Different Prevalence of Alarm, Dyspeptic and Reflux Symptoms in Patients with Cardia and Non-cardia Gastric Cancer.

BACKGROUND AND AIMS: Symptoms of patients with gastric cancer (GC) are often unspecific and differences in symptoms between patients with cardia and non-cardia GC have been poorly investigated. We aimed to characterize symptoms of patients with cardia and non-cardia GC. METHODS: Patients with cardia (Siewert type II and III) and non-cardia GC were recruited in the German multicenter cohort of the Gastric Cancer Research (staR) study between 2013 and 2017. Alarm, dyspeptic and reflux symptoms at the time of presentation were documented using a self-administered questionnaire. RESULTS: A completed self-administered questionnaire was available for 568/759 recruited patients (132 cardia GC, 436 non-cardia GC, male 61%, mean age 64 years). Dyspeptic symptoms were more common in patients with non-cardia GC (69.0 vs. 54.5%, p=0.0024). Cardia GC patients reported more frequently alarm symptoms (69.7 vs. 44.7%, p<0.0001), and were more likely to have Union for International Cancer Control (UICC) stage III-IV (54.1vs. 38.9%, p=0.0034). Especially, dysphagia and weight loss were more common in patients with cardia GC (49.2 vs. 6.4 %, p<0.0001 and 37.1 vs. 25.7%, p=0.02, respectively). No differences between the two groups were observed with respect to reflux symptoms. Patients with alarm symptoms were more likely to have UICC stage III-IV at presentation (69.4 vs. 42.9%, p<0.0001). CONCLUSIONS: In clinical practice the symptom pattern at presentation may serve as a hint for tumor localization. Despite the fact that they are common in the general population, dyspeptic symptoms offer a chance for earlier GC detection. Thus, in patients with dyspeptic symptoms who fail empiric approaches, endoscopy should not be delayed.

Advanced Pancreatic Ductal Adenocarcinoma: Moving Forward.

Globally, the death rate of pancreatic ductal adenocarcinoma (PDAC) has doubled over 30 years and is likely to further increase, making PDAC a leading cause of cancer-related death in the coming years. PDAC is typically diagnosed at an advanced stage, and modified FOLFIRINOX or nab-paclitaxel and gemcitabine are the mainstay of systemic therapy. For elderly patients with good performance status, low-dose treatment can preserve quality of life without compromising cancer control or survival. Maintenance therapy should be considered in PDAC patients achieving disease control with systemic therapy. In particular, olaparib has demonstrated a progression-free survival benefit of 3.6 months in a subgroup of PDAC patients with germline BRCA1/2 mutations (ca. 10% of all PDAC). Pancreatic enzyme replacement therapy is often omitted in the treatment of patients with PDAC, with possibly deleterious consequences. Small intestinal bacterial overgrowth is highly prevalent in patients with PDAC and should be considered in the diagnostic algorithm of PDAC patients with bloating and diarrhea. Rivaroxaban has been associated with a reduced risk of thrombosis without an increase in major bleeding events, and its use should be considered in every patient with advanced PDAC undergoing systemic therapy.

Maintenance Therapy with FOLFIRI after FOLFIRINOX for Advanced Pancreatic Ductal Adenocarcinoma: A Retrospective Single-Center Analysis.

OBJECTIVES: Patients with pancreatic ductal adenocarcinoma (PDA) receiving FOLFIRINOX often develop oxaliplatin-induced polyneuropathy, which limits the continuation of this therapy. We evaluated the efficacy and safety of FOLFIRI maintenance treatment after FOLFIRINOX induction in a retrospective single-center study. METHODS: Patients with advanced PDA treated with FOLFIRI as maintenance therapy after achieving disease control under FOLFIRINOX according to the local operating procedure between 2011 and 2016 were identified. Medical records of this group were evaluated retrospectively. RESULTS: Overall, 22 patients with PDA were treated with FOLFIRI (mean age 59 years, 55% female, 45% male). Before receiving FOLFIRI, all patients were treated with FOLFIRINOX for a median of 4 months. The median progression-free survival (PFS) under FOLFIRI maintenance therapy was 8 months. Side effects grade 3-4 (CTCAE v4.0) were observed in 18% of patients receiving FOLFIRI. Considering together FOLFIRINOX induction and subsequent FOLFIRI maintenance therapy, the median PFS was 11 months. The median overall survival (OS) from the beginning of palliative treatment was estimated at 46 months. CONCLUSIONS: In the selected group of PDA patients achieving disease control with FOLFIRINOX, FOLFIRI maintenance therapy was feasible, safe, and effective, with some patients achieving long-term disease stabilization.

The BRAF Status May Predict Response to Sorafenib in Gastrointestinal Stromal Tumors Resistant to Imatinib, Sunitinib, and Regorafenib: Case Series and Review of the Literature.

