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In the present study, the potential of Raman spectroscopy (RS) in predicting disease-free survival (DFS) in oral cancer patients has been explored. Raman spectra were obtained from the tumor and contralateral regions of 94 oral squamous cell carcinoma patients. These patients were managed surgically and recommended for adjuvant therapy. The Cox proportional survival analysis was carried out to identify the spectral regions that can be correlated to DFS. The survival analysis was performed with 95% confidence intervals, hazard ratio, and p-values in the 1200-1800 cm-1 spectral region. Out of a total of 182 spectral points, 76 were found to be correlating with DFS, suggesting their utility to predict the patient outcome. The cut-off points of each correlating RS-point values were defined and tested towards predicting the DFS. The performance of predicting the power of spectral points was validated through Brier value, and it was found to be closer to the actual progression. The 76 spectral points identified from the tumors have the potential to accurately predict DFS in oral squamous cell carcinoma through a relatively simplistic prediction model in the absence of confounding factors.

To determine how small bowel neuroendocrine neoplasms (SBNEN’s) are diagnosed and examine the effect of CT enterography (CTE) on diagnosis and rates of disease-free survival. Histopathologically-confirmed SBNEN’s diagnosed at our institution between 1996 and 2016 were identified. Clinical presentation, radiology, endoscopy, surgery, and pathology reports were reviewed and compared between consecutive 5-year periods. Of the 178 SBNEN initially diagnosed at our institution, the incidence increased 12-fold from 9 (during 1996–2000) to 114 (during 2011–2016). Comparing the first 5 to the last 5 years, GI bleeding and abdominal pain increased significantly as indications (with both increasing from 0 to > 25%, p ≤ 0.023). Initial diagnosis by radiology increased 2-fold [from 33% (n = 3) to 66% (n = 75); p = 0.263]. Detection of a small bowel mass and the suggestion that SBNEN was present varied significantly between imaging modalities (p

Background Multivisceral resection for T4b colon cancer constitutes a heterogeneous group of surgical procedures. The purpose of this study was to explore clinically distinct categories of multivisceral resection, with subsequent correlation to postoperative complications and oncological outcomes. Methods In this multicenter cohort study, all consecutive patients without metastases who underwent multivisceral resection for pT4bN0-2M0 colon cancer between 2000 and 2014 were included. Multivisceral resection was divided into four categories: (i) gastrointestinal (including the stomach), (ii) urologic ((partial) bladder and ureter), (iii) solid organ (spleen, kidney, liver, pancreas, and uterus), and (iv) abdominal wall/omentum/ovaries. The primary outcome was surgical complications and secondary outcomes were 5-year intra-abdominal recurrence, disease-free survival, and overall survival. Results In total, 130 patients who underwent curative intent resection of pT4 colon cancer were included. Patients who underwent multivisceral resection within multiple categories were assigned to one of the categories based on hierarchy of clinical impact after exploratory analysis. For the primary endpoint, 55 patients were assigned to gastrointestinal, 14 to urologic, 14 to solid organ, and 47 to abdominal wall/omentum/ovaries multivisceral resection. Gastrointestinal multivisceral resection was independently associated with surgical complications (HR 3.9, 95% CI 1.4–10.6). Abdominal wall/omentum/ovaries multivisceral resection was significantly related with intra-abdominal recurrence (HR 7.8, 95% CI 1.0–57.8). The 5-year disease-free survival and overall survival showed no significant differences per multivisceral resection category. Conclusions Multivisceral resections for T4b colon cancer are heterogeneous procedures considering risk profiles. The proposed multivisceral resection subclassification needs validation, but might improve comparability between studies and hospitals (auditing).

Systemic relapses remain a major problem in locally advanced rectal cancer. Using short-course radiotherapy followed by chemotherapy and delayed surgery, the Rectal cancer And Preoperative Induction therapy followed by Dedicated Operation (RAPIDO) trial aimed to reduce distant metastases without compromising locoregional control.In this multicentre, open-label, randomised, controlled, phase 3 trial, participants were recruited from 54 centres in the Netherlands, Sweden, Spain, Slovenia, Denmark, Norway, and the USA. Patients were eligible if they were aged 18 years or older, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, had a biopsy-proven, newly diagnosed, primary, locally advanced rectal adenocarcinoma, which was classified as high risk on pelvic MRI (with at least one of the following criteria: clinical tumour [cT] stage cT4a or cT4b, extramural vascular invasion, clinical nodal [cN] stage cN2, involved mesorectal fascia, or enlarged lateral lymph nodes), were mentally and physically fit for chemotherapy, and could be assessed for staging within 5 weeks before randomisation. Eligible participants were randomly assigned (1:1), using a management system with a randomly varying block design (each block size randomly chosen to contain two to four allocations), stratified by centre, ECOG performance status, cT stage, and cN stage, to either the experimental or standard of care group. All investigators remained masked for the primary endpoint until a prespecified number of events was reached. Patients allocated to the experimental treatment group received short-course radiotherapy (5 × 5 Gy over a maximum of 8 days) followed by six cycles of CAPOX chemotherapy (capecitabine 1000 mg/mBetween June 21, 2011, and June 2, 2016, 920 patients were enrolled and randomly assigned to a treatment, of whom 912 were eligible (462 in the experimental group; 450 in the standard of care group). Median follow-up was 4·6 years (IQR 3·5-5·5). At 3 years after randomisation, the cumulative probability of disease-related treatment failure was 23·7% (95% CI 19·8-27·6) in the experimental group versus 30·4% (26·1-34·6) in the standard of care group (hazard ratio 0·75, 95% CI 0·60-0·95; p=0·019). The most common grade 3 or higher adverse event during preoperative therapy in both groups was diarrhoea (81 [18%] of 460 patients in the experimental group and 41 [9%] of 441 in the standard of care group) and neurological toxicity during adjuvant chemotherapy in the standard of care group (16 [9%] of 187 patients). Serious adverse events occurred in 177 (38%) of 460 participants in the experimental group and, in the standard of care group, in 87 (34%) of 254 patients without adjuvant chemotherapy and in 64 (34%) of 187 with adjuvant chemotherapy. Treatment-related deaths occurred in four participants in the experimental group (one cardiac arrest, one pulmonary embolism, two infectious complications) and in four participants in the standard of care group (one pulmonary embolism, one neutropenic sepsis, one aspiration, one suicide due to severe depression).The observed decreased probability of disease-related treatment failure in the experimental group is probably indicative of the increased efficacy of preoperative chemotherapy as opposed to adjuvant chemotherapy in this setting. Therefore, the experimental treatment can be considered as a new standard of care in high-risk locally advanced rectal cancer.Dutch Cancer Foundation, Swedish Cancer Society, Spanish Ministry of Economy and Competitiveness, and Spanish Clinical Research Network.

