Multimodal treatment of gastric cancer in the west: Where are we going?

The incidence of gastric cancer (GC) is decreasing worldwide, especially for intestinal histotype of the distal third of the stomach. On the contrary, proximal location and diffuse Lauren histotype have been reported to be generally stable over time. In the west, no clear improvement in long-term results was observed in clinical and population-based studies. Results of treatment in these neoplasms are strictly dependent on tumor stage. Adequate surgery and extended lymphadenectomy are associated with good long-term outcome in early-stage cancer; however, results are still unsatisfactory for advanced stages (III and IV), for which additional treatments could provide a survival benefit. This implies a tailored approach to GC. The aim of this review was to summarize the main multimodal treatment options in advanced resectable GC. Perioperative or postoperative treatments, including chemotherapy, chemoradiotherapy, targeted therapies, and hyperthermic intraperitoneal chemotherapy have been reviewed, and the main ongoing and completed trials have been analyzed. An original tailored multimodal approach to non-cardia GC has been also proposed

The new TNM classification of lymph node metastasis minimises stage migration problems in gastric cancer patients

The present study aimed at investigating whether in gastric cancer patients stage migration occurs with extension of lymphadenectomy, when node metastases are staged according to the new pN classification (UICC 1997). The investigation involved 921 patients, who underwent R0 gastric resection for gastric cancer between 1988 and 1998 in three different Italian centres: Verona (n=236), Forlì (n=409), Siena (n=276). The relation among lymphadenectomy and pN category was assessed by Kendall's partial rank-order correlation coefficient, controlling for depth of tumour invasion. A direct evaluation of the Will Rogers phenomenon was accomplished in the Verona series, by comparing the number of positive nodes actually observed with the number of positive nodes which would have been retrieved by a less extended lymphadenectomy (D1). The number of positive nodes increased remarkably with the enlargement of lymphadenectomy, especially in pT2 patients (from 2.2±3.9 in D1 to 3.9±5.0 in D3) and in pT3/pT4 patients (from 5.1±5.9 in D1 to 11.3±12.6 in D3). Non-parametric statistics highlighted a weak (Kendall's partial T=0.128) but significant (P<0.001) correlation between pN category and extension of lymphadenectomy. In the direct analysis of the Verona series, 22 patients out of 230 (9.6%) migrated to a lower pN tier when ignoring positive nodes retrieved from the second and third level. This percentage increased to 39.1% (90 out of 230) when adopting the TNM 87 classification. In conclusion stage migration is of minor importance in gastric cancer patients, staged according to the new pN classification

Image-Guided Thermal Ablation as an Alternative to Surgery for Papillary Thyroid Microcarcinoma: Preliminary Results of an Italian Experience

Purpose: To report the results of our preliminary experience in treating patients with papillary thyroid microcarcinoma (PTMC) with image-guided thermal ablation, in particular estimating the feasibility, safety and short-term efficacy Materials and Methods: From 2018 patients with cytologically proven PTMC &lt; 10&nbsp;mm were discussed in a multidisciplinary team and evaluated for feasibility of image-guided thermal ablation. In case of technical feasibility, the three possible alternatives (i.e., image-guided thermal ablation, surgery, and active surveillance) were discussed with patients. Patients who agreed to be treated with image guided thermal ablation underwent radiofrequency (RFA) or laser ablation under local anesthesia and conscious sedation. Treatment feasibility, technical success, technique efficacy, change in thyroid function tests, side effects, minor and major complications, patients satisfaction and pain/discomfort perception during and after treatment, and disease recurrence during follow-up were recorded. Results: A total of 13 patients were evaluated, and 11/13 (84.6%) patients (9 female, 2 male, mean age 49.3 ± 8.7 years) resulted suitable for image-guided thermal ablation. All 11 patients agreed to be treated with image-guided thermal ablation. In addition, 3/11 (27.3%) were treated with laser ablation and 8/11 (72.7%) with RFA. All procedures were completed as preoperatively planned (technical success 100%). Technique efficacy was achieved in all 11/11 (100%) cases. Ablated volume significantly reduced from 0.87 ± 0.67&nbsp;ml at first follow-up to 0.17 ± 0.36 at last follow-up (p = 0.003). No change in thyroid function tests occurred. No minor or major complications occurred. All patients graded 10 the satisfaction for the treatment, and mean pain after the procedure was reported as 1.4 ± 1.7, and mean pain after the procedure as 1.2 ± 1.1 At a median follow-up of 10.2 months (range 1.5–12 months), no local recurrence or distant metastases were found. Conclusions: Image guided thermal ablations appear to be feasible and safe in the treatment of PTMC. These techniques hold the potential to offer patients a minimally invasive curative alternative to surgical resection or active surveillance. These techniques appear to be largely preferred by patients

