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

Conversion gastrectomy for stage IV unresectable gastric cancer: a GIRCG retrospective cohort study

Background: The aim of this study is to report the experience with conversion surgery from six Gruppo Italiano Ricerca Cancro Gastrico (GIRCG) centers, focusing our analysis on factors affecting survival and the risk of recurrence. Methods: A retrospective, multicenter cohort study was performed in patients who had undergone conversion gastrectomy between 2005 and 2017. Data were extracted from a GIRCG database including all metastatic gastric cancer patients submitted to surgery. Only stage IV unresectable tumors/metastases which became resectable after chemotherapy were included in this analysis. Results: Forty-five resected M1 patients were included in the analysis. Reasons for being deemed unresectable at diagnosis were peritoneal involvement (PCI > 6) (n = 38, 84.4%), distant metastatic nodes (n = 3, 6.6%) and extensive liver involvement (n = 4, 8.8%). Median follow-up was 25 months (IQR 9-50). Median overall survival from surgery was 15 months and 1-, 3- and 5-year survivals were 57.2, 36.1 and 24%, respectively. Median progression-free survival was 12 months with 1- and 3-year survival of 46.4 and 33.9%, respectively. At cox regression analysis the only independent prognostic factor for OS was the presence of more than one type of metastasis (HR 4.41, 95% CI 1.72\u201311.3, p = 0.002). A positive microscopic resection margin was the only risk factor for recurrence (HR 5.72, 95% CI 1.04\u201331.4, p = 0.045). Conclusions: Unresectable stage IV GC patients could benefit from radical surgery after chemotherapy and achieve long survivals. The main prognostic factor for these patients was the presence of more than one type of extra-gastric metastatic involvement

The Miocene – Pliocene boundary and the Messinian Salinity Crisis in the easternmost Mediterranean: insights from the Hatay Graben (Southern Turkey).

The Hatay Graben is one of three easternmost basins in the Mediterranean that preserve sediments that span the Miocene-Pliocene boundary, including gypsums from the Messinian Salinity Crisis (MSC). Here we integrate existing data and present new sedimentological and micropalaeontological data to investigate the palaeoenvironments of late Miocene to early Pliocene deposits and place this important area into a regional stratigraphic framework. Six sections are described along a ~ W – E transect illustrating the key features of this time period. Late Miocene (Pre-MSC) sediments are characterised by open marine marls with a benthic foraminiferal fauna suggestive of water depths of 100 – 200 m or less. Primary lower gypsum deposits are determined to be absent from the graben as sedimentological and strontium isotopes are characteristic of the resedimented lower gypsums. The intervening Messinian erosion surface is preserved near the basin margins as an unconformity but appears to be a correlative conformity in the basin depocentre. No Upper Gypsums or ‘Lago–Mare’ facies have been identified but available data do tentatively suggest a return to marine conditions in the basin prior to the Zanclean boundary. Sediments stratigraphically overlying the Messinian gypsums and marls are coarse-grained sandstones from coastal and Gilbert-type delta depositional environments. The Hatay Graben is not only strikingly similar to Messinian basins on nearby Cyprus but also to the overall model for the MSC, demonstrating the remarkable consistency of palaeoenvironments found in marginal basins across the region at this time

Lymphadenectomy: how to do it?

According to the more recent European guidelines, the D2 lymphadenectomy is considered the standard for curative intent treatment of patients with gastric cancer. Although, the surgical definition of D2 dissection and its technical aspects had been learned from Eastern surgeons in the past decades, some variations in the approach to D2 lymphadenectomy by European surgeons were detectable in randomized clinical trials dealing with lymphadenectomy. Despite in more recent years an improvement in surgical quality has been reported in European series, some differences in the practice of D2 dissection are thought to persist. As, these may contribute to discrepancies in gastric cancer survival observed across European countries, the standardization of surgical quality is an urgent need to improve the outcome of gastric cancer patients in Europe. In this manuscript, we focus on the technical aspects of the D2 dissection both in open and laparoscopic gastrectomy in order to contribute to the improvement of surgical care of gastric cancer in the West

High-resolution stratigraphy of the pre-evaporitic/evaporitic transition in the late Messinian Adriatic foreland domain

