The Problem of Diagnostic Criteria of Breast Implant Illness in Women After Breast Reconstruction: Review and Discussion of a Case.

INTRODUCTION: There has been a rising trend in the use of silicone breast implants for breast reconstructions after breast cancer treatment, as well as in the aesthetic breast procedures. A cluster of non-specific symptoms related to the presence of silicone implant has been called breast implant illness (BII). However, there are no strict criteria of BII which would specifically define this term. The increasing interest in BII among patients and physicians urges verifying own cases of "on-demand" explantations. MATERIAL AND METHODS: In this paper, we discussed a case of a patient with initial BII diagnosis, after breast reconstruction, and reviewed the literature on the BII symptoms and aetiology. A decision for aesthetic revision, not explantation, was made as the diagnosis of BII was questioned, and somatisation due to dissatisfaction with the aesthetic result of breast reconstruction was diagnosed. RESULTS: Improving aesthetics by implant exchange and contralateral mastopexy caused a full recovery from patient's symptoms. CONCLUSION: Based on our case, we point on the fact that BII diagnosis in patients after breast reconstruction is challenging. We suggest that while considering such a diagnosis and further proceedings, e.g. explantation, especially in patients after breast reconstruction, some exclusion criteria should be considered. Dissatisfaction with the result of the surgery can also lead to somatisation and the presence of real clinical symptoms, which should not be confused with the possible autoimmune reaction to silicone particles. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

SMAC protein expression as a potent favorable prognostic factor in locally advanced breast cancer.

Preoperative systemic therapy including neoadjuvant chemotherapy (NCT) is standard treatment in locally advanced breast cancer (LABC), the aim of which is to enable a radical surgery and to reduce the risk of local and distant recurrence. It has been established that NCT in LABC may effectively induce apoptosis. The study objective was to assess the role of a proapoptotic second mitochondria-derived activator of apoptosis (SMAC) in LABC. The study group comprised 56 patients with advanced non-metastatic breast cancer (stage IIB -node positive and III), who received NCT followed by surgery and adjuvant treatment. Expression of SMAC protein was analysed using the immunohistochemistry technique in core biopsies sampled from the patients' breasts before NCT and in surgical specimens collected after completion of NCT. Expression of SMAC was significantly higher in the breast cancer specimens after NCT (p < 0.01). High expression of SMAC in the core biopsy before NCT correlated with a pathological complete remission (pCR, p < 0.01). The patients with a high expression of SMAC in the surgical specimens after NCT had longer DFS. Our study proves a potential role of SMAC expression in LABC as a novel favourable prognostic factor in LABC for pCR and disease-free survival (DFS).

Molecular characterization and patient outcome of melanoma nodal metastases and an unknown primary site.

BACKGROUND: Melanoma of unknown primary site (MUP) is not a completely understood entity with nodal metastases as the most common first clinical manifestation. The aim of this multicentric study was to assess frequency and type of oncogenic BRAF/NRAS/KIT mutations in MUP with clinically detected nodal metastases in relation to clinicopathologic features and outcome. MATERIALS AND METHODS: We analyzed series of 103 MUP patients (period: 1992-2010) after therapeutic lymphadenectomy (LND): 40 axillary, 47 groin, 16 cervical, none treated with BRAF inhibitors. We performed molecular characterization of BRAF/NRAS/KIT mutational status in nodal metastases using direct sequencing of respective coding sequences. Median follow-up time was 53 months. RESULTS: BRAF mutations were detected in 55 cases (53 %) (51 V600E, 93 %; 4 others, 7 %), and mutually exclusive NRAS mutations were found in 14 cases (14 %) (7 p.Q61R, 4 p.Q61K, 2 p.Q61H, 1 p.Q13R). We have not detected any mutations in KIT. The 5-year overall survival (OS) was 34 %; median was 24 months. We have not found significant correlation between mutational status (BRAF/NRAS) and OS; however, for BRAF or NRAS mutated melanomas we observed significantly shorter disease-free survival (DFS) when compared with wild-type melanoma patients (p = .04; 5-year DFS, 18 vs 19 vs 31 %, respectively). The most important factor influencing OS was number of metastatic lymph nodes >1 (p = .03). CONCLUSIONS: Our large study on molecular characterization of MUP with nodal metastases showed that MUPs had molecular features similar to sporadic non-chronic-sun-damaged melanomas. BRAF/NRAS mutational status had negative impact on DFS in this group of patients. These observations might have potential implication for molecular-targeted therapy in MUPs.