Background Among patients with cancer, prior research suggests that patients with mental illness may have reduced survival. The objective was to assess the impact of psychiatric utilisation (PU) prior to cancer diagnosis on survival outcomes. Methods All residents of Ontario diagnosed with one of the top 10 malignancies (1997–2014) were included. The primary exposure was psychiatric utilisation gradient (PUG) score in 5 years prior to cancer: 0: none, 1: outpatient, 2: emergency department, 3: hospital admission. A multivariable, cause-specific hazard model was used to assess the effect of PUG score on cancer-specific mortality (CSM), and a Cox proportional hazard model for effect on all-cause mortality (ACM). Results A toal of 676,125 patients were included: 359,465 (53.2%) with PUG 0, 304,559 (45.0%) PUG 1, 7901 (1.2%) PUG 2, and 4200 (0.6%) PUG 3. Increasing PUG score was independently associated with worse CSM, with an effect gradient across the intensity of pre-diagnosis PU (vs PUG 0): PUG 1 h 1.05 (95% CI 1.04–1.06), PUG 2 h 1.36 (95% CI 1.30–1.42), and PUG 3 h 1.73 (95% CI 1.63–1.84). Increasing PUG score was also associated with worse ACM. Conclusions Pre-cancer diagnosis PU is independently associated with worse CSM and ACM following diagnosis among patients with solid organ malignancies.

Triple negative breast cancer (TNBC) comprises 15–20% of all invasive breast cancer and is associated with a poor prognosis. As therapy options are limited for this subtype, there is a significant need to identify new targeted approaches for TNBC patient management. The expression of the folate receptor alpha (FRα) is significantly increased in patients with TNBC and is therefore a potential biomarker and therapeutic target. We optimized and validated a FRα immunohistochemistry method, specific to TNBC, to measure FRα expression in a centrally confirmed cohort of 384 patients with TNBC in order to determine if expression of the protein is associated with invasive disease-free survival (IDFS) and overall survival (OS). The FRα IHC demonstrated exceptional performance characteristics with low intra- and interassay variability as well as minimal lot-to-lot variation. FRα expression, which varied widely from sample to sample, was detected in 274 (71%) of the TNBC lesions. In a multivariable model adjusted for baseline characteristics, FRα expression was associated with improved IDFS (HR = 0.63, p = 0.01) but not with OS. The results demonstrate the potential of targeting the FRα in the majority of TNBC patients and suggest that variable expression may point to a need to stratify on FRα expression in clinical studies.

Die Lunge ist das zweithaufigste Metastasierungsorgan bei Patienten mit einem kolorektalen Karzinom (CRC). Die lymphonodale Metastasierung des CRC stellt einen Prognosefaktor fur das Uberleben dar. In der vorliegenden Studie wurde untersucht, welchen Einfluss die lymphonodale Metastasierung des CRC auf die Lungenmetastasierung, insbesondere die thorakale Lymphknotenmetastasierung besitzt. Retrospektive Analyse von 88 Patienten (n = 56 mannlich) mit kurativer Resektion von Lungenmetastasen bei CRC. Primarer Endpunkt: Einfluss des Lymphknotenstatus des CRC auf Lungenmetastasen, sekundare Endpunkte krankheitsfreies Uberleben/Gesamtuberleben. Die statistische Auswertung erfolgte mit SPSS. Bei 48 Patienten bestand ein positiver Lymphknotenstatus des CRC, bei 9 Patienten ein N+-Status der Lungenmetastasierung. Der Lymphknotenstatus des CRC beeinflusste signifikant das Auftreten synchroner Metastasen (p = 0,03), das krankheitsfreie Intervall bis zur Ausbildung metachroner Lungenmetastasen (p = 0,012) und das Gesamtuberleben der Patienten mit einem CRC (p = 0,048). Die 5‑JUR fur CRC-Patienten mit Lungenmetastasen betrug nach pulmonaler Metastasektomie 48,7 %. Der thorakale Lymphknotenbefall beeinflusste das Uberleben ebenfalls signifikant (p = 0,001). Die Suche nach Lungenmetastasen sollte in das Staging und das Follow-up aller Patienten mit CRC einbezogen werden, insbesondere bei einem positiven Lymphknotenstatus des CRC.

