Elaboration of a nomogram to predict non sentinel node status in breast cancer patients with positive sentinel node, intra-operatively assessed with one step nucleic acid amplification method.

BACKGROUNDS: Tumor-positive sentinel node(SLN) biopsy results in a risk of nonsentinel node metastases in case of micro and macro metastases ranging from 20 to 50 %, respectively. Therefore, most patients underwent unnecessary axillary lymph node dissections. Thus, the development of a mathematical model for predicting patient-specific risk of non sentinel node(NSLN) metastases is strongly warranted. METHODS: The following parameters were recorded: CLINICAL: hospital, age, medical record number Bio-pathological: tumor (T) size, grading (G), multifocality, histological type, LVI, ER-PR status, HER-2, ki67, molecular classification (luminal A, luminal B, HER2 like, triple negative) Sentinel and nonsentinel lymph node related: number of removed SLNs, number of positive and negative SLNs, copy number of positive sentinel nodes, ratio: number of positive SLNs to number of removed SLNs, number of removed and number of positive nodes after ALND. A total of 2460 patients have been included in the database. All the patients have been provided by the authors of this paper. RESULTS: Multivariate logistic regression analysis demonstrated that only the number of a CK19 mRNA copies (p < 0.0001), T size (p < 0.0001) and LVI (p < 0.0001) were associated with NSN metastases. The discrimination of the model, quantified with the area under the receiver operating characteristics curve, was 0.71 (95 %, C.I. 0.69-0.73), thus confirming a good level of reliability. CONCLUSIONS: The nomogram may be employed by the surgeon as a decision making tool on whether to perform an intraoperative axillary lymph node dissection on breast cancer patients with SLN positive. The large population employed and the standardized method of measuring the value of CK19 mRNA copies are appropiate prerequisites for a reliable nomogram.

Multicentre evaluation of intraoperative molecular analysis of sentinel lymph nodes in breast carcinoma.

BACKGROUND: Ideally, intraoperative sentinel lymph node (SLN) analysis in breast cancer should be automated, have high concordance with extensive histopathology, and be applicable in any hospital setting. A prospective multicentre evaluation of the one-step nucleic acid amplification (OSNA) automated molecular diagnostic system of SLN analysis was undertaken. METHODS: Intraoperative examination of SLNs from 204 patients with breast cancer was performed by OSNA at four sites in the UK. Half of each SLN was assessed by OSNA (for cytokeratin 19 mRNA) and the remaining half was paraffin embedded for intensive histological examination at ten levels. Discordant cases were reanalysed by further molecular biological techniques and by additional histological examination of all remaining nodal material to ascertain whether the discordance was due to an uneven distribution of metastases, known as tissue allocation bias (TAB). RESULTS: After exclusion of samples affected by TAB, the overall concordance rate for OSNA versus histopathology was 96.0 per cent, with a sensitivity of 91.7 per cent and a specificity of 96·9 per cent. The median time to process a single SLN was 32 (range 22-97) min, and that for two nodes 42 (30-73) min. CONCLUSION: OSNA enables accurate automated intraoperative diagnosis and can be used successfully in different UK hospitals. When the SLN is shown to be positive, the patient can undergo immediate axillary clearance under the same anaesthetic rather than having a delayed second procedure.

Management of lobular carcinoma in-situ and atypical lobular hyperplasia of the breast--a review.

OBJECTIVES: To determine the incidence of malignancy (invasive carcinoma or DCIS) in patients diagnosed with lobular neoplasia (B3) on core needle biopsy (CNB) of breast lesions by reviewing the published literature. METHODS: Medline, Embase, OVID-database and reference lists were searched to identify and review all English-language articles addressing the management of LN diagnosed on CNB. Studies on mixed breast pathologies were excluded. RESULTS: Of 1229 LN diagnosed on CNB, 789 (64%) underwent surgical excision. 211 (27%) of excisions contained either DCIS or invasive disease. 280 of the excision specimens were classified as ALH, 241 as LCIS, 22 as pleomorphic LCIS and 246 unspecified LN on the original CNB. After surgical excision, 19% of the ALH cases, 32% of the LCIS cases and 41% of the PLCIS cases, contained malignancy. 29% of the unspecified LNs were upgraded to malignancy. The higher incidence of malignancy within excision specimens for LCIS and PLCIS compared to ALH was significant (P < 0.04, <0.003 respectively). CONCLUSION: There is a significant underestimation of malignancy in patients diagnosed with breast LN on CNB. 27% cases of CNB-diagnosed LN were found to contain malignancy following surgical excision. All patients diagnosed with LN on CNB should be considered for surgical excision biopsy.

