Local anaesthetic repair of paraumbilical hernia as a safe option across a range of body mass indices.

INTRODUCTION: Local anaesthetic repair of paraumbilical hernia (PUH) is a commonly performed operation. The aim of this study was to investigate whether local anaesthesia (LA) repair of PUH was feasible in patients with a high body mass index (BMI) and whether BMI had an impact on patient reported pain scores. METHODS: Patients undergoing PUH repair under the care of single consultant in a district general hospital between March 2010 and January 2018 were recruited. Patient demographics, BMI, duration of operation, volume of LA infiltrated and grade of operating surgeon were available from the consultant's database. The database also included prospectively recorded patient reported pain scores based on a numerical scale (0-100) and overall patient satisfaction measured as a percentage. Patients were divided into three BMI categories: <25kg/m2, 25-30kg/m2 and >30 kg/m2. RESULTS: A total of 123 patients underwent PUH repair under LA during the study period. Six patients had no recorded BMI and were excluded from the analysis. Of the remaining 117 patients, 36 (31%) were in the normal BMI range, 35 (30%) in the overweight range and 46 (39%) in the obese range. There was no statistically significant difference between the BMI groups in terms of volume of LA used, duration of operation, postoperative pain scores or patient satisfaction. CONCLUSIONS: LA repair of PUH is feasible for patients with a raised BMI and does not result in higher postoperative pain scores or the need for higher doses of LA.

Type 4 appendiceal diverticulum within a de Garengeot hernia.

A de Garengeot hernia is defined as an incarcerated femoral hernia containing the vermiform appendix. We describe the case of a patient with a type 4 appendiceal diverticulum within a de Garengeot hernia and delineate valuable learning points. A 76-year-old woman presented with a 2-week history of a non-reducible painless femoral mass. Outpatient ultrasonography demonstrated a 36mm × 20mm smooth walled, multiloculated, partially cystic lesion anterior to the right inguinal ligament in keeping with an incarcerated femoral hernia. Intraoperatively, the appendix was found to be incarcerated in the sac of the femoral hernia and appendicectomy was performed. Histopathology demonstrated no evidence of inflammation in the appendix. However, an incidental appendiceal diverticulum was identified. It is widely recognised that a de Garengeot hernia may present with concomitant appendicitis, secondary to raised intraluminal pressure in the incarcerated appendix. Appendiceal diverticulosis is also believed to develop in response to raised pressure in the appendix and may therefore develop secondary to incarceration in a de Garengeot hernia. To our knowledge, only one such case has been described in the literature. A de Garengeot hernia is a rare entity, which poses significant diagnostic challenges. A high index of clinical suspicion is necessary as these hernias are at particularly high risk of perforation and so prompt surgical management is paramount.

Local anaesthetic repair of uncomplicated paraumbilical hernia without sedation: peri-operative pain and patient satisfaction.

PURPOSE: Paraumbilical hernia (PUH) is a common condition that usually requires surgical repair. However, there is a dearth of literature on this surgery performed under local anaesthesia (LA) without the use of sedation. The aims of this study were to assess peri-operative pain and patient satisfaction in patients undergoing PUH repair using LA without sedation. METHODS: All patients having PUH repair under a single consultant between January 2010 and December 2011 were eligible to participate. If eligible for both, patients chose either general anaesthetic (GA) or LA repair. If only eligible for either LA or GA, they were offered this anaesthetic modality. Visual analogue scales were used to report peri-operative pain (10 point score) and satisfaction (%). Results were compared by grade of surgeon (higher surgical trainee (HST) versus consultant). RESULTS: A total of 63 patients underwent PUH repair (31 GA; 32 LA). Of them, only 28/32 of LA repair patients agreed to participate. LA and GA patients had equivalent age and sex distribution. LA patients had a lower body mass index (BMI) than GA [27.1 (3.7) versus 30.3 (5.1), p = 0.007]. The median length of LA procedure was 24 (17.5-30) minutes. The median LA solution infiltrated was 25 (20-32) ml. Peri-operative pain scores were low [1.1 (0.3-2.9) %] and patient satisfaction was high [96 (91-99) %]. There were no differences in pain, patient satisfaction, duration of procedure and amount of LA infiltrated with increasing BMI. Comparing HST to consultant, the former took longer [30 (25-36) versus 20 (16-24) minutes, p = 0.0007], infiltrated more LA [34.5 (26-47) versus 20 (19-25.5) ml, p = 0.0039], and patients reported more pain [2.75 (1.0-4.95) versus 0.4 (0.2-1.7) %, p = 0.029], but overall satisfaction was equivalent [95.5 (89-99.25) versus 96.3 (92.25-99) %, p = 0.684]. CONCLUSION: Open mesh PUH repair using LA without sedation is associated with low peri-operative pain and very high satisfaction when either a higher surgical trainee or a consultant grade is operating.

