Showing papers in "Journal of Gastrointestinal Cancer in 2014"
TL;DR: Chronic H. pylori infection causes gastric cancer via two mechanisms: the presence of virulence factors and the induction of chronic inflammation which ultimately leads to neoplastic transformation.
Abstract: Introduction
A strong association between chronic infection, inflammation, and cancer has been suggested.
51 citations
TL;DR: The outcome of clinical trials that used arsenic trioxide as a single agent as well as in combination settings in patients diagnosed with solid tumors are summarized and possible additional mechanisms by which ATO may be useful as a chemosensitizer in combination therapy are reviewed.
Abstract: In the past decade, the therapeutic potential of arsenic trioxide (ATO) in the treatment of acute promyelocytic leukemia (APL) was recognized. This encouraged other investigators to test the efficacy of ATO in the management of other hematological and solid tumor malignancies. Notably, as a single agent, arsenic trioxide did not benefit patients diagnosed with solid tumors. However, when it was combined with other agents, treatment benefit emerged. In this article, we have summarized the outcome of clinical trials that used arsenic trioxide as a single agent as well as in combination settings in patients diagnosed with solid tumors. We have also reviewed possible additional mechanisms by which ATO may be useful as a chemosensitizer in combination therapy. We hope that our review will encourage clinical investigators to rationally combine ATO with additional chemotherapeutic agents in treating patients diagnosed with solid tumors.
49 citations
TL;DR: Patients without mutations in commonly mutated cancer genes may be associated with a higher likelihood of having a pCR after preoperative CRT, and this should be confirmed in a prospective study.
Abstract: Purpose
Preoperative chemoradiation (CRT) for locally advanced rectal adenocarcinoma achieves pathologic complete response (pCR) in 8–20 % of patients. Mutations in critical cancer genes may contribute to lack of pCR. We retrospectively evaluated our institutional experience to determine potential mutational and clinical predictors of pCR in patients treated with CRT.
41 citations
TL;DR: The most recent treatment advances including FOLFIRINOX, gemcitabine plus nab-paclitaxel and novel approaches such as immune-mediated therapies, drugs that disrupt the tumor-stromal compartment, PARP inhibitors for BRCA pathway-deficient pancreatic cancer and new generations of conventional chemotherapeutics, which are in early phases of clinical development and have shown promising early results.
Abstract: Purpose
Over the last couple of years, we have witnessed the availability of a wide variety of different therapeutic agents and the identification of effective combinations of existing ones that have transformed the way we approach and treat pancreatic cancer. Proof of this are the recent validations that combinations of conventional chemotherapy drugs, the FOLFIRINOX regimen and gemcitabine plus nab-paclitaxel, significantly improves clinical outcomes in patients with metastatic disease. However, deeper and more sophisticated understanding of the biology of this cancer as well as the ability to develop better and perhaps more precise drugs predict that the landscape may be changing even more.
34 citations
TL;DR: A case of PHL developed in segment I of the liver is reported, and a review of the literature including clinical, radiological, histological, and therapeutic features of this disease is presented.
Abstract: Primary hepatic lymphoma (PHL) is confined to the liver with no evidence of lymphomatous involvement in other lymphoid structures. It is a very rare malignancy representing less than 1 % of all extra nodal lymphomas. The exact cause of PHL is unknown, but it seems that there is a strong association between hepatitis C virus (HCV) and PHL. The majority of PHL patients are middle-aged men who usually present nonspecific symptoms. Diagnosis of PHL requires a liver biopsy compatible with lymphoma and the absence of lympho-proliferative disease outside the liver. The rarity of the disease leads to problems of diagnosis and management. The optimal treatment is still unclear and the results are uncertain.
We report a case of PHL developed in segment I of the liver, and we present a review of the literature including clinical, radiological, histological, and therapeutic features of this disease.
This case report is approved by the patient herself. Informed consent has been obtained from the patient for publication of this case.
29 citations
TL;DR: Recent advances in molecular characterization holds promise in novel targeted therapies, and currently ongoing trials are exploring efficacy of targeted therapies and role of adjuvant therapy for adenocarcinoma and results are awaited.