Background: Anoctamin (ANO)/transmembrane member 16 (TMEM16) proteins mediate diverse physiological and pathophysiological functions including cancer cell proliferation. The present study aimed to identify the role of ANOs in pancreatic cancer. Methods: In an initial screen of ANOs, ANO9/TMEM16J was overexpressed in pancreatic cancer cells, and its role in the pathogenesis of pancreatic cancer was evaluated using an integrated in vitro and in vivo approach. To determine clinical relevance of the experimental findings, the prognostic value of ANO9 was evaluated in patients with pancreatic cancer. Results: The ANO9 mRNA and protein levels were increased in pancreatic cancer-derived cells. Exogenous expression of ANO9 in PANC-1 cells significantly increased cell proliferation in cell cultures and in mice. In contrast, knockdown of ANO9 in AsPC-1, BxPC-3, and Capan-2 cells strongly inhibited cell proliferation. Mechanistic analysis suggested that physical association of ANO9 with epidermal growth factor receptor (EGFR) underlies ANO9-induced cell proliferation. Knockdown of ANO9 augmented the effects of the EGFR inhibitor and the cytotoxic agent on pancreatic cancer cell proliferation. In addition, high ANO9 expression is a poor prognostic factor in patients with pancreatic cancer. Conclusions: The ANO9/TMEM16J appears to be a clinically useful prognostic marker for pancreatic cancer and a potential therapeutic target.

Background S-1 plus cisplatin is a standard regimen for advanced gastric cancer (AGC) in Asia. The ToGA trial established a fluoropyrimidine plus cisplatin and trastuzumab as a standard treatment for human epidermal growth factor receptor 2 (HER2)-positive AGC. In the HERBIS-1 trial, trastuzumab combined with S-1 plus cisplatin showed promising antitumor activity in patients with HER2-positive AGC. However, cisplatin has several important drawbacks, including vomiting and renal toxicity. These disadvantages of cisplatin are prominent in elderly patients. Therefore, we conducted a prospective phase II study of trastuzumab plus S-1 without cisplatin in elderly patients with HER2-positive AGC. Methods Patients 65 years or older who had HER2-positive AGC received S-1 orally on days 1–28 of a 42-day cycle and trastuzumab intravenously on day 1 of a 21-day cycle. Results A total of 51 patients were enrolled. Two patients were ineligible. The full analysis set thus comprised 49 patients. The median age was 71 years (range 65–85). The confirmed response rate was 40.8% (95% CI 27.1–54.6%), and the null hypothesis was rejected. The median follow-up period was 10.6 months. Median overall survival was 15.8 months. Median progression-free survival was 5.1 months, and time to treatment failure was 4.0 months. Major grade 3 or 4 adverse events included neutropenia (12.0%), anemia (24.0%), diarrhea (10.0%), and anorexia (12.0%). There was one treatment-related death. Conclusions Trastuzumab in combination with S-1 alone demonstrated promising antitumor activity and manageable toxic effects as well as promising survival results in elderly patients with HER2-positive AGC. Clinical trials registration UMIN000007368.

The study aimed to investigate the prognostic role of the preoperative carbohydrate antigen 19-9 (CA19-9) level in alpha-fetoprotein (AFP)-negative (AFP 25 ng/ml) hepatocellular carcinoma (HCC) patients.From December 2004 to December 2013, 750 patients diagnosed with AFP-negative HCC following curative resection were enrolled. Both univariate and multivariate analyses were performed to clarify the prognostic factors for overall survival (OS) and disease-free survival (DFS).The optimal cutoff point for preoperative CA19-9 was 32.6 U/ml, and the value of the area under the curve was 0.640. The 1-, 3-, and 5-year OS rates were 88.4, 72.2, and 57.0%, respectively, for the CA19-9 32.6 U/ml group and 97.0, 83.3, and 79.9%, respectively, for the CA19-9 ≤ 32.6 U/ml group (P 0.001). The 1-, 3-, and 5-year DFS rates were 71.8, 47.7, and 34.8%, respectively, for the CA19-9 32.6 U/ml group and 80.8, 63.6, and 55.5%, respectively, for the CA19-9 ≤ 32.6 U/ml group (P 0.001). The multivariate analysis showed that CA19-9 32.6 U/ml was one of the most significant unfavorable predictors of OS and DFS (P 0.001 for both).Preoperative CA19-9 32.6 U/ml is a predictor of dismal prognosis and can be employed as a prognostic marker for patient selection in AFP-negative HCC management.

Early, risk-adapted treatment with fludarabine in Binet stage A chronic lymphocytic leukemia patients: results of the CLL1 trial of the German CLL study group

Melanoma patients with additional positive lymph nodes in the completion lymph node dissection (CLND) following a positive sentinel lymph node (SLN) biopsy would have a poorer prognosis than patients with no additional positive lymph nodes. We hypothesize that the progression of disease from the SLN to the non-SLN compartment is orderly and is associated with the worsening of the disease status. Thus, the SLN and non-SLN compartments are biologically different in that cancer cells, in general, arrive in the SLN compartment before spreading to the non-SLN compartment. To validate this concept, we used a large cohort of melanoma patients from our prospective SLN database in an academic tertiary medical center. Adult cutaneous melanoma patients (n = 291) undergoing CLND after a positive SLN biopsy from 1994 to 2009 were analyzed. Comparison of 5-year disease-free survival and 5-year overall survival between positive (n = 66) and negative (n = 225) CLND groups was made. The 5-year disease-free survival rates were 55% (95% CI 49-62%) for patients with no additional LN on CLND versus 14% (95% CI 8-26%) in patients with positive LN on CLND (p

Purpose To compare the value of pretreatment functional and morphological imaging parameters for predicting survival in patients undergoing transarterial radioembolization using yttrium-90 (90Y-TARE) for unresectable hepatocellular carcinoma (uHCC).

