Inguinal and Ilio-inguinal Lymphadenectomy in Management of Palpable Melanoma Lymph Node Metastasis: A Long-Term Prospective Evaluation of Morbidity and Quality of Life.

PURPOSE: Prospective data are lacking on long-term morbidity of inguinal lymphadenectomy including the influence of extent of surgery, use of radiotherapy, and patient factors. The aim of this study is to evaluate the effects of these factors on patient outcome, quality of life (QOL), regional symptoms, and limb volumes after inguinal or ilio-inguinal lymphadenectomy for melanoma. METHODS: Analysis of the subgroup of patients with inguinal lymph node field relapse of melanoma, treated by inguinal or ilio-inguinal lymphadenectomy in the ANZMTG/TROG randomized trial of adjuvant radiotherapy versus observation. RESULTS: Sixty-nine patients, 46 having undergone inguinal and 23 ilio-inguinal lymphadenectomy, with median follow-up of 73 months were analyzed. Mean limb volume increased rapidly after surgery (7% by 3 months) and continued to increase for at least another 18 months. Patients with body mass index (BMI) ≥ 25 kg/m2 had greater limb volume increase than normal-weight patients (13.3% versus 6.9%, P = 0.030). QOL improved over the first 18 months, but despite initial improvement, regional symptoms persisted long term. Type of surgery (inguinal or ilio-inguinal lymphadenectomy) had no demonstrably significant effect on limb volume (9.9% versus 13.4%, P = 0.35), QOL (P = 0.68), or regional symptoms (P = 0.65). There was no difference in overall survival between inguinal and ilio-inguinal lymphadenectomy [hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.40-1.40, P = 0.43]. CONCLUSIONS: Inguinal lymphadenectomy for melanoma is a potentially morbid procedure with significant increases in limb volume. Patients report reasonable QOL but may have ongoing regional symptoms. Overweight/obesity is associated with poorer QOL, increased limb volume, and regional symptoms.

A comparison of the sensitivity of immunoperoxidase staining methods with high-sensitivity fluorescence flow cytometry-antibody quantitation on the cell surface.

Surface molecules present in low copy numbers can be detected with high-sensitivity fluorescence flow cytometry. Many cells previously thought not to express certain molecules on their surface can now be shown to have these molecules in very low copy numbers by high-sensitivity fluorescent cytometric methods. Detection of molecules by immunoperoxidase staining methods has not previously been compared with high-sensitivity flow cytometry techniques. Computerized video image analysis (VIA) is a method that allows measurement of area and density of the immunostain chromogen reaction product in a standardized fashion analogous to flow cytometry. In this study, we compared immunoperoxidase reaction products measured by VIA methods with high-sensitivity flow cytometric measurements for cells with 10,000 down to 50 antibody molecules bound to their surfaces. Detection of 100-200 surface molecules was possible with heavy metal-enhanced immunoperoxidase methods, whereas standard immunoperoxidase methods were not as sensitive. The sensitivity of the nickel-enhanced immunoperoxidase staining method was confirmed for detection of an epitope (Tac-IL2 receptor alpha-chain) present in low numbers on the surface of peripheral blood lymphocytes.

Laparoscopic versus open splenectomy for immune thrombocytopenic purpura.

BACKGROUND: We sought to determine whether laparoscopic techniques can reduce the operative morbidity of surgery in patients undergoing splenectomy for immune thrombocytopenic purpura (ITP). METHODS: All patients (60) undergoing splenectomy for ITP at the Royal Adelaide Hospital from January 1985 to November 1995 were reviewed. Results of patients undergoing open operation were obtained by means of retrospective case note review, whereas details of all patients undergoing laparoscopic splenectomy were collected prospectively and maintained on a computerized database. RESULTS: Forty-seven patients underwent splenectomy with an open technique and 13 with a laparoscopic technique. Patient groups were demographically similar. All laparoscopic procedures were completed with the laparoscopic technique. An accessory spleen was also removed at laparoscopic operation from two (15%) patients and at open operation from three patients (6%). Two more accessory spleens were missed at the original procedure, one at open operation and one at laparoscopic operation. These required later removal by using open and laparoscopic techniques, respectively. Blood and platelet transfusion requirements were reduced by the laparoscopic approach. Although mean operating times were similar (87 versus 88 minutes), laparoscopic splenectomy was associated with a greatly reduced postoperative hospital stay (10 versus 2 days, median; p < 0.0001) and no major morbidity. Long-term normalization of platelet counts was similar for the two techniques. The laparoscopic approach resulted in a reduction in hospital treatment costs from $4224 to $2238 per case (cost savings of $1986 per case). CONCLUSIONS: Laparoscopic splenectomy results in improved clinical outcomes and reduced costs for patients undergoing elective splenectomy for ITP.