Abstract: Primary small-bowel malignancies (SBM) are rare tumors but their incidence is rising. An estimated 9160 new cases and 1210 deaths due to SBM may occur in the USA in 2014. We review advances made in tumor biology, immunohistochemistry, and discuss treatment strategies for these malignancies. Relevant articles from PubMed/Medline and Embase searches were collected using the phrases “small-bowel adenocarcinoma, gastrointestinal carcinoids, gastrointestinal stromal tumors, small-bowel leiomyosarcoma, and small-bowel lymphoma”. Advances in imaging techniques such as wireless capsule endoscopy, CT and MRI enterography, and endoscopy (balloon enteroscopy) along with discovery of molecular markers such as c-kit and PDGFRA for GIST tumors have improved our ability to diagnose, localize, and treat these patients. Early detection and surgical resection offers the best chance for long-term survival in all tumors except bowel lymphoma where chemotherapy plays the main role. Adjuvant therapy with imatinib has improved overall survival for GIST tumors, somatostatin analogs have improved symptoms and also inhibited tumor growth and stabilized metastatic disease in carcinoid disease, but chemotherapy has not improved survival for adenocarcinoma. Recent advances in molecular characterization holds promise in novel targeted therapies. Currently ongoing trials are exploring efficacy of targeted therapies and role of adjuvant therapy for adenocarcinoma and results are awaited. Early detection and aggressive surgical therapy for all localized tumors and lymph node sampling particularly for adenocarcinoma remains the main treatment modality.
26 citations
TL;DR: The results of this study indicate that DNA repair system is adversely affected byHypermethylation of hMLH1 in a fraction of gastric cancer patients and E-cadherin hypermethylation seen in a subset of gastrics cancer patients is consistent with other reports showing correlation with aggressiveness and metastasis.
Abstract: Introduction
Gastric cancer (GC) is one of the leading causes of cancer-related death in Iran. Genome stability is one of the main genetic issues in cancer biology which is governed via the different repair systems such as DNA mismatch repair (MMR). A clear correlation between MMR defects and tumor progression has been shown. Beside the genetic mutations, epigenetic changes also have a noticeable role in MMR defects.
26 citations
TL;DR: The results of the current study showed that high MCD in the invasive edge of tumor is related to tumor progression and decreased survival rate following surgery.
Abstract: Squamous cell carcinoma (SCC) of the esophagus is one of the most common malignancies of the gastrointestinal tract and carries poor prognosis. The role of mast cell density (MCD) in the prognosis of most human tumors is partly known, and there is a growing body of studies addressing it. However, the prognostic value of MCD has not been investigated in esophageal SCC, and thus, it was the subject during this study. In this study, 78 patients with esophageal SCC in pT = 3 were selected, their MCD was evaluated with toluidine blue staining, and the relationship with survival rate was analyzed. Patients were compared in identical groups of lymph node involvement and post-surgery complementary therapy. Survival rate was significantly decreased in patients with high MCD based on Kaplan–Meier analysis (P < 0.001). This relationship was also found in groups with similar lymph node involvement and post-surgery therapies. The results of the current study showed that high MCD in the invasive edge of tumor is related to tumor progression and decreased survival rate following surgery.
25 citations
TL;DR: It is concluded that for the first time, the expression of MT2 receptor in gastric adenocarcinoma tissues which was in parallel with breast and colon cancer studies and high expression of this receptor in the marginal tissues indicate refractory mechanism which shows the defending role of melatonin in the GI system.
