Gastric cancer : epidemiology, risk factors, classification, genomic characteristics and treatment strategies

Gastric cancer (GC) is one of the most common malignancies worldwide and it is the fourth leading cause of cancer-related death. GC is a multifactorial disease, where both environmental and genetic factors can have an impact on its occurrence and development. The incidence rate of GC rises progressively with age; the median age at diagnosis is 70 years. However, approximately 10% of gastric carcinomas are detected at the age of 45 or younger. Early-onset gastric cancer is a good model to study genetic alterations related to the carcinogenesis process, as young patients are less exposed to environmental carcinogens. Carcinogenesis is a multistage disease process specified by the progressive development of mutations and epigenetic alterations in the expression of various genes, which are responsible for the occurrence of the disease

Zasady chirurgii onkologicznej układu pokarmowego

Mimo ogromnego postępu w leczeniu systemowym, leczenie chirurgiczne pozostaje głównym narzędziem w walce z rakiem — jego możliwości, które nie zostały wykorzystane podczas pierwszego zabiegu chirurgicznego, zwykle pozostają stracone na zawsze. Skuteczne leczenie nowotworów układu pokarmowego wymaga współpracy chirurga onkologa, patologa, radiologa, chemioterapeuty, radioterapeuty oraz gastroenterologa. Postępowanie z chorym powinno mieć charakter interdyscyplinarny, uwzględniać także choroby współistniejące i zaburzenia metaboliczne. Ostatnio postęp w leczeniu nowotworów układu pokarmowego wiąże się z leczeniem celowanym molekularnie, które jest zwykle elementem leczenia skojarzonego. Gastroenterologia Kliniczna 2011, tom 3, nr 1, 1–

Cyklooksygenaza-2 i jej rola w kancerogenezie

Cyclooxygenase is an enzyme involved in many physiological and pathological processes. It catalyzes the formation of prostaglandins, prostacyclins and thromboxanes from arachidonic acid. It has been reported that cyclooxygenase-2 (COX-2) modulates the secretion of proinflammatory mediators and its expression is associated with the promotion of the process of tumorigenesis initiation, transformation, progression and cancer metastasis. Increased expression of COX-2 in premalignant lesions makes it a key element in a chain of changes leading to cancer. So far, advances in the evaluation of COX-2 molecular mechanisms did not bring spectacular discoveries. Pathomechanisms of COX-2 activities are still not sufficiently understood and therefore, require further research. Currently, COX-2 inhibitors are one of the most commonly used medications. Unfortunately, their long-term use causes many side effects. The first report about the use of plant substances with anti-inflammatory and analgesic activity (COX-2 inhibitors) was reported by Hippocrates in the 5th century BC. The present review discusses the most important mechanisms by which a particular COX-2 isomer leads to the formation and development of cancer

Data on the quality of life after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal malignancies: does it concern patients with gastric cancer?

AbstractIntroduction.So far there are no reports devoted exclusively to the quality of life after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in metastatic gastric cancer. Current literature concerning this issue was, thus, reviewed in order to: 1) search for such data concerning metastatic gastric cancer; 2) assess if the latest reviews evenly pertain to all peritoneal surface malignancies; and 3) conclude if they are a reliable source of data for patients with metastatic gastric cancer.Materials and Methods.The electronic PubMed/MEDLINE and EMBASE databases were retrieved for studies concerning the influence of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy on quality of life in patients with metastatic gastric cancer and regardless of initial diagnosis. The data on the number of patients with particular tumours were analysed and the results were presented in the form of a table.Results.Approximately half of all patients encompassed by the reviews had a form of primary peritoneal surface malignancies. Within peritoneal metastases, the most numerous were colorectal (21-24%) and ovarian cancers (5-15%). Gastric cancers and sarcomas were the smallest defined subgroups (4% each).Conclusions.The promising outcomes in quality of life after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in primary peritoneal surface malignancies might differ from rarely reported ones in metastatic gastric cancer. The problem needs further, gastric cancer-devoted investigations

High-throughput sequencing of gastric cancer patients : unravelling genetic predispositions towards an early-onset subtype

