Therapeutic Targets and Tumor Microenvironment in Colorectal Cancer

Colorectal cancer (CRC) is a genetically, anatomically, and transcriptionally heterogeneous disease. The prognosis for a CRC patient depends on the stage of the tumor at diagnosis and widely differs accordingly. The tumor microenvironment (TME) in CRC is an important factor affecting targeted cancer therapy. The TME has a dynamic composition including various cell types, such as cancer-associated fibroblasts, tumor-associated macrophages, regulatory T cells, and myeloid-derived suppressor cells, as well as extracellular factors that surround cancer cells and have functional and structural roles under physiological and pathological conditions. Moreover, the TME can limit the efficacy of therapeutic agents through high interstitial pressure, fibrosis, and the degradation of the therapeutic agents by enzymatic activity. For this reason, the TME is a fertile ground for the discovery of new drugs. The aim of this narrative review is to present current knowledge and future perspectives regarding the TME composition based on strategies for patients with CRC

Anti-Ri-associated paraneoplastic ophthalmoplegia-ataxia syndrome in a woman with breast cancer. A case report and review of the literature

Background: Breast cancer is the most common cancer in women. However, in the management of breast cancer, paraneoplastic neurological syndromes represent a diagnostic and therapeutic challenge. The diagnosis of paraneoplastic neurological syndromes is difficult due to the heterogeneity of symptoms, the timing of presentation, and the absence of antibodies, and it generally occurs before the diagnosis of breast cancer in 80% of patients who develop paraneoplastic neurological syndromes. We describe a 72-year-old woman with subacute ophthalmoplegia-ataxia syndrome who was subsequently diagnosed as having breast cancer and anti-Ri antibodies. Case presentation: A 72-year-old post-menopausal Caucasian woman, with a positive medical history for diabetes mellitus and hypertension, presented with a 3-month onset of blurred vision, diplopia, and progressive gait disturbance. Serological tests were positive for well-characterized onconeural antibodies (anti-Ri). A whole-body computed tomography scan revealed a nodular opacity under her left nipple and axillary adenopathy. A biopsy of her left breast was performed, and histological examination showed ductal carcinoma. She underwent a superoexternal quadrantectomy with left axillary dissection. The final diagnosis showed infiltrating ductal carcinoma of the breast (T1c N1 M0, stage IIA) associated with paraneoplastic ophthalmoplegia-ataxia syndrome. At a 6-month follow-up, she showed no clinical or instrumental evidence of neoplastic recurrence with partial clinical improvement of neurological symptoms, such as ataxia and diplopia. Conclusion: The diagnosis of paraneoplastic neurological syndromes is often late, as in this patient, but treatment at an early stage may provide a good prognosis. Furthermore, this is one of several cases of an anti-Ri paraneoplastic neurological syndrome not associated with myoclonus, which reinforces the belief that opsoclonus myoclonus syndrome is not pathognomonic of the associated anti-Ri paraneoplastic neurological syndromes

The "journal of functional morphology and kinesiology" journal club series: Highlights of recent papers in pediatric exercise

We are glad to introduce the ninth Journal Club. This edition is focused on several relevant studies published in the last years in the field of Pediatric Exercise, chosen by our Editorial Board members and their colleagues. We hope to stimulate your curiosity in this field and to share with you the passion for the sport as seen also from the scientific point of view. The Editorial Board members wish you an inspiring lecture

Mast cells, microRNAs and others: The role of translational research on colorectal cancer in the forthcoming era of precision medicine

Colorectal cancer (CRC) is a heterogeneous disease, molecularly and anatomically, that develops in a multi-step process requiring the accumulation of several genetic or epigenetic mutations that lead to the gradual transformation of normal mucosa into cancer. In fact, tumorigenesis is extremely complex, with many immunologic and non-immunologic factors present in the tumor microenvironment that can influence tumorigenesis. In the last few years, a role for mast cells (MCs), microRNAs (miRNAs), Kirsten rat sarcoma (KRAS) and v-raf murine sarcoma viral oncogene homologue B (BRAF) in cancer development and progression has been suggested, and numerous efforts have been made to thoroughly assess their correlation with CRC to improve patient survival and quality of life. The identification of easily measurable, non-invasive and cost-effective biomarkers, the so-called “ideal biomarkers”, for CRC screening and treatment remains a high priority. The aim of this review is to discuss the emerging role of mast cells (MCs), microRNAs (miRNAs), KRAS and BRAF as diagnostic and prognostic biomarkers for CRC, evaluating their influence as potential therapy targets in the forthcoming era of precision medicine

Esophageal resection in the ederly

The aging of the population and longer life expectancy entails an increased number of elderly patients with esophageal cancer and benign pathologies referred for surgical treatment. Esophageal cancer is a pathology that mainly involves elderly patients. The aim of this study is to assess the effects of age on the outcome of surgery for esophageal cancer and benign pathologies in patients treated in our departmen