Abstract: Gastric cancer accounts 8 % of the total cancer cases and 10 % of total cancer deaths worldwide. The indoleamine N-acetyl-5-methoxytryptamine, better known as melatonin, is the principal hormone produced by the pineal gland. Recently, it has shown some anticancer role in some malignancies such as breast and colon cancer; also, some of its protective roles in the GI tract are as free radical scavenger and as antimitogenic and apoptotic agents. Based on the anticancer effects of melatonin and wide distribution of this neurohormone in the GI tract and some proposed physiologic and pharmacologic roles for this neurohormone, this study is initially scheduled to determine the expression of melatonin receptor MT2 in tissue samples of adenocarcinoma cancer patients. For this aim, a total of 30 gastric adenocarcinoma patients and 30 normal individuals were selected and examined for MT2 gene expression by real-time PCR. Our results have shown interestingly high expression for MT2 receptor in cancer and marginal cancer tissues compared with normal people. According to our results, it is concluded that for the first time, the expression of MT2 receptor in gastric adenocarcinoma tissues which was in parallel with breast and colon cancer studies and high expression of this receptor in the marginal tissues indicate refractory mechanism which shows the defending role of melatonin in the GI system. Our experiments has not shown any relationship between MT2 receptor expression and grade and clinicopathological features of gastric tumor, so we cannot conclude any relationship between this receptor expression and progression of the tumor, although this expression can be considered as an etiology.
25 citations
TL;DR: This meta-analysis implies moderation in capsaicin consumption in order to derive its protective benefits, and given outcomes from the tests of interaction, high Capsaicin intake is significantly different from the protection that low consumption offers.
Abstract: Reported associations of capsaicin with gastric cancer development have been conflicting. Here, we examine 10 published articles that explore these associations using 2,452 cases and 3,996 controls. We used multiple search strategies in MEDLINE through PubMed to seek for suitable articles that had case-control design with gastric cancer as outcome. The outcomes of our study shows protection (odds ratio [OR] 0.55, P = 0.003) and susceptibility (OR 1.94, P = 0.0004), both significant with low and medium-high intake of capsaicin, respectively, although under relatively heterogeneous conditions (P
heterogeneity = <0.0001). Outlier analysis resulted in loss of overall heterogeneity (P = 0.14) without affecting the pooled ORs. Among the subgroups, low intake elicited protection in both Korean (OR 0.37) and Mexican (OR 0.63) populations while high intake rendered these subgroups susceptible (OR 2.96 and OR 1.57, respectively). These subgroup values were highly significant (P = 0.0001–0.01) obtained in heterogeneous conditions (P
heterogeneity < 0.0001–0.04). The homogeneous (P
heterogeneity = 0.27–0.37) H. pylori (OR 0.60 and 1.69) effects were highly significant (P < 0.001) in the low and medium-high intake analyses, respectively. Given outcomes from the tests of interaction, high capsaicin intake is significantly different from the protection that low consumption offers. This meta-analysis implies moderation in capsaicin consumption in order to derive its protective benefits.
24 citations
TL;DR: Evidence supports the belief of a causal relationship between cirrhosis and hepatocellular carcinoma, but one that differs between high- and low-incidence regions of the tumor, and a direct hepatocarcinogenic effect of some of the causal agents.
Abstract: Abundant evidence supports the belief of a causal relationship between cirrhosis and hepatocellular carcinoma, but one that differs between high- and low-incidence regions of the tumor. In high-incidence regions, the cirrhosis is of the macronodular variety, is typically asymptomatic, and is caused predominantly by chronic hepatitis B virus infection, whereas in low-incidence regions, the cirrhosis, although usually macronodular, may be micronodular, is commonly symptomatic and of long-standing, and is caused by chronic hepatitis C virus infection, alcohol abuse over many years, the metabolic syndrome, or hereditary hemochromatosis. In a minority of patients, hepatocellular carcinoma develops in the absence of cirrhosis, supporting a direct hepatocarcinogenic effect of some of the causal agents. Cirrhosis is the major risk factor for tumor formation in patients with chronic hepatitis C virus infection. This virus does not integrate into cellular DNA, and malignant transformation results from increased liver cell turnover induced by recurring injury and regeneration of cells in the context of persisting inflammation, oxidative DNA damage, fibrosis, cirrhosis, and changes induced by the virus at a DNA level that have yet to be fully defined. Hepatitis B virus causes malignant transformation by both direct and indirect routes. The direct route results, in part, from integration of the viral DNA into host cellular DNA; transcriptional activation of host growth regulatory genes by hepatitis B virus-encoded proteins; and effects on apoptosis, cell signaling, and DNA repair. The direct route may share some similarities with that of hepatitis C virus infection. The metabolic syndrome may cause malignant transformation by production of oxidative stress and the induction of a variety of mutations, including some in the p53 gene.