Touch imprint cytology of core needle biopsy specimens: a useful method for immediate reporting of symptomatic breast lesions.

AIMS: The aim of this study was to determine the diagnostic value and accuracy of touch imprint cytology (TIC) of core needle biopsy (CNB) specimens in predicting the final benign or malignant histology in patients presenting with symptomatic breast lesions. METHODS: One hundred and twenty-eight patients underwent CNB under ultrasonographic guidance with subsequent TIC preparation. TIC results were correlated with the histology of the core or the surgical resection specimen. RESULTS: The 128 lesions analysed included 106 malignancies and 22 benign lesions. TIC accurately predicted the final histology in 96.7% of cases, with a sensitivity of 96.2% and a specificity of 100%. CONCLUSIONS: The routine use of TIC to complement CNB can provide an immediate and reliable cytological diagnosis of symptomatic breast lesions. The potential use of this technique in a breast clinic setting may help allay patient anxiety and expedite the planning of further surgical management.

Use of paravertebral block anesthesia in the surgical management of breast cancer: experience in 156 cases.

OBJECTIVE: To assess safety and efficacy of the regional anesthetic technique paravertebral block for operative treatment of breast cancer, and to compare postoperative pain, nausea, vomiting, and length of hospital stay in patients undergoing breast surgery using paravertebral block and general anesthesia. BACKGROUND: General anesthesia is currently the standard technique used for surgical treatment of breast cancer. Increasing hospital costs have focused attention on reducing the length of hospital stay for these patients. However, the side effects and complications of general anesthesia preclude ambulatory surgery for most patients undergoing breast surgery. In April 1994, the authors initiated the use of paravertebral block anesthesia for patients undergoing primary breast cancer surgery. A review of our early experience revealed that this regional anesthetic technique enables effective anesthesia for operative procedures of the breast and axilla, reduces postoperative nausea and vomiting, and provides prolonged postoperative sensory block that minimizes narcotic requirements. METHODS: A retrospective analysis of 145 consecutive patients undergoing 156 breast cancer operations using paravertebral block and 100 patients undergoing general anesthesia during a 2-year period was performed. Anesthetic effectiveness and complications, inpatient experience with postoperative pain, nausea, vomiting, and length of stay were measured. RESULTS: Surgery was successfully completed in 85% of the cases attempted by using paravertebral block alone, and in 91% of the cases, surgery was completed by using paravertebral block supplemented with local anesthetic. There was a 2.6% incidence of complications associated with block placement. Twenty percent of patients in the paravertebral group required medication for nausea and vomiting during their hospital stay compared with 39% in the general anesthesia group. Narcotic analgesia was required in 98% of general anesthesia patients, as opposed to 25% of patients undergoing paravertebral block. Ninety-six percent of patients having paravertebral block anesthesia were discharged within the day of surgery, compared with 76% of patients who had a general anesthetic. CONCLUSIONS: Paravertebral block can be used to perform major operations for breast cancer with minimal complications and a low rate of conversion to general anesthesia. Paravertebral block markedly improves the quality of recovery after breast cancer surgery and provides the patient with the option of ambulatory discharge.

