The Multifaceted Role of Confocal Laser Endomicroscopy in Head and Neck Surgery: Oncologic and Functional Insights.

(1) Background: Confocal laser endomicroscopy (CLE) has emerged as a transformative tool in head and neck surgery, with applications spanning oncologic insights and functional evaluations. This study delves into CLE's potential in these domains. (2) Methods: We performed CLE in head and neck oncologic surgery, focusing on tumor margin identification and precise resection. We also employed CLE for functional assessment in allergic rhinitis, observing real-time mucosal changes during nasal provocation testing. (3) Results: In oncologic surgery, CLE enabled real-time visualization of tumor margins and cellular patterns, aiding resection decisions. In allergic rhinitis assessment, CLE captured dynamic morphological alterations upon allergen exposure, enhancing understanding of mucosal reactions. (4) Conclusions: The integration of CLE with evolving technologies such as deep learning and AI holds promise for enhanced diagnostic accuracy. This study underscores CLE's expansive potential, highlighting its role in guiding surgical choices and illuminating inflammatory processes in the head and neck.

EVI1 expression in early-stage breast cancer patients treated with neoadjuvant chemotherapy.

BACKGROUND: Overexpression of the EVI1 (ecotropic viral integration site 1) oncogene has recently been implicated as a prognostic factor in breast cancer (BC), particularly in triple-negative BC (TNBC). In this study we aimed to investigate frequency and clinical relevance of EVI1 expression in newly diagnosed BC treated with neoadjuvant chemotherapy. METHODS: EVI1 expression was determined by immunohistochemistry using H-score as a cumulative measurement of protein expression in pretherapeutic biopsies of BC patients treated with anthracycline/taxane based neoadjuvant chemotherapy within the GeparTrio trial. EVI1 was analyzed as a continuous variable and dichotomized into low or high based on median expression. Endpoints were pathological complete response (pCR), disease-free survival (DFS) and overall survival (OS). RESULTS: Of the 993 tumors analyzed, 882 had available subtype information: 50.8% were HR + /HER2-, 15% HR + /HER2 + , 9.8% HR-/HER2 + , and 24.5% TNBC. Median EVI1 H-score was 112.16 (range 0.5-291.4). High EVI1 expression was significantly associated with smaller tumor size (p = 0.002) but not with BC subtype. Elevated EVI1 levels were not significantly associated with therapy response and survival in the entire cohort or within BC subtypes. However, TNBC patients with high EVI1 showed a trend towards increased pCR rates compared to low group (37.7% vs 27.5%, p = 0.114; odds ratio 1.60 (95%CI 0.90-2.85, p = 0.110) and numerically better DFS (HR = 0.77 [95%CI 0.48-1.23], log-rank p = 0.271) and OS (HR = 0.76 [95% 0.44-1.31], log-rank p = 0.314) without reaching statistical significance. CONCLUSION: EVI1 was not associated with response to neoadjuvant therapy or patient survival in the overall cohort. Further analyses are needed to verify our findings especially in the pathological work-up of early-stage HER2-negative BC patients. TRIAL REGISTRATION: NCT00544765.

Assessing and Evaluating the Scope and Constraints of Idylla Molecular Assays by Using Different Source Materials in Routine Diagnostic Settings.

For cancer treatment, diagnostics concerning tumor type and determination of molecular markers in short TAT is critical. The fully automated, real-time PCR-based molecular diagnostic Idylla assays are well established in many laboratories for qualitative detection, short TAT and routine screening of clinically relevant oncogenic mutations. According to the manufacturer, all IVD assays are recommended for use only with FFPE tissue samples of 5-10 µM dissections with at least 10% tumor content. In this study, we tested the performance and accuracy of the IVD assays along with the gene fusion assay (RUO) with different tissue/source materials like isolated DNA/RNA, cryomaterial, etc. The study also included testing archival FFPE tissue sections dating back from 20 years and a performance check for different pan-cancer samples individually. All the assays tested with FFPE sections and gDNA/RNA input showed above 96% accuracy and sensitivity, individually with 100% specificity. The Idylla assays also performed exceptionally well on the archival FFPE tissues, and the use of assays for other solid tumors was also remarkable. The performance test and accuracy of Idylla assays showed high efficiency with certain limitations. For the use of Idylla assays, both qualitative and quantitative applicability of different tumor source materials could produce efficient results in different diagnostic settings within a short TAT.