Metachronous hepatic metastases from gastric carcinoma: a multicentric survey

BACKGROUND: The treatment of hepatic metastases from gastric cancer is controversial, due to biologic aggressiveness of the disease. OBJECTIVE: To survey the clinical approach to the subset of atients presenting with metachronous hepatic metastases as sole site of recurrence after curative resection of gastric cancer, focusing on the results achieved by different therapies and to investigate the prognostic factors of major clinical relevance. METHODS: Retrospective multi-center chart review evaluating 73 patients, previously submitted to D >or= 2 gastrectomy for gastric cancer, who developed exclusive hepatic recurrence. Prognostic factors related to the patient, to the gastric malignancy and its treatment, and to the metastatic disease and its therapy were evaluated. RESULTS: Forty-five patients received supportive care, 17 were submitted to chemotherapy, and 11 to hepatic resection. Survival was independently influenced by the variables T (p=0.019), N (p=0.05) and G (p=0.018) of the gastric primary and by the therapeutic approach to the metastases (p<0.005). In particular, T4 gastric cancer, presence of lymph-node metastases and G3 tumor displayed a negative prognostic value. Therapeutic approach to the metastases was the principal prognostic variable: 1, 2, and 3 years survival rates were 22.2%, 4.4% and 2.2%, respectively, for patients without specific treatment; 44.9%, 12.8% and 6.4% after chemotherapy (p=0.08) and 80.8%, 30.3% and 20.2% after surgical resection (p<0.001). CONCLUSIONS: Our data suggest some clinical criteria that may facilitate selection of therapy for patients with hepatic recurrence after primary gastric cancer resection. The best survival rates are associated with surgical treatment, which should be chosen whenever possible

Bis(1,3-benzothia­zol-2-amine-κN 3)silver(I) nitrate acetone solvate

In the title compound, [Ag(C7H6N2S)2]NO3·C3H6O, the AgI ion is coordinated to two benzothia­zol-2-amine ligands via the thia­zole N atoms in an approximately linear arrangement. The dihedral angle between the mean planes of the two 1,3-benzothia­zole groups is 5.9 (3)°. Both amine groups on the ligands are oriented in the same direction and are engaged in N—H⋯O hydrogen bonding with the nitrate counter-anion, forming one-dimensional columns along the b-axis direction. Voids created by inefficient crystal packing are occupied by acetone solvent mol­ecules which are disordered over two sites with occupancies of 0.563 (11) and 0.437 (11)

Chronification of migraine: what clinical strategies to combat it?

Once migraine becomes chronic and has transformed into a form of headache that occurs daily or almost, the treatment options available are few and complex. This makes it important to take action before this point is reached, using all the measures that can be obtained from our current knowledge of chronic migraine (or transformed migraine) on the one hand, and on the potential factors of chronification (or transformation) on the other. Therefore, in order to reduce the risk of migraine chronification, it would appear important to: (a) administer suitable preventive treatments for subjects who have been suffering from migraines 654 days a month for 653 months; (b) take special care not to overuse symptomatic medications, particularly when they contain substances with a sedative effect; and (c) investigate the concomitant presence of depression, hypertension and excess weight and administer appropriate treatment when presen

Biomonitoramento ativo de metais traço e efeito biológico em mexilhões transplantados para área de influência de efluente de indústria de beneficiamento de aço - Fase I