Active immunization using dendritic cells mixed with tumor cells inhibits the growth of primary breast cancer.

BACKGROUND: Dendritic cells (DCs) are potent antigen-presenting cells regarded as crucial in the priming of an immune response. The goal of our study was to test whether bone marrow-generated DCs are capable of inducing protective immunity against a murine breast carcinoma (4T1). METHODS: DCs were grown from Balb/c mice by culturing lymphocyte-immunodepleted bone marrow in murine granulocyte-macrophage colony-stimulating factor containing medium for 10 days. Balb/c mice (five to eight per group) were immunized intradermally with 1 x 10(6) DCs mixed with 2 x 10(6) lethally irradiated 4T1 cells on day 0. Mice in control groups were given intradermal inoculations of phosphate-buffered saline solution, 1 x 10(6) DCs, or lethally irradiated 4T1 cells alone. Booster intraperitoneal immunizations of 2 x 10(6) lethally irradiated 4T1 cells were given on days 7 and 14. All mice were challenged with 5 x 10(3) 4T1 cells subcutaneously 7 days after the final immunization. Animals were examined daily, and tumor volume was recorded twice weekly with calipers. RESULTS: At 21 days there was a significant reduction in tumor growth in mice immunized with DCs mixed with irradiated 4T1 cells as compared with the control groups (p = 0.0005, Kruskal-Wallis test). CONCLUSIONS: These results suggest that DCs mixed with tumor cells as a source of undefined tumor antigen can induce an effective antitumor immune response. This finding provides a rationale for the use of cultured DCs in immunotherapy of breast and other cancers.

Inhibition of established pancreatic cancers following specific active immunotherapy with interleukin-2 gene-transduced tumor cells.

Pancreatic cancer has a poor prognosis even when complete resection can be accomplished. Recent studies have demonstrated that the immune system is capable of mounting effective tumor-specific immune responses even against "nonimmunogenic" tumors. The studies reported herein were conducted to determine if induction of tumor-specific immune responses of inhibiting in vivo pancreatic tumor growth could be achieved through active immunization with pancreatic tumor cells genetically engineered to secrete interleukin-2 (IL-2). A relevant poorly immunogenic subcutaneous model of murine ductal pancreatic cancer was first developed using an implantable tumor cell line Panc02 in C57BL/6 mice. Panc02 cells were then genetically engineered to secrete human IL-2 (Panc02/IL2). The ability of irradiated Panc02/IL2 cells to stimulate an immune response capable of rejecting a subsequent tumor challenge was first demonstrated. Ninety percent of animals vaccinated with irradiated parental Panc02 and subsequently challenged with parental Panc02 cells developed tumors by 48 days (mean tumor volume of 234 mm3) compared to only 40% (P < .05, chi square) of animals vaccinated with irradiated Panc02/IL2 and challenged with parental Panc02 (14 mm3, P < .004, tau test). The therapeutic benefit of active immunization in tumor-bearing animals was then examined. Mice with 3-day-old established subcutaneous tumors were administered a series of 4 weekly vaccinations with irradiated Panc02 or Panc02/IL2 cells. A significant reduction in tumor growth was present in those animals vaccinated with Panc02/IL2 (P < .005, tau test) versus Panc02 or saline. Animals whose established tumors regressed following vaccinations with IL-2-secreting Panc02 cells were found to have long-lasting immunity as demonstrated by rejection of a tumor challenge presented over 140 days following inoculation of the primary tumor. We conclude that an immune response capable of inhibiting established pancreatic tumors can be generated by vaccination with IL-2-secreting tumor cells. Furthermore, long-term immunological memory was established in mice that rejected the original established tumor. These studies provide preclinical evidence to support the use of cytokine gene-transduced tumor cell vaccinations in patients with pancreatic cancer.