Status quo of ALK testing in lung cancer: results of an EQA scheme based on in-situ hybridization, immunohistochemistry, and RNA/DNA sequencing.

With this external quality assessment (EQA) scheme, we aim to investigate the diagnostic performance of the currently available methods for the detection of ALK alterations in non-small cell lung cancer on a national scale, namely, in situ hybridization (ISH), immunohistochemistry (IHC), and RNA/DNA sequencing (NGS). The EQA scheme cohort consisted of ten specimens, including four ALK positive and six ALK negative samples, which were thoroughly pretested using IHC, ISH, and RNA/DNA NGS. Unstained tumor sections were provided to the 57 participants, and the results were retrieved via an online questionnaire. ISH was used by 29, IHC by 38, and RNA/DNA sequencing by 19 participants. Twenty-eight institutions (97%) passed the ring trial using ISH, 33 (87%) by using IHC, and 18 (95%) by using NGS. The highest sensitivity and interrater agreement (Fleiss ' kappa) was observed for RNA/DNA sequencing (99%, 0.975), followed by ISH (94%, 0.898) and IHC (92%, 0.888). However, the proportion of samples that were not evaluable due to bad tissue quality was also higher for RNA/DNA sequencing (4%) compared with ISH (0.7%) and IHC (0.5%). While all three methods produced reliable results between the different institutions, the highest sensitivity and concordance were observed for RNA/DNA sequencing. These findings encourage the broad implementation of this method in routine diagnostic, although the application might be limited by technical capacity, economical restrictions, and tissue quality of formalin-fixed samples.

[Interstitial lung disease associated with connective tissue disease]. / Interstitielle Lungenparenchymveränderungen bei rheumatischen Systemerkrankungen.

Interstitial lung disease (ILD) is the most frequent organ manifestation in rheumatic autoimmune disease. Depending on the underlying autoimmune disease, differently pronounced affections of small airways, interstitial parenchyma, and vessels are found. The group of rheumatic autoimmune diseases mainly includes connective tissue diseases (CTDs), also known as collagen vascular diseases, such as rheumatoid arthritis (RA), systemic sclerosis, (SSc), systemic lupus erythematosus, primary Sjögren's syndrome, idiopathic inflammatory myositis (IIM), and interstitial pneumonia with autoimmune features (IPAF). Frequency and manifestations of parenchymal lung disorders are described clinically, radiologically, and morphologically in these entities. For the precise diagnosis and for the differentiation between the wide range of parenchymal disorders with known possible cause or with unknown origin, also called unclassifiable or idiopathic interstitial pneumonias (IIPs), high resolution computed tomography (HRCT) findings represent the diagnostic gold standard. A transbronchial biopsy, surgical biopsy, or cryobiopsy will be used in unclassifiable findings to confirm a definitive histological confirmation. A precise diagnosis of these ILDs is crucial since the different pathologies that encompass ILD have different therapeutic options. In this sense, the participation of a pneumologist, rheumatologist, radiologist, and pathologist become essential in the multidisciplinary evolution of ILD.

Dataset on patients with Recurrent Borderline Ovarian Tumors and Table with Review of Literature on Fertility and Oncologic Outcomes of patients with Borderline Ovarian Tumors.

