Randomized phase II placebo-controlled study to evaluate the efficacy of topical pure emu oil for joint pain related to adjuvant aromatase inhibitor use in postmenopausal women with early breast cancer: JUST (Joints Under Study).

PURPOSE: Aromatase inhibitors are standard of care in women with hormone receptor-positive early breast cancer. Published evidence demonstrates that adverse effects may have an impact on drug compliance, with arthralgias being one of the most commonly reported adverse effects. METHODS: Eligible patients were postmenopausal women who had experienced arthralgia following initiation of an aromatase inhibitor. Patients who experienced arthralgias following a minimum of a 3-month treatment on the aromatase inhibitor were randomized to emu oil or placebo oil. The primary endpoint was to assess for a reduction in pain as measured by a visual analogue score after 8 weeks of treatment. RESULTS: Seventy-three patients comprised the intent-to-treat population, and there was no statistically significant benefit with use of EO. However, there was a statistically significant improvement in pain (visual analogue score was -1.28; p < 0.001) and Brief Pain Inventory severity score -0.88 (p < 0.001), as well as functional interference (Brief Pain Inventory interference -1.10 (p < 0.001) for the entire population following an 8-week administration of EO or placebo oil. CONCLUSIONS: Arthralgias, as a result of aromatase inhibitor use, may be ameliorated by the use of topical oil massaged onto the joint. Further research into interventions for this common side effect is needed.

Microbubble detection and ultrasound-guided vacuum-assisted biopsy of axillary lymph nodes in patients with breast cancer.

AIMS: To assess the feasibility of undertaking microbubble-guided vacuum-assisted biopsy (VAB) of the sentinel lymph node (SLN) and determine its sensitivity in detecting metastases. Patient experience and the impact of VAB on subsequent axillary surgery were also evaluated. MATERIALS AND METHODS: Patients with a normal axillary ultrasound or benign core biopsy planned for surgical SLN biopsy were recruited. Part 1 of the study was used to establish the technique of ultrasound microbubble contrast to detect the SLN. In Part 2 microbubble detection of the SLN was followed by 13 G VAB. All patients subsequently had surgical histological correlation. RESULTS: One hundred and thirty-nine patients were recruited: 36 to Part 1 and 103 to Part 2. Of the 100 patients in Part 2 included for analysis, 82 (82%) underwent successful biopsy. Sensitivity for detecting metastases was 58.8% (95% confidence interval: 32.9%, 81.6%). The procedure was generally well tolerated; however, VAB interfered adversely with subsequent surgical SLN biopsy with surgeons reporting moderate or severe interference in 48% of patients and an additional 8.3% with complete failure of SLNB. CONCLUSION: It is possible to perform VAB of microbubble-detected SLNs. Although the sensitivity for detecting metastases was reasonable, the adverse effect on subsequent surgery was significant.

The clinical relevance of static disease (no change) category for 6 months on endocrine therapy in patients with breast cancer.

This study reports on the clinical relevance of the static disease (SD) category in 255 breast cancer patients on endocrine therapy. All patients had received first- and second-line endocrine therapy and were assessed for response by the International Union Against Cancer (UICC) criteria. We did not include patients who received first-line endocrine therapy but did not or have not yet proceeded to second-line hormone therapy, e.g. died from rapidly progressive disease, started chemotherapy for rapidly progressive disease, remained in long-term remission on first-line endocrine therapy. We analysed survival from initiation of first-line endocrine therapy by the remission criteria, i.e. complete response (CR), partial response (PR), static disease (SD) or progressive disease (PD), achieved on that therapy. Patients were divided into those with metastatic breast cancer (MBC) and non-metastatic disease. There was no significant difference in survival from starting first-line endocrine therapy between patients who obtained CR, PR or SD: all three groups of patients survived significantly longer than patients who showed PD within 6 months (all P < 0.0001 except CR versus PD [MBC] which was P < 0.002). Equally, for second-line endocrine therapy there was no difference in survival between patients who obtained CR, PR or SD: all three groups (CR, PR and SD) survived significantly longer than PD (all P < 0.0003 except for CR versus PD which was P < 0.003 for non-metastatic and P < 0.059 for MBC). Durable SD appears to be a clinically useful criteria of therapeutic remission.

Locally advanced breast cancer: early results of a randomised trial of multimodal therapy versus initial hormone therapy.