Inconsistent data suggests extranodal spread (ENS) is an adverse prognostic factor in Stage III melanoma patients but it remains contentious. By rigorously matching cohorts, this study sought to clarify associations with recurrence and survival. Melanoma patients with lymph node metastases (AJCC Stage III), with or without ENS, sub-classified on the basis of known (MKP) or unknown primary (MUP), were identified from a single institution prospective database. Of 725 ENS patients identified, 567 were able to be precisely matched 1:1 with a non-ENS cohort. Clinicopathologic factors were analyzed for associations with outcome. There were 481 MKP and 86 MUP patients in each cohort. ENS, compared to non-ENS, was an independent predictor of worse melanoma specific survival (MSS) (HR = 1.71, 95% CI = 1.39–2.11, P

Diagnosis and relapse: cytogenetically normal acute myelogenous leukemia without FLT3 -ITD or MLL -PTD

Background The purpose of this comprehensive meta-analysis was to assess the association of aldehyde dehydrogenase (ALDH) expression with overall survival (OS) and disease-free survival (DFS)/progression-free survival (PFS) in ovarian cancer patients. Methods Systematic searches of Pubmed databases was performed to identify relevant literature published before February 28, 2018. A total of 14 studies (13 articles) with 2210 ovarian cancer patients were pooled. All included studies were performed by using Immunohistochemistry (IHC) for detection of ALDH expression. Hazard ratio (HR) and 95% confidence interval (CI) were extracted from included studies to evaluate the correlation of ALDH expression with OS and DFS/PFS. Results High expression of ALDH was associated with worse OS (HR: 1.43; 95% CI: 1.18–1.73) and poor DFS/PFS (HR: 1.55, 95% CI: 1.12–2.14). No evidence of publication bias was observed in OS (Begg’s test, P = 0.113; Egger’s test, P = 0.355) and DFS/PFS (Begg’s test, P = 0.655; Egger’s test, P = 0.189) in ovarian cancer patients. The subgroup of studies with cut-off value of low expression showed that high expression of ALDH was correlated with poor OS (HR: 1.36; 95% CI: 1.14–1.62) and DFS/PFS (HR: 1.79; 95% CI: 1.45–2.20) in ovarian cancer patients, with no observed heterogeneity (OS: I2 = 0%, P = 0.45; DFS/PFS: I2 = 0%, P = 0.55). Conclusion In conclusion, high expression of ALDH is correlated with worse survival profiles in ovarian cancer patients, indicating that ALDH might act as a potential molecular biomarker for prognosis of ovarian cancer.

Die onkologische Wertigkeit der laparoskopischen vs. offenen Rektumresektion wurde in vier multizentrischen randomisiert kontrollierten Studien untersucht. Wahrend die COLOR-II- und die COREAN-Studie die onkologische Gleichwertigkeit belegten, kamen die ACOSOG- und die ALaCaRT-Studie zu einem anderen Ergebnis. Mit einem Kombinationsendpunkt, der die mesorektale Praparatequalitat sowie die Tumorfreiheit des zirkumferenziellen und des distalen Resektionsrandes beurteilt, zeigten sie ein besseres Abschneiden der offenen Chirurgie. Allerdings ist die Validitat dieses Kombinationsendpunktes nicht belegt, und keine Aussage kann hinsichtlich harter onkologischer Endpunkte gemacht werden. Damit bleiben die COLOR-II- und die COREAN-Studie die bis dato einzigen mit harten primaren Endpunkten (Lokalrezidivrate bzw. krankheitsfreies Uberleben) und einer zumindest mittellangen Nachuntersuchungszeit von 3 Jahren. Allerdings muss die Vergleichbarkeit der Studiengruppen zumindest in der COLOR-II-Studie angezweifelt werden, da nur die Expertise der laparoskopisch operierenden Chirurgen uberpruft wurde. Jedoch scheint mit einer Lokalrezidivrate von 5 % in beiden Gruppen eine gute onkologische Qualitat vorzuliegen, sodass nicht von einer systematisch schlechten Kontrollgruppe ausgegangen werden muss. Somit kann derzeit geschlossen werden, dass in Expertenhanden mit der laparoskopischen Rektumresektion ein gutes onkologisches Ergebnis erreicht werden kann. Fur die abschliesende Beurteilung mussen die Langzeitergebnisse der laufenden Studien abgewartet werden. Sollten sich dabei die fur die Laparoskopie positiven Ergebnisse der COLOR-II-Studie bestatigen, ware in der Zukunft die laparoskopische Rektumresektion in erfahrenen Handen der offenen Resektion aufgrund der allgemein bekannten perioperativen Vorteile der minimal-invasiven Chirurgie vorzuziehen.

Gastrointestinale Stromatumoren (GIST) sind mit einer Inzidenz von 1–2/100.000 die haufigste mesenchymale Neoplasie des Verdauungstraktes. Ihre spezifische Tumorbiologie mit Mutationen in den Protoonkogenen c-KIT und PDGFRα als Antreiber des Tumorwachstums ermoglicht die zielgerichtete Therapie mit Tyrosinkinaseinhibitoren. Hieraus ergeben sich spezifische Indikationen zum chirurgischen Vorgehen bei fortgeschrittenen GIST. Diskussion des Stellenwertes der Chirurgie in der multimodalen Therapie fortgeschrittener GIST. Selektive Literaturrecherche unter Einbeziehung eigener Studien und Kasuistiken. Bei grosen oder anatomisch ungunstig gelegenen GIST, die nicht organerhaltend resektabel sind, soll bei Nachweis einer therapiesensitiven Mutation im c-KIT-Protoonkogen eine neoadjuvante Therapie mit Imatinib durchgefuhrt werden. Hierdurch ist fast immer eine Verkleinerung des Resektionsausmases ohne erhohte perioperative Morbiditat moglich. In der metastasierten Situation kann ein chirurgisches Vorgehen (Residualtumorresektion) bei generalisiertem Ansprechen auf die medikamentose Therapie nicht sicher die Prognose der Patienten verbessern. Bei fokaler Progression unter antiproliferativer Therapie leisten lokale Therapieverfahren einen wichtigen Beitrag zur multimodalen Tumorkontrolle. Bei generalisiertem Progress sollte eine Operation nur in Ausnahmefallen zur Symptomkontrolle durchgefuhrt werden. Lokal ablative Therapien wie die Radiofrequenzablation (RFA), irreversible Elektroporation (IRE) oder selektive interne Radiotherapie (SIRT) stellen vor allem fur hepatische Metastasen eine therapeutische Erganzung dar. In der multimodalen Therapie fortgeschrittener GIST hat die Chirurgie einen hohen Stellenwert in der neoadjuvanten Therapie, aber nur eine eingeschrankte Wertigkeit in der metastasierten Situation, bei der die medikamentose Therapie im Vordergrund steht.