The data presented here is related to the research article entitled "FERTILITY-SPARING SURGERY AND REPRODUCTIVE-OUTCOMES IN PATIENTS WITH BORDERLINE OVARIAN TUMORS" by Plett et al. in Journal of Gynecologic Oncology [1] and is analysed and discussed in detail. 18 Patients with Recurrent Borderline Ovarian Tumors (BOT) were identified and listed in Table 1. All patients underwent treatment for primary BOT either per radical surgery (RS) or fertility sparing surgery (FSS) by the same team in Horst Schmidt Klinik (HSK) in Wiesbaden and the Department of Gynecology and Gynecologic Oncology at Kliniken Essen-Mitte between January 2000 and December 2018 and were followed up closely. Details on patients` and surgical characteristics are given as well as management of character of recurrent disease. In Table 2 important publications from the last 20 years are listed in order to visualize better the oncologic outcomes (invasive and non-invasive relapses) and calculated risks of recurrence with the purpose to understand better the important findings of the related article cited above.

Fertility-sparing surgery and reproductive-outcomes in patients with borderline ovarian tumors.

BACKGROUND: Borderline ovarian tumors (BOT) are considered a biological category with increased epithelial proliferation and cellular atypia in the absence of invasive growth. Since BOT occur often in young patients fertility sparing surgery (FSS) is an important issue. With this study we aimed to evaluate risk factors for relapses and fertility of patients after FSS. METHODS: Patients diagnosed with BOT and treated between 2000 and 2018 were included. External pathological review was done in all patients. FSS was performed after individual discussion and a complete surgical staging according to FIGO, without lymphadenectomy and with a waiver for preservation of uterus and one ovary. RESULTS: Among 352 Patients 80.2% had FIGO I and 63.9% had a serous BOT. Eighteen patients (5.1%) relapsed and 4 cases of malignant transformation were reported (1.1%). One patient of the latter died, all others have no evidence of disease. The overall recurrence-rate was 1.1% in FIGO-Stage I and 25.5% in FIGO III-IV (HR = 27; 95%-CI 7.7-95; p ≤.001). 95 patients underwent FSS. Thirteen (13.7%) of these patients relapsed, all as BOT. In multivariate analysis FIGO stages II-IV (HR = 27; 95%-CI: 8.1-102; p ≤.001) and FSS (HR = 12; 95%-CI: 2.9-47; p = .001) remained significant risk factors for recurrent disease. Pregnancy rate among forty-one patients attempting to conceive was 82.9%. 29 patients experienced at least one life-birth, in total 38 life-births were reported. CONCLUSION: FSS in stage I is a safe procedure and life-birth-rates after FSS are high. More advanced FIGO stages have to be discussed individually and relapse rates have to be weighed against FSS. A central review of pathology, as we performed routinely, is mandatory and may have contributed to our low rate of invasive relapses.

Impact of Nuclear Oestrogen Receptor Beta Expression in Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy.

Introduction Oestrogen receptor beta (ER-ß) is abundantly expressed in breast cancer (BC), but its impact on neoadjuvant chemotherapy outcome is unknown. Patients and Methods Patients treated in the neoadjuvant GeparTrio trial with available tissue for immunohistochemical analyses were included. Nuclear ER-ß expression was correlated with clinico-pathologic characteristics. The impact of its expression on pathological complete response (pCR [ypT0/ypN0]) and survival was determined. Results Samples of 570 patients were available. Low nuclear ER-ß expression (IRS < 9) was observed in 48.4% of hormone receptor positive and 58.6% of hormone receptor negative tumours. Low nuclear ER-ß expression was associated with higher pCR rates compared to high nuclear ER-ß expression (16.1% vs. 4.7%, p = 0.026). Low ER-ß expression was no independent predictor of pCR in multivariate analyses. Disease-free and overall survival were not statistically different between patients with high and low nuclear ER-ß expression. Triple-negative BCs showed low nuclear ER-ß expression in 57.7%, and pCR rates were 27.1% and 0% (p = 0.23) in low and high ER-ß expressing tumours, respectively. Conclusion Low ER-ß expression is associated with improved pCR rates in univariate analyses. However multivariate analyses and survival analyses do not indicate an impact of ER-ß on survival in patients undergoing neoadjuvant chemotherapy. Further examination of ER-ß as predictor for endocrine therapy might be of value.

