Prognosis and tumor biology of pancreatic cancer patients with isolated lung metastases: translational results from the German multicenter AIO-YMO-PAK-0515 study.

BACKGROUND: Pulmonary metastasis (M1-PUL) as first site of dissemination in pancreatic ductal adenocarcinoma (PDAC) is a rare event and may define a distinct biological subgroup. PATIENTS AND METHODS: Arbeitsgemeinschaft Internistische Onkologie-Young Medical Oncologists-Pankreas-0515 study (AIO-YMO-PAK-0515) was a retrospective German multicenter study investigating clinical and molecular characteristics of M1-PUL PDAC patients; 115 M1-PUL PDAC patients from 7 participating centers were included. Clinical characteristics and potential prognostic factors were defined within the M1-PUL cohort. Archival tumor samples were analyzed for Her2/neu, HNF1A and KRT81 expression. Additionally, messenger RNA (mRNA) expression analysis (using a 770-gene immune profiling panel) was carried out in the M1-PUL and in a control cohort (M1-ANY). RESULTS: Median overall survival in the entire M1-PUL cohort was 20 months; the most favorable prognosis (median survival: 28 months) was observed in the subgroup of 66 PDAC patients with metachronous lung metastases after previous curative-intent surgery. The number of metastatic lesions, uni- or bilateral lung involvement as well as metastasectomy were identified as potential prognostic factors. Her2/neu expression and PDAC subtyping (by HNF1A and KRT81) did not differ between the M1-PUL and the M1-ANY cohort. mRNA expression analysis revealed significant differentially expressed genes between both cohorts: CD63 and LAMP1 were among the top 20 differentially expressed genes and were identified as potential mediators of organotropism and favorable survival outcome of M1-PUL patients. CONCLUSION: M1-PUL represents a clinically favorable cohort in PDAC patients. Site of relapse might already be predetermined at the time of surgery and could potentially be predicted by gene expression profiling.

Real-World Efficacy of Nintedanib Plus Docetaxel After Progression on Immune Checkpoint Inhibitors: Results From the Ongoing, Non-interventional VARGADO Study.

AIMS: To evaluate the efficacy and safety of nintedanib plus docetaxel in patients with advanced adenocarcinoma non-small cell lung cancer (NSCLC) who progressed after chemotherapy and immune checkpoint inhibitor (ICI) therapy. MATERIALS AND METHODS: VARGADO (NCT02392455) is an ongoing, prospective, non-interventional, real-world study of nintedanib plus docetaxel after first-line chemotherapy in the routine clinical treatment of patients with locally advanced, metastatic or locally recurrent adenocarcinoma NSCLC. Data were collected during routine visits. We report the results from cohort B (n = 80), who received third-line nintedanib plus docetaxel after first-line chemotherapy and second-line ICI therapy. RESULTS: The median duration of follow-up was 12.4 months. Median progression-free survival from initiation of third-line nintedanib plus docetaxel was 6.4 months (95% confidence interval 4.8, 7.3); median overall survival was 12.1 months (95% confidence interval 9.4, 13.5). The 1-year overall survival rate after initiation of third-line nintedanib plus docetaxel treatment (primary end point) was 52% (95% confidence interval 38.0%, 64.4%). Among 64 patients with a documented response, the objective response rate was 50% (n = 32; one complete response and 31 partial responses) and the disease control rate was 86% (n = 55). There were no new safety signals or unexpected toxicities. Among all treated patients, 74% (n = 59) experienced drug-related adverse events, most commonly (nintedanib-related/docetaxel-related) diarrhoea (34%/24%), a decreased white blood cell count (11%/19%) and nausea (13%/16%). CONCLUSIONS: Nintedanib plus docetaxel demonstrated a high response rate and disease stabilisation in the third-line setting after failure of prior chemotherapy and ICI treatment, with a manageable safety profile. These results suggest that nintedanib plus docetaxel represents an efficient treatment option after failure of prior ICIs. The ongoing VARGADO study provides valuable real-world data to inform clinical decision-making regarding treatment sequencing after chemotherapy and ICI failure in patients with adenocarcinoma NSCLC.

