Nipple discharge and the efficacy of duct cytology in evaluating breast cancer risk.

BACKGROUND: Nipple discharge accounts for up to 5% of referrals to breast surgical services. With the vast majority of breast carcinomas originating in the ductal system, symptomatic dysfunction of this system often raises disproportionate clinical concern. The aim of this study is firstly, to evaluate the clinical importance of nipple discharge as an indicator of underlying malignancy and secondly, to assess the diagnostic application of duct cytology in patients presenting with nipple discharge. STUDY DESIGN: We performed a retrospective analysis of all patients presenting with nipple discharge as their primary symptom to the symptomatic breast unit at a tertiary referral center over a 30-month period (n = 313). The Hospital Inpatient Enquiry (HIPE) System and BreastHealth database were used to identify our study cohort. Parameters evaluated included patient demographics, clinical presentation, clinical evaluation, radiological assessment and histological/cytological analysis. RESULTS: Three-hundred and thirteen patients presented with nipple discharge as their primary complaint. Invasive breast carcinoma was diagnosed by Triple Assessment in 5% of patients. 24% of patients presenting with nipple discharge underwent nipple aspiration and cytological analysis. Duct cytology was diagnostic of the underlying breast carcinoma in 50% of triple assessment diagnosed carcinoma. Four risk factors were identified as having a significant association with breast carcinoma, these included (a) age >50 years (p < 0.0001), (b) bloody nipple discharge (p < 0.008), (c) presence of a breast lump (p < 0.0001) and (d) single duct discharge (p < 0.006). CONCLUSIONS: Nipple discharge is a poor indicator of an underlying malignancy. Use of nipple aspiration and duct cytology for the assessment of nipple discharge is of limited diagnostic benefit. However, by utilizing the systematic, gold standard approach of Triple Assessment (clinical, radiological and cytological evaluation), the risk of underlying carcinoma can be accurately defined.

Induction of nitric oxide synthase is a key determinant of progression to pulmonary injury in experimental pancreatitis.

BACKGROUND: The immunomodulatory potential of nitric oxide provides prospective strategies to attenuate inappropriate inflammatory reactions. This study tested the hypothesis that inhibition of nitric oxide synthase (NOS) reduces end-organ injury in pancreatitis. METHODS: Pancreatitis was induced in male Sprague-Dawley rats by intraperitoneal (i.p.) injection of 20% L-arginine (500 mg/100 g of body weight). Animals were randomized into four groups of 45: Pancreatitis without intervention; pre-treatment with i.p. aminoguanidine (AMG) (50 mg/kg), an isoform-specific inhibitor of inducible NOS; post-treatment with AMG (50 mg/kg); and controls. Pancreatic and pulmonary pathology, neutrophil infiltration (myeloperoxidase activity), endothelial permeability (bronchoalveolar lavage, wet:dry weight ratio), NOS expression, and concentrations of pro-inflammatory cytokines (tumor necrosis factor-alpha; interleukin-6) were assessed. RESULTS: Inhibition of iNOS significantly reduced end-organ injury. Pancreatic and pulmonary injury scores were markedly attenuated in the AMG treatment groups compared with no intervention (p < 0.05). Increased endothelial permeability (2,411.1 +/- 47.9) and neutrophil sequestration (1.99 +/- 0.01) were manifest in the untreated animals compared with AMG pretreatment (1,286.8 +/- 35.1 and 1,548.0 +/- 0.1; p < 0.05). In addition, a significant reduction in inflammatory cytokine concentrations was observed (p < 0.05). CONCLUSIONS: Inhibition of inducible NOS encourages a more benign immunologic profile, minimizing the deleterious effects of unrestrained neutrophil sequestration subsequent to pancreatitis.

Electronic learning can facilitate student performance in undergraduate surgical education: a prospective observational study.

BACKGROUND: Our institution recently introduced a novel internet accessible computer aided learning (iCAL) programme to complement existing surgical undergraduate teaching methods. On graduation of the first full cycle of undergraduate students to whom this resource was available we assessed the utility of this new teaching facility. METHOD: The computer programme prospectively records usage of the system on an individual user basis. We evaluated the utilisation of the web-based programme and its impact on class ranking changes from an entry-test evaluation to an exit examination in surgery. RESULTS: 74.4% of students were able to access iCAL from off-campus internet access. The majority of iCAL usage (64.6%) took place during working hours (08:00-18:00) with little usage on the weekend (21.1%). Working hours usage was positively associated with improvement in class rank (P = 0.025, n = 148) but out-of hours usage was not (P = 0.306). Usage during weekdays was associated with improved rank (P = 0.04), whereas weekend usage was not (P = 0.504). There were no significant differences in usage between genders (P = 0.3). Usage of the iCAL system was positively correlated with improvement in class rank from the entry to the exit examination (P = 0.046). Students with lower ranks on entry examination, were found to use the computer system more frequently (P = 0.01). CONCLUSION: Electronic learning complements traditional teaching methods in undergraduate surgical teaching. Its is more frequently used by students achieving lower class ranking with traditional teaching methods, and this usage is associated with improvements in class ranking.