Prognostic value of XIAP and survivin expression in locally advanced breast cancer patients treated with anthracycline-based neoadjuvant chemotherapy.

Introduction: Neoadjuvant treatment in locally advanced breast cancer (LABC) is intended to decrease the cancer mass, increase the likelihood of radical resection and improve survival. Resistance to chemotherapy may depend on cellular expression of anti-apoptotic proteins. XIAP and survivin are the most potent inhibitors of apoptosis (IAP), but their role in drug-induced cancer cell apoptosis remains unclear. This study was designed to evaluate the impact of pre-treatment expression of XIAP and survivin on pathological complete response and survival in LABC patients. Material and methods: The study included 60 LABC patients treated with anthracycline-based chemotherapy. XIAP and survivin expression was assessed immunohistochemically in pre-treatment core biopsy specimens. Results: Pathological complete response was achieved in 33% of the LABC patients. Low/intermediate expression of both XIAP and survivin was significantly associated with pathological complete response (p ≤ 0.04 and p < 0.001, respectively) and positively correlated with disease-free survival (p = 0.017 and p < 0.001) and overall survival (p = 0.052 and p < 0.001). The area under receiver operating characteristics curves (AUC) revealed predictive value of survivin expression for relapse and death in breast cancer patients (AUC = 0.63, p = 0.001 and AUC = 0.8, p < 0.001, respectively). Conclusions: Our findings suggest that downregulation of XIAP and survivin in LABC patients might predict better treatment outcomes after anthracycline-based chemotherapy. This, in turn, may indicate XIAP and survivin proteins as potential targets for innovative anticancer therapies.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) in Poland: analysis of patient series and practical guidelines for breast surgeons.

Introduction: Although breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is infrequent, with less than 1000 noted cases worldwide, patients consenting for breast implant surgery should be aware of its risk. We describe the first Polish multicenter case-series data on BIA-ALCL patients and present diagnostic and treatment recommendation for breast surgeons. Material and methods: In cooperation with the Polish Society of Surgical Oncology and Polish Lymphoma Research Group, we collected BIA-ALCL cases in Poland. Results: We retrospectively reviewed clinical data of seven BIA-ALCL patients, diagnosed between July 2013 and November 2019. The median time from implant placement to the first BIA-ALCL symptoms was 65 months (range: 33-96 months). All the patients were exposed to textured implants at presentation. Capsulectomy with implant removal was performed in all the patients with immediate reimplantation in 2 cases. In a median follow-up of 19 months (range 5-81 months), there was no recurrence and all the patients stayed alive. Between 2013 and 2019, the incidence of BIA-ALCL in Polish female population age 30 and above ranged from 0 to 0.021/100 000/year. Conclusions: BIA-ALCL is scarce in the Polish population. In a short-term follow-up, patients' prognosis remains excellent. Due to the withdrawal of roughly textured implants from the market and the exclusion of likely the most potent etiologic factor, it might be expected that the incidence of BIA-ALCL will become even rarer.

[Influence of antidepressant pharmacotherapy on the course of cancer]. / Wplyw farmakoterapii przeciwdepresyjnej na przebieg choroby nowotworowej.