Active immunization with tumor cells transduced by a novel AAV plasmid-based gene delivery system.

Ex vivo genetically engineered cytokine-secreting tumor cell vaccines have been shown to prevent metastatic disease in animal models of lung and breast cancer. Because of the inefficiency of existing modes of gene delivery in transducing primary human tumor cells, it has been difficult to clinically apply this strategy. In this study, liposome-mediated delivery of an adeno-associated virus (AAV)-based plasmid containing the sequence for murine gamma-interferon (gamma-IFN) (pMP6A-mIFN-gamma) was used to generate cytokine-secreting murine tumor cell vaccines. High levels of gamma-IFN and elevated class I major histocompatibility complex expression after transfer of pMP6A-mIFN-gamma into the murine lung cancer cell line, D122, was demonstrated. The efficiency of gene transfer was determined by two different methods and was estimated to be 10-15%. Irradiated gamma-IFN D122 cells generated by this novel gene delivery system (D122/pMP6A-mIFN-gamma) and also by standard retroviral methods (DIF2) were administered as weekly vaccinations by intraperitoneal injection to animals bearing 7-day-old intrafootpad D122 tumors. Hindlimb amputation was performed when footpad diameters reached 7 mm, and lungs were harvested 28 days later. Animals vaccinated with gamma-IFN-secreting D122 cells produced by AAV-based plasmids delivery demonstrated a significant delay in footpad tumor growth when compared with controls and DIF2 cells. Fifty-seven percent of animals vaccinated with D122/pMP6A-mIFN-gamma were free of pulmonary metastases 28 days after amputation, significantly improved from the 0, 7, and 15% observed in animals vaccinated with irradiated parental D122 cells, irradiated D122 cells lipofected with an empty-cassette vector (pMP6A), or DIF2 cells, respectively. These results and the ability to transfer genes with this delivery system to a broad range of tumor types support its use in the generation of cytokine-secreting tumor cell vaccinations for use in clinical trials.

Active immunotherapy of pancreatic cancer with tumor cells genetically engineered to secrete multiple cytokines.

BACKGROUND: Vaccination of tumor-bearing animals with tumor cells genetically engineered to secrete cytokines including interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) has been shown to induce effective tumor-specific immune responses capable of inhibiting local and metastatic disease. Previous unsuccessful attempts to enhance this immune response by means of the secretion of multiple cytokines possessing different immunologic mechanisms of action may have been due to the inherent inefficiency of the gene transfer systems used. We postulated that tumor cells genetically engineered by means of a novel gene transfer method resulting in high level secretion of both cytokines would be more effective than tumor cells secreting a single cytokine in inhibiting the growth of existing tumors. METHODS: Nonimmunogenic, murine pancreatic cancer cells (Panc02) were engineered to secrete IL-2, IFN-gamma, IL-2 and IFN-gamma, or neomycin phosphotransferase. Mice were inoculated with 5 x 10(5) parental Panc02 tumor cells subcutaneously. Beginning 3 days later, animals then received a series of four weekly vaccinations with irradiated Panc02/Neo, Panc02/IL2, Panc02/IFN, or Panc02/IL-2/IFN. RESULTS: Treatment with Panc02/Neo, Panc02/IL-2, or Panc02/IFN resulted in 0%, 40%, and 30% tumor-free survival, respectively. In contrast, 80% of animals vaccinated with Panc02/IL2/IFN were free of tumor at 100 days. All animals free of disease were resistant to subsequent tumor challenges. CONCLUSIONS: These data show that vaccination with tumor cells that secrete high levels of multiple cytokines was more effective in treating established pancreatic tumors and represents an improvement over existing single cytokine strategies.

Active immunotherapy with transiently transfected cytokine-secreting tumor cells inhibits breast cancer metastases in tumor-bearing animals.