The aim of this study was to investigate initial treatment of locally advanced breast cancer. Patients were randomised to "multimodal" therapy (pre-operative chemotherapy, Patey mastectomy, flap irradiation and adjuvant hormone therapy) (n = 55), or initial "hormone" therapy (n = 53) with further therapy upon tumour progression. The objective response to chemotherapy was 57% (31/54) after four cycles. Of patients on hormone therapy, 36% (19/53) had an objective response and 32% (17/53) disease stasis at a 6 month assessment. At a median 30 months follow-up, there was no notable difference in development of metastases or survival: only 6 patients have uncontrolled loco-regional relapse (4 "hormonal", 2 "multimodal"). The number of treatments per patient required for this loco-regional control was lower in the "hormone" group (mean 2.13 versus 4.20 in the "multimodal" group). This small study has shown that the use of consecutive therapies, with the aim of tumour control, does not appear to compromise outcome in comparison with initial "multi-modal" therapy. Adopting such a policy may allow some patients to avoid unnecessary treatments.

Onapristone, a progesterone receptor antagonist, as first-line therapy in primary breast cancer.

The progesterone receptor antagonist, Onapristone, is an effective endocrine agent in experimental breast cancer models. This study aimed to investigate this agent as first-line endocrine therapy in patients with breast cancer. However, owing to the recognition in this and other clinical studies that some patients on Onapristone developed liver function test abnormalities, the development of this drug and recruitment to the study stopped in 1995. 19 patients either with locally advanced breast cancer (n = 12) or who were elderly, unfit patients with primary breast cancer (n = 7) received Onapristone 100 mg/day. Seventeen of the 19 tumours expressed oestrogen receptors (ER) whilst 12 of the 18 tumours tested expressed progesterone receptors (PgR). Tumour remission was categorised by International Union Against Cancer criteria. One patient was withdrawn after 4.5 months while her disease was static. Of the remaining 18 patients, 10 (56%) showed a partial response and 2 (11%) durable static disease (> or = 6 months), giving an overall tumour remission rate of 67%. The median duration of remission was 70 weeks. Transient liver function test abnormalities developed in a number of patients, mainly during the first 6 weeks of treatment. In conclusion Onapristone can induce tumour responses in human breast cancer.

Locally advanced primary breast cancer: medium-term results of a randomised trial of multimodal therapy versus initial hormone therapy.

We report the medium-term (median follow-up=52 months) results of a prospective randomised trial of multimodal therapy (neoadjuvant chemotherapy, Patey mastectomy, postoperative radiotherapy and adjuvant hormone therapy) (n=56) versus initial hormone therapy (n=52) for locally advanced primary breast cancer. Compared with multimodal therapy, initial hormone therapy was associated with reduced number of therapies for disease control (mean=3.6 versus 4.9) and mastectomy rate (31%). Multimodal therapy conferred better initial locoregional control and a longer disease-free interval. Nevertheless, there was no statistically significant differences in the rates of survival, metastasis and uncontrolled locoregional disease, as well as in the time to metastasis between the two therapy groups. Regardless of the therapy groups, oestrogen receptor positivity conferred a lower metastasis rate, better survival and locoregional control. Thus, initial hormone therapy may be a reasonable option for managing locally advanced primary breast cancer, especially for oestrogen receptor-positive tumours.

Early laparoscopic cholecystectomy for acute cholecystitis: a safe procedure.

Acute cholecystitis is increasingly managed by laparoscopic cholecystectomy. Some reports have shown conversion and complication rates that are increased in comparison to elective laparoscopic cholecystectomy. This study reviews the combined experience of two hospitals where the intention was to perform early laparoscopic cholecystectomy for acute cholecystitis. A total of 152 cases of laparoscopic cholecystectomy for acute cholecystitis (evidence of acute inflammation clinically and pathologically) were identified. Conversion to open cholecystectomy was required in 14 cases (9%) in the total series. Laparoscopic cholecystectomy was performed within 2 days of admission in 76% (115 of 152) of patients. Conversion was significantly less likely in patients undergoing laparoscopic cholecystectomy within 2 days of admission (4 of 115) compared to those undergoing surgery beyond 2 days (10 of 37; P<0.0001). Eleven patients (7%) had postoperative complications; however, there were no cases of injury to the biliary system and no perioperative deaths. This series shows that laparoscopic cholecystectomy can be performed safely in patients with acute cholecystitis and suggests that early laparoscopic cholecystectomy is preferable to delaying surgery. Although the conversion rate to open surgery is higher than for elective cholecystectomy, the majority of patients (91%) still derive the well-recognized benefits of laparoscopic cholecystectomy. Early laparoscopic cholecystectomy is an acceptable approach to acute cholecystitis for the experienced laparoscopic surgeon.

Locally advanced breast cancer.