A technique for successful transplantation of tumours into ear-pouches of nude mice to maintain and study the tumour microenvironment.

We have applied a technique which was originally used for cardiac transplantation in mice, to the transplantation of human breast cancers. To our knowledge previous reports of this method for tumour xenografting have not been made. This technique has wider application for many non-vascularised tissue allografts, including for example synovial grafts for arthritis research or other tumour types in oncology research. The method is simple and reproducible within the limits of the experiments reported.

CD1a positive putative tumour infiltrating dendritic cells in human breast cancer.

CD1a molecules are expressed on dendritic cells (DC) during certain maturational phases coincident with the functions of antigen capture and processing. During these phases, CD1a is anchored to the cytoplasmic membrane through its cytoplasmic domain and the antigenic binding domain is projected from the cell surface. Membrane bound HLA Class I and II molecules are also expressed at relatively high levels on DC, but it is not known whether there is any interdependence between CD1 expression and that of the classical histocompatability molecules. Recent information concerning the structure, function and likely role of CD1 in presentation of hydrophobic lipid and carbohydrate antigens to the immune system is detailed. The potential relevance of the lipid presenting functions of CD1 molecules for the detection and recognition of tumour glycolipid antigens is hypothesised and discussed. CD1 a tumour infiltrating putative dendritic cells are discussed in terms of their density, separation, culture and possible function in breast cancers in the light of recent findings.

Differences between standard and high-sensitivity immunohistology in tissue sections--comparison of immunoperoxidase staining methods using computerized video image analysis techniques.

High-sensitivity immunoperoxidase labelling can be achieved using heavy metal enhancement of the di-amino (DAB) reaction product. For example nickel chloride combined with DAB improves the sensitivity of the method approximately 7-10 fold. This allows detection of approximately 100-200 molecules on cell surfaces. This has an obvious advantage over standard non-enhanced DAB methods which detect 1000-2000 molecules under similar conditions. This study compares standard and nickel enhanced DAB immunoperoxidase staining of cells in tissue sections using video-image analysis (VIA) measurement techniques. VIA is an objective method of evaluation of immunoperoxidase staining of separated cells and for immunostained cells in tissue sections. Nickel enhancement of the DAB reaction product reveals more positively stained cells, with higher contrast over background, giving superior qualities for VIA analysis providing continuous, reproducible, and objective data for statistical analysis.

Setting up a health education website: practical advice for health professionals.

Recently, both popular and professional publications about health care have begun to express enthusiasm for the Internet as a source of medical information and possibly of psychological support for those with serious illnesses. However, there are pitfalls for practitioners and researchers who seek to capitalise on these patient education possibilities. We describe here the process and mixed outcomes of the efforts of a multidisciplinary team to set up and evaluate a website for rural women with breast cancer. We provide recommendations for other health professionals contemplating similar ventures, and also identify some future steps to develop and research this potentially valuable form of patient education and support.

Identification and isolation of CD1a positive putative tumour infiltrating dendritic cells in human breast cancer.

Identification of dendritic cells (DC) in human tissues has been technically problematic due to the lack of truly specific immunohistochemical markers for DC's. Human dendritic cells express CD1a glycoprotein at certain points in their life cycle. CD1a positive cells are present in many human tumours and have been associated with improved survival. However, little information exists concerning the separation of DC from human tumours. The current study reports that human breast carcinomas have low densities of CD1a positive cells with dendritic morphology, and details are shown of a technique for successful separation of these cells from tumour tissues.