Alterations in regulatory T cells and immune checkpoint molecules in pancreatic cancer patients receiving FOLFIRINOX or gemcitabine plus nab-paclitaxel.

PURPOSE: This pilot study aimed on generating insight on alterations in circulating immune cells during the use of FOLFIRINOX and gemcitabine/nab-paclitaxel in pancreatic ductal adenocarcinoma (PDAC). PATIENTS AND METHODS: Peripheral blood mononuclear cells were isolated before and 30 days after initiation of chemotherapy from 20 patients with advanced PDAC. Regulatory T cells (FoxP3+) and immune checkpoints (PD-1 and TIM-3) were analyzed by flow cytometry and immunological changes were correlated with clinical outcome. RESULTS: Heterogeneous changes during chemotherapy were observed in circulating T-cell subpopulations with a pronounced effect on PD-1+ CD4+/CD8+ T cells. An increase in FoxP3+ or PD-1+ T cells had no significant effect on survival. An increase in TIM3+/CD8+ (but not TIM3+/CD4+) T cells was associated with a significant inferior outcome: median progression-free survival in the subgroup with an increase of TIM-3+/CD8+ T cells was 6.0 compared to 14.0 months in patients with a decrease/no change (p = 0.026); corresponding median overall survival was 13.0 and 20.0 months (p = 0.011), respectively. CONCLUSIONS: Chemotherapy with FOLFIRNOX or gemcitabine/nab-paclitaxel induces variable changes in circulating T-cell populations that may provide prognostic information in PDAC.

Afatinib plus gemcitabine versus gemcitabine alone as first-line treatment of metastatic pancreatic cancer: The randomised, open-label phase II ACCEPT study of the Arbeitsgemeinschaft Internistische Onkologie with an integrated analysis of the 'burden of therapy' method.

BACKGROUND: Targeting the epidermal growth factor receptor pathway remains controversial in pancreatic cancer. Afatinib is an oral irreversible ErbB family blocker approved in non-small-cell lung cancer. This open-label, multicenter, randomised phase II trial evaluated gemcitabine plus afatinib (Gem/afatinib) versus gemcitabine (Gem) alone as first-line treatment for metastatic pancreatic cancer. PATIENTS AND METHODS: Patients were randomised in a 2:1 ratio to either Gem (1000 mg/m2 weekly for three weeks followed by one week of rest, repeated every four weeks) and afatinib (40 mg orally once daily) or Gem alone. Overall survival (OS) was the primary study end-point. The novel BOTh©™ methodology was implemented to derive a quantitative estimate for the 'Burden of Therapy/Toxicity' (BOTh) for each patient on every day during the clinical study. RESULTS: One hundred nineteen patients from 25 centres were randomised, 79 patients for Gem/afatinib and 40 for Gem. Median OS was 7.3 months in the Gem/afatinib arm versus 7.4 months in the Gem-alone arm (hazard ratio [HR]: 1.06, p = 0.80). Median progression-free survival was identical in both arms (3.9 months versus 3.9 months, HR: 0.85, p = 0.43). Adverse events were more frequent in the Gem/afatinib arm, especially diarrhoea (71% vs. 13%) and skin rash (65% vs. 5%). The BOTh©™ analysis revealed a significantly higher burden of toxicity in the combination arm (p = 0.0005). CONCLUSION: The addition of afatinib to Gem did not improve treatment efficacy and was more toxic. The BOTh©™ methodology allowed a detailed insight into the course of treatment-related adverse events over the study period. The trial was registered at clinicaltrials.gov (NCT01728818) and Eudra-CT (2011-004063-77).

[Lymphangiomatosis: Rare Cause of Pleural Effusion]. / Lymphangiomatose − seltene Ursache eines Pleuraergusses.