BACKGROUND: Metastatic disease remains the most frequent cause of treatment failure in the management of patients with breast cancer. A novel method that allows delivery of a gene into primary tumor cells was used to generate tumor cell vaccines to inhibit metastasis formation in tumor-bearing hosts. METHODS: Inoculation of 2.5 x 10(4) 4T1 murine breast cancer cells into the footpads of BALB/c mice reliably leads to tumor growth and pulmonary metastases. Interleukin-2 (IL-2)-secreting 4T1 cells (4T1-pMP6A/IL-2) and control transduced 4T1 cells (4T1-pMP6A) were generated by lipofection with a cationic liposome complexed to an adeno-associated viral plasmid bearing the IL-2 gene (pMP6A/IL-2). Unmodified 4T1 cells were inoculated into the footpads on day 0, and weekly immunization with phosphate-buffered saline solution or 2 x 10(6) irradiated 4T1, 4T1-pMP6A, or 4T1-pMP6A/IL-2 cells commenced on day 21. Hindlimb amputation was performed when tumors measured 6 mm in diameter. Mice were killed 24 days after amputation, and metastatic disease was determined by weighing lungs at time of harvest. RESULTS: A significant reduction was seen in the pulmonary metastatic load of mice receiving IL-2 gene-modified tumor cell immunization (4T1-pMP6A/IL2) when compared with mice given control immunizations. CONCLUSIONS: These results suggest that active immunization strategies with cytokine gene-modified tumor cells generated by clinically relevant gene delivery systems may prove useful in inhibiting the development of metastases from primary breast cancer.

Generation of tumor-specific T lymphocytes for the treatment of posttransplant lymphoma.

BACKGROUND: The incidence of lymphoproliferative disease, including B-cell lymphomas (BCL) in patients who have undergone heart or combined heart-lung transplants, has been reported to be as high as 15%. The majority of these tumors contain Epstein-Barr virus (EBV) DNA and regress when immunosuppressive agents are discontinued. This tumor regression is thought to be secondary to cytotoxic T lymphocytes (CTL) reactive to EBV-infected cells whose function is impaired in patients receiving immunosuppressive agents. We hypothesize that EBV-CTL expanded in the absence of these agents may demonstrate an antitumor effect against an EBV-expressing human BCL in vitro and in vivo. METHODS AND RESULTS: An EBV-expressing BCL from a heart transplant recipient was isolated and expanded in culture. EBV-CTL were generated by stimulation of peripheral blood leukocytes with irradiated autologous tumor cells in low-dose interleukin-2. Autologous BCL, HLA-mismatched BCL, lymphokine-activated killer target cell line (Daudi), and the natural killer target cell line (K562) were used in a standard 4-hour cytotoxicity assay using 51CrO4 after 7, 14, and 28 days of stimulation. There was significant percent specific lysis of autologous BCL targets (78%) at an effector-to-target ratio as low as 20:1 as compared with control cells. EBV-CTL were then adoptively transferred into SCID mice (provided by Duke University Vivarium) that had been engrafted with autologous BCL 7 days before. There was a significant survival advantage to those mice engrafted with EBV-CTL as compared with control cells. CONCLUSIONS: The results indicate that ex vivo expansion of EBV-CTL in the absence of immunosuppressive agents results in a population that has significant antitumor activity. This strategy may be useful in the generation of EBV-CTL that might be effective antitumor agents in transplant recipients with EBV-associated lymphomas.

The clinical value of CEA and CA 15-3 in breast cancer management.