Die kritische Extremitatenischamie (CLI) als schwerstes Stadium der peripheren arteriellen Verschlusskrankheit zeichnet sich durch hohe Amputations-, Morbiditats- und Mortalitatsraten aus. Die Revaskularisierung ist ein essenzieller Therapieschritt zum Erhalt der betroffenen Extremitat. Obwohl die Bypasschirurgie lange Zeit den Standard in der Behandlung der CLI darstellte, kam es in den letzten Jahren trotz fehlender Level-I-Daten zu einer uberproportionalen Zunahme von endovaskularen Therapiemasnahmen. In der vorliegenden Ubersichtsarbeit sollen anhand der vorliegenden Daten die Indikation und die Ergebnisse der endovaskularen Therapie bei der CLI dargelegt werden. Anhand einer Literaturrecherche wurden zum einen Veroffentlichungen, die die Ergebnisse der endovaskularen Therapie mit der Bypasschirurgie vergleichen, und zum anderen Beobachtungsstudien uber unterschiedliche endovaskulare Techniken identifiziert. Die BASIL-Studie stellt die hochwertigste Studie zum Vergleich der endovaskularen und operativen Therapie der CLI dar. Die Langzeitdaten der BASIL-Studie zeigen, dass auser bei Patienten mit einer geeigneten Vene und einer Lebenserwartung von mehr als zwei Jahren eine endovaskulare First-line-Therapie der operativen Therapie gleichwertig ist. Die Gleichwertigkeit konnte auch in einem Vergleich einer operativen und endovaskularen Metaanalyse zur Behandlung der CLI nachgewiesen werden. Die CLI stellt eine Erkrankung mit einem hohen Mortalitats- und Morbiditatsrisiko dar. Anhand der vorliegenden Daten lasst sich bei den meisten Patienten aufgrund vergleichbarer amputationsfreier Uberlebenszeiten bei geringerem Komplikationsprofil eine Endovascular-first-Strategie in erfahrenen Zentren rechtfertigen.

Multiple myeloma with extramedullary disease: impact of autologous stem cell transplantation on outcome

The original version of this article, published on 21 February 2020, unfortunately contained a mistake.

Background Malignant extrarenal rhabdoid tumor of the gastrointestinal tract is rarely reported in the literature. It is characterized by poor prognosis and aggressive metastatic features. A literature review evidenced only 19 cases, with poor outcome. Case presentation We report a case of a colonic “pure” malignant extrarenal rhabdoid tumor with metastatic nodes in a 65-year-old Caucasian man. He was treated surgically with no recurrence, no adjuvant chemotherapy, and with 4-year survival without disease at the time of the submission of this article. Conclusions We present an extraordinary case of long-term survival due to the extended surgical treatment. We believe that the absence of organ metastasis at presentation is a positive prognostic factor, although pathology confirmed node involvement (13/38 positive) on microscopy.

Five randomized trials have been conducted to prove that shorter duration of trastuzumab treatment (9 weeks or 6 months) can replace the standard duration (1 year). The results of PERSEPHONE, the most recent trial, suggest that the efficacy of a 6-month treatment is non-inferior to that of 1 year, although not for all patients. We discuss these results in the context of current treatment standards.

The International Society of Paediatric Oncology (SIOP)–Paediatric Oncology in Developing Countries (PODC) Collaborative Wilms Tumour Africa project delivered treatment in eight centres across five countries in sub-Saharan Africa. Setting up a collaboration like this is easier said than done, and herein we share the lessons we learned along the way.

The impact of pre-transplant body weight on short- and long-term outcomes after allogeneic hematopoietic cell transplantation in adults using different weight classification tools