A 33-year-old man presented to us with slowly progressive dyspnea. At the physical examination we found pleural effusion on the right side, lymph edema of the left lower limb and foot and blotchy map-like skin changes. The pleural puncture revealed a chylous effusion. In whole body MRI we saw the pleural effusion on the right, an increase in lymph vessels in the pelvis and paraaortic, and prominent chylous vessels. There was no bone involvement. The abdominal thoracic duct was enlarged by up to 3 mm. We diagnosed a general lymphatic anomaly (GLA) - lymphangiomatosis. GLA is a rare disease of unknown origin with dysplasia of the lymphatic system. The thoracic manifestation is often the development of chylous pleural effusions. However, many other organs can also be involved. Therapy includes in most cases symptomatic relief and the attempt to slow the progression of the disease.

[Lung Cancer with Prominent Mediastinal Lymphadenopathy - Who Thinks of NUT Carcinoma?] / Lungenkarzinom mit ausgeprägter mediastinaler Lymphadenopathie ­ wer denkt an ein NUT-Karzinom?

A 39-year-old woman presented with back pain at an orthopaedic clinic. Magnet resonance tomography revealed a spinal tumour. Further imaging also showed a pulmonary tumour, massive mediastinal lymphadenopathy as well as unilateral pleural effusion. Histology from biopsies from the spinal tumour and from a mediastinal lymph node revealed NUT carcinoma. The NUT carcinoma that earlier has been named NUT midline carcinoma is a very rare, aggressive tumour with a poor prognosis. Initially, the NUT carcinoma was thought to develop from organs in the midline such as upper airways or mediastinal cavity. However, the NUT carcinoma is not limited to structures in the midline. NUT carcinoma often affects young patients. Due to its low incidence, a standardized therapy could not be established until now.

Neurotrophic tropomyosin receptor kinase (NTRK) and nerve growth factor (NGF) are not expressed in Caucasian patients with biliary tract cancers: pooled data from three independent cohorts.

BACKGROUND: Neuronal signaling has been implicated in the pathophysiology of multiple malignancies. In biliary tract cancers (BTCs), tumor cell expression of nerve growth factor (NGF) and its receptor neurotrophic tropomyosin receptor kinase (NTRK) has been reported in Asian patients and linked to inferior clinical outcome. Furthermore, NTRK fusions have emerged as a promising target in various cancers. Expression patterns of these markers in Caucasian patients remain unknown. METHODS: In this study, 106 patients with BTCs were included. Immunohistochemistry for pan-NTRK and NGF-beta was performed on > 90 samples of this cohort. Additionally, samples from two independent cohorts, incorporating 254 cases, were used to confirm the findings of the original cohort. RESULTS: While expression of pan-NTRK and NGF-beta was readily detectable in peri-tumoral nerves, these markers were not detectable in malignant epithelial cells in our cohort. CONCLUSIONS: In a large cohort of Caucasian patients with BTC, NTRK and NGF-beta were not detectable, underscoring potential differences between Caucasian and Asian patient populations.

Repeated mutKRAS ctDNA measurements represent a novel and promising tool for early response prediction and therapy monitoring in advanced pancreatic cancer.

