EpCAM expression varies significantly and is differentially associated with prognosis in the luminal B HER2(+), basal-like, and HER2 intrinsic subtypes of breast cancer.

BACKGROUND: Epithelial cell adhesion molecule (EpCAM) is frequently expressed in breast cancer, and its expression has been associated with poor prognosis. Breast cancer can be subdivided into intrinsic subtypes, differing in prognosis and response to therapy. METHODS: To investigate the association between EpCAM expression and prognosis in the intrinsic subtypes of breast cancer, we performed immunohistochemical studies on a tissue microarray encompassing a total of 1365 breast cancers with detailed clinicopathological annotation and outcomes data. RESULTS: We observed EpCAM expression in 660 out of 1365 (48%) cases. EpCAM expression varied significantly in the different intrinsic subtypes. In univariate analyses of all cases, EpCAM expression was associated with a significantly worse overall survival. In the intrinsic subtypes, EpCAM expression was associated with an unfavourable prognosis in the basal-like and luminal B HER2(+) subtypes but associated with a favourable prognosis in the HER2 subtype. Consistently, specific ablation of EpCAM resulted in increased cell viability in the breast cancer cell line SKBR3 (ER(-), PR(-), and HER2(+)) but decreased viability in the breast cancer cell line MDA-MB-231 (ER(-), PR(-), and HER2(-) ). CONCLUSION: The differential association of EpCAM expression with prognosis in intrinsic subtypes has important implications for the development of EpCAM-targeted therapies in breast cancer.

PTP1B expression is an independent positive prognostic factor in human breast cancer.

Protein tyrosine phosphatase 1B (PTP1B) is a non-transmembrane protein tyrosine phosphatase that has come into focus as a critical regulator of multiple signaling pathways. The role of PTP1B in breast cancer remains unclear with evidence suggesting that PTP1B can exert both tumor-suppressing and tumor-promoting effects. To better define the role of PTP1B in human breast cancer, and its relationship with HER2, we performed immunohistochemical studies on a large cohort of functionally annotated primary breast cancer specimens. 683 of 1,402 (49 %) evaluable primary breast cancers are positive for PTP1B. There is no statistically significant association between PTP1B expression and age, tumor size, T stage, histologic grade, lymph node status, or histological subtype. Of note, there is no significant association between PTP1B expression and HER2 expression (PTP1B expression 53.1 % in HER2(+) cancers vs. 47.5 % in HER2(-) cancers, p = 0.0985). However, PTP1B expression is significantly associated with estrogen receptor expression (PTP1B expression 50.7 % in ER(+) cancers vs. 43.1 % in ER(-) cancers, p = 0.0137) and intrinsic molecular subtype (PTP1B expression 53.9 % in the luminal B HER2(+) subtype and 37.9 % in the basal-like subtype). Of note, multivariate analyses demonstrate that PTP1B is an independent predictor of improved survival in breast cancer (HR 0.779, p = 0.006). Taken together, we demonstrate in the largest study to date that (1) PTP1B is commonly expressed in breast cancer, (2) there is no association or functional impact of PTP1B expression in HER2(+) breast cancer, and (3) PTP1B expression in breast cancer is associated with significantly improved clinical outcome. Until additional studies are performed, caution should be exercised in using PTP1B inhibitors in human breast cancer.

The post ACOSOG Z0011 era: does our new understanding of breast cancer really change clinical practice?