The value of tumour-associated antigens CEA and CA 15-3 was studied in patients with breast cancer over a 4-year period. A total of 252 patients with primary or recurrent disease had available and corresponding CEA and CA 15-3 values at diagnosis and during follow-up and were studied in detail. Preoperative and three-monthly serial postoperative levels were measured in each patient. Ten of 11 patients presenting with primary and concurrent metastatic disease had elevated CA 15-3 levels (> 25 I.U./ml) as compared to 6 with CEA (> 5 ng/ml). Fourty-seven patients developed locoregional recurrence of which 15 had concurrent metastatic disease. CA 15-3 was elevated in 14 cases while CEA in 11. Of 32 patients with locoregional recurrence alone, 18 later developed metastatic disease at a mean follow-up time of 17.5 months. There was a significant correlation between CA 15-3 value at locoregional recurrence and time to subsequent metastasis (r = 0.-0.57, P = 0.0133). CEA was elevated in 64%, CA 15-3 in 87% and either marker in 94% of 87 patients diagnosed with metastatic disease. Of 53 patients with serial markers and metastatic disease, 72% (38/53) had rising CA 15-3 levels prior to diagnosis with a mean lead time of 9.9 months. Use of CEA in conjunction improved lead time detection to 83%. This study demonstrates that CA 15-3 is superior to CEA at detecting metastatic disease at initial presentation and during follow-up. Use of CEA in conjunction with CA 15-3 improves the detection of systemic disease.

Directed enzyme pro-drug gene therapy for pancreatic cancer in vivo.

BACKGROUND: Directed enzyme pro-drug therapy incorporates the delivery of a gene to a cancer cell that will be specifically expressed and will confer sensitivity to a therapeutic agent. Tumor-specific gene expression can be achieved by coupling the promoter for the carcinoembryonic antigen (CEA) to a gene such as herpes simplex virus thymidine kinase (HSV-tk), which phosphorylates ganciclovir to a potent DNA synthesis inhibitor. METHODS: Retroviral vectors were constructed to contain the CEA promoter coupled to HSV-tk (LN-CEA-TK) and were used to transduce the CEA-expressing pancreatic carcinoma cell line BXPC3. Recombinant pancreatic carcinoma cell lines expressing HSV-tk (BXPC3CEA-TK) were then tested for sensitivity to the toxic effects on ganciclovir after engraftment into severe combined immunodeficient mice. Tumors were generated by subcutaneous inoculation of 20 x 10(6) tumor cells consisting of BXPC3 and/or BXPC3CEA-TK cells in ratios of 100:0, 90:10, 50:50, 10:90, and 0:100. After 3 days mice received daily ganciclovir (0.1 mg/kg) or phosphate-buffered saline solution by intraperitoneal injection and were monitored for tumor growth. RESULTS: All severe combined immunodeficient mice inoculated with BXPC3 or BXPC3CEA-TK cells in any proportion developed large pancreatic tumors. As expected, a significant reduction in tumor size was seen in the BXPC3CEA-TK engrafted mice receiving ganciclovir compared with mice receiving phosphate-buffered saline solution or mice engrafted with only BXPC3. In addition, all animals with any fraction of cells expressing HSV-tk exhibited a significant reduction in tumor growth, including animals with only 10% of cells expressing HSV-tk. CONCLUSIONS: These results suggest the potential utility of directed enzyme pro-drug therapy in patients with CEA-expressing pancreatic carcinoma.

Varicocele and the horizontal testis: a change in position?

Horizontal lie of the testis has recently been observed in association with varicoceles in a pediatric population. Six children with a varicocele presented to the surgical department during a 6-month period. All had an associated horizontal lie of the testis. In two of these cases, high ligation of internal spermatic veins was performed, after which one reverted to a vertical position with resolution of the varicocele. Seven children who underwent high ligation of a varicocoele over a 5-year period were examined. All were found to have no evidence of the varicocele at follow-up. All but one had a vertical lie. Horizontal lie of the testis in children is a new clinical sign that should alert the examiner to the possibility of an underlying varicocele.

Reasons underlying negative mammography in patients with palpable breast cancer.