Background: The presence of mutated KRAS (mutKRAS ctDNA) in plasma samples has been consistently shown to be a negative prognostic indicator in pancreatic cancer (PC). Only small pilot studies have evaluated the value of serial mutKRAS ctDNA-measurements in PC. Patients and methods: The aim of the present study was to explore the potential of repeated mutKRAS ctDNA measurements for response prediction and therapy monitoring in advanced PC patients. We used the BEAMing technology to determine levels of mutKRAS ctDNA, CA 19-9, CEA and CYFRA 21-1 in 284 plasma samples of 54 patients with advanced PC receiving gemcitabine-based chemotherapy. Absolute levels and kinetics of mutKRAS ctDNA, CA 19-9, CEA and CYFRA 21-1 were correlated to radiological response, progression-free and overall survival. Results: mutKRAS ctDNA was present in a majority of advanced PC patients (n = 36/54, 67%) and indicated tissue KRAS mutation status with a high sensitivity (75%) and specificity (100%). The presence of mutKRAS ctDNA, as well as higher levels of CA 19-9, CEA and CYFRA 21-1 before initiation of the first-line chemotherapy, was significantly correlated to an adverse overall survival. During therapy, changes in mutKRAS ctDNA levels were more rapid and pronounced than changes in protein-based tumor markers. A decrease in mutKRAS ctDNA levels during therapy was an early indicator of response to therapy, while there was no significant correlation between kinetics of CA 19-9, CEA or CYFRA 21-1 and response to chemotherapy during the first four weeks of treatment. Repeated mutKRAS ctDNA measurements during follow-up appeared to be superior to protein-based tumor markers in detecting progressive disease (sensitivity: 83%, specificity: 100%). Conclusion: mutKRAS ctDNA kinetics appear to be a powerful and highly specific tool in early response prediction and therapy monitoring of advanced PC patients receiving chemotherapy.

Impact of TP53 mutation status on systemic treatment outcome in ALK-rearranged non-small-cell lung cancer.

Background: We analyzed whether co-occurring mutations influence the outcome of systemic therapy in ALK-rearranged non-small-cell lung cancer (NSCLC). Patients and methods: ALK-rearranged stage IIIB/IV NSCLC patients were analyzed with next-generation sequencing and fluorescence in situ hybridization analyses on a centralized diagnostic platform. Median progression-free survival (PFS) and overall survival (OS) were determined in the total cohort and in treatment-related sub-cohorts. Cox regression analyses were carried out to exclude confounders. Results: Among 216 patients with ALK-rearranged NSCLC, the frequency of pathogenic TP53 mutations was 23.8%, while other co-occurring mutations were rare events. In ALK/TP53 co-mutated patients, median PFS and OS were significantly lower compared with TP53 wildtype patients [PFS 3.9 months (95% CI: 2.4-5.6) versus 10.3 months (95% CI: 8.6-12.0), P < 0.001; OS 15.0 months (95% CI: 5.0-24.9) versus 50.0 months (95% CI: 22.9-77.1), P = 0.002]. This difference was confirmed in all treatment-related subgroups including chemotherapy only [PFS first-line chemotherapy 2.6 months (95% CI: 1.3-4.1) versus 6.2 months (95% CI: 1.8-10.5), P = 0.021; OS 2.0 months (95% CI: 0.0-4.6) versus 9.0 months (95% CI: 6.1-11.9), P = 0.035], crizotinib plus chemotherapy [PFS crizotinib 5.0 months (95% CI: 2.9-7.2) versus 14.0 months (95% CI: 8.0-20.1), P < 0.001; OS 17.0 months (95% CI: 6.7-27.3) versus not reached, P = 0.049] and crizotinib followed by next-generation ALK-inhibitor [PFS next-generation inhibitor 5.4 months (95% CI: 0.1-10.7) versus 9.9 months (95% CI: 6.4-13.5), P = 0.039; OS 7.0 months versus 50.0 months (95% CI: not reached), P = 0.001). Conclusions: In ALK-rearranged NSCLC co-occurring TP53 mutations predict an unfavorable outcome of systemic therapy. Our observations encourage future research to understand the underlying molecular mechanisms and to improve treatment outcome of the ALK/TP53 co-mutated subgroup.

[Granular Cell Tumor of the Lung - a Visual Diagnosis on Bronchoscopy?] / Granularzelltumor der Lunge ­ eine bronchoskopische Blickdiagnose?

A 38 years old patient presented with a progressive reduction of his general condition and weight loss. Chest imaging revealed consolidations and cavities suggesting a mycobacterial infection. For further diagnosis, a bronchoscopy was performed. In fact, a nontuberculous mycobacterial infection was found. As an incidental finding, we saw a white polypoid tumor in the middle lobe bronchus. The histology of this tumor revealed a granular cell tumor (GCT). The GCT is a rare tumor entity which occurs at different anatomical locations. In the lungs, the GCT may become symptomatic as it can cause bronchial obstruction. In chest imaging, it can manifest as infiltration, atelectasis or nodule. Likewise, GCT can be found as an incidental finding in bronchoscopy. First choice treatment is surgical resection of the tumor.

