Palliation with a multimodality treatment including hypoxic pelvic perfusion for unresectable recurrent rectal cancer: outcomes based on a retrospective study

Patients with unresectable recurrent rectal cancer that progresses after systemic chemotherapy and radiotherapy are candidates for palliation with hypoxic pelvic perfusion (HPP). The aim of this observational retrospective study was to evaluate if a multimodality treatment including HPP and targeted-therapy may be useful to prolong clinical responses and survival of these patients. From a cohort of 77 patients with unresectable recurrent rectal cancer in progression after standard treatments and submitted to HPP, 21 patients underwent repeat HPP using mitomycin C (MMC) at the dose of 25 mg/m2. After the last HPP, 7 patients received a targeted-therapy with cetuximab according to overexpression of epidermal growth factor receptor in recurrence cancer cells. The median overall survival of these 21 patients from the diagnosis of unresectable recurrent rectal cancer was 23 months (iqr 18-24). After the first HPP, the median survival of the 21 patients until death or end of follow-up was 10 months (iqr 9-13). The 1-year and 2-year survival rates were 71.4%, and 4.8%, respectively. From the first HPP, age\u2009>\u200960 years, a recurrence shrinkage of at least 30% (partial response), and the addition of a post-HPP targeted-therapy with cetuximab significantly affected survival (P\u2009<\u20090.04). In conclusion, repeated MMC-HPP followed by targeted-therapy seems to be an effective palliative treatment for patients with unresectable recurrent rectal cancer in progression after systemic chemotherapy and radiation but the results of this study have to be confirmed by a larger phase III trial

Food and Wine Tourism in Basilicata

AbstractThe study attempted to investigate the potential role of labelled food and wine products on the development process of an essentially rural region such as Basilicata. The main objective that raises the research is a mapping of the territories affected by the phenomenon of food and wine tourism in order to define a positioning map built on the comparison of two variables: the food and wine product dimension and the supply of local tourist services dimension, in order to determine districts and related products more suited to express a food and wine tourism product.It contains important policy guidance for those involved in the agriculture supply chain and tourism in Basilicata

Para-aortic lymphadenectomy in surgery for gastric cancer: current indications and future perspectives

Involvement of para-aortic nodes (PAN) has been detected at pathological examination in 10-25% of locally advanced gastric cancer. Based on these data of nodal diffusion, the lymphadenectomy of para-aortic stations would be desirable in locally advanced gastric cancer. However, the debate on the oncological benefit of para-aortic nodes dissection is still not solved. A review of the literature was performed and papers reporting either the rate of para-aortic nodal metastases or the long-term survival outcomes after D2+ para-aortic nodes dissection (PAND) or D3 lymphadenectomy were descriptively reported. The literature survey yielded 14 studies. Most of the papers show the outcome of series of advanced gastric cancer treated with surgery alone, while starting from 2012, 3 articles report the outcomes of D2 + PAND or D3 lymphadenectomy after preoperative chemotherapy. The rate of PAN metastases ranges between 8.5 and 28% in surgical series. Survival outcomes largely improved in series of patients treated with multimodal approach compared to those of surgery alone. In patients with clinically detected para-aortic nodal metastases, preoperative chemotherapy followed by PAND is indicated. More data are needed to clarify the indication to prophylactic PAND in the era of multimodal treatment, anyway super-extended lymphadenectomies have to be performed by experienced surgeons in dedicated centres

Extension of lymphadenectomy for gastric cancer:Audit at European specialist centres.