TL;DR: This novel combination chemotherapy was feasible and showed promising results in pancreatic cancer patients with malignant ascites and a partial response was achieved in two patients and a disease control rate of 50 %.
Abstract: Objectives
Here, we reported an interim analysis of feasibility and safety in the first 10 cases of 30 cases in a phase II trial of intravenous and intraperitoneal paclitaxel combined with S-1 for gemcitabine-refractory pancreatic cancer with malignant ascites.
TL;DR: The second female case of pulmonary HAC who presented with elevated AFP and was treated with lobectomy and 3 cycles of adjuvant platinum-doublet chemotherapy is reported.
Abstract: Hepatoid adenocarcinoma (HAC) is a rare type of extrahepatic cancer, with pathologic features largely indistinguishable from hepatocellular carcinoma. Thirty cases of HAC have been described. The majority of HAC cases arise in the lung. Extrapulmonary HAC occurs in the stomach [1], and cases have been reported in the mediastinum, esophagus, gallbladder, pancreas, ampulla of Vater, renal pelvis, bladder, endometrium, ovary, and testicle [2–5]. In addition to the pathologic similarities to hepatocellular cancer, a large proportion of HACs produce AFP, and plasma levels may be very high [6]. Alpha-fetoprotein (AFP) was first detected in the serum of a patient with a primary liver tumor in 1965 [7] and has since been used as a tumor indicator for either primary liver or yolk sac tumors [8,9]. Certain gastrointestinal tumors such as gastric, rectal, and pancreatic carcinomas as well as lung cancer also secrete AFP [10–12]. We are reporting the second female case of pulmonary HAC who presented with elevated AFP and was treated with lobectomy and 3 cycles of adjuvant platinum-doublet chemotherapy. Case Presentation
TL;DR: HAE is an effective and well-tolerated therapeutic option for GIST liver metastases and should be considered as an alternative or adjuvant to third-line or even second-line systemic treatment.
Abstract: The purpose of the study is to determine the efficacy of hepatic artery embolization (HAE) as a therapy for gastrointestinal stromal tumor (GIST) in patients who are refractory to imatinib and sunitinib. After institutional review board approval, a retrospective review revealed 11 patients with GIST metastatic to the liver who underwent 15 HAEs between February 2002 and May 2013. These patients were stratified into two groups according to the previous treatment: (a) those treated with HAE as second-line treatment after failing first-line imatinib (n = 3) and (b) those treated with HAE as third-line therapy after failing first-line imatinib and second-line sunitinib (n = 8). Initial therapeutic response, overall survival (OS), progression-free survival (PFS), and safety were evaluated. Initial therapeutic response rates at 3 months after HAE were 27.3 % (95 % confidence interval (CI), 6.0–61.0 %) by Response Evaluation Criteria in Solid Tumor (RECIST) version 1.0 and 45.5 % (95 % CI, 16.7–76.6 %) by modified RECIST (mRECIST). The median OS and PFS after HAE were 14.9 and 3.9 months in group A and 23.8 and 3.4 months in group B, respectively. No procedure-related mortality or major complication was observed. HAE is an effective and well-tolerated therapeutic option for GIST liver metastases. Although larger studies are necessary, HAE should be considered as an alternative or adjuvant to third-line or even second-line systemic treatment.
TL;DR: This study is the first report that elucidated the HES1 underexpression in ESCC and revealed its correlation with the invasiveness of ESCC.