Primary signet-ring stromal tumour of the testis: case report with literature review.

Primary signet-ring stromal tumour of the testis (PSRSTT) is a very rare type of primary testicular tumour, which is not actually mentioned in the current WHO categorization of tumours of the male genital organs. In this case we report about histologically and immunohistochemically features of this rare tumour. In the present case, PSRTT was found in the orchiectomy preparation of a 69-year-old man with painless swelling of his left testicle. The tumour was well circumscribed and separated from the normal testicular tissue by a fibrous capsule. The tumour cells showed a signet-ring pattern and were separated by thin collagen bundles. No mitotic activity and necrosis were found inside the tumour. Immunohistochemically, the tumour was positive for vimentin, neuron-specific enolase (NSE), S-100 protein, ß-catenin and cyclin D1. No expression of cytokeratin, actin, SALL4, OCT3/4, and especially, inhibin and calretinin were detected. In conclusion, the presence of signet-ring cell formation can be found in different tumours of the testis. PSRSTT is a rare tumour that needs to be considered, in particular, to distinct them from other tumours with signet-ring cell pattern.

Lymph Node Retrieval is Inferior in the Modified Merendino Resection for Early Barrett's Carcinoma: A Matched-Pair Comparison with Ivor Lewis Resection.

AIM OF THE STUDY: A matched-pair comparison between the modified Merendino resection (MER) and Ivor Lewis resection (ILR) for early Barrett's carcinoma. BACKGROUND: Early adenocarcinoma of the esophagus (eACE) with positive risk factors for lymph node metastasis (LNM) needs surgery for cure. MER appeared to be an alternative to ILR. METHODS: Between July 2000 and July 2012, 156 patients with high-grade dysplasia or eACE received ILR, whereas in 30 cases MER was performed in a tertiary care center for GI Surgery. A matched-pair analysis was performed on the basis of sex, age, BMI, ASA classification and tumor stage. Thirty patients were assigned to each group. The data were analyzed regarding perioperative aspects (e.g., operating time, hospital stay, complications, number of lymph nodes) and survival analysis. RESULTS: The mean operating time was 301.7 min for ILR, compared to 255.4 min for MER (p = 0.044). The hospital stay following ILR was significantly longer than for MER (22.4 days ILR vs. 16.4 days MER, p = 0.023). There was no statistically significant difference regarding complications between the two groups (p = 0.463). The number of resected lymph nodes was significantly lower in the MER group (median 21) compared to the ILR group, where a median of 31 lymph nodes could be removed (p < 0.001). There was no statistically significant difference in overall (p = 0.145) or tumor-specific survival (p = 0.353). CONCLUSIONS: Lymph node retrieval is significantly inferior in the MER. Postoperative complication rates were comparable between the two operating techniques, although the operation time for ILR took longer and these patients required a longer hospital stay. MER should not be applied in cases with high risk of LNM.

Prognostic risk factors of early gastric cancer-a western experience.

PURPOSE: Lymph node metastasis (LNM) is the leading cause of tumor recurrence in early gastric cancer (EGC). Since endoscopic resection (ER) can be performed in EGC with curative intention when no LNM are present, this study wants to determine the risk factors for LNM in EGC. METHODS: One hundred twenty-four patients who have had an operative resection because of EGC were analyzed. Histopathological workup included tumor infiltration depth, lymphatic and vascular infiltration, lymph node infiltration, tumor differentiation, and the classification of Ming. A complete follow-up was achieved. RESULTS: There was no LNM among tumors meeting the standard or extended criteria for an ER. Lymphatic infiltration (p < 0.001) and infiltration of the submucosal layers (p = 0.018) proved to be the strongest risk factors for LNM. Tumors with a deeper infiltration depth (p = 0.015) and a lower grade of differentiation (p = 0.029) presented with a higher grade of lymphatic infiltration. Tumors located in the body of the stomach (p = 0.003) and tumors with infiltrative growth according to Ming (p = 0.021) had a significantly higher risk for lymphatic infiltration. The 5-year overall survival was 84 % in nodal negative patients and 42 % in patients with LNM (p = 0.002). CONCLUSIONS: ER within the extended criteria with a meticulous histological workup should be performed in EGC to determine whether risk factors for LNM are present. If lymphatic infiltration is observed, surgery with lymphadenectomy is recommended. Tumors exceeding the extended criteria should undergo primary surgery with adequate lymphadenectomy.