The coexistence of two or more diseases in one patient, especially in old age, is a common situation. The problem of drug effects, specifically speaking, their interaction and impact on the second condition still remains not fully explored and thus is very interesting. At the same time, it is commonly known that depression and cancer are some of the most frequently met disorders and following the WHO forecasts, their prevalence will constantly increase. In addition, it is worth noting that both the psychological and physical health of the patient suffering from cancer, are essential for proper co-operation, especially when it comes to adoption of recommended drugs. The case is aggravated by the fact that no standards of conduct in case of coexistence of the two diseases have been established and the results of research are very often contradictory. Therefore the issue discussed in this study seems to be very important and still valid. In this monograph the problem of the influence of antidepressant pharmacotherapy on the course of disease will be presented.

Modern Breast Cancer Surgery 1st Central-Eastern European Professional Consensus Statement on Breast Cancer.

This text is based on the recommendations accepted by the 4th Hungarian Consensus Conference on Breast Cancer, modified on the basis of the international consultation and conference within the frames of the Central-Eastern European Academy of Oncology. The recommendations cover non-operative, intraoperative and postoperative diagnostics, determination of prognostic and predictive markers and the content of cytology and histology reports. Furthermore, they address some specific issues such as the current status of multigene molecular markers, the role of pathologists in clinical trials and prerequisites for their involvement, and some remarks about the future.

Operating room environment assessment and biofilm risk for breast implants. A case series.

AIM: Breast implant-associated anaplastic large cell lymphoma, is a rare cancer. Several theories are speculated that may constitute its etiological factors. None of them has been clearly proven. The case report we present is intended to indicate the leading cause of this disease entity. CASE PRESENTATION: Air samples taken in varying conditions at appropriate intervals by the MicroFlow Alfa 90 device in the operating room during five breast implant surgery were analyzed. Samples were taken four times during each operation. After the air was taken and delivered to the laboratory, the plates were immediately incubated under aerobic conditions. The incubation was carried out for up to 7 days. It has been shown that there is a significant difference between the total number of microorganisms during air intake carried out without and with the supply of air to purify the area in a given area by air recirculation of the operating block and cleaning it from bacteria and particles. No air colony-forming units were grown from air samples taken in the supply. However, from air samples taken without blowing, they were raised in various quantities. CONCLUSION: Laminar free airflow used in operating room conditions significantly reduces the risk of infection of the surgical site, and thus may reduce the risk of developing breast implant-associated anaplastic large cell lymphoma. KEY WORDS: BIA-ALCL ethiological factors, Biofilm, Breast implants, Laminar air flow, Surgical site infections.

The role of NF-κB and Smac/DIABLO proteins in the treatment response and survival of acute myeloid leukemia patients.

INTRODUCTION: The misbalance between a family of inhibitor of apoptosis proteins (IAP), regulated by the nuclear factor kappa B (NF-κB) and their natural antagonist second mitochondrial-derived activator of caspases/direct IAP binding protein with low pI (Smac/DIABLO) are important to biology of acute myeloid leukemia (AML). MATERIAL AND METHODS: The aim of the study was to assess NF-κB and Smac/DIABLO proteins expression in blasts of 109 newly diagnosed AML patients using the multicolor flow cytometry and evaluate their influence on AML patients outcome. RESULTS: Expression of NF-κB and of Smac/DIABLO proteins were found in 95% and 98% of the patients, respectively. A negative correlation between Smac/DIABLO and NF-κB was observed. Age < 60 years old as well as higher Smac/DIABLO expression were associated with a higher probability of complete response achievement in the multivariate analysis. Longer overall survival (OS) in the univariate and multivariate analyses was influenced by age < 60 years old, a favorable or intermediate-risk karyotype and high Smac/DIABLO expression. Additionally, in the survival analysis of the subgroups, the patients aged < 60 years old, with high Smac/DIABLO expression, lower NF-κB expression and < 50% of bone marrow blasts who were treated with standard treatment had better OS. CONCLUSIONS: Lower NF-κB and higher Smac/DIABLO expression may influence AML patients outcome.

94% accuracy of intraoperative imprint touch cytology of sentinel nodes in skin melanoma patients.