Surgical site infection rate is lower in laparoscopic than open colorectal surgery.

OBJECTIVE: Few studies have investigated whether surgical site infection (SSI) incidence differs between laparoscopic colorectal surgery (LCS) and open colorectal surgery (OCS). This study investigated the SSI incidence using the validated UK SSI Surveillance Service (SSISS) criteria for diagnosing wound infections. METHOD: Prospective data collection recorded patients' demographics, operative details, antibiotic use, wound evaluation and microbiological wound culture results, for consecutive patients undergoing elective resectional LCS and OCS. Postdischarge surveillance consisted of patient questionnaires sent out at 30 days and the primary care communication. RESULTS: A total of 122 patients underwent colorectal resections over 1 year (LCS 43; OCS 79). Patients' demographics and operative case-mix were similar for both groups, including body mass index (BMI), diabetic and smoking status. Operative duration was longer in the LCS group compared with OCS group (P = 0.012, Mann-Whitney U-test), but hospital stay was shorter for LCS (P = 0.0001, Mann-Whitney U-test). The SSI rate was significantly lower in the LCS than OCS group (7%vs 25% respectively; P = 0.015, two-tailed Fisher's exact test). BMI > 30 and operation length > 4 h influenced the risk of SSI formation (P < 0.05, chi-squared test). One LCS patient required conversion to a limited laparotomy. CONCLUSIONS: Surgical site infection incidence is significantly lower following LCS when compared with OCS. Confounding factors in this study include patient selection for LCS and nonrandomization.

Oncological considerations of skin-sparing mastectomy.

AIM: To review evidence concerning the oncological safety of performing skin-sparing mastectomy (SSM) for invasive breast cancer and ductal carcinoma in situ (DCIS). Furthermore, the evidence concerning RT in relation to SSM and the possibility of nipple preservation was considered. METHODS: Literature review facilitated by Medline and PubMed databases. FINDINGS: Despite the lack of randomised controlled trials, SSM has become an accepted procedure in women undergoing mastectomy and immediate reconstruction for early breast cancer. Compared to non-skin-sparing mastectomy (NSSM), SSM seems to be oncologically safe in patients undergoing mastectomy for invasive tumours smaller than 5 cm, multicentric tumours, DCIS or risk-reduction. However, the technique should be avoided in patients with inflammatory breast cancer or in those with extensive tumour involvement of the skin in view of the high risk of local recurrence. SSM with nipple areola complex (NAC) preservation appears to be oncologically safe, provided the tumour is not close to the nipple and a frozen section protocol for the retro-areolar tissue is followed. Although radiotherapy (RT) does not represent a contraindication to SSM, the latter should be used with caution if postoperative RT is likely, since it detracts from the final cosmetic outcome.

Multiple, large, benign peritoneal cysts--a case report.

This case report describes a unique case of large (up to 17 cm!) peritoneal cysts of uncertain aetiology. It illustrates the diagnostic and management difficulties encountered with such a rare problem. Although subsequently proven to be benign, they were thought to represent an extreme form of endosalpingiosis after a literature review.

T1 G1 NO ER positive breast cancer--adjuvant therapy is needed.