It is well recognized that a negative mammogram report does not exclude the presence of breast carcinoma. This study examines the accuracy of mammography in patients with palpable breast cancer. In particular, the study evaluates the reasons underlying negative mammography in breast cancer. All patients with Paget's disease, carcinoma in situ lesions or lesions infiltrating skin were excluded. A total of 291 patients presenting with palpable breast carcinoma underwent mammography prior to biopsy. False negative reports occurred in 16.5% (48). The sensitivity of mammography increased with age, from 70% (14/20) in 31-40-year-olds to 91% (113/124) in women over 60 years. Retrospective review of false negative mammograms showed that 30% of these were deemed normal while 20% were obvious oversights. The remaining 50% showed subtle radiographic abnormalities, consistent with but not diagnostic of malignancy.

Effect of closing dead space on seroma formation after mastectomy--a prospective randomized clinical trial.

To evaluate the effect of closing dead space on seroma formation after mastectomy, 39 patients undergoing 40 mastectomies with axillary node clearance were randomized to undergo suturing of skin flaps to underlying muscle or conventional skin closure. Duration of closed suction drainage, 72 h, and shoulder exercises, commencing on the first post-operative day, were standardized for both groups. Closed suction drainage was significantly less (P < 0.05) in the group that had flaps sutured, 272 +/- 46 ml vs 393 +/- 39 ml. Also fewer patients in the flap sutured group developed seromas, 5 (25%) vs 17 (85%) chi 2 = 12.2 P < 0.001. Three patients in the group that had conventional skin closure had breakdown of wound edges, two developing a prolonged serous discharge, while none occurred in the sutured group. A functional range of shoulder motion was attained at 6 months in 14 (70%) patients in the flap sutured group compared with nine (45%) in the conventional skin closure group (P = NS). These results confirm the value of suturing skin flaps to underlying muscle in reducing local morbidity after mastectomy and suggest that this technique should be included in the closure of all mastectomy wounds.

CA 15-3 in patients with locoregional and metastatic breast carcinoma.

BACKGROUND: The value of circulating CA 15-3 levels was assessed in 129 patients with recurrent breast carcinoma. METHODS: Patients were divided into four subgroups, according to the following: Group A, locoregional recurrence alone; Group B, locoregional and subsequent systemic recurrence; Group C, combined locoregional and systemic recurrence; and Group D, differing sites of systemic disease. RESULTS: One of 14 patients with locoregional disease alone had increased levels of CA 15-3 (> 25 U/ml). However, 96% of patients (22 of 23 patients) with combined local and systemic disease had increased tumor marker levels. The difference in CA 15-3 levels in patients with combined disease compared with patients with local disease alone was statistically significant (117.0 versus 17.5 U/ml, respectively; P < 0.02). Twenty-four patients with locoregional recurrence later had distant metastasis develop. In this group, patients with an increased CA 15-3 value had a significantly shorter lead time to the development of distant metastases compared with patients with normal tumor marker levels (20.8 +/- 3.3 versus 10.3 +/- 2.7 months, respectively; P < 0.03). CA 15-3 values at diagnosis were increased in 88% of 115 patients with metastatic disease. There was no significant difference in CA 15-3 levels among metastases to lung, liver, and bone nor was there any difference between single and multiple sites of distant metastasis. CA 15-3 is an excellent marker for systemic recurrence of breast carcinoma. CONCLUSIONS: Increased levels and no clinical evidence of recurrence strongly indicate the presence of occult metastatic disease.

Mammographic needle localisation of impalpable breast lesions.

Refinements in mammography have led to an increased number of needle localised breast biopsies for impalpable breast lesions. This paper review 139 needle guided biopsies from June 1986 to December 1990 in 132 patients. Forty four patients (32%) biopsied had malignant lesions the vast majority (91%) of which were reported as either non-invasive or invasive less than 2 cm in diameter. Fourteen patients in this group had ductal carcinoma in-situ. When compared with 100 consecutive palpable breast carcinomas during the same period, needle localised biopsies had a higher proportion of non-invasive lesions and fewer were associated with lymph node involvement. Needle guided breast biopsy detects carcinoma at an earlier stage and may reduce morbidity and mortality from breast cancer.