Gastric cancer is still one of the leading causes of cancer-related deaths worldwide, and its treatment management differs between Eastern Asia and Western countries. Screening program, early diagnosis, and surgical treatment was primarily established in Japan and was rapidly disseminated to other countries. In other parts of the world, such as the USA and Western Europe, the incidence of gastric cancer has declined, and efforts for screening and early detection have not been an issue of higher priority over the management of other diseases. Thus, gastric cancer in the West is often more advanced and is either inoperable or needs more radical surgery for resection. The only treatment method that can potentially cure gastric cancer is the surgical approach. Depending on the extension of the tumor, surgeons may execute an operation that involves removing all or part of the stomach with some nearby lymph nodes (lymphadenectomy). Lymphadenectomy is a crucial step during surgical operation that involves the removal of one or more lymph nodes located in the drainage area of a tumor, in which there is a high possibility of lymph node metastasis. The Japanese guidelines define the criteria of lymphadenectomy procedure into D1 D1+ or D2 according to the type of gastrectomy executed. The extent of lymphadenectomy has long been a subject of debate. Indeed, Japanese surgeons introduced extended lymphadenectomy (D2), which has also been progressively adopted in Europe and included in almost all international guidelines. However, the procedure requires a long learning curve, which involves a high volume of interventions; therefore, US guidelines do not recommend the D2, and many Italian and European centres do not yet perform this procedure. Indeed, the current European Consensus guidelines recommend D2 dissection in regional specialist centres for patients with moderate comorbidity. However, compliance with guidelines is unclear, and in some recent RCTs, the standard approach of surgical treatment is at the "surgeon's discretion." This study aims to evaluate the current practice of D2 lymphadenectomy in Europe to determine any variation in practice and compare it with the Japanese guidelines. The study consists of two parts: first, a questionnaire based on hypothetical clinical scenarios was administered to expert surgeons belonging to European Chapter of the International Gastric Cancer Association from high-volume European centers. They were asked to select the appropriate lymphadenectomy extension for each hypothetical case and the associated lymph node stations to remove. In the second part of the study, the same surgeons were asked to collect their data about gastric cancer gastrectomies performed in 2015 for comparative analysis. The study results show that the expert surgeons of high-volume centres are quite in agreement with the choice of D2 lymphadenectomy in the different clinical scenarios. The surgical choice seems to have been influenced by the tumor stage, site, and histology of the tumor. More specifically, the D2 procedure is recommended for cases with diffuse histology compared to tumors with intestinal histology. However, the selection of the D2 dissection procedure rarely conformed to Japanese guidelines: the choice of lymph node stations revealed the presence of a wide variation in execution. In the review of the gastrectomy experience, it was observed that a high surgical standard was achieved: in fact, in 97% of gastric cancer gastrectomies after D2, an adequate number of lymph nodes (≥15 nodes) were removed. In conclusion, even if an adequate lymphadenectomy was obtained in almost all cases in dedicated centers, there is still significant variability in the number of recovered lymph nodes. The histology of the tumor largely influences the surgeon's choice regarding the extent of the lymphadenectomy; however, the role of histology in the planning of surgical procedures is not considered in the current guidelines and must be verified in prospective studies

Methylation Dynamics of RASSF1A and Its Impact on Cancer

5-methyl cytosine (5mC) is a key epigenetic mark entwined with gene expression and the specification of cellular phenotypes. Its distribution around gene promoters sets a barrier for transcriptional enhancers or inhibitor proteins binding to their target sequences. As a result, an additional level of regulation is added to the signals that organize the access to the chromatin and its structural components. The tumor suppressor gene RASSF1A is a microtubule-associated and multitasking scaffold protein communicating with the RAS pathway, estrogen receptor signaling, and Hippo pathway. RASSF1A action stimulates mitotic arrest, DNA repair and apoptosis, and controls the cell cycle and cell migration. De novo methylation of the RASSF1A promoter has received much attention due to its increased frequency in most cancer types. RASSF1A methylation is preceded by histones modifications and could represent an early molecular event in cell transformation. Accordingly, RASSF1A methylation is proposed as an epigenetic candidate marker in many cancer types, even though an inverse correlation of methylation and expression remains to be fully ascertained. Some findings indicate that the epigenetic abrogation of RASSF1A can promote the alternative expression of the putative oncogenic isoform RASSF1C. Understanding the complexity and significance of RASSF1A methylation is instrumental for a more accurate determination of its biological and clinical role. The review covers the molecular events implicated in RASSF1A methylation and gene silencing and provides a deeper view into the significance of the RASSF1A methylation patterns in a number of gastrointestinal cancer types

Surgical treatment of hepatic metastases from gastric cancer

The purpose of the study was to investigate the clinical factors influencing the prognosis of patients submitted to hepatectomy for metastases from gastric cancer and their clinical role. We conducted a retrospective multicentre review. We evaluated how survival from surgery was influenced by patient-related, tumour-related and treatment-related prognostic factors. We analysed data on 144 patients submitted to hepatectomy for metastases from gastric cancer, in the synchronous and metachronous setting. In 117 cases, an R0 resection was achieved, while in 27 an R\u2009+\u2009hepatic resection was performed. Chemotherapy was administered to 55 patients. Surgical mortality was 2.1% and morbidity 21.5%. One-, 3-, and 5-year OS rates after surgery were 49.9, 19.4 and 11.6%, respectively, with a median OS of 12.0 months. T4 gastric cancer, H3 hepatic involvement, non-curative resection, recurrence after surgery, and abstention from chemotherapy were associated with a worse prognosis. Factor T and H displayed a clear (p\u2009<\u20090.001) cumulative effect. Our data show that R0 resection must be pursued whenever possible. The treatment of T4 gastric cancer with hepatic bilateral and diffuse metastasis (H3) should be considered carefully or it should be probably avoided. Finally, a multimodal treatment associating surgery and chemotherapy offers the best survival results

Multicenter Study of Presentation, Management, and Postoperative and Long-Term Outcomes of Septegenerians and Octogenerians Undergoing Gastrectomy for Gastric Cancer