Das Auftreten einer Anastomoseninsuffizienz (AI) nach einer sphinktererhaltenden tiefen vorderen Rektumresektion bei Patienten mit einem Rektumkarzinom des mittleren und unteren Drittels ist mit einer erhohten postoperativen Morbiditats- und Mortalitatsrate vergesellschaftet. Der Einfluss auf das Langzeituberleben hingegen ist nach wie vor nicht ausreichend untersucht und Gegenstand einer aktuell kontrovers gefuhrten Diskussion. Das Ziel der vorliegenden Arbeit war es, den Einfluss der AI auf das Langzeituberleben bei Patienten mit einem Rektumkarzinom des mittleren und unteren Drittels nach einer sphinktererhaltenden Rektumresektion zu analysieren. Aus einer prospektiv angelegten auditfahigen Datenbank „Kolorektales Karzinom“ der Universitatsklinik fur Chirurgie Salzburg wurden im Zeitraum von Januar 2003 bis Oktober 2010 alle kurativ sphinktererhaltend operierten Patienten im UICC-Stadium (y)0–III mit einem histologisch gesicherten primaren Adenokarzinom des mittleren und unteren Rektumdrittels (n = 108) in die Analyse eingeschlossen und der Einfluss der AI auf das 5-Jahres-Gesamtuberleben [OS] sowie das tumorspezifische [CSS] und rezidivfreie [RFS] Uberleben untersucht. Die Gesamt-AI-Rate betrug 17,6 % (Grad A: 4,6 %, Grad B: 4,6 % und Grad C: 8,3 %). Bei einer medianen Nachuntersuchungszeit von 70 Monaten (24–123) hatten Patienten mit einer AI jeweils eine signifikant ungunstigere 5-Jahres-OS- (63,6 vs. 87,8 %; p = 0,02), CSS- (72,2 vs. 93,5 %; p = 0,02) und RFS-Rate (61,1 vs. 84,2 %; p = 0,01). Die AI wurde in der univariaten Cox-Regressionsanalyse als unabhangiger Risikofaktor fur das OS (Hazard Ratio [HR] 3,05, 95 %-Konfidenzintervall [KI]: 1,11–8,39; p = 0,03), CSS (HR 4,21, 95 %-KI: 1,13–15,70; p = 0,03) und RFS (HR 3,02, 95 %-KI: 1,20–7,58; p = 0,02) identifiziert. Die AI war in unserer Kohorte mit einem signifikant ungunstigen Einfluss auf das 5-Jahres-Gesamt- und onkologische Uberleben assoziiert.

Flexible ureteroscopy (URS) is increasingly being used as the first-line treatment for patients with renal stones. Despite this increase in use, substantial variations exist in the reported stone-free rates (SFR) following flexible URS. These variations are a result of inconsistencies in the definition of 'stone-free', which reflect variations in the type of imaging used to assess the presence of stones postoperatively and the timing of the assessment. Other possible factors such as the importance of residual fragments following stone surgery, and the size and position of the stones might also account for variations in stone-free rates. In order to obtain an accurate estimate of the SFR, especially within subgroups defined by stone characteristics and exact technique, we compare reported SFRs from studies that use imaging other than CT for follow-up and those that use only CT. We also review the evidence on the importance of active retrieval of fragments during flexible URS and whether this technique improves the outcomes of patients with kidney stones.

Background: Sunitinib is approved worldwide for treatment of advanced pancreatic neuroendocrine tumours (pNET), but no validated markers exist to predict response. This analysis explored biomarkers associated with sunitinib activity and clinical benefit in patients with pNET and carcinoid tumours in a phase II study. Methods: Plasma was assessed for vascular endothelial growth factor (VEGF)-A, soluble VEGF receptor (sVEGFR)-2, sVEGFR-3, interleukin (IL)-8 (n=105), and stromal cell-derived factor (SDF)-1α (n=28). Pre-treatment levels were compared between tumour types and correlated with response, progression-free (PFS), and overall survival (OS). Changes in circulating myelomonocytic and endothelial cells were also analysed. Results: Stromal cell-derived factor-1α and sVEGFR-2 levels were higher in pNET than in carcinoid (P=0.003 and 0.041, respectively). High (above-median) baseline SDF-1α was associated with worse PFS, OS, and response in pNET, and high sVEGFR-2 with longer OS (P⩽0.05). For carcinoid, high IL-8, sVEGFR-3, and SDF-1α were associated with shorter PFS and OS, and high IL-8 and SDF-1α with worse response (P⩽0.05). Among circulating cell types, monocytes showed the largest on-treatment decrease, particularly CD14+ monocytes co-expressing VEGFR-1 or CXCR4. Conclusions: Interleukin-8, sVEGFR-3, and SDF-1α were identified as predictors of sunitinib clinical outcome. Putative pro-tumorigenic CXCR4+ and VEGFR-1+ monocytes represent novel candidate markers and biologically relevant targets explaining the activity of sunitinib.

Due to concerns about patients' wellbeing, open end-of-life communication is associated with reservation. Furthermore, sociocultural differences must be considered. The objective of this pilot study was therefore to investigate the information preferences of Austrian patients regarding cure rates and prognosis.The information preferences of 50 advanced lung cancer patients were assessed at their first visit to the Department of Radiation Oncology, Medical University of Vienna. Preferences in terms of content (cure rates and/or prognosis) and depth of the information (additional quantitative estimates) were addressed. After the individually adapted medical consultation, patients' satisfaction with the consultation and the emotional responses to the information were evaluated.The majority of patients (76 %) requested information about cure rates and/or prognosis; nearly half of these (47 %) wanted additional quantitative estimates. Neither sociodemographic variables, disease characteristics, nor time since diagnosis had an impact on the information preferences. The individually adapted medical information showed no overall negative influence on the emotional responses; only patients receiving prognostic information had significantly higher distress scores after the consultation. High satisfaction with the individually adapted medical consultation was reported by 92 % of patients.Austrian physicians may offer end-of-life communication and directly ask patients about their information preferences, since patients seem able to decide whether or not prognostic information would overwhelm their emotional capacity and therefore to accept or reject the invitation. The disclosure of cure rates and/or prognosis with or without quantitative estimates-according to the patients' preferences-shows overall no negative impact on emotional reactions. The individually adapted consultation results in high patient satisfaction. Nevertheless, prognostic information may lead to higher distress.