AIMS: To assess the outcome of treating patients with excellent prognosis (T1 G1 N0 ER +ve) breast cancers with breast conserving surgery alone. METHODS: One hundred and twenty-one women with grade 1, node negative, ER+ tumours, smaller than 20 mm who were treated by breast conserving surgery alone between 1991 and 2000. Margin width was always at least 5 mm. The following were recorded: local recurrence (LR), distant recurrence, new contra-lateral primaries and death. Recurrence rates were then compared to those in the largest series. RESULTS: One hundred and twenty-one women were followed up for a median of 68 months. Fourteen developed further breast cancer in the same side and eight new cancers in the contra-lateral breast. There was one case of distant metastasis and no deaths. Local recurrence rate was significantly higher than other studies (p=0.006). CONCLUSIONS: Although there is no detrimental effect on survival after this length of follow-up, the omission of radiotherapy and tamoxifen appears to increase the probability of LR. Patients with T1 G1 N0 ER+ breast cancer treated by breast conserving surgery should be offered both radiotherapy and tamoxifen.

Acute epididymo-orchitis in an undescended testicle.

Establishing the diagnosis of a groin lump may be difficult, largely due to the large number of potential differential diagnoses. Indeed, this case was originally referred as a strangulated hernia. Despite the final diagnosis being infection of an undescended testicle, the patient did not report that he only ever had one scrotal testicle despite his 78 years of age.

Evidence for the management of mastalgia.

Mastalgia is the commonest breast symptom presenting to general practitioners and breast surgeons alike. To make a full assessment of the cause, all patients require a full history, examination and, sometimes, investigations. Diary cards are often helpful. The commonest cause is cyclical mastalgia. Most women require reassurance only and the pain often settles spontaneously after a few months. For the remainder, simple lifestyle changes should be suggested initially, such as wearing a well-fitted sports bra, weight reduction, regular exercise and a reduction in caffeine intake. Unfortunately, there is a paucity of evidence for the usefulness of these measures. If pain is persistent or severe, a variety of pharmacological agents exist. The most effective with least side effects is a 3-6-month course of low-dose tamoxifen (10mg). Other proven agents include danazol and bromocriptine, but these have a higher side-effect profile and are rarely indicated nowadays. Newer treatments include lisuride maleate and topical non-steroidal anti-inflammatory preparations.

Acute ulcerative colitis in a Meckel's diverticulum.

This report describes the case of a patient with acute ulcerative colitis who underwent an emergency colectomy and removal of an incidental Meckel's diverticulum which appeared inflamed. Histology showed acute inflammation of colonic epithelium within the Meckel's diverticulum, justifying its removal and confirming that this was indeed a 'skip lesion'.

Radiotherapy and tamoxifen after breast-conserving surgery for DCIS.

The main controversies surrounding the management of DCIS evolve around the need for adjuvant radiotherapy (RT) after adequate local excision (LE) of localized lesions and the role of adjuvant endocrine therapy. Three recent randomized controlled trials (RCTs) have demonstrated that adjuvant RT significantly reduces the incidence of ipsilateral breast tumor recurrence (IBTR) after "adequate" LE. The role of adjuvant tamoxifen in the treatment of DCIS was evaluated in two RCTs: one demonstrated a significant reduction in IBTR with tamoxifen and the other did not. Retrospective subgroup analysis of the former demonstrated that the reduction in all breast cancer events was even greater for ER positive tumors, but no benefit was observed for ER negative lesions. The effect of tamoxifen was greater in both trials for women under 50 years.

From PCR to RCA: a surgical trainee's guide to the techniques of genetic amplification.

With the advent of evidence-based medicine and the Calman-Hine Report, more and more surgical trainees are undertaking a period of research, either before entering or during their Specialist Registrar training. Many will encounter concepts in science uncommon in daily clinical settings. This paper will elucidate the techniques of genetic amplification available today with their potential for usage in clinical research.

Lymphangiogenesis and breast cancer metastasis.

Breast cancer is one of the commonest malignancies in women in the western world. It spreads predominantly via the lymphatic system. However, the understanding of the formation of lymphatics, lymphangiogenesis, has been limited. This has been largely due to the previous lack of lymphatic specific markers. The most specific marker used in humans has been the vascular endothelial growth factor receptor 3 (VEGFR-3). However, this is also found on blood vessel endothelium. The other vascular endothelial factor receptors (VEGFR-1 and -2) are primarily blood vessel receptors. More recently, novel, specific markers for lymphatics have been discovered, such as LYVE-1, prox I and podoplanin, enabling further research into this new field. Each of these new markers is described in detail. The article also outlines the current understanding in breast cancer metastasis, with an emphasis on the more recent research into lymphangiogenesis. Since these specific markers are now available, quantitation of lymphangiogenesis is now possible by using either immunohistochemistry or quantitative PCR approaches. In addition, to breast cancer, research into many other cancers is now possible using these methods and new markers. With this in mind, possible therapeutic strategies for the future are discussed.