UNLABELLED: The aim of the present study was to assess whether the reliability of imprint touch cytology (ITC) of sentinel nodes in skin melanoma patients allows intraoperative decisions regarding simultaneous radical lymphadenectomy to be made. PATIENTS AND METHODS: The results of ITC of sentinel nodes were compared with the results of standard histopathological and immunohistochemical examinations. RESULTS: A total of 148 sentinel nodes were identified in 98 lymph node groups in 85 skin melanoma patients. ITC revealed the presence of metastases in 7 out of 16 melanoma-positive sentinel nodes (sensitivity, 43.7%). There were no false-positive results of ITC of sentinel nodes (specificity, 100%). The negative predictive value of ITC was 93.6%, the positive predictive value was 100%, and the accuracy of the method was 93.9%. CONCLUSION: ITC of sentinel nodes is a reliable method. There was no risk of overtreatment due to false-positive results of sentinel node ITC in our study. High accuracy of the method warrants its clinical use.

Recurrence of cholangiogenous carcinoma in port-sites two years after laparoscopic removal of noncancerous gallbladder.

We present a unique case of carcinoma diagnosed in port-site, two years after uncomplicated laparoscopic cholecystectomy for benign cholecystitis. Analysis of morphology and cytokeratin profile (CK19+ and CK20+/-) of resected port-site tumor allows us to establish the diagnosis of tubular carcinoma with probable cholangiogenic origin. The primary carcinoma was not diagnosed in archival gallbladder tissue, despite repeated histological examination. No other primary tumor was identified during follow-up. Patient history and histological/immunohistochemical picture of the recurrent tumor suggested that primary carcinoma was probably located in the gallbladder, but was not detected during initial and repeated histological examinations of postoperative specimen. The patient is still alive, 12 months after the first port-site recurrence and 36 months after initial laparoscopy.

Ex vivo search for sentinel node in postmastectomy specimens: should we use a transverse incision for mastectomy?

BACKGROUND: According to the concept of sentinel node (SN), the lymphatic pathway leading to SN should be regarded as the main and the most important lymphatic route from primary tumor to regional lymph nodes. We performed ex vivo blue-dye SN mapping in postmastectomy specimens to assess whether the main lymphatic tract leading to SN is completely removed during mastectomy. We assumed that ex vivo identification of SN may be possible only if the entire lymphatic tract leading to sentinel node is removed from within the postmastectomy specimen. METHODS: Blue dye (1 mL) was injected intracutaenously, periareolary into each of 28 postmastectomy specimens. In 13 cases mastectomy was performed with the use of transverse skin incision; in 15 cases oblique incision was used. RESULTS: The use of transverse skin incision during modified radical mastectomy allowed identification of the sentinel node and removal of the entire lymphatic pathway leading to sentinel node only in 4 of 15 cases (31%). Conversely, the use of oblique skin incision during modified radical mastectomy allowed identification of the sentinel node and removal of the entire lymphatic pathway leading to sentinel node in 12 of 15 cases (80%). CONCLUSIONS: Our experiment revealed that the use of transverse skin incision during modified radical mastectomy may not be the best choice for breast cancer patients. In our opinion, this observation may be especially important for patients not irradiated postoperatively.

The first description of sentinel node biopsy in a patient with amelanotic melanoma of the glans penis.

We present the first description of sentinel node biopsy in a patient with amelanotic melanoma of the glans penis. The patient underwent partial amputation of the penis due to tumor of the glans. Pathologic examination of the postoperative specimen revealed the presence of a very rare malignancy--amelanotic melanoma. Sentinel node biopsy, with the use of the combined radiotracer/blue dye technique, was performed. Preoperative lymphoscintigraphy was performed the day before surgery. During surgery, blue dye mapping and intraoperative detection of gamma radiation were used. Two sentinel nodes were identified in the left inguinal region and one sentinel node in the right inguinal region. All sentinel nodes were an intense violet color; in each case, the level of radiation in the sentinel node was almost 20 times higher than the level of radiation in the node bed. Routine hematoxylin and eosin staining and immunohistochemistry (HMB-45) revealed the presence of micrometastasis in one of the sentinel nodes harvested from the left inguinal region. Consequently, left inguinal, iliac and obturatory lymphadenectomies were performed. The final pathologic examination revealed the presence of one metastasis (diameter, 2 mm) in one of the resected non-sentinel nodes. No relapse has been observed during 18 months of follow-up.