Efficacy of gemcitabine plus erlotinib in rash-positive patients with metastatic pancreatic cancer selected according to eligibility for FOLFIRINOX: A prospective phase II study of the 'Arbeitsgemeinschaft Internistische Onkologie'.

INTRODUCTION: In metastatic pancreatic ductal adenocarcinoma (mPDAC) treatment, erlotinib is known to be more effective in patients developing skin rash. Treatment with the FOLFIRINOX regimen is only performed in fit patients following defined inclusion criteria. The present study investigates the efficacy of gemcitabine plus erlotinib (gem/erlotinib) in rash-positive patients fit for FOLFIRINOX. PATIENTS AND METHODS: For this prospective phase II study, 150 patients were recruited in 20 centres. All patients received gem/erlotinib for 4 weeks (run-in phase); the subsequent treatment was determined by the development of skin rash: patients with rash grades 1-4 continued with gem/erlotinib, rash-negative patients were switched to FOLFIRINOX. Primary study end-point was to achieve a 1-year survival rate in rash-positive patients ≥40%. RESULTS: Ninety patients were deemed positive for skin rash by the end of the run-in phase, showing a 1-year survival rate of 40.0% (95% confidence interval [CI] 29.8-50.9). Median overall survival (OS) was 10.1 months, progression-free survival (PFS) was 3.8 months and overall response rate (ORR) was 23.3%. Patients switched to FOLFIRINOX (n = 27) had a 1-year survival rate of 48.1% (95% CI 28.7-68.1), a median OS of 10.9 months, a median PFS of 6.6 months and an ORR of 33.3%. Rash-negative patients had a lower quality of life at baseline but seemed to experience an improved control of pain during FOLFIRINOX. CONCLUSIONS: First-line treatment with gem/erlotinib was effective in fit, rash-positive mPDAC patients achieving a 1-year survival rate comparable to previous reports for FOLFIRINOX. The study was registered at clinicaltrials.gov (NCT0172948) and Eudra-CT (2011-005471-17).

The Amsterdam Cohort of Gender Dysphoria Study (1972-2015): Trends in Prevalence, Treatment, and Regrets.

BACKGROUND: Over the past decade, the number of people referred to gender identity clinics has rapidly increased. This raises several questions, especially concerning the frequency of performing gender-affirming treatments with irreversible effects and regret from such interventions. AIM: To study the current prevalence of gender dysphoria, how frequently gender-affirming treatments are performed, and the number of people experiencing regret of this treatment. METHODS: The medical files of all people who attended our gender identity clinic from 1972 to 2015 were reviewed retrospectively. OUTCOMES: The number of (and change in) people who applied for transgender health care, the percentage of people starting with gender-affirming hormonal treatment (HT), the estimated prevalence of transgender people receiving gender-affirming treatment, the percentage of people who underwent gonadectomy, and the percentage of people who regretted gonadectomy, specified separately for each year. RESULTS: 6,793 people (4,432 birth-assigned male, 2,361 birth-assigned female) visited our gender identity clinic from 1972 through 2015. The number of people assessed per year increased 20-fold from 34 in 1980 to 686 in 2015. The estimated prevalence in the Netherlands in 2015 was 1:3,800 for men (transwomen) and 1:5,200 for women (transmen). The percentage of people who started HT within 5 years after the 1st visit decreased over time, with almost 90% in 1980 to 65% in 2010. The percentage of people who underwent gonadectomy within 5 years after starting HT remained stable over time (74.7% of transwomen and 83.8% of transmen). Only 0.6% of transwomen and 0.3% of transmen who underwent gonadectomy were identified as experiencing regret. CLINICAL IMPLICATIONS: Because the transgender population is growing, a larger availability of transgender health care is needed. Other health care providers should familiarize themselves with transgender health care, because HT can influence diseases and interact with medication. Because not all people apply for the classic treatment approach, special attention should be given to those who choose less common forms of treatment. STRENGTHS AND LIMITATIONS: This study was performed in the largest Dutch gender identity clinic, which treats more than 95% of the transgender population in the Netherlands. Because of the retrospective design, some data could be missing. CONCLUSION: The number of people with gender identity issues seeking professional help increased dramatically in recent decades. The percentage of people who regretted gonadectomy remained small and did not show a tendency to increase. Wiepjes CM, Nota NM, de Blok CJM, et al. The Amsterdam Cohort of Gender Dysphoria Study (1972-2015): Trends in Prevalence, Treatment, and Regrets. J Sex Med 2018;15:582-590.