Lymphangiogenesis quantification using quantitative PCR and breast cancer as a model.

The detection of lymphangiogenesis (formation of new lymphatics) has previously been difficult to measure, primarily due to the lack of specific markers for lymphatic endothelium. Using conventional PCR (polymerase chain reaction), DNA sequencing, plasmid synthesis, and real-time quantitative PCR (RTQPCR), we report a new approach to enable the measurement of lymphangiogenesis using LYVE-1, a novel, specific lymphatic marker in breast cancer tissue. By using a Scorpion-based probe system with the RTQPCR analyser, a highly sensitive and specific detection and quantitation of LYVE-1 was possible. It was found that lymphangiogenesis occurred in all breast specimens and that higher levels were found in tumours which had spread to the lymph nodes.

Aromatase inhibitors.

The new non-steroidal and steroidal aromatase inhibitors are at least as effective as megestrol acetate (MA) as second-line hormonal agents in postmenopausal women with breast cancer. However, they are superior to MA in terms of tolerability and adverse effects. Letrozole and exemestane have been shown to be superior to MA in terms of efficacy. Furthermore, exemestane and anastrozole demonstrated a survival advantage over MA. These drugs are therefore considered established second-line hormonal agents. There is a growing body of evidence supporting the role of third-generation aromatase inhibitors as first-line therapy for ER-and/or PgR-positive advanced breast cancer in postmenopausal women, and as a neoadjuvant therapy in postmenopausal women with hormone receptor positive tumours unsuitable for breast conserving surgery. Studies comparing these drugs head-to-head and with adjuvant tamoxifen are currently in progress. The potential role of these drugs in breast cancer prevention is worth investigating.

Anatomical variants of the intercostobrachial nerve encountered during axillary dissection.

Recent reports have described attempts at preserving the intercostobrachial nerve in patients undergoing axillary clearance for breast cancer. However, the anatomy of the nerve encountered by the surgeon operating in the axilla has not been previously described in any detail. In this study, we were able to document the anatomy of this nerve in 45 out of 50 consecutive patients undergoing axillary clearance. We found the anatomy variable, but have illustrated six main variants. In addition, we were able to preserve the nerve in 40 out of 50 cases.

Pre-operative electrocardiograph examination.

The leading cause of death following surgery is a cardiac event, and an electrocardiogram is the most common pre-operative test to investigate coronary artery disease. Fifty adults, who required an electrocardiogram, undergoing general surgical procedures, were recruited into this pilot study, which investigated the examination rate of electrocardiographs by doctors pre-operatively. Each tracing was folded in one corner and a paperclip prevented full pre-operative viewing without its removal. Results suggest that 30% of ECGs were not opened and the records of 58% patients overall had no mention of the ECG having been performed. Further analysis showed no correlation with the examination rate of the electrocardiograph with patient age or fitness. If this reflects normal clinical practice, it is sub-optimal use of resources and warrants further audit.

Junior doctor training in breast and axillary examination: a comparative study.

To date, there has been a lack of published data concerning the training of breast and axillary examination, yet this remains an essential part of the triple assessment of breast lumps. In this study, we aimed to determine the competence of junior doctors in examining the breast and axilla, and whether this skill improved with time. We compared the findings of a specialist registrar and senior house officer with those of a consultant in 15 consecutive one-stop breast clinics in a district general hospital. The results suggested that although specialist registrars become proficient after this period, senior house officers do not progress at the same rate. This may have important implications for training and the organization of breast clinics.

Superior mesenteric vein occlusion presenting with a massive vascular malformation of the colon.

Superior mesenteric vein occlusion is a rare condition which has protean clinical manifestations. It frequently occurs secondary to an underlying coagulation defect. We present the case of a young female who presented uniquely with a massive colonic vascular malformation and who had various predisposing factors, the most serious being a protein C deficiency.