In vitro studies suggest p53 and bcl-2 may be important in the apoptotic response to irradiation, and that rapidly proliferating cells are more sensitive to radiotherapy. The clinical relevance of biological factors in predicting radiotherapy response was investigated in 62 patients with locally advanced breast cancer. Immunocytochemical staining for p53 protein, BCL-2 protein and MIB 1 antigen on the primary tumour, showed that none of these factors significantly predicted radiotherapy response (BCL-2 p=0.45, p53 p=1.0, MIB 1 p=0.92) and appear to be of no clinical value. A semi-quantitative assessment of MIB 1 staining showed a reduction in positive cells following radiotherapy (p=0.04), consistent with a reduced proliferation associated with response.

Audit of a conservative management policy of the axilla in elderly patients with operable breast cancer.

Between April 1982 and February 1994, 344 women aged > 70 years with cancers < 5 cm in diameter were treated at the City Hospital Breast Unit. The majority were enrolled in two successive randomized trials. One hundred and sixty patients had primary therapy with tamoxifen alone and were subsequently treated with mastectomy if the primary cancer progressed. Fifty-three women with a high oestrogen receptor (ER) status in the tumour received mastectomy and post-operative tamoxifen. One hundred and thirty-one patients underwent primary surgery (104, mastectomy; 27, wide local excision) and did not receive adjuvant tamoxifen. Only the 184 (131 + 53) patients who underwent primary definitive surgery have been included in this study. Patients undergoing primary surgery without palpable lymph nodes (n = 159) did not undergo axillary exploration. Twenty-five women who were noted pre-operatively to have clinically palpable lymph nodes underwent excision of obviously enlarged lymph nodes in the axilla in addition to primary surgery; small nodes that measured less than around 1 cm were left in place. None received axillary clearance or axillary irradiation. The median follow-up is 54 months. Twenty-three of 159 (14%) patients without palpable nodes, and four of 25 (16%) with palpable nodes, have subsequently developed axillary recurrence. Grade 3 tumours were associated with a higher rate of regional recurrence. Regional relapse was treated successfully with different therapeutic modalities (surgery, radiotherapy or endocrine manipulation) and none have died from uncontrolled regional disease.

Locally advanced breast cancer: long-term results of a randomized trial comparing primary treatment with tamoxifen or radiotherapy in post-menopausal women.

We have previously reported the early results of a randomized cross-over study of radical radiotherapy vs tamoxifen in patients with locally advanced breast cancer. This study has now recruited 143 patients with a median time from randomization of almost 10 years for both groups. Seventy-three patients received 20 mg tamoxifen twice daily, and 70 had primary radiotherapy at a dose of 40 Gy, which is a lower dose than currently administered. The treatment groups were similar in age, size of tumour and oestrogen receptor status. There was no significant difference between the two treatment groups for the combined initial response and static disease rates (89% for radiotherapy and 78% for tamoxifen, P = 0.15). The median duration of initial response was 12 months for both groups. When patients crossed over to the alternative therapy on local relapse, there was no difference in response/static disease rates (P = 0.34) and duration of response (P = 0.76). A non-significant prolongation of the metastatic-free interval in favour of tamoxifen (P = 0.08) was identified, although there was no difference in survival outcome (P = 0.38). This study shows that in this group of patients primary tamoxifen offers a similar clinical benefit to primary radiotherapy at a dose of 40 Gy, and is therefore an acceptable alternative primary treatment.

Serum tissue polypeptide specific antigen (TPS) in breast cancer patients: comparison with CA 15.3 and CEA.

Pre-treatment TPS serum levels from patients with Stage IV breast cancer (n = 66) (1386.0 +/- 3504.5) were significantly higher (p < 0.0001), than normal controls (n = 47), (75.5 +/- 111.5 U/L), benign breast disease patients (n = 84) (58.5 +/ 57.1 U/L), and breast cancer patients with Stage I/II (n = 79) (52.7 +I- 49.5U/L) or Stage III disease (n = 57) (166.7 +/- 218.8). Analysis of sequentially obtained samples from Stage IV patients during endocrine treatment showed TPS alone or in combination with CEA and CA 15.3 was less accurate in predicting response than the combination of CEA with CA 15.3. In this study TPS did not usefully add to the established marker combination of CEA and CA 15.3.

Evaluation of the IMMULITE BR-MA and CEA assays and comparison with immunoradiometric assays for CA15-3 and CEA in breast cancer.

