cells analysed was developed. This method afforded a simple means of comparing the different tumor sites in a single patient and might also be applied to sequential samples from patients.

Chromosome Aberrations↗
PubMed1990

Diethylstilbestrol revisited in advanced breast cancer management.

Prior to the introduction of tamoxifen, diethylstilbestrol (DES) was widely used as the first-line endocrine therapy in postmenopausal women with advanced breast cancer. Since randomized trials reported that tamoxifen has a similar response rate but fewer side effects than DES, its use has declined markedly. We administered DES in a dose of 10-20 mg daily to 11 postmenopausal women with advanced breast cancer, all of whom had received previous endocrine and some cytotoxic therapy also. Four women showed tumour responses to DES (1 complete and 3 partial), 5 had stable disease, and 2 progressive disease. Amongst the patients who responded, 2 had previously been unresponsive to other endocrine treatments. Of the women with stable disease, 3 had prolonged relief of symptoms. No withdrawal responses were noted. The major side effects were nausea (severe in 2 patients, mild in 1) and cardiac failure (2 patients). We conclude that DES remains a useful, active agent in the management of advanced breast cancer in postmenopausal women, even in patients with tumours unresponsive to other endocrine therapy.

Aged↗
PubMed1990

Cytogenetic study of solid ovarian tumors.

With the use of a short-term tissue culture method, 27 solid ovarian tumor specimens (from 22 patients) were successfully karyotyped. The majority of the specimens were from serous carcinoma (18 specimens, 2 of which were not invasive). Adenocarcinomas (two specimens), two endometrioid carcinomas, and one each of clear cell, mucinous, sarcoma, squamous carcinoma, and an unclassified sex cord carcinoma were also analyzed. The specimens showed marked cytogenetic heterogeneity, ranging from a normal karyotype (46,XX) to very grossly aneuploid, with multiple rearrangements. All chromosomes, excepting 13, 15, 19, 20, and 21 were positively identified in at least one rearrangement. Chromosomes 1, 6, and 7 were most commonly involved. Identified rearrangements were not limited to one carcinoma type. The most common deletions of 1p and 6q were identified in both serous carcinoma and adenocarcinoma. Deletion of 7q,(del(7)(q32)), was observed only in serous carcinoma but was limited to three patients. Correlations of modal chromosome count and number of marker chromosomes appeared to be associated with good prognosis for patients with serous carcinoma.

Adult↗