BACKGROUND: Sorafenib has shown efficacy in patients with imatinib-, sunitinib-, and regorafenib-resistant gastrointestinal stromal tumors (GISTs). No biomarker is currently available for predicting response to sorafenib in patients with GIST. METHODS: We herein report 3 patients with imatinib-, sunitinib-, and regorafenib-resistant metastasized GISTs, who were treated with sorafenib. Besides receptor tyrosine kinase KIT and platelet-derived growth factor receptor α, also BRAF was tested for mutations. RESULTS: Sorafenib therapy induced a long-term disease control in 2 out of 3 patients over a period of 49 and 19 months, respectively. Sorafenib-responsive GISTs were BRAF wild-type, whereas the sorafenib-resistant GIST carried a BRAF V600E mutation. CONCLUSION: We confirm sorafenib as an effective therapeutic option in patients with imatinib-, sunitinib-, and regorafenib-resistant GISTs. Larger studies are required to corroborate whether BRAF mutation may predict sorafenib resistance in GISTs.

Helicobacter pylori eradication therapy is not associated with the onset of inflammatory bowel diseases. A case-control study.

BACKGROUND AND AIMS: A negative association between H. pylori and inflammatory bowel disease (IBD) has been previously reported. There were also case reports suggesting a new onset of IBD 6-12 months after H. pylori eradication therapy. In a case-control study we investigated whether previous H. pylori eradication therapy was associated with the risk of developing IBD. METHODS: IBD outpatients with both Crohn´s disease (CD) and ulcerative colitis (UC) were enrolled. Age- and sex-matched blood donors served as controls in a 1:2 fashion. Information on demographics, medical history, previous H. pylori infection and eradication therapy was recorded. Serum samples for H. pylori serology testing (anti-H. pylori-IgG and anti-CagA-IgG) were obtained. Controls that received H. pylori eradication therapy during the 12 months previous to enrollment were excluded. RESULTS: Overall, 127 IBD patients (CD N= 90; UC N=37) and 254 controls were enrolled. The prevalence of H. pylori infection (positive H. pylori serology and/or previous eradication) in IBD patients and controls was 11% and 23%, respectively (OR 0.4, 95% CI 0.21-0.74, p<0.003). Four patients (3%) developed IBD (3 MC and 1 CU) after receiving successful H. pylori eradication (latency 6-12 months). The rate of previous H. pylori eradication therapy in patents who successively developed IBD was lower but not statistically different from that observed in the control group (OR 0.43, 95% CI 0.14-1.29, p=0.16). CONCLUSIONS: In our study previous H. pylori eradication therapy was not associated with the onset of IBD. Whether in a subgroup of patients, H. pylori eradication therapy may trigger a latent IBD, cannot be excluded.

Combined Systemic Chemotherapy and CT-Guided High-Dose-Rate Brachytherapy for Isolated Local Manifestation of Pancreatic Cancer after Surgical Resection.

BACKGROUND: Prospective data on the optimal management of patients with pancreatic ductal adenocarcinoma (PDA) and isolated local manifestation (ILM) after surgery are lacking. Hence, no statements with respect to this entity have been released from most international guidelines including European Society for Medical Oncology, National Comprehensive Cancer Network, and American Society for Clinical Oncology. METHODS: We report for the first time a case-series of 3 patients with PDA and ILM receiving combined systemic chemotherapy and CT-guided high-dose-rate interstitial brachytherapy (CT-HDRBT). RESULTS: CT-HDRBT allowed in all patients with pronounced chemotherapy-induced side effects either a pause of cytostatic treatment or de-escalation to a "maintenance" therapy (dose reduction, interval prolongation, scheme modification with withdrawal of most toxic drugs). CONCLUSION: Combining CT-HDRBT to systemic chemotherapy in patients with PDA and ILM is feasible and safe. As for patients with PDA and ILM no standard of care exists, designing an appropriate randomized prospective trial for this highly selected group of patients is challenging.

Recurrent diffuse gastric bleeding as a leading symptom of gastrointestinal AL amyloidosis.

Amyloidosis is a rare disease (incidence about 0.8/100 000) characterized by extracellular tissue deposition of fibrils composed of low molecular weight subunits of a variety of serum proteins. Clinical manifestations are largely determined by the type of precursor protein, the tissue distribution and the amount of amyloid deposition. Gastrointestinal (GI) manifestations of amyloidosis are even more uncommon (3 % of all amyloidosis patients). Symptoms of GI amyloidosis are nonspecific, heterogeneous, and include weight loss, GI bleeding, heartburn, early satiety, diarrhea and abdominal pain. The histopathological examination of biopsy specimens from the GI tract leads to the diagnosis.Herein we report the case of a 63-year-old woman with recurrent diffuse gastric bleeding. Endoscopic biopsies revealed distinct amyloid deposits in the mucosa of the stomach. Further histochemical assessment confirmed systemic light chain (AL) amyloidosis with clinically predominant gastrointestinal manifestation. An induction therapy with bortezomib and dexamethasone was initiated.Our report illustrates the importance of the multidisciplinary approach for diagnosis and management of AL amyloidosis. Current treatment of systemic AL amyloidosis is based on cytostatic targeting of immunoglobulin producing plasma cells. Therapeutic options are limited and highly toxic, making the development of novel treatment approaches an urgent need.