BACKGROUND: The ACOSOG Z0011 trial (Z0011) expanded our thinking about breast cancer (BC) and showed that limited metastatic disease left behind in the axilla did not compromise oncological safety in a selected group of patients. The aim of the current study was to assess the potential impact of Z0011 on clinical practice by testing the applicability of its criteria to a European patient population. METHODS: We reviewed a consecutive series of 389 sentinel lymph node biopsies (SLNB) performed for invasive BC at the University Hospital Basel between 2003 and 2009 (65.6% of all surgically treated patients, n = 593). RESULTS: When compared to the axillary lymph node dissection (ALND) arm of Z0011, our patients had significantly less advanced LN involvement (≥ 3 LN: 8.5% vs. 21.0%, p = 0.048). Thirty-five patients (9.0%) met the Z0011 inclusion criteria and had 1-2 SLNs with macrometastases (5.9% of all surgically treated BC patients). If the inclusion criteria of Z0011 had been applied, a considerable number of LNs would have been missed in two cases (0.5% of all SLNBs). CONCLUSIONS: The application of the Z0011 led to the omission of completion ALND in less than 10% of all SLNB procedures (<6% of all surgically treated BC patients); therefore, we do not think that the perception of Z0011 as "practice changing" is justified. On the other side, skeptics of the routine implementation of the Z0011 protocol may overestimate its potential hazards. When performing a thorough preoperative clinical axillary staging, the number of patients who would have been undertreated is minimal.

Increasing rates of contralateral prophylactic mastectomy - a trend made in USA?

BACKGROUND: Numerous recent studies conducted in the USA reported a considerable rise in the rates of contralateral prophylactic mastectomy (CPM) in early-stage breast cancer (BC). However, this aggressive surgical approach only showed an evidence-based improvement in prognosis for a small subgroup of high-risk BC patients. We present the first European study reporting CPM rates in an unselected cohort of patients with BC. PATIENTS & METHODS: The data of 881 patients (≤ 80 years) who underwent surgery for stage I-III BC from 1995 to 2009 at the University of Basel Breast Center was analyzed. RESULTS: CPM was performed in 23 of 881 patients (2.6%). Of the entire patient population, 37.5% underwent ipsilateral mastectomy and of those, only 7.0% chose to undergo CPM. Importantly, there was no trend over time in the rate of CPM. Women who chose CPM were significantly younger (54 vs. 60 years, p < 0.001), had more often a positive family history (39.1% vs. 24.4%, p = 0.032) and tumors of lobular histology (30.5% vs. 13.9%, p = 0.035). CONCLUSIONS: Our analysis of CPM rates in BC patients, conducted at a European University breast center, does not show the considerably rising CPM rates observed in the USA. We hypothesize that different medico-social and cultural factors, which are highlighted by a different public perception of BC and a different attitude toward plastic surgery, determine the varying CPM rates between the USA and Europe.

Prognosis of early-stage synchronous bilateral invasive breast cancer.

BACKGROUND: Contradictory data exists concerning the prognosis of patients with synchronous bilateral breast cancer (SBBC). Most authors report a worse prognosis for SBBC patients compared to unilateral breast cancer (UBC) patients. There are a few studies that did not support these findings. This study gives a comprehensive picture of SBBC and tests the hypothesis that outcome of this entity is based on the tumor with the worse prognosis (reference lesion). PATIENTS & METHODS: The data of two prospective Swiss breast cancer databases covering a 20-year period (1990-2009) was reviewed. Forty-six cases of SBBC were identified. In 34 patients with early-stage SBBC, the reference lesions (defined as the tumor with the more advanced stage or, in cases where both tumors had the same stage, the larger tumor) were compared in a case-control approach with 100 patients having UBC (SBBC/UBC ratio = 1/3). The controls were matched for age, time of diagnosis, tumor size, axillary node status, histological grade and estrogen-receptor status. Differences in terms of survival curves were analyzed using the log rank test; the possible correlation between matched groups was evaluated by a frailty Cox model. RESULTS: There were no significant differences in disease-specific survival between SBBC and its unilateral controls (HR, 0.932; 95% CI, 0.322-1.07; p = 0.90). CONCLUSIONS: The prognosis of SBBC was determined by the reference lesion; the contralateral second tumor had no additional impact on outcome.

Sentinel lymph node biopsy in primary breast cancer: trust the radiolabeled colloid method and avoid unnecessary procedures.