Differential miRNA-Expression as an Adjunctive Diagnostic Tool in Neuroendocrine Tumors of the Lung.

Pulmonary malignancies with neuroendocrine differentiation represent a rare subclass of lung carcinomas, which vary in the extent of differentiation and grade of biological aggressiveness. In particular, neuroendocrine tumors are classified into well differentiated typical and atypical carcinoids as well as poorly differentiated large cell neuroendocrine and small cell lung carcinomas. Tiny MicroRNAs have been identified as reliable classifiers in distinct cancer types and seem to play important roles in cellular processes like regulation of cell growth, differentiation and apoptosis. In the present study, two different microRNAs (miR-21 and miR-34a) were explored for their involvements in pathogenesis of subtypes and finally in differential diagnosis of pulmonary neuroendocrine tumors. miR-21 was upregulated in poorly differentiated neuroendocrine tumors (mean rank: 26.8; 28.75) as compared to carcinoids (mean rank: 12.33; 12.07) with a significance of 0.00033. High-expression levels of miR-34a were associated with atypical carcinoids (p = 0.010). A close association is implicated between the elevated miR-21 values in high-grade and miR-34a patterns in low-grade atypical neuroendocrine lung carcinomas, which could potentially be exploited as practical supportive markers for differential lung cancer diagnosis in routine. However, some additional extended research and validation studies are needed to utilize them as routine markers or potential molecular targets for personalized medicine.

[Rare gastroenterologic finding as a cause of hypochromic microcytic anemia]. / Seltener gastroenterologischer Befund als Ursache für eine hypochrome mikrozytäre Anämie.

CASE HISTORY: A 66-year-old woman suffering from skin paleness and weakness presented an increasing hypochromic, microcytic anemia. Diagnostic: In an ambulant setting a capsule endoscopy of the small intestine was carried out because of multiple polyps of the colon (colonoscopy) in addition to non-invasive (Hämoccult-Test) and invasive (gastroscopy) diagnostic. The patient was then admitted to hospital to clarify a suspicious ulcer of the small bowl. According to biopsies taken via balloon enteroscopy, an adenocarcinoma of the small intestine was diagnosed. THERAPY AND CLINICAL COURSE: After staging and exploratory laparotomy, histology findings showed an advanced tumour stage. A palliative chemotherapy, analogue to colon cancer treatment, was conducted. CONCLUSION: Small bowel diagnostics should be carried out if the aetiology of an anemia is not certain with an existing polyposis of the colon. Individuals with personal or family history of cumulative colorectal adenomas should undergo assessment for an adenomatous polyposis syndrom.

The frequency of lymph node metastasis in early-stage adenocarcinoma of the esophagus with incipient submucosal invasion (pT1b sm1) depending on histological risk patterns.