Neoadjuvant treatment with cisplatin and S-1 in elderly patients with oesophagogastric adenocarcinoma and locoregional disease: Two case reports and review of the literature.

Perioperative platinum/fluoropyrimidine-based chemotherapy is the therapeutic standard for oesophagogastric cancer (OAC) patients with locoregional disease. The preoperative condition directly affects postoperative prognosis; thus, particularly for elderly patients, a perioperative regimen with a favourable side effect profile is highly desirable. In the palliative setting, the combination of cisplatin and S-1 (Cis/S-1) was found to be as effective as cisplatin/5-fluorouracil, but with a more favourable side effect profile. However, no data on this combination have been reported in the perioperative setting in Caucasian patients. To the best of our knowledge, this is the first report on the treatment outcome of two elderly Caucasian OAC patients with locoregional disease receiving two neoadjuvant 4-week cycles of intravenous Cis/S-1. Both patients tolerated the doublet therapy well. No treatment delay or dose reduction was required. In both cases, preoperative staging revealed a clear response and complete surgical resection could be performed without any complications.

Perioperative Therapy of Oesophagogastric Adenocarcinoma: Mainstay and Future Directions.

Perioperative chemotherapy improves overall survival in patients with oesophagogastric adenocarcinoma (OAC) and locoregional disease. The mainstay of perioperative chemotherapy in these patients is a platinum/fluoropyrimidine combination. The phase III FLOT4 trial has shown that the FLOT triplet regimen (oxaliplatin, infusional 5-FU, and docetaxel) improves the outcome of patients with OAC and locoregional disease as compared to the ECF triplet (epirubicin, cisplatin, and infusional 5-FU). Targeted therapies have currently no role in the perioperative setting for the treatment of patients with OAC. For patients with oligometastatic disease, upfront gastrectomy followed by chemotherapy did not show any survival benefit compared with chemotherapy alone and thus should be discouraged. Whether surgery should be offered to patients with metastatic OAC achieving a systemic control after upfront chemotherapy is under scrutiny in the phase III FLOT5/Renaissance trial. After neoadjuvant treatment, lymph node status but not pathologic tumor response is an independent factor in the prediction of overall survival. Growing evidence suggests that perioperative chemotherapy may be associated with an increased mortality risk in patients with microsatellite instable (MSI)/mismatch repair-deficient (MMRD) adenocarcinoma, thus validating poor responsiveness to chemotherapy in MSI patients with locoregional disease.

Safe administration of S-1 after 5-fluorouracil-induced cardiotoxicity in a patient with colorectal cancer.

Cardiotoxicity is a rare but challenging complication of 5-fluorouracil (5-FU) therapy. Compared with 5-FU, after application of S-1 lower plasma levels of the cardiotoxic metabolite alpha-fluoro-beta-alanine have been reported. Evidence for safe administration of S-1 following 5-FU cardiotoxicity is limited to a case report in an Asian patient. Herein we report the first case of S-1 application after 5-FU cardiotoxicity in a Caucasian patient.A 67-year-old man with right-sided metastatic colorectal cancer and history of 5-FU cardiotoxicity had a progressive disease after 8-month therapy with irinotecan and bevacizumab. In consideration of known 5-FU cardiotoxicity, he was referred to our department for therapy counselling. We started a combination therapy with S-1, oxaliplatin and bevacizumab. The treatment was well tolerated without any cardiac problems.Our report confirms the safety of S-1 in cases of 5-FU cardiotoxicity also in a Caucasian patient.

Prevalence of Helicobacter pylori infection among blood donors in Saxony-Anhalt, Germany - a region at intermediate risk for gastric cancer.

Background In the federal state of Saxony-Anhalt, gastric cancer (GC) incidence ranks among the highest in Germany. Helicobacter pylori prevalence is a surrogate marker for GC risk in a given population. In 2010 we reported an H. pylori seroprevalence of 44.4 % in patients at the emergency ward of the University Hospital of Magdeburg, the capital of Saxony-Anhalt. Our aim is to update these findings in a cohort of healthy blood donors from the same region. Materials and methods The sera of 516 consecutive blood donors (40.1 ±â€Š14.1 years; 286 males and 230 females) were tested for antibodies against H. pylori and CagA. Data on demographics and previous H. pylori eradication therapy were obtained by means of a structured questionnaire. Blood donors with positive serology for H. pylori or CagA and/or history of eradication therapy were classified as H. pylori-positive. Results Overall, 28.9 % of the study cohort were H. pylori-positive. The prevalence was higher in older generations (9 % in 18 - 20 years up to 47 % in 61 - 70 years). In 44.4 % of H. pylori IgG-positive donors, CagA serology was also positive. This proportion was not age-dependent. Study participants with siblings were by trend more often H. pylori-positive (p = 0.066). Conclusion Compared to our previous study in patients at the emergency ward, we found by trend lower age-related H. pylori prevalence rates. In our cohort of healthy blood donors, we confirmed a lower H. pylori prevalence in younger generations.