BACKGROUND: With regard to the sentinel lymph node (SLN) procedure in breast cancer, the study analyzed the impact of discrepancies between the number of clinically and histologically identified SLN, the impact of removing additional non-hot/non-blue but clinically conspicuous lymph nodes (LN), and whether the application of blue dye for mapping is necessary. METHODS: We analyzed 391 SLN procedures in which 928 SLN were removed. In all cases, radiolabeled colloid and blue dye were used for SLN mapping. RESULTS: In 60 cases (15.3%), additional LN that were not identified by the surgeon were found by histological examination. In 22 cases (5.3%), tissue which clinically resembled an SLN but was histologically connective tissue, was removed. In 76 cases (19.4%), 133 non-hot/non-blue but clinically conspicuous LN were removed. These additionally removed LN, however, did not alter the axillary staging. In 50.8% of the cases (n = 471), the SLN were marked only by radiolabeled colloid. In 27 cases (2.9%), the surgeon identified the LN through blue coloration alone; however, in all of the latter cases, these SLN were not deciding for axillary staging. CONCLUSION: The mapping agents may accumulate in axillary tissue and mimic the existence of an SLN. The radiolabeled colloid method alone gives excellent mapping results. The additional application of blue dye is avoidable. Exact surgical preparation enables removal of the SLN only and avoids removal of LN-containing adjacent tissue. The removal of further clinically identifiable enlarged non-hot LN should only be done if there is strong suspicion of metastatic involvement.

[Futility: a concept in routine surgery?]. / Futility: ein Begriff im chirurgischen Alltag?

In surgical practice we are often confronted with ethically challenging situations when treating patients not capable of expressing their own wishes. Issues of futile treatment by indicating operations arise particularly with regard to severe dementia. The concept of futility describes forms of therapy which are not appropriate to improve the patient's condition, but for application in clinical practice the concept is insufficiently defined.In ethically challenging situations, e.g. in the treatment of severely demented patients, we need to balance the medical condition and prognosis with the documented or assumed wishes of the patients. Involving the relatives competently is essential. The indication for surgery in patients with severe dementia, for example, needs to be individualized striving for optimal care, a clear communication about treatment goals with the relatives and preventing distress and burnout for staff. Co-operation with specialists in medical ethics is recommended.

Impact of concomitant thyroid pathology on preoperative workup for primary hyperparathyroidism.

BACKGROUND: The former standard surgical treatment in patients with primary hyperparathyroidism (pHPT) has been bilateral cervical exploration. New localization techniques and the possibility of intraoperative measurement of intact parathormone (iPTH) permit a focused, minimally invasive parathyroidectomy (MIP). The introduction of MIP without complete neck exploration leads to the potential risk of missing thyroid pathology. The aim of the present study is to evaluate the value of MIP in respect to coexisting thyroid findings and their impact on preoperative workup for primary hyperparathyroidism. METHODS: This is a prospective study including 30 consecutive patients with pHPT (median age 65 years; 17 females, 13 males). In all patients preoperative localization was performed by ultrasonography and 99m Tc-MIBI scintigraphy- Intraoperative iPTH monitoring was routinely done. RESULTS: Ten patients (33%) had a concurrent thyroid finding requiring additional thyroid surgery, and two patients (7%) with negative localization results underwent bilateral neck exploration. Therefore, MIP was attempted in 18 (60%) patients. The conversion rate to a four gland exploration was 6% (1/18). The sensitivities of 99m Tc-MIBI scanning and ultrasonography were 83.3% and 76.6%, respectively. The respective accuracy rates were 83.3% and 76.6%. Of note, the combination of the two modalities did not improve the sensitivity and accuracy in our patient population. During a median follow-up of 40 months, none of the patients developed persistent or recurrent hypocalcaemia, resulting in a 100% cure rate. CONCLUSION: Coexisting thyroid pathology is relatively frequent in patients with pHPT in our region. Among patients having pHPT without any thyroid pathology, the adenoma localization is correct with either ultrasonography or 99m Tc-MIBI scintigraphy in the majority of cases. MIP with iPTH monitoring are highly successful in this group of patients and this operative technique should be the method of choice.

Sentinel lymph node biopsy is associated with improved survival compared to level I & II axillary lymph node dissection in node negative breast cancer patients.