Abstract: Notch signaling is one of the main involved pathways in cell differentiation and organogenesis, and its deregulation may lead to tumorigenesis. In this pathway, targeted to the CSL (CBF1, Suppressor of Hairless or Lag-1) complex, notch intracellular domain (NICD) releases corepressors and recruits MAML1 as coactivator triggering the activation of notch signaling transcription complex. Hairy enhance of split-1 (HES1) is one of the notch signaling target genes which is a basic helix-loop-helix (bHLH) transcription factor acting as a proliferation stimulator through the suppression of cell cycle inhibitors such as p27 and p21. In this study, we aimed to analyze the role of HES1 in the progression of esophageal squamous cell carcinoma (ESCC). Messenger RNA (mRNA) expression of HES1 in fresh tumoral tissues and their margin normal samples were assessed in 50 ESCC patients by real-time polymerase chain reaction (RT-PCR). Thirteen out of 50 cases (26 %) had HES1 underexpression, while HES1 overexpression was observed only in 4 (8 %) samples. HES1 underexpression was significantly correlated with tumor depth of invasion (P = 0.035). Although we have not observed any significant correlation between the HES1 expression and notch activation in ESCC, this study is the first report that elucidated the HES1 underexpression in ESCC and revealed its correlation with the invasiveness of ESCC.
TL;DR: The aim of this review is to outline the risk stratification systems currently available to oncologists who are treating patients with GIST, so they can be optimally applied for clinical decision-making.
Abstract: Introduction
Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors of the gastrointestinal tract, which are characterized in the majority of cases by activating mutations in KIT and platelet-derived growth factor receptor alpha (PDGFRA). The introduction of tyrosine kinase inhibitors has revolutionized the management of patients with metastatic GIST. However, complete surgical resection remains the mainstay of management for those with localized disease. Recently, three large trials have confirmed the benefit of adjuvant imatinib therapy in patients who were at high risk of recurrence following complete resection. In this setting, it is critical that oncologists understand the various GIST risk assessment criteria and be able to apply these methods to accurately assess the risk of recurrence and the need for adjuvant imatinib therapy.
TL;DR: An algorithm for standardizing management so as to identify and treat posthepatectomy liver failure as early as possible is made.
Abstract: In literature, the reported mortality of posthepatectomy liver failure is <5 % and morbidity is 15–30 %. Around 3–8 % of patients develop liver failure after major hepatic resection. The objective of the study was to provide current definitions and managing posthepatectomy liver failure (PHLF) as per severity and ISGLS grading. A systemic search of pubmed indexed articles was done and relevant articles were selected to formulate latest guidelines for PHLF. We were able to make an algorithm for standardizing management so as to identify and treat PHLF as early as possible.
TL;DR: Results of GE cancer were comparable irrespective of surveillance strategy, and intensive follow-up with routine imaging and endoscopy may not be justified given the financial implications of these costly investigations.
Abstract: Our aims were to examine surveillance strategies after curative treatment of early gastroesophageal (GE) cancer and to evaluate the impact of different approaches on outcomes. A total of 292 patients with non-metastatic GE cancer who were referred to the BC Cancer Agency from 2001 to 2010 for curative intent treatment were analyzed. Surveillance practices were classified into the following: cohort 1 (discharge to general practitioner), cohort 2 (follow-up by oncologist with clinical assessments), cohort 3 (specialist follow-up with laboratory investigations), and cohort 4 (specialist follow-up with imaging or endoscopy). Outcomes were compared across cohorts using Kaplan–Meier methods and Cox regression. In total, median age was 63 years and 76 % were men. Eighty-nine (30 %), 18 (6 %), 32 (11 %), and 152 (53 %) patients were classified into cohorts 1 to 4, respectively. Patients with primary lesions involving the distal esophagus were more likely to undergo intensive surveillance which involved imaging studies and endoscopic procedures (p = 0.001). Individuals affected by specific histological subtypes, such as squamous cell carcinoma and the signet cell variant, and those whose disease were managed with definitive chemoradiotherapy without surgery were also more inclined to receive intensive follow-up (p = 0.008 and p = 0.001, respectively) There were no significant differences in overall (p = 0.34) or relapse-free survival (p = 0.59) among the different surveillance strategies, even after adjusting for measured prognostic factors. In this population-based analysis, outcomes of GE cancer were comparable irrespective of surveillance strategy. Intensive follow-up with routine imaging and endoscopy may not be justified given the financial implications of these costly investigations.
TL;DR: Serum CCL5 levels might be utilized as a predictive marker of tumor behavior and disease prognosis in patients with gastric adenocarcinoma and its relation with histological grade and tumor stage, as well as the disease prog outlook.