This study was designed to evaluate the performance of a new automated assay system, the IMMULITE Automated Immunoassay Analyzer in comparison with more commonly used IRMA assays for measuring circulating tumour marker levels in breast cancer patients. The assays investigated measure the MUC1 mucin (CA15-3 antigen) or CEA. Serum samples from breast cancer patients with various stages of disease and from a group of normal individuals were analysed. Significant correlations were found between tumour marker levels measured using the IMMULITE BR-MA and the CA15-3 assays and between levels measured using the two CEA assay formats. Levels of IMMULITE BR-MA and CEA correlated with stage of disease suggesting that both are markers of tumour burden Levels in Stage III breast cancer patients were found to be significantly higher than those of normals using the IMMULITE system but not the IRMA assays. This would suggest a role for the automated system in the monitoring of breast cancer at an earlier stage than that at which tumour markers are routinely used. Elevated marker levels did not correspond to any particular site of metastasis however, a greater proportion of patients with multiple sites of metastasis had elevated levels compared with those with secondary disease at a single site. We conclude that the IMMULITE Automated Immunoassay Analyzer is of value in the routine surveillance of tumour marker levels.

C-erbB2 expression predicts response to preoperative chemotherapy for locally advanced breast cancer.

BACKGROUND: Previous work suggests that the presence of c-erbB2 oncoprotein immunostaining and the proliferation rate of tumours, may be relevant to chemo-sensitivity in breast cancer. PATIENTS AND METHODS: To investigate this we assessed pretreatment biopsies from 50 patients with locally advanced breast cancer for expression of c-erbB2 and MIB1 (proliferative marker) in relation to clinical response after 3 months preoperative chemotherapy. RESULTS: Objective response was significantly more likely (22/30, 73%) for tumours negative for c-erbB2 membrane staining, compared to positively staining tumours (6/20, 30%, p = 0.0025). The percentage of cells staining positively for MIB1 was not predictive of response (p = 0.56). CONCLUSIONS: This study has shown an increased likelihood of response to preoperative chemotherapy for breast cancers negative for c-erbB2 staining. Previous studies have shown that c-erbB2 immunostaining can correlate with either chemo-resistance or chemo-response. We postulate that this conflict may be due to differences in the type of chemotherapy administered. This raises the possibility of biological markers being use to assist in the selection of the type of chemotherapy regimen administered to particular tumour biological phenotype.

Male breast cancer: pathological and immunohistochemical features.

BACKGROUND: male breast cancer is uncommon and studies regarding the potential clinical relevance of the histopathological and immunohistochemical features are infrequently reported. MATERIALS AND METHODS: We investigated the biological characteristics of forty-one male patients with invasive breast cancer by assessing histopathological and multiple immunohistochemical features. RESULTS: The majority were no special type (ductal) (37/41), lobular cancer was not seen. 73% were histological grade 3, 93% were positive for oestrogen receptor and 73% for progesterone receptor. The proportion of cancers positive for c-ebB-2 (45%), EGFR (20%), p53 (58%), MiB1 (40%), NCRC11 (78%), were similar to reports for female breast cancer. Nonsignificant associations between poor survival outcome and grade 3 tumours, and positive tissue staining for MiB1 and p53 were seen. CONCLUSION: While there ar similarities in the biological features of breast cancer in males and females, some differences were identified. Male breast cancer is more likely to be grade 3 tumours and hormone receptor positive.

The significance of p53 autoantibodies in the serum of patients with breast cancer.

Serum p53 autoantibodies were studied in 82 patients with Stage 1 or 2 breast cancer using an ELISA assay. Tissue expression of p53 in these patients was also examined. High levels of serum p53 autoantibodies were detected in 48% (39/82) patients, while 23% (19/82) were tissue positive. Patients with high serum p53 autoantibodies levels were not significantly different to those with low levels with respect to, tissue p53, tumour grade, size, stage or oestrogen receptor status. Tissue immunoreactivity for p53 was significantly associated with tumour grade and negative oestrogen receptor status. Patients in both groups were followed for a median of over five years but the presence of p53 autoantibodies in serum was not prognostic with respect to disease free interval or survival. In this study detection of p53 autoantibodies in serum does not correlate with any of the usual tumour related prognostic factors, nor does it correlate with clinical outcome.

A comparison outcome of male breast cancer with female breast cancer.

BACKGROUND: It is unclear whether breast cancer has a similar prognosis in males and females. METHODS: A 20-year retrospective study of all male breast cancer patients in our region was undertaken. We compared this series with a group of females matched for the major prognostic factors and an unmatched series of female patients treated over the same period. RESULTS: Forty-one patients with invasive cancer and 2 with ductal carcinoma in situ were identified. One invasive cancer was treated with radiotherapy, 40 had surgery. Local recurrence occurred in 23% and axillary recurrence in 40% of cases. Male and female patients (n = 123) matched for the major prognostic factors showed a similar outcome for disease-free interval (P = 0.90) and survival (P = 0.27). However, both the above groups had a significantly worse outcome than the unmatched series of female patients with breast cancer. CONCLUSIONS: When prognostic factors are allowed for, male and female breast cancer patients have a similar outcome. This suggests that such features should be taken into account when determining management for males with breast cancer just as they are in females.