Quality assurance in a multidisciplinary symptomatic breast assessment clinic.

BACKGROUND: Although quality assurance guidelines for surgeons have been issued and adopted for use in population-based breast screening programs in Australia, similar guidelines are unavailable for women referred with symptomatic breast problems. METHODS: Six hundred and ninety-six women who attended the Royal Adelaide Hospital Women's Health Centre between February and November 1998 for investigation and management of a new breast-related complaint were prospectively evaluated. Investigation strategies and outcomes of the initial consultation were determined and the results compared with the performance quality standards for symptomatic breast disease according to the British Association of Surgical Oncology (BASO) Breast Surgeons' Group. RESULTS: A breast lump was the presenting symptom in 45%, while breast pain was present in 26%. Ninety per cent of women referred with breast symptoms were given a definitive benign or malignant diagnosis at the initial clinic visit. Although the median time delay between the date of general practitioner referral and breast clinic appointments for all patients was < or =7 days, the time delay for 'urgent' cases was not met according to BASO performance indicators. All other Royal Adelaide Hospital Breast Clinic audit data were within the range suggested by BASO performance indicators for new consultations in a symptomatic breast assessment clinic. CONCLUSIONS: A multidisciplinary breast clinic in a public hospital setting is able to provide clinical services to symptomatic women, with the majority of patients obtaining a confident diagnosis at the first presentation. Performance indicators for symptomatic breast disease are useful in identifying inadequacies at the clerical or clinical level which, following the implementation of subsequent changes, may lead to improvement in patient outcomes.

CD1a-positive infiltrating-dendritic cell density and 5-year survival from human breast cancer.

Infiltrating CD1a(+) dendritic cells (DCs) have been associated with increased survival in a number of human cancers. This study investigated DC infiltration within breast cancers and the association with survival. Classical established prognostic factors, of tumour size, lymph node status, histological grade, lympho-vascular invasion, the KI-67 (MIB-1) fraction and the Nottingham Prognostic Index (NPI) were also compared. A total of 48 breast cancer patients were followed from the time of surgery and CD1a density analysis for 5 years or until death. Our data set validated previous studies, which show a relationship between survival and the NPI (P<0.001), tumour size (P<0.01) and lymph node status (P<0.05). Although more patients were alive at the 5-year time point in the group with higher CD1a DC density than the lower CD1a DC group, this failed to reach statistical significance at the P=0.05 level. Analysis at 10 years postsurgery is required to investigate the association further.

Immunohistochemical localization of CD1a-positive putative dendritic cells in human breast tumours.

The presence of a high number of infiltrating CD1a+ cells in malignant neoplasms has been reported to be associated with an improved prognosis, reduced tumour recurrence and fewer metastases. This study identified a population of CD1a+ cells within the lymphoid cell infiltrate in human ductal breast carcinoma (n = 52), which was significantly different from normal breast tissue, in which only two out of nine cases expressed CD1a+ cells (P = 0.0192). In the majority of cases, the infiltrate was low compared with the number of macrophages and T cells present (results not shown). There was no correlation between the number of CD1a+ cells and tumour grade, with all tumour grades expressing similar numbers of infiltrating CD1a+ cells. There was clear evidence, however, that the CD1a+ cells were closely associated with tumour cells. It is likely that CD1a+ cells have a role in antigen capture and presentation in human tumours, and this study documents the density of CD1a+ cells in a large sample of all histological grades of human breast carcinomas.

Intestinal passage of the PEG end-piece: is it safe?