One of the most spectacular evaporative event in the Earth history occurred in the Mediterranean Basin, during the late Messinian (Messinian Salinity Crisis, MSC), as a consequence of the restriction in the Atlantic-Mediterranean connection. Enclosed marine environments could record evaporative deposition undergo restriction in circulation coupled with climate forcing. The aim of this paper is to investigate what happened in the sedimentary basin of the Adriatic foreland domain approaching the MSC by using an interdisciplinary study, which includes stratigraphy, paleontology, mineralogy, and magnetostratigraphy. The study area is the NW flank of the Maiella Mountains, where the MSC is well recorded by both the deposition of the Lower Evaporites and the post-evaporitic deposits of the Lago-Mare event. For getting a complete record of the pre-evaporitic/evaporitic transition in the study area, a 23m depth borehole was drilled starting from the 20cm-thick carbonate horizon (Calcare di Base) just at the base of the first gypsum cycle of the Lower Evaporites. Beneath the Calcare di Base, the sedimentary core recovered 3.8 m of dark clays rich in organic matter, punctuated by 5 carbonate-rich layers. The rest of the recovered sedimentary core is characterized by limestones and marly limestones rich in small lithotamnium, bryozoa, and benthic foraminifera, pertaining to the uppermost part of the Bolognano Formation. All the sedimentary core was analysed, collecting 5-10 cm thick samples. The occurrence of the carbonate-rich layers within the dark clays allows us to recognize 5 sedimentary cyles, possibly forced by precessional cyclicity. Calcareous nannofossils show two peaks of Sphenolithus abies within the 2nd and 4th cycle from the top. Small Reticulofenestra and Helicosphaera carteri show one peak within the 1st cycle, as well as in the 3rd and 4th cycles. Among the planktonic foraminifera, Turborotalita multiloba shows a peak within the 4th cycle whereas Orbulina universa has two peaks, within the 3rd and 4th cycles. The uppermost 50cm of the sedimentary core are completely barren. Although no major changes in lithology can be recognized in the fine-grained deposits, magnetic susceptibility decreases to extremely low values in the 1st and 2nd cycles, in the upper part of the sedimentary core. The depletion of magnetic minerals in this interval seems higher than can be attributed solely to dilution by magnetite-poor sediments, which implies that magnetite dissolution could have occurred. Our analyses on the paleontological record of the pre-evaporitic deposits in the Maiella foreland basin show results very similar to other pre-evaporitic Messinian successions from the Mediterranean Basin. Finally, the calibration of the sedimentary core with the insolation curve allow us to confirm the precessional forcing of the sedimentary record in the Messinian Adriatic foreland basin during the pre-evaporitic stage

Impact of super-extended lymphadenectomy on relapse in advanced gastric cancer.

Background: In gastric cancer the incidence of loco-regional recurrences decreases when lymphadenectomy is expanded from D1 to D2. The present study aimed at evaluating whether the pattern of recurrence in advanced gastric cancer (AGC) is further modified when lymphadenectomy is expanded from D2 to D3. Methods: 568 patients undergoing curative gastrectomy for AGC (274 D2 and 294 D3) were considered; none of them received preoperative chemotherapy. MantelHaenszel test of homogeneity was used to verify whether the relation between extension of lymphadenectomy and recurrence varied as a function of each risk factor considered. The impact of D2 and D3 on relapse was further investigated by multivariable logistic regression model. Results: Cumulative incidence of recurrence did not significantly differ after D2 and after D3 in the whole series (45.3% vs 46.3%; p \ubc 0.866). However, the association between recurrence and extension of lymphadenectomy was significantly affected by histology (ManteleHaenszel test of homogeneity: p \ubc 0.007). The risk of recurrence was higher after D3 than after D2 (45.1% vs 35.3%) in the intestinal histotype while the pattern was reversed in the mixed/diffuse histotype (48.3% vs 61.5%). This pattern was confirmed in multivariable logistic regression: the interaction between histology and extension of lymphadenectomy was highly significant (p \ubc 0.004). In particular, cumulative incidence of locoregional recurrences was higher in the diffuse histotype after D2, while being higher in the intestinal histotype after D3. Conclusions: D3 reverses the negative impact of diffuse histotype on relapses, especially on locoregional recurrences. Therefore D3 could be considered a valid therapeutic option in histotype-oriented tailored treatment of AGC

Inhibitory effect of PCSK9 on Abca1 protein expression and cholesterol efflux in macrophages