Magnetic resonance guided renal denervation using active tracking: first in vivo experience in Swine.

Interventional cardiovascular magnetic resonance (iCMR) might evolve as a technique to improve procedural success rates in cardiovascular interventions by combining intraprocedural guidance and simultaneous lesion imaging. The objective of the present study was to prove feasibility and estimate safety of renal sympathetic denervation guided by real-time iCMR using active tracking. Six pigs were examined in a 1.5 T MRI-System (Achieva, Philips Healthcare, Best, Netherlands) equipped with non-invasive hemodynamic control and in-room monitors displaying an interventional software platform [Interventional MRI Suite (iSuite), Philips Research, Hamburg, Germany]. MR-guided renal denervation was performed using a MR conditional non-irrigated ablation catheter with active tracking (Imricor, Burnsville, MN, USA). Real-time imaging for device guidance was performed with a TFE sequence, vessel patency was assessed with a 3D non-contrast angiography and velocity encoded imaging. Oedema of the renal artery was visualized by a high-resolution T2 SPIR sequence. Renal sympathetic denervation was feasible in all cases with survival of all animals. Non-contrast angiography displayed renal artery patency accompanied by equal flow conditions before and after the ablation in all cases as measured by velocity encoded imaging. Oedema imaging displayed a significant increase in relative signal intensity at renal artery ablations sites pre and post intervention (p < 0.05). The histologic examination revealed no signs of perforation or bleeding, while sufficient ablation lesions could be depicted. MR-guided renal sympathetic denervation using active tracking is feasible and the initial data suggest safety of this procedure. MR-guided renal sympathetic denervation offers the inherent strength of high soft tissue contrast thereby providing target information without the use of iodinated contrast agents or radiation.

[Bronchitis Plastica - Acute Dyspnea and Branching Airway Casts]. / Bronchitis plastica ­ Akute Luftnot und bronchiale Ausgusspräparate.

A 65 year old female presented to the emergency department with dyspnea and progressive cough with very viscous elongated secretion plugs. She suffered from multiple cardiac comorbidities and chronic heart failure. The CT scan of the thorax demonstrated extensive pulmonary infiltrates, unspecific mediastinal lymphadenopathy and enlargement of pulmonary lymph vessels. Bronchoscopy was performed and showed extensive occlusive bronchial casts. We diagnosed a case of bronchitis plastica. Therapy with inhalative heparin led to clinical improvement. CONCLUSION: bronchitis plastica is a rare disease with formation of occlusive bronchial casts. They are often found in cardiac disease or lymphatic disease.

Epstein-Barr virus-associated gastric cancer reveals intratumoral heterogeneity of PIK3CA mutations.