Abstract: Gastric cancer is the second leading cause of cancer-related deaths worldwide and the most common gastrointestinal cancer in Iran. Chemokine ligand 5 (CCL5/RANTES) is one of the most potent angiogenic factors that plays an important role in tumor growth, invasion, and metastasis. We aimed to assess the serum level of CCL5 in patients with gastric adenocarcinoma and its relation with histological grade and tumor stage, as well as the disease prognosis. Seventy-four patients with gastric adenocarcinoma that had undergone gastrectomy and 96 non-tumoral cases in which gastric cancer was ruled out by gastroscopy and biopsy were enrolled. Demographic and epidemiological characteristics and patient survival data were reviewed. Histological type, grade, and tumor stage (TNM) were determined by a single expert pathologist. Helicobacter pylori infection status and CCL5 serum level were measured by ELISA. Data were analyzed using SPSS software version 16. Patients with gastric adenocarcinoma had significantly higher serum CCL5 level compared with control group (P < .001). Higher serum CCL5 levels were associated with lower histological differentiation (P < .001), higher depth of tumor invasion (P = .022), more frequent lymph nodes involvement (P = .028), and advanced tumor stage (P = .002). The overall survival of patients with CCL5 levels higher than 70,671 pg/ml was significantly lower than those with lower than this cutoff (P = .043). Serum CCL5 levels might be utilized as a predictive marker of tumor behavior and disease prognosis in patients with gastric adenocarcinoma. Further studies to assess tissue expression of CCL5 and its gene polymorphisms are suggested.
TL;DR: DLTs affect the majority of patients on adjuvant FOLFOX for high-risk colon cancer, but RFS and OS do not appear to be affected by the associated lower RDI of oxaliplatin and 5-FU.
Abstract: Purpose
Adjuvant folinic acid, fluorouracil, and oxaliplatin (FOLFOX) chemotherapy for resected high-risk colon cancer is associated with a low risk of febrile neutropenia (FN) Neutropenia, however, is a common cause of dose modification or delay with unknown consequences on outcomes We examined the effect of neutropenia-related and other dose-limiting toxicities and relative dose intensity of oxaliplatin and 5-FU, on relapse-free and overall survival in patients treated with FOLFOX chemotherapy for resected high-risk colon cancer
TL;DR: EUS is less accurate in staging tumors which are not on either ends of the spectrum (mucosally based or clearly transmural) in this challenging group of patients, and it is suspect that newer generation EUS systems, which provide better imaging, will result in improved accuracy in staging thisgroup of patients.
Abstract: Accurate staging of esophageal carcinoma (EC) is important since it directs further management. Endoscopic ultrasound (EUS) is the best tool available in the locoregional staging of EC; however, differentiating depth of tumor invasion (T) and nodal involvement (N) can be challenging. Accurate staging is particularly important to differentiate T1-2 N0 cancers, which can proceed directly to surgical resection versus TXN1 or T3N0/1 cancers, which benefit from induction chemoradiation prior to surgery. We report the accuracy of EUS staging for cT2N0 lesions. Six hundred six patients underwent EUS for staging of EC between October 2003 and February 2013 by a single interventional endoscopist specially trained in endoscopic ultrasound. Thirty-eight patients were diagnosed with T2N0 tumors and underwent surgical resection without preoperative chemoradiation. EUS staging was compared to surgical pathology to evaluate accuracy. Patient follow-up was obtained from a retrospective chart review. Thirty-eight patients (34 men, mean age 65.8 ± 10.5 years) with cT2N0 tumors by EUS underwent surgical resection of EC without chemoradiation after a mean of 22.4 ± 13.7 days post-EUS. When compared with final pathologic outcomes, 12 (32 %) were understaged by EUS and 18 (47 %) were overstaged. Understaging occurred due to tumor depth (T) in two patients (17 %), nodal disease (N) in six (50 %), and both in four (33 %). Overstaging occurred due to pathology consistent with pT1b tumors instead of T2 tumors in all 17 cases. Based on EUS, 74 % were referred for appropriate therapy. While EUS is highly accurate in staging EC, it is less accurate in staging tumors which are not on either ends of the spectrum (mucosally based or clearly transmural). In this challenging group of patients, EUS understaged EC in 32 % of cases resulting in surgical resection when neoadjuvant chemoradiation may have been beneficial. We suspect that newer generation EUS systems, which provide better imaging, will result in improved accuracy in staging this group of patients.