BACKGROUND: A prerequisite for endoscopic treatment (ET) of not only mucosal, but also submucosal early adenocarcinoma of the esophagus (EAC) would be a rate of lymph node (LN) metastasis below the mortality rate of esophagectomy (2-5%). The aim of the present study was to evaluate the rate of LN metastasis in patients with pT1b sm1 EAC. METHODS: 1996-2010, 1,718 patients with suspicion of EAC were referred to the Department of Internal Medicine II at HSK Wiesbaden. In 123/1718 patients, the suspicion (endoscopic ultrasound, EUS) or definitive diagnosis of sm1 EAC (ER/surgery) was made. Rate of LN metastasis was analyzed separately for low-risk (LR; G1-2, L0, V0) and high-risk lesions (HR; G3, L1, V1; ≥ 1 risk factor). LN metastasis was only evaluated in patients who had a proven maximum invasion depth of sm1 (ER and/or surgery), and who in case of ET had a follow-up (FU) by EUS of at least 24 months. RESULTS: Of the 72/123 patients included into the study, 49 patients had LR (68%) and 23 HR lesions (32%). In endoscopically treated LR patients (37/49), mean EUS-FU was 60 ± 30 mo (range 25-146); in HR patients undergoing ET (6/23), it was 63 ± 17 mo (46-86; p = 0.4). Mean number of resected LN was 27 ± 16 (12-62) in operated LR patients and 27 ± 10 (12-47) in HR-patients. The rate of LN metastasis was 2% in the LR (1 patient) and 9% in the HR group (2 patients; p = 0.24). Mortality of esophagectomy was 3%. CONCLUSIONS: The rate of LN metastasis in pT1b sm1 early adenocarcinoma with histological LR pattern was lower than the mortality rate of esophagectomy. ER may therefore be used alternatively to surgery in this group of patients.

Multicenter immunohistochemical ALK-testing of non-small-cell lung cancer shows high concordance after harmonization of techniques and interpretation criteria.

INTRODUCTION: Detection of anaplastic lymphoma kinase (ALK)-gene rearrangements in non-small-cell lung cancer (NSCLC) is mainly performed by fluorescence in-situ hybridization (FISH). The question was raised if FISH might be replaced by immunohistochemistry (IHC) in a reliable and reproducible manner across different laboratories. METHODS: After calibration of the staining instruments and training of the observers to binary interpretation (positive versus negative), 15 NSCLC were independently tested for ALK protein expression by IHC only in a multicenter setting (16 institutes). Each laboratory utilized the VENTANA ALK-D5F3 IHC assay. As demonstrated by FISH the samples displayed unequivocal ALK break-positivity (6×) and negativity (7×), as well as ALK positive-"borderline" character (2×), which is challenging for FISH diagnosis and thus was RT-PCR-confirmed. RESULTS: All seven ALK FISH-negative cases were homogenously scored as ALK-IHC negative. All 16 participants scored the two ALK positive-"borderline" samples as unequivocally positive according to their protein expression. Concordant IHC interpretation was also noticed in four of six unequivocal ALK break positive cases. In two of six some observers described a weak/heterogeneous ALK-IHC staining. This would have resulted in a subsequent ALK-testing (FISH/PCR) in a routine diagnostic setting. CONCLUSIONS: This so-called "ALK-Harmonization-Study" shows for the first time that predictive semiquantitative IHC reveals reliable and reproducible results across several labs when methodology and interpretation are strictly defined and the pathologists are uniquely trained. The application of validated ALK IHC assays and its comparison to ALK-FISH is highly needed in future clinical trials. This might answer the question if ALK-IHC cannot only serve as a prescreening tool, but as a stand-alone test at least in cases displaying an unequivocally staining pattern as well as an alternative predictive test in samples with reduced FISH interpretability.

Prognostic risk factors of early esophageal adenocarcinomas.