Two rare but life-threatening complications of percutaneous endoscopic gastrostomy (PEG) are reported: small bowel perforation and obstruction. Both resulted from impaction of the PEG end-piece after separation at skin level. Review of the literature revealed very few complications from intestinal passage of PEG end-pieces. The free intragastric PEG end-piece routinely passes through the gastrointestinal tract in most cases. One of these two cases was drawn from a series of 100 patients with intentional intestinal passage of PEG end-pieces to give a severe complication rate of 1%. A case can be made for routine endoscopic per-oral removal of PEG end-pieces in the elective setting, but this is more costly and not without hazard. Previous laparotomy and/or known adhesions is a relative indication for endoscopic retrieval of the PEG end-piece. Oesophageal disease or intolerance of endoscopy is a relative indication for intestinal passage. Close clinical follow up is recommended to ensure that the PEG end-piece has passed per-rectum. If the PEG end-piece has not passed and is shown in the small bowel on plain X-ray at approximately 3 weeks after separation then lodgement has probably occurred and early operative intervention is warranted.

Soft-tissue sarcoma of the extremity. Experience with limb-sparing surgery.

OBJECTIVES: To assess the degree to which limb-sparing surgery is implemented in patients with soft-tissue sarcoma, and its outcome. DESIGN AND SETTING: A detailed review of 40 patients who were all tertiary referrals to one surgeon, and general review of all 215 patients with sarcoma treated in South Australia between 1986 and 1992. INTERVENTIONS: Conservation of the limb by wide resection or marginal resection of soft tissue, combined when necessary with radiotherapy. Amputation was used when limb conservation failed or was not possible. MAIN OUTCOME MEASURES: Median survival time after treatment. RESULTS: Limb-sparing treatment was successful in 37 of the group of 40 patients. Thirty-two patients received adjuvant radiotherapy, and 19 received chemotherapy. Median survival time was 35 months. Review of all 215 patients with sarcoma revealed a higher initial amputation rate and a lower use of combined treatment methods than in our series. Twenty-six patients (65%) were initially incorrectly diagnosed before referral, resulting in a median delay in treatment of 16 weeks. CONCLUSIONS: The concept of limb-sparing surgery is well established, but is not yet as widely practised for limb sarcomas as it could be. Delay in diagnosis is a significant problem.

The utility of the proliferative index in pretreatment biopsy specimens of esophageal squamous cell carcinoma.

The proliferative index detected immunohistochemically by monoclonal antibody MIB-1 from pre-treatment biopsy tissues of 33 patients with esophageal squamous cell carcinoma who underwent preoperative concurrent chemoradiotherapy was evaluated in relation to clinicopathologic features and chemoradiotherapeutic responses. The response to chemoradiotherapy was assessed both endoscopically and pathologically and classified as complete or partial response. Higher MIB-1 LI was significantly associated with lymph node metastases, suggesting that detection of MIB-1 LI from biopsy tissues may contribute to pre-treatment staging of tumors and prediction of persistence of lymph node involvement after chemoradiotherapy, which would permit the optimization of systemic treatment for individual patients. Statistically, significant correlation existed between higher MIB 1-LI and poor overall survival, implicating the prognostic significance of the MIB-1 LI in patients undergoing multimodality treatment. No significant relationship was found between the MIB-1 LI and either endoscopic or pathologic responses, although a trend for tumors with lower MIB-1 LI to have better responses was observed.

Lymphoid cell infiltration during breast cancer growth: a syngeneic rat model.

The systematic study of potential alterations in lymphoid infiltrates during tumour growth is extremely limited in humans. Therefore, development of a model utilizing a spontaneously arising mammary adenocarcinoma in Dark Agouti rats was adopted for the study of the dynamics of lymphoid cell infiltration during tumour development. Syngeneic rats were inoculated with tumour cell suspensions and the tumours were resected from 5 to 15 days. Serial sections were immunohistochemically stained using a panel of monoclonal antibodies. Irrespective of tumour age, ED2 (macrophages) and W3/25 (CD4)-positive cells were the most prominent cell infiltrates in tumours. There were no significant differences in cell counts for any marker between 8-day and 15-day tumours. However, in 5-day tumours there were significantly fewer macrophages, OX19+ T cells, W3/25+ cells, OX8+ (CD8) cells and OX62+ dendritic cells. Interleukin-2 receptor alpha chain expression was low at all examined stages of tumour growth, indicating a lack of tumour infiltrating lymphocyte (TIL) activation and/or possible TIL anergy. B cell staining was absent in all tumours, negating the possibility of these cells mediating coregulatory signals for TIL activation in the micro-environment of established tumours. The results parallel previous immunohistochemical findings in humans, suggesting that a dysfunctional local immune response in breast cancer may be determined very early during tumour development.