Background: Gastric cancer is the fourth most common cause of cancer-related death. Currently, it is broadly accepted that the molecular complexity and heterogeneity of gastric cancer, both inter- and intra-tumor, display important barriers for finding specific biomarkers for the early detection and diagnosis of this malignancy. Early-onset gastric cancer is not as prevalent as conventional gastric carcinoma, but it is a preferable model for studying the genetic background, as young patients are less exposed to environmental factors, which influence cancer development. Aim: The main objective of this study was to reveal age-dependent genotypic characteristics of gastric cancer subtypes, as well as conduct mutation profiling for the most frequent alterations in gastric cancer development, using targeted next-generation sequencing technology. Patients and methods: The study group included 53 patients, consisting of 18 patients with conventional gastric cancer and 35 with an early-onset subtype. The DNA of all index cases was used for next-generation sequencing, employing a panel of 94 genes and 284 single nucleotide polymorphisms (SNPs) (TruSight Cancer Panel, Illumina), which is characteristic for common and rare types of cancer. Results: From among the 53 samples processed for sequencing, we were able to identify seven candidate genes (STK11, RET, FANCM, SLX4, WRN, MEN1, and KIT) and nine variants among them: one splice_acceptor, four synonymous, and four missense variants. These were selected for the age-dependent differentiation of gastric cancer subtypes. We found four variants with C-Score ≥ 10, as 10% of the most deleterious substitutions: rs1800862 (RET), rs10138997 (FANCM), rs2230009 (WRN), and rs2959656 (MEN1). We identified 36 different variants, among 24 different genes, which were the most frequent genetic alterations among study subjects. We found 16 different variants among the genes that were present in 100% of the total cohort: SDHB (rs2746462), ALK (rs1670283), XPC (rs2958057), RECQL4 (rs4925828; rs11342077, rs398010167; rs2721190), DDB2 (rs326212), MEN1 (rs540012), AIP (rs4930199), ATM (rs659243), HNF1A (rs1169305), BRCA2 (rs206075; rs169547), ERCC5 (rs9514066; rs9514067), and FANCI (rs7183618). Conclusions: The technology of next-generation sequencing is a useful tool for studying the development and progression of gastric carcinoma in a high-throughput way. Our study revealed that early-onset gastric cancer has a different mutation frequency profile in certain genes compared to conventional subtype

Results of the treatment of patients with solid tumours and liver metastases: 8 years experience of one institution

Wstęp. Leczenie chirurgiczne przerzutów nowotworów litych do wątroby powinno odbywać się w ramach zespołu wielodyscyplinarnego.Cel pracy. Celem pracy jest ocena wyników leczenia skojarzonego chorych na różne nowotwory lite z przerzutami do wątroby przez zespół wielodyscyplinarny jednego ośrodka onkologicznego w ciągu ostatnich 8 lat.Materiał i metody. Retrospektywną analizą objęto 166 chorych (84 kobiety i 82 mężczyzn) w wieku od 19 do 78 lat (średnia 58 ± 11,2), leczonych z powodu przerzutów do wątroby pierwotnych nowotworów litych o różnej lokalizacji, z wyjątkiem guzów neuroendokrynnych. Każdorazowo rozważano okołooperacyjne leczenie systemowe zgodnie z aktualnymi zaleceniami Polskiej Unii Onkologii.Wyniki. W czasie obserwacji (mediana 35 miesięcy) zmarło 46% chorych. Resekcje wątroby wykonano u 107 (65%)chorych, w tym u 19 chorych połączono je z (RF-)termoablacją zmian przerzutowych, którą wykonano jako samodzielny zabieg u dalszych 59 (36%) chorych. Śmiertelność pooperacyjna wyniosła 1,2%. Powikłania II° wg klasyfikacji Clavien-Dindo wystąpiły u 33 (19,8%) chorych, natomiast III° i IV° — u 8 (4,8%) chorych. Przeżycia 1-roczne, 3-letniei 5-letnie wyniosły odpowiednio 78%, 41% i 37%. Pięcioletnie przeżycia całkowite u chorych na raka jelita grubego po resekcjach przerzutów metachronicznych wyniosły 48%.Wnioski. Skojarzone leczenie chorych na nieendokrynne nowotwory lite z przerzutami do wątroby przez zespół wielodyscyplinarny jest bezpieczne i skuteczne. W starannie dobranej grupie chorych można osiągnąć blisko 50% całkowitych przeżyć 5-letnich. Resekcja wątroby jest optymalną metodą leczenia chirurgicznego przerzutów do wątroby.Introduction. Surgical treatment of liver metastases from solid tumours should be provided by multidisciplinary teams.Aim. The aim of the present study is to analyse results of the combined treatment of patients with different solid tumours and liver metastases by single institution multidisciplinary team for last 8 years.Material and methods. This is a retrospective analysis of 166 patients (84 females and 82 males), aged from 19 to 78 years (mean 58 ± 11.2), treated due to liver metastases from solid tumours in various primary localizations: except neuroendocrine tumours. In every patient, perioperative systemic therapy was evaluated in agreement with current recommendations of the Polish Union of Oncology.Results. In the follow-up time available (median 35 months) 46% of patients died. Liver resections were performed in 107 (65%) patients, including 19 patients in whom resections were supplemented with (RF-)thermoablations of their liver metastases. This was the sole surgical treatment in the 59 (36%) patients. Perioperative mortality was 1.2%. Grade II complications according to the Clavien-Dindo classification were found in 33 (19.8%) patients, whereas grade III and IV complications were treated in 8 (4.8%) patients. One-, 3-, and 5-year survival rates were respectively 78%, 41%, and 37%. Five-year overall survival in patients with colorectal carcinoma after liver resection of metachronous metastases was 48%. We conclude that combined treatment of patients with liver metastases from non-endocrine solid tumours by the multidisciplinary team is safe and effective. A nearly 50% 5-year survival is achievable in a carefully selected group of patients. We also conclude that hepatic resection is an optimal method of surgical treatment of liver metastases