OBJECTIVE: To define prognostic risk factors in patients with early adenocarcinomas of the esophagus (eACEs) who were treated by esophagectomy. BACKGROUND: Although endoscopic resection (ER) is more accepted for eACEs limited to the mucosa, the reported prevalence of lymph node metastases once the tumor infiltrates the submucosa seems to necessitate surgery in these cases. METHODS: We analyzed the results of 168 patients who had an esophageal resection because of an eACE. On the basis of specimen histologies and clinical follow-up (median, 64 months), we investigated the influence of lymph node metastases (N+), tumor infiltration depth, tumor differentiation (G1-3), and lymphatic or venous infiltration (L+ or V+) on overall and tumor-specific survival and recurrence rates. RESULTS: The 5-year survival rate was 79%. Lymph node infiltration was the only prognostic factor for the overall survival [hazard ratio (HR), 2.856; 1.314-6.207; P = 0.008], tumor-specific survival (HR, 8.336; 2.734-25.418; P < 0.001), and tumor recurrence (HR, 8.031; 3.041-21.206; P < 0.001) that was consistently present in all multivariate hazard Cox regression analyses. A total of 47% of the patients who had an N+ status developed tumor recurrences compared with 5.2% of those who had no lymph node involvement (P = <0.001). We found a significant correlation between N+ status and increasing depth of tumor infiltration (P = 0.004), lymphatic vessel infiltration (P = 0.002), tumor differentiation (G1 + G2 vs G3; P = 0.014) and vascular infiltration (P = 0.01). CONCLUSIONS: Lymph node status is the only independent risk factor for survival and recurrence rates. Tumor infiltration depth correlates with the rate of the lymph node metastases, but a clear watershed between deep mucosal and submucosal infiltration does not exist. As a consequence, careful staging procedures, including diagnostic ER, are mandatory to determine which patients can be treated by ER and which require an esophagectomy.

Synchronous ovarian and endometrial cancer--an international multicenter case-control study.

OBJECTIVES: This study aimed to compare the prognosis of patients with synchronous endometrial and ovarian cancer (SEOC) to matched controls with either endometrial cancer (EC) or ovarian cancer (OC). METHODS: A retrospective case-control study including all patients with SEOC who had been treated at 5 European tertiary gynecologic oncology centers between 1996 and 2011 and patients with either EC or OC matched for age, International Federation of Gynecology and Obstetrics (FIGO) stage, histology, year of diagnosis, and Eastern Cooperative Oncology Group performance score. RESULTS: The study cohort comprised 77, 132, and 126 patients with SEOC, EC, and OC, respectively. The patient characteristics confirmed an equal distribution of matching factors, and the median follow-up did not differ (P = 0.44). 48.1% of the patients with SEOC showed early FIGO stage I for both EC and OC. The 5-year PFS rates differed between SEOC and EC (76.3% vs 86.3%; P = 0.047) but not the 5-year overall survival rates (71.6% vs 79.8%; P = 0.12) and did not differ between SEOC and OC (76.3% vs 63.8%; P = 0.19 and 71.6% vs 69.3%; P = 0.61, respectively). After the adjustment for the FIGO stage of the 2 components of SEOC, neither PFS nor overall survival rates were different. CONCLUSIONS: Prognosis of patients with SEOC tended to be the same in comparison with matched controls with either one EC or OC. Therefore, it could be considered that patients with SEOC may be eligible for clinical trials of the advanced tumor component if no additional therapy is indicated for the other component.

Outcome of early breast cancer treated in an urban and a rural breast cancer unit in Germany.

BACKGROUND: Conflicting evidence has been published concerning survival disadvantages in the outcome of breast cancer patients in relationship to their residency in urban or rural communities. METHODS: The primary aim of this study was to evaluate differences in patients and treatment characteristics between an urban and a rural breast cancer unit. Therefore, all early breast cancer patients treated consecutively between 1999 and 2007 in a rural and an urban breast cancer unit were included. Patient and tumor characteristics, treatment strategies, and guideline adherence were included to evaluate the prognoses of both populations. RESULTS: Overall, data from 2,566 patients were included in this analysis. The 610 patients treated in the rural unit showed significantly more negative prognostic criteria than the 1,956 patients treated in the urban center. No differences were observed with respect to surgical and systemic treatment after adjustment for prognostic parameters. Adherence to national guidelines did not differ significantly between both settings and ranged between 78.0 and 95.6%. Furthermore, no differences regarding recurrence-free and overall survival were observed. CONCLUSIONS: The stage-adjusted pattern of care was similar in 2 German breast care units in a rural region and an urban area. Nevertheless, an earlier diagnosis of breast cancer should be enforced in rural areas to avoid extended treatment burden.

pT2 Adenocarcinoma of the esophagus: early or advanced cancer?