Laparoscopic splenectomy using the lateral position: an improved technique.

An alternative approach to laparoscopic splenectomy is described. This technique uses a lateral position and modified port placement. Initial experience with three patients has demonstrated advantages over previously described approaches, by providing a more direct view of the splenic hilum and by eliminating the need for retraction of adjacent organs.

Clinicians and computers: friends or foes?

BACKGROUND: Computer-aided learning is accepted by students as a learning resource, but the views of the teaching community are largely unknown. PURPOSE: To document clinicians' experience with computers and to record their attitudes toward computer usage in clinical practice and student education. METHODS: Questionnaire mailed out to all clinicians, including interns and residents, fellows, and attending physicians in 3 major teaching hospitals in South Australia, with a total of 646 clinical staff. RESULTS: Replies were received from 246 staff. Eighty percent of clinicians had at least 2 years of experience with computers and used computers for at least 2 hr each week. Despite this, there was an obvious lack of conviction among clinicians that computer-aided learning was of use in student education and assessment. This may reflect their lack of experience with this medium as an educational tool. CONCLUSIONS: If computer-aided learning is to make any significant impact on medical student education, it must be carefully and objectively evaluated, and its benefit must be clearly demonstrated to clinical teachers.

Intraoperative scintigraphic localization and laparoscopic excision of accessory splenic tissue.

The recent advent of laparoscopic splenectomy for the treatment of refractory idiopathic thrombocytopenic purpura (ITP) has been embraced by surgeons and hematologists in many institutions. However, the occurrence of accessory splenic tissue in a proportion of such splenectomies, either concurrently or later, raises the question of how to deal with this problem when it arises. We report that the laparoscopic approach, facilitated by lateral positioning, can be successfully used for the treatment of an accessory spleen causing recurrent ITP. The use of intraoperative nuclear imaging can greatly aid the localization and provide confirmation of complete excision of the nuclear focus, especially for a very small accessory spleen.

Dendritic cell density and activation status in human breast cancer -- CD1a, CMRF-44, CMRF-56 and CD-83 expression.

Low CD1a-positive putative dendritic cell numbers in human breast cancer has recently been described and may explain the apparent 'poor immunogenicity' previously reported in breast cancer. Little attention has been given to dendritic cell activation within the tumour microenvironment, which is another reason why the in-situ immune response may be severely deficient. We have therefore examined CD1a expression as a marker for dendritic cells, together with CMRF-44 and -56 as markers of dendritic cell activation status, in 40 human breast cancers. The results demonstrate few or no CD1a-positive putative dendritic cells and minimal or no expression of the dendritic cell activation markers. Both dendritic cell number and dendritic cell activation appear substantially deficient in human breast cancers, regardless of tumour histological grade.

Bilateral testicular and adrenal malignant lymphoma of pre B-cell type.

A rare case of pre B-lymphoblastic lymphoma of the testes and adrenal glands is presented. No lymph node, central nervous system or bone marrow involvement was demonstrated at diagnosis. The primary presentation was of acute unilateral pain and swelling, mimicking simple orchitis. The diagnosis was made using aspiration cytology and the lymphoma characterized using immunohistochemical, electron microscopic and karyotype analysis techniques. Pre B-cell markers were clearly demonstrated by all criteria used. Monoclonal antibodies (FMC 29 and FMC 31) were used to define the early B-cell nature of the lymphoma. Confirmation using karyotype analysis in addition to immunoglobulin and T-cell beta-receptor gene rearrangement was obtained. Intrathecal chemotherapy was used prophylactically. Combination chemotherapy produced regression of the primary lymphomatous lesions, but subsequent bone marrow spread led to death.