The expression and role of periostin in meningiomas remains unknown. Tissue specimens of 175 convexity meningiomas were immunohistochemically examined with antibodies against periostin and Ki67. The expression levels of periostin and Ki67 were compared among different WHO groups. The role of periostin and Ki67 in postoperative prognosis of meningiomas was also analyzed. Negative (-) expression of Ki67 was observed in 101 (57.7 %) cases of all the surgical tissue samples. The Ki67 expressions differed significantly among the WHO groups (P < 0.001) and correlated positively with the WHO grade (r = 0.673, P < 0.001). Low/negative staining of periostin was observed in 116 (66.3 %) cases. The periostin expressions differed significantly among the WHO groups (P < 0.001). Periostin expression correlated positively with the WHO grade (r = 0.742, P < 0.001). There was a positive correlation between Ki67 expression and periostin (r = 0.513, P < 0.001). Both Ki67 expression and periostin expression was found statistically different between brain invasion tumor and non-invasion tumor (p < 0.001). The recurrence rate and PFS rate in both varied Ki67 expression groups and periostin expression groups was statistically different (P < 0.001). The survival time and PFS time in both varied Ki67 expression groups and periostin expression groups was also statistically different (P < 0.001). Periostin was expressed in tumor stroma of meningiomas. Both periostin and Ki67 may behave as a maker in predicting the grade and prognosis in meningiomas. Drugs that targets periostin aims at reducing invasion of meningioma patients should be further researched.

Aim of work To detect the diagnostic value of PET/CT in breast cancer patients. We compared the performance of PET/CT with that of conventional imaging in detection of recurrence and distant metastasis and evaluated the impact PET/CT results have on disease free survival. Materials and methods We retrospectively studied 50 patients with breast cancer with clinical suspicion of recurrent or metastatic lesion and who underwent PET/CT and conventional imaging procedures. The imaging results were retrospectively compared with histopathology and clinical follow-up as a reference standard. Results PET/CT detected distant metastases with a sensitivity of 97% and a specificity of 93%. In contrast, the sensitivity and specificity of combined conventional imaging procedures were 75% and 73%, respectively, disease-free survival was significantly shorter in the 34 M1-PET/CT patients than in the 14 M0-PET/CT patients (log-rank P = 0.002) also PET/CT detected recurrence in 1 patient with equivocal mammographic findings. Conclusion In breast cancer, PET/CT is superior to conventional imaging procedures for detection of recurrence, distant metastases and PET/CT can be used to improve prediction of the clinical outcome of breast cancer patients.

Background: Telomeres are TTAGGG tandem repeats capping chromosomal ends and partially controlled by the telomerase enzyme. The EGFR pathway putatively regulates telomerase function, prompting an investigation of telomere length (TL) and its association with anti-epidermal growth factor receptor (EGFR) therapy in metastatic colorectal cancer (mCRC). Methods: Colorectal cancer cell lines were treated with multiple drugs and sensitivity determined. Clinical information was gathered from 75 patients who had received anti-EGFR drugs. Telomere length was measured using a validated qRT–PCR technique. Results: In CRC cell lines, TL independently predicted cetuximab sensitivity. Cells with shorter TL had growth inhibition of 18.6±3.41% as compared with 41.39±8.58% in longer TL (P=0.02). These in vitro findings were validated clinically, in a robust multivariate model. Among patients with KRas WT tumours, those with longer TL had a superior median progression-free survival (PFS) of 24.9 weeks than those with shorter TL; median 11.1 weeks, HR 0.31; P=0.048. Conclusion: Telomere length could be a potential unique biomarker predictive of clinical benefit (PFS) of mCRC patients treated with anti-EGFR therapy. This is the novel demonstration of a complex hitherto undescribed interaction, placing anti-EGFR therapy, EGFR pathway, and the telomerase complex within a clinical context.

oder inguinal) oder das Vorliegen eines Kapseldurchbruchs. In den Jahren 2003 bis 2007 wurden 123 Patienten zur adjuvanten Radiotherapie (davon 109 auswertbar) und 127 zur Beobachtung (davon 108 auswertbar) randomisiert. Die adjuvante Radiotherapie wurde mit 48 Gy in 20 Sitzungen uber maximal 30 Tage durchgefuhrt. Die Nachbeobachtung erfolgte alle 3 Monate in den Jahren 1–2, alle 6 Monate in den Jahren 3–5, danach jahrlich. Primarer Endpunkt war ein Rezidiv im Bereich der regionaren LK-Station. Daruber hinaus wurden Rezidive in der In-Transit-Region und in entfernten Regionen, Nebenwirkungen der Radiotherapie sowie die Lebensqualitat erfasst und ausgewertet.

Objective: This study aimed to assess prognosis of isolated local recurrence (ILR) of renal cell carcinoma (RCC) after radical nephrectomy (RN). Patients and Methods: This retrospective study involved 22 cases (16 men and 6 women) of ILR from two centers with a mean age of 60.1 ± 8.5 years. All cases were managed surgically. Results: Primary tumors were mainly clear cell carcinoma (n = 17). Nine patients had T3 and T4 tumors. Local recurrence involved mainly the operative bed (n = 17); 4 among them had nodal recurrence as well. The median interval to local recurrence was 13.5 months (7–25 months). Stages T3 and T4 were significantly associated with shorter interval. Complete excision was possible in 9 patients (41%); 8 tumors were irresectable. It was associated with significantly higher overall and median disease-free survival (DFS). Advanced disease stage (p = 0.002) and shorter interval to recurrence (p 15 months. Conclusion: ILR after radical nephrectomy for RCC is more common with more advanced stages, where interval to recurrence tends to be shorter. The management should be surgical, which was possible in nearly 60% of cases. Complete excision was associated with better overall and disease free survival.