Diagnostic Imaging Efficacy In Metastases From Unknown Primary Site--Own Material.

UNLABELLED: Cancer of Unknown Primary Origin (CUPO) is defined by the presence of metastatic lesions, diagnosed by means of cytological or pathological evaluation, for which no primary site can be detected during a thorough examination. The clinical investigation, directed at locating the site of the neoplastic lesion, is determined by the results of laboratory tests, imaging procedures, and pathological examinations. It is also essential to conduct a complete medical history and thorough physical examination. The detection of the primary site allowed to introduce specific therapy, which can offer clinical benefits, considering a favorable prognosis. The aim of the study was to assess the range of diagnostic procedures performed in patients with CUPO and efficacy in identifying the primary lesion. MATERIAL AND METHODS: Retrospective analysis comprised a group of 29 patients with CUPO, operated between January, 2002 and December, 2011, at the Department of Surgical Oncology, Medical University in Lódz. The study group comprised 16 male and 13 female patients; median age at presentation was 58.3 years (ranging between 30-79 years). RESULTS: Detailed diagnostic management depending on the location of metastatic lesions and their histological type was performed in 20 of the 29 study patients (69%). Considering the remaining 9 (31%) patients detailed diagnostics was not performed, due to the patients' poor general condition. In 55% (11/20) of patients subject to detailed diagnostics, the primary neoplastic lesion was determined. CONCLUSIONS: Considering the study group, most patients with cancer of unknown primary origin were characterized by a favorable prognosis, which justified thorough diagnostics, in order to establish the primary neoplastic lesion. The introduction of diagnostic examinations enabled to identify the primary site of the tumor in more than 50% of patients. With the development of imaging methods one can expect improvement of unsatisfactory results, considering the detection of primary neoplastic foci.

Prognostic value of inhibitor of apoptosis protein family expression in patients with acute myeloid leukemia.

The inhibitor of apoptosis protein (IAP) family acts as an inhibitor of apoptosis pathways. The potential prognostic value of the expression of selected IAP family members, XIAP, cIAP-1, cIAP-2 and survivin protein, was evaluated with regard to treatment response and survival of 56 newly diagnosed adult patients with acute myeloid leukemia (AML). The presence of these IAP members influenced the achievement of a complete response (CR). In addition, overall survival (OS) was influenced by low survivin expression in univariate and multivariate analysis (p = 0.014 and p = 0.013, respectively). A strong correlation was observed between members of the IAP family (XIAP and cIAP-1, XIAP and cIAP-2, cIAP-1 and cIAP-2, p < 0.001 for all comparisons), while Smac/DIABLO demonstrated an inverse correlation with XIAP, cIAP-1 and cIAP-2 (p < 0.001 for all comparisons). Further studies should be undertaken to better demonstrate the mode of action of IAP members, as well as their prognostic and therapeutic potentials.

Significance of Bax expression in breast cancer patients.

UNLABELLED: Bax protein, the proapoptotic member of Bcl-2 protein family, plays the key role in apoptosis pathway. THE AIM OF THE STUDY was to assess the expression of Bax protein in breast cancer cells. MATERIAL AND METHODS: Sixty-two breast cancer patients were included in the study. The control group encompassed 11 fibroadenoma patients. Single cells were isolated from defrosted samples and prepared for flow cytometry measurement. RESULTS: Median expression of Bax protein in study group was 7.9% (range: 0-49.4%) and was significantly lower than in control (median expression 15.8%; range 4.9-30.9%; p=0.034). Expression of Bax correlated with expression of p53 and caspase-3 proteins (p<0.01, rank Spearman test). In patients under 70 years old and with positive estrogen receptors status the expression of Bax protein was significantly higher (p=0.03 and p=0.01 respectively). CONCLUSIONS: Lower expression of Bax protein in breast cancer cells may suggest the potential way of apoptosis avoidance of tumor cells. Correlations among Bax protein, p53 and caspase-3 are likely associated with active apoptotic mechanism in breast cancer cells expressing Bax protein. Further investigation with long time follow-up should be performed to establish the prognostic role of Bax protein expression in breast cancer patients.