Background: Recent whole-genome sequencing identified four molecular subtypes of gastric cancer (GC), of which the subgroup of Epstein-Barr virus-associated GC (EBVaGC) showed a significant enrichment of PIK3CA mutations. We here aimed to validate independently the enrichment of PIK3CA mutations in EBVaGC of a Central European GC cohort, to correlate EBV status with clinico-pathological patient characteristics and to test for a major issue of GC, intratumoral heterogeneity. Patients and methods: In a first step, 484 GCs were screened for EBV and PIK3CA hot spot mutations of exon 9/20 using EBER in situ hybridization and pyrosequencing, respectively. Secondly, an extended sequencing of PIK3CA also utilizing next generation sequencing was carried out in all EBVaGCs and 96 corresponding lymph node metastases. Results: Twenty-two GCs were EBER-positive, all being of latency type I. Intratumoral heterogeneity of EBER-positivity was found in 18% of EBVaGCs. Twenty-three GCs held PIK3CA mutations in hot spot regions of exon 9 or 20, being significantly more common in EBVaGCs (P < 0.001). Subsequent extended sequencing of PIK3CA of EBVaGCs showed that 14% harvested three to five different PIK3CA genotypes (including wildtype) in the same primary tumor, albeit in histologically and spatially distinct tumor areas, and that intratumoral heterogeneity of PIK3CA was also present in the corresponding lymph node metastases. Conclusions: Our findings unravel issues of tumor heterogeneity and illustrate that the assessment of the EBV status in tissue biopsies might carry the risk of sampling errors, which may significantly hamper adequate molecular tumor classification in a more clinical setting. Moreover, this is the first report of intratumoral heterogeneity of PIK3CA mutations in GC, and our findings lead to the conclusion that PIK3CA mutant and -wildtype tumor subclones are skilled to metastasize independently to different regional lymph nodes.

[Pulmonary hypertension due to chronic lung disease: Recommendations of the Cologne Consensus Conference 2016]. / Pulmonale Hypertonie bei Lungenkrankheiten: Empfehlungen der Kölner Konsensus-Konferenz 2016.

The 2015 European Guidelines on Pulmonary Hypertension did not cover only pulmonary arterial hypertension (PAH) but also some aspects of pulmonary hypertension (PH) associated with chronic lung disease. The European Guidelines point out that the drugs currently used to treat patients with PAH (prostanoids, endothelin receptor antagonists, phosphodiesterase-5 inhibitors, sGC stimulators) have not been sufficiently investigated in other forms of PH. Therefore, the European Guidelines do not recommend the use of these drugs in patients with chronic lung disease and PH. This recommendation, however, is not always in agreement with medical ethics as physicians feel sometimes inclined to treat other form of PH which may affect quality of life and survival of these patients in a similar manner. To this end, it is crucial to consider the severity of both PH and the underlying lung disease. In June 2016, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany, to discuss open and controversial issues surrounding the practical implementation of the European Guidelines. Several working groups were initiated, one of which was dedicated to the diagnosis and treatment of PH in patients with chronic lung disease. The recommendations of this working group are summarized in the present paper.

HER2/neu testing in primary colorectal carcinoma.

BACKGROUND: Anti-HER2/neu therapy is well-established in breast and gastric carcinoma. The increased understanding of this pathway led to the identification of new promising drugs in addition to trastuzumab, offering further perspectives. The role of HER2/neu in colorectal carcinoma is controversially discussed, as discrepant data has been reported. METHODS: Here, we retrospectively assessed the prevalence of HER2/neu positivity in a large series of colorectal carcinoma, testing HER2/neu status according to current recommendations. We correlated the results to clinico-pathological data and patient survival. RESULTS: Overall, in 1645 primary colorectal carcinoma cases, 1.6% of the cases were HER2/neu positive. HER2/neu positivity significantly correlated with higher UICC stages (P=0.017) and lymph node metastases (P=0.029). In the subgroup of sigmoideal and rectal carcinomas, positive HER2/neu status was associated with T-category (P=0.041) and higher UICC stages (P=0.022). Although statistically not significant, HER2/neu-positive colorectal carcinomas displayed a tendency to poorer overall survival. CONCLUSIONS: These results illustrate the importance of testing HER2/neu by approved diagnostic techniques and scoring systems. We assume that although the prevalence of HER2/neu positivity in colorectal carcinoma is low, HER2/neu testing in advanced, nodal-positive colorectal carcinoma is reasonable, offering a potential target in high risk colorectal carcinoma.