OBJECTIVE: The few long-term follow-up data for sentinel lymph node (SLN) negative breast cancer patients demonstrate a 5-year disease-free survival of 96-98%. It remains to be elucidated whether the more accurate SLN staging defines a more selective node negative patient group and whether this is associated with better overall and disease-free survival compared with level I & II axillary lymph node dissection (ALND). METHODS: Three-hundred and fifty-five consecutive node negative patients with early stage breast cancer (pT1 and pT2< or =3 cm, pN0/pN(SN)0) were assessed from our prospective database. Patients underwent either ALND (n=178) in 1990-1997 or SLN biopsy (n=177) in 1998-2004. All SLN were examined by step sectioning, stained with H&E and immunohistochemistry. Lymph nodes from ALND specimens were examined by standard H&E only. Neither immunohistochemistry nor step sections were performed in the analysis of ALND specimen. RESULTS: The median follow-up was 49 months in the SLN and 133 months in the ALND group. Patients in the SLN group had a significantly better disease-free (p=0.008) and overall survival (p=0.034). After adjusting for other prognostic factors in Cox proportional hazard regression analysis, SLN procedure was an independent predictor for improved disease-free (HR: 0.28, 95% CI: 0.10-0.73, p=0.009) and overall survival (HR: 0.34, 95% CI: 0.14-0.84, p=0.019). CONCLUSIONS: This is the first prospective analysis providing evidence that early stage breast cancer patients with a negative SLN have an improved disease-free and overall survival compared with node negative ALND patients. This is most likely due to a more accurate axillary staging in the SLN group.

[No ordinary anal fistula...]. / Keine gewöhnliche perianale Fistel...

We present the case of a 63 year-old male Swiss patient with chronic diarrhea, mucous anal discharge, anal fistula, chronic anal ulceration and history of tuberculosis 56 years ago. Imaging and endoscopy was highly suspicious for Crohn's Disease, but histology and culture for M. tuberculosis proved tuberculous proctitis with perianal involvement and fistulation. The consideration of extrapulmonal tuberculosis with its various manifestations is crucial for the investigation of chronic abdominal complaints in order to avoid serious consequences of tuberculosis treated with immunosuppressive therapy.

Ruptured hydatid cyst in the right thorax: differential diagnosis to pleural empyema.

We present a case of a hydatid cyst (Echinococcus granulosus) rupturing into the right pleural cavity. Clinical and radiological findings were consistent with a pleural effusion caused by pneumonia and led primarily to a wrong diagnosis. Pleural fluid analysis was suspicious for parapneumonic pleural empyema. After thoracoscopy led to the correct diagnosis a combined surgical and chemotherapy approach achieved complete remission.

[Injection site abscesses in intravenous drug users. Frequency of associated complications related to localisation]. / Spritzenabszesse bei intravenös Drogenabhängigen. Häufigkeit assoziierter Komplikationen in Abhängigkeit der Lokalisation.

BACKGROUND: Skin and soft tissue infections are the most frequent cause of hospital admissions among intravenous drug users. Associated complications include septic arthritis, septic thrombosis and embolisation, peripheral ischaemia due to intra-arterial injections, venous and arterial pseudoaneurysms, local destruction of adjacent structures, and necrotising fasciitis. METHODS: We conducted a retrospective review of the associated complications of 85 patients with 130 abscesses treated during 108 hospital stays. RESULTS: The majority of abscesses (55%) were located on the lower extremities, where the complication rate following injections was significantly higher than in other parts of the body (12/71 vs 0/55, P=0.0005). Patients with abscesses on the lower extremities had significantly longer hospital stay than those with abscesses on other localisations (8.5 days vs 4.2 days, P=0.0005) and therefore were more expensive to treat. CONCLUSIONS: Surgeons treating abscesses caused by intravenous drug use must be aware of the higher rate of associated complications after injection in the lower extremities. Prevention in drug addiction programs could reduce complications and costs related to drug use by avoiding injection sites on the lower extremities.