TRAIL protein expression in breast cancer cells correlates with nuclear grade.

INTRODUCTION: TRAIL protein may serve as an escape mechanism for cancer cells from the immune response. The aim of the study was to assess whether the presence of TRAIL protein correlates with unfavourable prognostic factors in breast carcinoma. MATERIAL AND METHODS: The study group was composed of breast cancer patients treated surgically in the Department of Surgical Oncology, Medical University of Lodz, Poland, from January to December 2003. Inclusion criteria for the study were fulfilled by 117 women. The immunohistochemical study of TRAIL protein expression was performed in 118 breast carcinomas diagnosed in the study group. TRAIL protein expression was correlated with other variables: tumour size, lymph node status, grade, histological type of carcinoma, oestrogen and progesterone receptor status, HER2 expression, presence of lymphovascular invasion and age of the patient. RESULTS: Expression of TRAIL protein was present in 73% of breast carcinomas. The percentage of TRAIL-expressing breast carcinoma cells correlated with the nuclear grade (τ = 0.26, p < 0.05; Tau Kendall test). The intensity of TRAIL expression (intensity of staining) in breast carcinoma cells correlated with the nuclear grade (τ = 0.15, p < 0.05; Tau Kendall test). TRAIL expression in breast carcinoma did not correlate with other studied variables. CONCLUSIONS: Our analysis revealed that expression of TRAIL protein in breast carcinoma cells correlates with nuclear grade of carcinoma.

Long-term survival of endometrioid endometrial cancer patients.

INTRODUCTION: To establish risk factors for onset and progression of endometrioid endometrial cancer still remains the aim of scientists. The aim of the study was to determine disease-free survival (DFS) and overall survival (OS) in women with endometrioid endometrial cancer. MATERIAL AND METHODS: A retrospective review of 142 patients with endometrioid endometrial cancer after surgery treated with adjuvant radiotherapy and/or chemotherapy in the Regional Cancer Centre in Lodz between 2002 and 2004 was performed. Clinical and pathological data were correlated with clinical outcome and survival. RESULTS: In 3 patients (2.1%) clinical progression was diagnosed during the treatment. In 23 patients (16.7%) after primary remission, relapse was diagnosed 2-56 months after treatment. DFS and OS were 81.7% and 83.1% respectively. Better DFS significantly correlated with larger number of pregnancies (> 1), stage I of the disease and optimal surgery. Lower stage of disease, pelvic lymph node dissection, optimal surgery and depth of myometrial infiltration ≤ 50% were independent prognostic factors for better OS. CONCLUSIONS: The results of our study provided significant evidence that early detection of endometrioid endometrial cancer enables optimal surgery. It reduces the indications for adjuvant therapy in stage I of the disease, and makes the prognosis significantly better. Other clinical and pathological factors such as numerous pregnancies, pelvic lymphadenectomy, and depth of myometrial infiltration, although important, are of less significance. Further prospective, randomized studies are necessary to prove the role of these factors.

Influence of high expression of Smac/DIABLO protein on the clinical outcome in acute myeloid leukemia patients.

The role of the Smac/DIABLO protein, a novel apoptosis agonist, in acute myeloid leukemia (AML) is not clearly determined. The expression of Smac/DIABLO protein in AML leukemic cells and its relationship with clinical outcome was evaluated in this study. The intracellular expression of Smac/DIABLO protein was assessed using multi-color flow cytometry in 71 newly diagnosed AML patients treated with conventional chemotherapy. It was found that the high expression of Smac/DIABLO protein was an independent prognostic factor in terms of higher complete remission rate (p<0.001) and longer overall survival (p=0.003). Moreover the low expression of Smac/DIABLO protein was associated with poor karyotype.