Transperitoneal laparoscopic exposure for lumbar interbody fusion.

STUDY DESIGN: A prospective clinical trial of the transperitoneal laparoscopic approach to the lumbar spine in a consecutive series of patients undergoing anterior lumbar interbody fusion. OBJECTIVES: To determine safety and effectiveness, and to document technique and perioperative complications of a laparoscopic exposure for lumbar interbody fusion. SUMMARY OF BACKGROUND DATA: With the widespread adoption of laparoscopic techniques, the benefits of minimal access surgery are now well recognized--in general, gynecologic and urologic surgery. Only recently have minimal access techniques been applied to spinal procedures. METHODS: Forty-seven patients with symptomatic degenerative disc disease underwent transperitoneal laparoscopic exposure of the lumbar spine to facilitate implantation of cylindrical threaded interbody fusion cages. These patients were prospectively followed and all perioperative considerations and complications were documented and analyzed. The surgical technique of laparoscopic exposure will be described. RESULTS: The laparoscopic approach was attempted in 47 consecutive patients. Forty-four were completed laparoscopically--36 single level fusions, seven two level fusions, and one three level fusion. Early in the series, conversion to open surgery was required in one patient (case #3) because of bleeding from the presacral veins which hindered the view. In one case, mobilization of the great vessels proved to be difficult, and in one other case the patient could not tolerate abdominal insufflation. The mean blood loss for the entire group was 105 mls. Complications related to the endoscopic exposure were few. There were no injuries to major vascular structures or to bowel, and no mortalities. In two patients, the cages were malpositioned necessitating repeat endoscopic exposure for cage realignment. One patient required a laparotomy for a postoperative small bowel obstruction. The median postoperative stay was 4 days. CONCLUSIONS: Transperitoneal laparoscopic exposure for single or multiple level, anterior lumbar interbody fusion can be performed with low risk. Experience in open anterior spinal surgery and laparoscopic general surgery is vital in minimizing the risks.

Randomized clinical trial of single-dose antibiotic prophylaxis for non-reconstructive breast surgery.

BACKGROUND: The aim of this randomized clinical trial was to determine whether a single intravenous dose of 2 g flucloxacillin could prevent wound infection after primary non-reconstructive breast surgery. METHODS: The study included 618 patients undergoing local excision (n = 490), mastectomy (n = 107) or microdochectomy (n = 21). Patients were randomized to receive either a single dose of flucloxacillin immediately after the induction of anaesthesia or no intervention. Wound morbidity was monitored by an independent research nurse for 42 days after surgery. RESULTS: The incidence of wound infection was similar in the two groups: 10 of 311 (3.2 percent) in the flucloxacillin group and 14 of 307 (4.6 percent) in the control group (chi(2) = 0.75, P = 0.387; relative risk 0.71, 95 percent confidence interval 0.32 to 1.53). The groups also had similar wound scores and rates of moderate or severe cellulitis. Wound infection presented a median of 16 days after surgery. CONCLUSION: The administration of a single dose of flucloxacillin failed to reduce the rate of wound infection after non-reconstructive breast surgery.

Traumatic diaphragmatic rupture.

Twenty-three cases of traumatic diaphragmatic rupture due to blunt and penetrating trauma are reviewed. The need for early diagnosis is stressed. Chest radiography was the most sensitive diagnostic method (66% for blunt trauma), although other techniques are discussed. The high incidence of associated intra-abdominal injury (83%) mandates primary abdominal approach to repair. An overall mortality of 31% reflects the severity of the trauma.

Endosurgical treatment for spontaneous pneumothorax.

When spontaneous pneumothorax is recurrent or persistent, an open pleurodesis with excision or ligation of the bullae is the procedure of choice but can lead to significant morbidity. Thorascopic surgery for the management of spontaneous pneumothorax was first introduced in 1937 but this has become a useful technique only since the introduction of video-controlled thorascopic surgery and the availability of suitable endothoracic instrumentation. A review was made of nine patients having endosurgery for recurrent (six) or persistent (three) pneumothorax. At surgery the bullae were ligated with an endoloop (four) or excluded with an endostapler (five). Pleurodesis was obtained by a combination of strip pleurectomy, diathermy and installation of an alcohol iodine solution. The early results are similar to those following an open operation with considerably reduced hospital stay and morbidity.