Abstract Background and aims: Proprotein convertase subtilisin/kexin type 9 (PCSK9) may have extra-hepatic effects on cholesterol homeostasis of vascular macrophages. In this study, we aimed to investigate PCSK9 role on the anti-atherogenic process of ATP binding cassette transporter A1 (Abca1)-mediated cholesterol efflux. Methods: Abca1-mediated cholesterol efflux was evaluated by a radioisotopic technique in mouse peritoneal macrophages (MPM) from wild-type (WT) or LDL receptor knock-out (Ldlr(-/-)) mice exposed to human recombinant PCSK9, in the presence of liver X receptor/retinoid X receptor (LXR/RXR) ligands or acetylated LDL (AcLDL) to stimulate Abca1 expression. Protein and gene expression was evaluated by Western blot and quantitative real time PCR, respectively. Results: PCSK9 inhibited Abca1-mediated cholesterol efflux induced by LXR/RXR agonists in WT MPM (-55%, p < 0.05) but not in Ldlr(-/-) MPM. This effect was fully abrogated by the co-incubation with an anti-PCSK9 antibody. The inhibition of Abca1-dependent efflux induced by PCSK9 was associated with a reduction of Abca1 protein expression only in WT cells. Abca1 gene expression was significantly downregulated by PCSK9 in WT macrophages (-64%, p < 0.001) and, to a lesser extent, in MPM lacking Ldlr (-35%, p < 0.001). The inhibitory effect on Abca1-mediated efflux was also confirmed in AcLDL-treated macrophages. PCSK9 had a marginal or no effect on the expression of the lipid transporters Srb1 and Abcg1. Conclusions: PCSK9 plays a direct role on Abca1-mediated cholesterol efflux through a downregulation of Abca1 gene and Abca1 protein expression. This extrahepatic effect may influence relevant steps in the pathogenesis of atherosclerosis, such as foam cell formation

Gastric Cancer and Synchronous Hepatic Metastases: Is It Possible to Recognize Candidates to R0 Resection?

PURPOSE: Management of patients with synchronous hepatic metastases as the sole metastatic site at diagnosis of gastric cancer is debated. We studied a cohort of patients admitted to surgical units, investigating prognostic factors of clinical relevance and the results of various therapeutic strategies. METHODS: Retrospective multicentre chart review. We evaluated how survival from surgery was influenced by patient-related, gastric cancer-related, metastasis-related and treatment-related candidate prognostic factors. RESULTS: Forty-four patients received palliative surgery without resection, 98 palliative gastrectomy (in 16 cases associated with R+ hepatectomy), whereas 53 patients received both curative gastrectomy and hepatic resection(s) (R0). Adjuvant chemotherapy was administered to 44 patients. Therapeutic approach was selected on the basis of extension of disease, patient's general conditions and surgeon's attitude. Surgical mortality was 4.6 % and morbidity was 17.4 %. Survival was independently influenced by the factor T of the gastric primary (p = 0.036) and by the degree of hepatic involvement (p = 0.010). T > 2 and H3 liver involvement were associated with worse prognosis with cumulative effect (p = 0.002). Therapeutic approach to the metastases (p = 0.009) and adjuvant chemotherapy (p < 0.001) displayed independent impact upon survival, with benefit for those receiving aggressive multimodal treatment. The 1-, 3-, and 5-year survival rates were 50.4, 14.0, and 9.3 %, respectively, for patients submitted to curative surgery, 16, 8.5, and 4.3 % after palliative gastrectomy, and 6.8, 2.3, and 0 % after palliative surgery without resection. CONCLUSIONS: Our data suggest some clinical criteria that may facilitate selection of candidates to curative surgery, which offers the best survival chances, especially when associated with adjuvant chemotherapy

Krukenberg Tumors of Gastric Origin: The Rationale of Surgical Resection and Perioperative Treatments in a Multicenter Western Experience

Background: In case of Krukenberg tumor (KT) of gastric origin it is controversial and debated whether radical surgery in case of synchronous KT or metastasectomy in case of metachronous ones is associated with additional benefits. Role of perioperative treatments is unclear. Methods: Among 2515 female patients who were diagnosed with gastric cancer between January 1990 and December 2012 from 9 Italian centers, 63 presented simultaneously or developed KT as recurrence. Results: Thirty patients presented with synchronous KT, while 33 developed metachronous ovarian metastases during follow-up. The differences between the two groups were analyzed and compared. The median age of 63 patients was 48.0 years (range 31-71). Resection was possible in 53 patients (20 synchronous and 33 metachronous). Twelve patients in the synchronous group and 15 patients of the metachronous group underwent hyperthermic intraperitoneal chemotherapy after resection of KT. All of them underwent adjuvant chemotherapy after KT resection. The median survival for all population was 23 months (95 % confidence interval, 7-39 months). The median survival time in the metachronous group was 36 months, which was significantly longer than that in the synchronous group, 17 months, p < 0.0001. Conclusions: KT remains a clinical challenge for gastric cancer therapy. The extent of disease and feasibility of removal of the metastatic lesion must be carefully evaluated prior to surgery to define the patients group who could benefit most from a resection associated with perioperative treatment