Peroral and transgastric esophageal anastomosis with flexible shaft remote-control stapler (SurgASSIST).

Stapled cervical esophageal anastomoses are technically challenging and are associated with relatively high complication rates, particularly in leaks and anastomotic strictures. We describe the use of a flexible shaft, remote-control, circular stapling device in forming high esophageal anastomoses in 2 patients. Retrograde transgastric and prograde peroral approaches are evaluated comparing ease of technical application and outcomes. Both procedures were performed after total esophagectomy for cancer in a 72-year-old male patient with preoperative down-staging and a 78-year-old female who proceeded directly to surgery. The introduction of rigid staplers in the esophagus by either route can be difficult and technical pointers and the potential applications of the flexible SurgASSIST device are discussed. Potential benefits include shorter time for constructing the anastomosis and a wider lumen resulting in possible cost benefit. Both patients had uneventful technical construction of stapled anastomoses, and the only complication in the female was a leak in the gastric close-off at the site of introduction of the flexshaft. Both are alive and well without recurrence at 2 years and 22 months.

Role of sentinel lymph node biopsy in high-risk ductal carcinoma in situ patients.

BACKGROUND: The role of sentinel lymph node biopsy (SLNB) for ductal carcinoma in situ (DCIS) is poorly defined. However, up to 20% of patients with DCIS will have invasive carcinoma; these patients require staging for axillary metastasis. The aim of this study was to identify patients with a core biopsy diagnosis of DCIS who may benefit from SLNB. METHODS: In a prospective study, we performed SLNB on patients with a preoperative diagnosis of >2.5 cm of high-grade DCIS or DCIS when mastectomy was indicated. RESULTS: Sixty-two patients underwent surgery for high-grade DCIS, and 35 of these patients underwent SLNB. Postsurgical excision histology revealed invasive disease in 20 patients, 19 of whom had undergone SLNB. Before the adoption of SLNB in selected DCIS patients, all 20 with occult invasive disease would have required second surgery axillary staging (P < .01, chi-square test). CONCLUSIONS: SLNB should not be performed routinely for all patients with an initial diagnosis of DCIS. However, selective lymphadenectomy may be a useful clinical adjuvant in selected high-risk DCIS patients.

Promoter switch: a novel mechanism causing biallelic PEG1/MEST expression in invasive breast cancer.

We have previously reported on the biallelic expression of the imprinted PEG1/MEST gene in infiltrating carcinomas of the breast. Putative loss of imprinting (LOI) of PEG1/MEST has subsequently also been implicated in the aetiology of lung adenocarcinomas and colon cancer. Taking advantage of our previous study, identifying seven infiltrating carcinomas of the breast, displaying biallelic PEG1/MEST expression, we have analysed the allelic usage of the two alternative PEG1/MEST transcripts encoding isoforms 1 and 2, separately. In addition, expression levels of the two transcripts have been measured by real-time RT-PCR, in order to elucidate the mechanism behind the switch from monoallelic transcription in normal breast tissue to biallelic expression in invasive cancer. The isoform 1 transcript is imprinted in both the paired normal tissue and the breast carcinomas. In contrast, the isoform 2 transcript is biallelically expressed, or in one case expressed from the opposite allele to isoform 1, raising the possibility that isoform 2 is polymorphically imprinted in normal breast tissue. In all the paired normal samples, isoform 1 is predominantly expressed, explaining the monoallelic profiles of these samples. However, in four of the seven biallelic carcinomas, isoform 2 is expressed at higher levels than isoform 1, indicating that a switch in expression from isoform 1 to isoform 2 is responsible for the biallelic profiles in these samples. Our results not only suggest a novel mechanism leading to biallelic expression detected when analysing the common 3'-UTR of the PEG1/MEST transcriptional unit, they are also indicative of the existence of further alternative PEG1/MEST transcripts.