TL;DR: Elevated CA 19-9 demonstrated a greater likelihood of PDAC diagnosis relative to benign pancreatic pathology, and higher levels of CA19-9 were in line with worse PDAC stage, and these patients may benefit from more diligent EUS examination or perhaps closer follow-up management.
Abstract: Purpose
Recent data suggest the use of carbohydrate antigen (CA) 19-9 as a potential marker in the early detection of pancreatic ductal adenocarcinoma (PDAC) when used in the appropriate clinical setting. Here, we assess the utility of CA19-9 in PDAC detection in a select population of pancreatic endoscopic ultrasound (EUS) referrals.
TL;DR: Given that EAC is associated with accumulated genomic instability, high ML in less severe histology may identify BE disease at greater risk of progression to EAC and may help to better manage BE in early histological stages and when histology alone provides insufficient information.
Abstract: Purpose
Progression of Barrett's esophagus (BE) to esophageal adenocarcinoma (EAC) is associated with accumulated genomic instability. Current risk stratification of BE for EAC relies on histological classification and grade of dysplasia. However, histology alone cannot assess the risk of patients with inconsistent or non-dysplastic BE histology. We, therefore, examined the presence and extent of genomic instability in advanced and less advanced BE histology using mutational load (ML).
TL;DR: A case of a young woman with bilobar neuroendocrine metastases where PVE failed to induce hypertrophy of the FRL, but the tumours were successfully resected using the ALPPS approach is reported.
Abstract: Liver resection has been recommended as the standard treatment for patients with low-volume neuroendocrine liver metastasis (NELM), where complete debulking of the liver metastases can be accomplished through a hepatectomy [1]. The recovery and morbidity including the risk of posthepatectomy liver failure (PHLF) following a major hepatectomy is directly related to the volume and quality of the future remnant liver (FRL). Conventionally, portal vein occlusion (through embolization, a more commonly and occasionally surgical ligation) has been the accepted modality enabling hypertrophy of the liver remnant and thereby facilitating successful liver resection with curative intent [2]. Adequate response to portal vein embolization (PVE) depends also on the initial FRL volume and on the absence of parenchymal injury. In a recent review, PVE was reported to induce a mean liver hypertrophy by 37.9±0.1 % [2]. However, PVE may technically fail in 3.9 % patients and may fail to produce adequate hypertrophy to facilitate hepatectomy in 2.8 % of patients [2]. More recently, Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS), a new two-stage technique for liver resection, has been reported and has shown promise as a safe, effective and rapid technique of inducing hypertrophy of the FRL [3–6]. We report here a case of a young woman with bilobar neuroendocrine metastases where PVE failed to induce hypertrophy of the FRL, but the tumours were successfully resected using the ALPPS approach.
TL;DR: The importance of rarity, diagnosis, and combined modality management of hepatoblastoma in a child with liver tumor in a 3-year-old female child is highlighted.
Abstract: Hepatoblastoma is a rare malignant tumor of the liver and usually occurs in the first 3 years of life [1]. Most of these tumors arise in the embryo. The hepatic tumors in a child raise diagnosis and therapy problems because of their rarity, comprising 1–4 % of solid tumors [2]. It occurs more frequently in children who were born very prematurely (early) with very low birth weights. The exact cause is unknown; however, there are a number of genetic conditions that are associated with an increased risk for developing hepatoblastoma. These include Beckwith-Wiedemann syndrome, familial adenomatous polyposis, and hemihypertrophy [3]. Other risk factors are exposure to hepatitis B infection at an early age and biliary atresia. The suspicion of hepatoblastoma is based on age, history, clinical, biological, and imaging data, correlated with the alpha-fetoprotein level. We here present a rare case of hepatoblastoma in a 3-year-old female child. This case is reported to highlight the importance of rarity, diagnosis, and combined modality management of hepatoblastoma in a child with liver tumor.