Neue Operationstechniken in der kolorektalen Chirurgie verfolgen das Ziel einer moglichst geringen Patientenbelastung bei mindestens aquivalenter und moglichst verbesserter Behandlungs- und Ergebnisqualitat. Hochwertige klinische Studien sind in der Evaluation sinnvoll erscheinender Innovationen notwendig und sollen die Machbarkeit, aber auch die Vorteile (oder Nachteile) neuer Operationstechniken bewerten. Die laparoskopische Kolonkarzinomchirurgie ist durch eine Reihe exzellenter prospektiv randomisierter Studien hinsichtlich Sicherheit und onkologischer Qualitat untersucht (COST-Study, COLOR-I, CLASICC). Die Patienten profitieren von den Vorteilen des geringeren Zugangstraumas, ohne Einschrankungen in der onkologischen Radikalitat hinnehmen zu mussen. Konnen diese positiven Ergebnisse auf die Rektumkarzinomchirurgie ubertragen werden? In der Rektumkarzinomchirurgie konnten aktuell die Fruhergebnisse der COLOR-II-Studie veroffentlicht werden, in der eindeutig nachgewiesen werden konnte, dass die laparoskopische Technik dem konventionellen offenen Vorgehen nicht unterlegen ist. Hinsichtlich Blutverlust, postoperativem Schmerzniveau, Krankenhausverweildauer und lateralem Sicherheitsabstand im distalen Rektumdrittel fanden sich signifikante Vorteile fur die laparoskopische Operationstechnik. Die onkologischen Langzeitergebnisse (Lokalrezidivrate als primarer Endpunkt der Studie) zeigen ebenfalls einen gunstigen Trend fur die minimal-invasive Rektumchirurgie und werden demnachst publiziert. Die Sicherheit und die onkologische Qualitat laparoskopischer Resektionsverfahren beim Rektumkarzinom sind durch klinische Studien gut belegt. In erfahrenen Zentren wird die laparoskopische Operationstechnik immer mehr zum Goldstandard in der Rektumkarzinomchirurgie.

BACKGROUND: Preoperative radiotherapy (RT) is widely used to downstage rectal tumours, but the rate of recurrence varies significantly. Therefore, new biomarkers are needed for better treatment and prognosis. It has been shown that astrocyte elevated gene-1 (AEG-1) is a key mediator of migration, invasion, and treatment resistance. Our aim was to analyse the AEG-1 expression in relation to RT in rectal cancer patients and to test its radiosensitising properties. METHODS: The AEG-1 expression was examined by immunohistochemistry in 158 patients from the Swedish clinical trial of RT. Furthermore, we inhibited the AEG-1 expression by siRNA in five colon cancer cell lines and measured the survival after irradiation by colony-forming assay. RESULTS: The AEG-1 expression was increased in the primary tumours compared with the normal mucosa independently of the RT (P

Early assessment of response at 3 months of tyrosine kinase inhibitor treatment has become an important tool to predict favorable outcome. We sought to investigate the impact of relative changes of BCR-ABL transcript levels within the initial 3 months of therapy. In order to achieve accurate data for high BCR-ABL levels at diagnosis, beta glucuronidase (GUS) was used as a reference gene. Within the German CML-Study IV, samples of 408 imatinib-treated patients were available in a single laboratory for both times, diagnosis and 3 months on treatment. In total, 301 of these were treatment-naïve at sample collection.(i) with regard to absolute transcript levels at diagnosis, no predictive cutoff could be identified; (ii) at 3 months, an individual reduction of BCR-ABL transcripts to the 0.35-fold of baseline level (0.46-log reduction, that is, roughly half-log) separated best (high risk: 16% of patients, 5-year overall survival (OS) 83% vs 98%, hazard ratio (HR) 6.3, P=0.001); (iii) at 3 months, a 6% BCR-ABL(IS) cutoff derived from BCR-ABL/GUS yielded a good and sensitive discrimination (high risk: 22% of patients, 5-year OS 85% vs 98%, HR 6.1, P=0.002). Patients at risk of disease progression can be identified precisely by the lack of a half-log reduction of BCR-ABL transcripts at 3 months.

Patienten mit Hochrisikoweichteilsarkomen (FNCLCC-Grad 2–3, > 5 cm und tief gelegen) haben ein hohes Risiko sowohl fur das Auftreten eines Lokalrezidivs als auch von Fernmetastasen trotz bestmoglicher Tumorresektion. Es sollte daher ein multimodales Vorgehen fur die Therapie dieser prognostisch ungunstigen Tumoren gewahlt werden. Neben Chirurgie, Strahlentherapie und Chemotherapie bildet die Hyperthermie die 4. Saule im Kontext multimodaler Behandlungskonzepte. Hyperthermie meint dabei die uber Mikrowelleneinstrahlung moglichst selektive Erwarmung der tumortragenden Region auf Temperaturen von 40–43 °C fur eine Zeitdauer von 60 min in Erganzung zu einer simultanen Chemotherapie oder Strahlentherapie. In einer randomisierten Phase-III-Studie konnte durch die Hinzunahme der Hyperthermie zu einer neoadjuvanten Chemotherapie eine deutliche Verbesserung des Tumoransprechens verbunden mit einem sehr niedrigen Risiko der Fruhprogression gegenuber alleiniger Chemotherapie gezeigt werden. Die Hinzunahme der Hyperthermie zu einer multimodalen Therapie bei Patienten mit Hochrisikoweichteilsarkomen, bestehend aus Chirurgie, Strahlentherapie und Chemotherapie, entweder neoadjuvant oder auch adjuvant nach einer unvollstandigen bzw. marginalen Tumorresektion, fuhrten zu einer signifikanten Verbesserung des lokalrezidiv- und krankheitsfreien Uberlebens. Basierend auf diesen Ergebnissen und in Verbindung mit der nur moderaten zusatzlichen Belastung des Patienten durch eine Hyperthermiebehandlung sollte der Einsatz dieses Verfahrens in Kombination mit einer Chemotherapie im Rahmen multimodaler Therapieansatze als Standardtherapieoption erwogen werden.