Preliminary results from an environmental monitoring program of an industrial submarine outflow are presented. Introduced mussels technique with Perna perna was applied. Two evaluations were carried out; one thirty days after the transplant and, another one, sixty days after the first one. Trace metal bioaccumulation and the associated cellular damage were determined. In the first evaluation, in the beginning of the industrial activity, concentrations significantly higher of some metals in mussels of the area of the emissary in comparison with the control site had been registered. In the second evaluation higher concentrations were recorded only for Cd, Zn and Ni at submarine outflow zone. Despite this, the recorded concentrations remained in the range considered normal for the studied species and below of the maximum level accepted by law for human consumption. The Neutral Red Assay, the biomarker applied, evidenced no cellular damage.Preliminary results from an environmental monitoring program of an industrial submarine outflow are presented. Introduced mussels technique with Perna perna was applied. Two evaluations were carried out; one thirty days after the transplant and, another one, sixty days after the first one. Trace metal bioaccumulation and the associated cellular damage were determined. In the first evaluation, in the beginning of the industrial activity, concentrations significantly higher of some metals in mussels of the area of the emissary in comparison with the control site had been registered. In the second evaluation higher concentrations were recorded only for Cd, Zn and Ni at submarine outflow zone. Despite this, the recorded concentrations remained in the range considered normal for the studied species and below of the maximum level accepted by law for human consumption. The Neutral Red Assay, the biomarker applied, evidenced no cellular damage

Disentangling the Ultrafast Nonlinear Optical Behavior of Plasmonic Resonances Near the Interband Transition

The photoexcitation of plasmonic nanostructures with ultrashort laser pulses allows for elucidating the mechanisms underlying the ultrafast nonlinear optical response of such systems, gaining insight into the fundamental processes triggered by light absorption at the nanoscale. To date, the complex temporal and spectral features of the photoinduced response are not fully understood, especially when the photon energies are close to the interband transitions of the metallic medium. Herein, the effects of photoexcitation of plasmonic nanostructures are studied by resorting to a combinaion of broadband transient absorption spectroscopy and semiclassical nonlinear simulations of the energy relaxation processes following illumination. The proposed approach enables an in-depth disentanglement of all the contributions to the ultrafast transient optical response of supported gold nanocrystals. From these methods, the apparent transient blue shift of the localized plasmon resonance observed in the pump-probe signals is rationalized as an interplay between different and spectrally dispersed permittivity modulations, instead of a simple negative permittivity change, as it could be concluded based on the Fröhlich condition. The results provide a comprehensive understanding of the thermo-modulational nonlinearities of plasmonic nanostructures exhibiting resonances close to the interband transition threshold

Comprehensive molecular portrait using next generation sequencing of resected intestinal-type gastric cancer patients dichotomized according to prognosis

In this study, we evaluated whether the presence of genetic alterations detected by next generation sequencing may define outcome in a prognostically-selected and histology-restricted population of resected gastric cancer (RGC). Intestinal type RGC samples from 34 patients, including 21 best and 13 worst prognostic performers, were studied. Mutations in 50 cancer-associated genes were evaluated. A significant difference between good and poor prognosis was found according to clinico-pathologic factors. The most commonly mutated genes in the whole population were PIK3CA (29.4%), KRAS (26.5%), TP53 (26.5%) MET (8.8%), SMAD4 (8.8%) and STK11 (8.8%). Multiple gene mutations were found in 14/21 (67%) patients with good prognosis, and 3/13 (23%) in the poor prognosis group. A single gene alteration was found in 5/21 (24%) good and 6/13 (46%) poor prognosis patients. No mutation was found in 2/21 (9.5%) and 4/13 (31%) of these groups, respectively. In the overall series, ß-catenin expression was the highest (82.4%), followed by E-Cadherin (76.5%) and FHIT (52.9%). The good prognosis group was characterized by a high mutation rate and microsatellite instability. Our proof-of-principle study demonstrates the feasibility of a molecular profiling approach with the aim to identify potentially druggable pathways and drive the development of customized therapies for RGC

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