Mutations in the SPG7 gene cause chronic progressive external ophthalmoplegia through disordered mitochondrial DNA maintenance.

Despite being a canonical presenting feature of mitochondrial disease, the genetic basis of progressive external ophthalmoplegia remains unknown in a large proportion of patients. Here we show that mutations in SPG7 are a novel cause of progressive external ophthalmoplegia associated with multiple mitochondrial DNA deletions. After excluding known causes, whole exome sequencing, targeted Sanger sequencing and multiplex ligation-dependent probe amplification analysis were used to study 68 adult patients with progressive external ophthalmoplegia either with or without multiple mitochondrial DNA deletions in skeletal muscle. Nine patients (eight probands) were found to carry compound heterozygous SPG7 mutations, including three novel mutations: two missense mutations c.2221G>A; p.(Glu741Lys), c.2224G>A; p.(Asp742Asn), a truncating mutation c.861dupT; p.Asn288*, and seven previously reported mutations. We identified a further six patients with single heterozygous mutations in SPG7, including two further novel mutations: c.184-3C>T (predicted to remove a splice site before exon 2) and c.1067C>T; p.(Thr356Met). The clinical phenotype typically developed in mid-adult life with either progressive external ophthalmoplegia/ptosis and spastic ataxia, or a progressive ataxic disorder. Dysphagia and proximal myopathy were common, but urinary symptoms were rare, despite the spasticity. Functional studies included transcript analysis, proteomics, mitochondrial network analysis, single fibre mitochondrial DNA analysis and deep re-sequencing of mitochondrial DNA. SPG7 mutations caused increased mitochondrial biogenesis in patient muscle, and mitochondrial fusion in patient fibroblasts associated with the clonal expansion of mitochondrial DNA mutations. In conclusion, the SPG7 gene should be screened in patients in whom a disorder of mitochondrial DNA maintenance is suspected when spastic ataxia is prominent. The complex neurological phenotype is likely a result of the clonal expansion of secondary mitochondrial DNA mutations modulating the phenotype, driven by compensatory mitochondrial biogenesis

Definition and classification of chyle leak after pancreatic operation: A consensus statement by the International Study Group on Pancreatic Surgery

Recent literature suggests that chyle leak may complicate up to 10% of pancreatic resections. Treatment depends on its severity, which may include chylous ascites. No international consensus definition or grading system of chyle leak currently is available. The International Study Group on Pancreatic Surgery, an international panel of pancreatic surgeons working in well-known, high-volume centers, reviewed the literature and worked together to establish a consensus on the definition and classification of chyle leak after pancreatic operation. Chyle leak was defined as output of milky-colored fluid from a drain, drain site, or wound on or after postoperative day 3, with a triglyceride content ≥110 mg/dL (≥1.2 mmol/L). Three different grades of severity were defined according to the management needed: grade A, no specific intervention other than oral dietary restrictions; grade B, prolongation of hospital stay, nasoenteral nutrition with dietary restriction, total parenteral nutrition, octreotide, maintenance of surgical drains, or placement of new percutaneous drains; and grade C, need for other more invasive in-hospital treatment, intensive care unit admission, or mortality. This classification and grading system for chyle leak after pancreatic resection allows for comparison of outcomes between series. As with the other the International Study Group on Pancreatic Surgery consensus statements, this classification should facilitate communication and evaluation of different approaches to the prevention and treatment of this complicatio