Background: The optimal treatment strategy for elderly patients with gastric cancer is still controversial. This study aimed to assess the impact of age on short- and long-term outcomes after treatment for primary gastric cancer. Methods: From January 2004 to December 2014, a total of 507 patients underwent gastrectomy for gastric adenocarcinoma at two high-volume upper gastrointestinal (GI) centers. The patients were classified into three groups as follows: group A (patients ≤ 69 years old, n = 266), group B (patients 70–79 years old, n = 166), and group C (patients ≥ 80 years old, n = 75). Clinicopathologic characteristics as well as, short- and long-term outcomes were compared between the groups. Results: The patients in groups B and C had more comorbidities, whereas the younger subjects (group A) had more advanced tumor stages. Less extensive surgery was performed in the groups B and C. Older patients (age ≥ 70 years) had more postoperative medical complications. Moreover, group C had a higher postoperative mortality rate (8.1%) than group A (1.8%) or group B (1.9%). In the multivariable analysis, age older than 80 years (group C) was a negative independent factor for overall survival (OS) (hazard ratio [HR], 2.36) compared with group A, whereas group B seemed to have a comparable risk (HR, 1.37). Notably, the three groups did not show significant differences in disease-related survival (DRS). Conclusion: The data suggest that patients 70–79 years of age show a risk of postoperative death comparable with that of younger subjects. However, patients older than 80 years should be carefully selected for surgical treatment due to the increased risk of postoperative mortality

Antithrombotic therapy in patients undergoing transcatheter aortic valve replacement: the complexity of the elderly

Along with epidemiologic transitions of the global population, the burden of aortic stenosis (AS) is rapidly increasing and transcatheter aortic valve replacement (TAVR) has quickly spread; indeed, it is nowadays also employed in treating patients with AS at intermediate operative risk. Nonetheless, the less invasive interventional strategy still carries relevant issues concerning post-procedural optimal antithrombotic strategy, given the current indications provided by guidelines are not completely supported by evidence-based data. Geriatric patients suffer from high bleeding and thromboembolic risks, whose balance is particularly subtle due to the presence of concomitant conditions, such as atrial fibrillation and chronic kidney disease, that make the post-TAVR antithrombotic management particularly insidious. This scenario is further complicated by the lack of specific evidence regarding the 'real-life' complex conditions typical of the geriatric syndromes, thus, the management of such a heterogeneous population, ranging from healthy ageing to frailty, is far from being defined. The aim of the present review is to summarize the critical points and the most updated evidence regarding the post-TAVR antithrombotic approach in the geriatric population, with a specific focus on the most frequent clinical settings

Iron overload enhances human mesenchymal stromal cell growth and hampers matrix calcification

Background Iron overload syndromes include a wide range of diseases frequently associated with increased morbidity and mortality. Several organs are affected in patients with iron overload including liver, heart, joints, endocrine glands, and pancreas. Moreover, severe bone and hemopoietic tissue alterations are observed. Because of the role of bone marrow mesenchymal stromal cells (BM-MSCs) in bone turnover and hematopoiesis, iron effects on primary BM-MSCs cultures were evaluated. Methods Primary human BM-MSCs cultures were prepared and the effects of iron on their proliferation and differentiation were characterized by biochemical analyses and functional approaches. Results Addition of iron to the culture medium strongly increased BM-MSCs proliferation and induced their accelerated S phase entry. Iron enters BM-MSCs through both transferrin-dependent and transferrin-independent mechanisms, inducing the accumulation of cyclins E and A, the decrease of p27Kip1, and the activation of MAPK pathway. Conversely, neither apoptotic signs nor up-regulation of reactive oxygen species were observed. Iron inhibited both differentiation of BM-MSCs into osteoblasts and in vitro matrix calcification. These effects result from the merging of inhibitory activities on BM-MSCs osteoblastic commitment and on the ordered matrix calcification process. Conclusions We demonstrated that BM-MSCs are a target of iron overload. Iron accelerates BM-MSCs proliferation and affects BM-MSCs osteoblastic commitment, hampering matrix calcification. General Significance Our study reports, for the first time, that iron, at concentration found in overloaded patient sera, stimulates the growth of BM-MSCs, the BM multipotent stromal cell component. Moreover, iron modulates the physiological differentiation of these cells, affecting bone turnover and remodeling

Primary Tumor Resection for Metastatic Colorectal, Gastric and Pancreatic Cancer Patients: In Search of Scientific Evidence to Inform Clinical Practice

The management of the primary tumor in metastatic colorectal, gastric and pancreatic cancer patients may be challenging. Indeed, primary tumor progression could be associated with severe symptoms, compromising the quality of life and the feasibility of effective systemic therapy, and might result in life-threatening complications. While retrospective series have suggested that surgery on the primary tumor may confer a survival advantage even in asymptomatic patients, randomized trials seem not to definitively support this hypothesis. We discuss the evidence for and against primary tumor resection for patients with metastatic gastrointestinal (colorectal, gastric and pancreatic) cancers treated with systemic therapies and put in context the pros and cons of the onco-surgical approach in the time of precision oncology. We also evaluate current ongoing trials on this topic, anticipating how these will influence both research and everyday practice