BACKGROUND: There is an increasing trend to include patients with esophageal carcinoma invading the muscularis propria (pT2) in neoadjuvant therapy regimens. But it is unclear which patients have prognostic benefit from this strategy. The aim of this study was to assess the prognosis and prognostic factors in patients with pT2 esophageal adenocarcinoma to further optimize treatment strategies. METHODS: Included were patients with pT2 esophageal adenocarcinoma treated operatively at three centers specializing in upper gastrointestinal surgery. There were 159 patients (139 male) without induction therapy; median age was 64.5 years. Survival was analyzed by univariate and multivariate analysis. RESULTS: In 37% of patients (n = 59), no lymph node involvement (pN0) was detected. Overall 5-year survival rate for all patients was 37%; for pN0 patients it was 62%, and for patients with lymph node metastases (pN+) it was 24%. Median number of examined lymph nodes was 26. Extracapsular lymph node involvement (ELNI) was evident in 55 of 100 pN+ patients with a 5-year survival rate of 14%. Patients without ELNI had a 5-year survival rate of 36% (p = 0.041). Results were comparable in all participating hospitals. Thirty-day and 90-day mortality rates of the entire collective were 2.6% and 3.8%, respectively. Multivariate analysis of prognosis revealed the lymph node ratio (p < 0.001) and the pN-ELNI category (p = 0.005) as significant parameters (pN0 hazard ratio 1 [reference]; pN+ without ELNI hazard ratio 2.2, 95% confidence interval: 1.2 to 3.8); pN+ with ELNI hazard ratio 2.5, 95% confidence interval: 1.5 to 4.5). CONCLUSIONS: The prognosis of patients with esophageal adenocarcinoma invading the muscularis propria without lymph node metastasis is very good. However, in this study, about 30% had extracapsular lymph node involvement, which reflects particularly aggressive biological tumor behavior.

Signature of microsatellite instability, KRAS and BRAF gene mutations in German patients with locally advanced rectal adenocarcinoma before and after neoadjuvant 5-FU radiochemotherapy.

BACKGROUND: Multiple activating mutations of the signal- and repair pathway, such as BRAF-, KRAS-mutations and microsatellite instabilities are involved in colorectal cancer pathogenesis. Molecular characterization of specifically locally advanced rectal cancers is scarce. Therefore the retrospective study addresses the intratumoral status of KRAS, BRAF and microsatellites loci with respect to tumor response and patients' antecedent including nicotine abusus, familial history, and health care to further molecularly identify rectal cancer patients. METHODS: The study assesses the molecular status of 50 rectal cancer samples (25 before and 25 after neoadjuvant 5-FU radiochemotherapy). KRAS and BRAF mutations were examined through two independent analytical methods (sequencing and SNaPshot) to ensure efficient mutation detection. The microsatellite analysis was conducted using a fluorescent multiplex PCR-based method. RESULTS: KRAS mutations were found in 9 of 25 (36%) rectal cancer patients and were not significantly associated with the response to therapy (P=0.577), age (P=0.249) or sex of the patient (P=0.566). No link exists between KRAS mutation status and nodal (P=0.371) or metastatic stage (P=0.216). For two patients, KRAS mutation status changed after application of neoadjuvant 5-FU radiochemotherapy. All tumor samples were diagnosed BRAF-negative. Two rectal cancer patients exhibited a MSI-H phenotype and showed no tumor response. CONCLUSIONS: So one can conclude that (I) KRAS mutations status may change after neoadjuvant 5-FU radiochemotherapy relevant for further therapeutic decisions; (II) MSI-H patients do not respond to neoadjuvant 5-FU radiochemotherapy. Further prospective studies are needed to validate these results.