Salt Tolerance of Archaeal Extremely Halophilic Lipid Membranes

The membranes of extremely halophilic Archaea are characterized by the abundance of a diacidic phospholipid, archaetidylglycerol methylphosphate (PGP-Me), which accounts for 50-80 mol% of the polar lipids, and by the absence of phospholipids with choline, ethanolamine, inositol, and serine head groups. These membranes are stable in concentrated 3-5 m NaCl solutions, whereas membranes of non-halophilic Archaea, which do not contain PGP-Me, are unstable and leaky under such conditions. By x-ray diffraction and vesicle permeability measurements, we demonstrate that PGP-Me contributes in an essential way to membrane stability in hypersaline environments. Large unilamellar vesicles (LUV) prepared from the polar lipids of extreme halophiles, Halobacterium halobium and Halobacterium salinarum, retain entrapped carboxyfluorescein and resist aggregation in the whole range 0-4 m NaCl, similarly to LUV prepared from purified PGP-Me. By contrast, LUV made of polar lipid extracts from moderately halophilic and non-halophilic Archaea (Methanococcus jannaschii, Methanosarcina mazei, Methanobrevibacter smithii) are leaky and aggregate at high salt concentrations. However, adding PGP-Me to M. mazei lipids results in gradual enhancement of LUV stability, correlating with the PGP-Me content. The LUV data are substantiated by the x-ray results, which show that H. halobium and M. mazei lipids have dissimilar phase behavior and form different structures at high NaCl concentrations. H. halobium lipids maintain an expanded lamellar structure with spacing of 8.5-9 nm, which is stable up to at least 100 degrees C in 2 m NaCl and up to approximately 60 degrees C in 4 m NaCl. However, M. mazei lipids form non-lamellar structures, represented by the Pn3m cubic phase and the inverted hexagonal H(II) phase. From these data, the forces preventing membrane aggregation in halophilic Archaea appear to be steric repulsion, because of the large head group of PGP-Me, or possibly out-of-plane bilayer undulations, rather than electrostatic repulsion attributed to the doubly charged PGP-Me head group

From 3-Port to New Laparoendoscopic Single-Site (LESS) Cholecystectomy : A Critical Analysis of Available Evidence.

In recent years, laparoendoscopic single-site surgery (LESS) has gained greater interest and diffusion for the treatment of gallstones. This critical review aims to evaluate the feasibility and safety of LESS cholecystectomy versus the 3-port technique (TPT) through a comparative analysis of 5 parameters: mean operative time, intraoperative and postoperative complications, conversion to open, conversion to the 4-trocar technique and postoperative hospital stay. The authors performed a systematic search of the medical literature through a search of PubMed and Ovid EMBASE. Inclusion criteria were as follows: publication date between January 1, 2005, and December 31, 2010; English or Italian language; human participants and series of 20 operations or more. There were 5 manuscripts meeting the inclusion criteria for TPT and 23 for LESS. Only one prospective randomized controlled trial comparing TPT and LESS was identified. Operative time is significantly longer in the single-incision group. Complications and conversion rates to the 4-port technique are higher in LESS. Postoperative hospital stay is similar in the 2 groups. Rate of conversion to open is higher in TPT. Despite the number of publications on LESS cholecystectomy, the vast majority of data available in the literature are from small case series without any comparative data. Although LESS cholecystectomy is a fashionable technique there are few data available for an evidence-based determination as to the real benefits of this technique. Well-designed comparative studies are suggested to validate the clinical benefits and ensure that there are no new complications or added costs associated with the new technique

Mesoglycan for pain control after open excisional HAEMOrrhoidectomy (MeHAEMO). An observational multicentre study on behalf of the Italian Society of Colorectal Surgery (SICCR)

Background: Excisional haemorrhoidectomy is the gold standard technique in patients with III and IV degree haemorrhoidal disease (HD). However, it is associated with a significant rate of post-operative pain. The aim of our study was to evaluate the efficacy of mesoglycan in the post-operative period of patients who underwent open excisional diathermy haemorrhoidectomy (OEH). Methods: This was a retrospective multicentre observational study. Three hundred ninety-eight patients from sixteen colorectal referral centres who underwent OEH for III and IV HD were enrolled. All patients were followed-up on the first post-operative day (T1) and after 1 week (T2), 3 weeks (T3) and 6 weeks (T4). BMI, habits, SF-12 questionnaire, VAS at rest (VASs), after defecation (VASd), and after anorectal digital examination (VASe), bleeding and thrombosis, time to surgical wound healing and autonomy were evaluated. Results: In the mesoglycan group, post-operative thrombosis was significantly reduced at T2 (p < 0.05) and T3 (p < 0.005), and all patients experienced less post-operative pain at each time point (p < 0.001 except for VASe T4 p = 0.003). There were no significant differences between the two groups regarding the time to surgical wound healing or post-operative bleeding. There was an early recovery of autonomy in the mesoglycan group in all three follow-up periods (T2 p = 0.016; T3 p = 0.002; T4 p = 0.007). Conclusions: The use of mesoglycan led to a significant reduction in post-operative thrombosis and pain with consequent early resumption of autonomy. Trial registration NCT0448169

Palliative treatment of malignant esophageal-cardiac stricture in the ederly

The aging of the population and longer life expectancy entails an increased number of elderly patients with esophageal cancer and benign pathologies referred for surgical treatment. Esophageal cancer is a pathology that mainly involves elderly patients. The aim of this study is to assess the effects of age on the outcome of surgery for esophageal cancer and benign pathologies in patients treated in our department

Seasonal Pattern of Hospitalization from Acute Respiratory Infections in Yaounde, Cameroon

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