TL;DR: The potential role of the STAT3 signaling pathway in the pathogenesis of obesity-related gastrointestinal malignancy and the potential therapeutic role of STAT3 blockade are examined given its status as a signaling hub for a number of inflammatory adipocytokines.
Abstract: A large body of evidence has implicated the signal transducer and activator of transcription (STAT) family and particularly the ubiquitously expressed STAT3 protein in the pathogenesis of colorectal, hepatocellular, gastric and pancreatic carcinoma. Concomitantly, an increasing body of epidemiological evidence has linked obesity and its associated pro-inflammatory state with the development of gastrointestinal cancers. Visceral adipose tissue is no longer considered inert and is known to secrete a number of adipocytokines such as leptin, interleukin (IL)-6, IL-8, IL-1β and tumour necrosis factor-alpha (TNF-α) into the surrounding environment. Interestingly, these adipocytokines are strongly linked with the Janus kinase (JAK)/STAT pathway of signal transduction and there is experimental evidence linking IL-1β, IL-8 and TNF-α to JAK/STAT signaling in other tissues. The result is an up-regulation of a wide range of anti-apoptotic, pro-metastatic and pro-angiogenic genes and processes. This is particularly relevant for gastrointestinal malignancy as these factors have the potential to signal adjacent endothelial cells in a paracrine manner. This review examines the potential role of the STAT3 signaling pathway in the pathogenesis of obesity-related gastrointestinal malignancy and the potential therapeutic role of STAT3 blockade given its status as a signaling hub for a number of inflammatory adipocytokines.
TL;DR: Results of LT for angiosarcoma have been disappointing with no long-term survivors, and indication for LT for hepatic metastasis from neuroendocrine tumors (NETs) is mainly for patients with unresectable tumors and for palliation of medically uncontrollable symptoms.
Abstract: Liver transplantation (LT) has become an acceptable and effective treatment for selected patients with hepatocellular carcinoma with excellent outcomes. More recently, LT has been tried in different primary and secondary malignancies of the liver. The outcomes of LT for very selected group of patients with hilar cholangiocarcinoma (CCA) have been promising. Excellent results have been reported in LT for patients with unresectable hepatic epithelioid hemangioendothelioma (HEHE). In contrast to excellent results after LT for HEHE, results of LT for angiosarcoma have been disappointing with no long-term survivors. Hepatoblastoma (HB) is the most common primary liver cancer in pediatric age group. Long-term outcomes after LT in patients with unresectable tumor and good response to chemotherapy have been promising. Indication for LT for hepatic metastasis from neuroendocrine tumors (NETs) is mainly for patients with unresectable tumors and for palliation of medically uncontrollable symptoms. Posttransplant survival in those patients with low tumor activity index is excellent, despite recurrence of the tumor. More recent limited outcomes data on LT for unresectable hepatic metastases from colorectal cancer have claimed some survival benefit compared to the previous reports. However, due to the high rate of tumor recurrence in a very short time after LT, especially in the era of organ shortage, this indication has not been favored by the transplant community.
TL;DR: Benign liver tumors represent a chapter always more interesting of liver disease and a careful differential diagnosis with the forms of malignant tumor is often required in such a way so to direct the patient to the correct therapy.
Abstract: Background
Benign liver tumors are common. They do not spread to other areas of the body, and they usually do not pose a serious health risk. In fact, in most cases, benign liver tumors are not diagnosed because patients are asymptomatic. When they are detected, it’s usually because the person has had medical imaging tests, such as an ultrasound (US), computed tomography (CT) scan, or magnetic resonance imaging (MRI), for another condition.
TL;DR: Percutaneous endoscopic gastrostomy tube insertion is a useful means of providing enteral nutrition to patients with swallowing problems and patients with head and neck cancer who are likely to develop dysphagia should be assessed promptly for PEG tube insertion before the start of radiation.
Abstract: Dysphagia, with associated malnutrition is a common feature in up to 64 % of patients with cancers of the head and neck region, the oesophagus and the gastro-oesophageal junction (Donaldson and Lenon Cancer 43(Suppl 5):2036–52, 1979). These patients usually require alternate routes of feeding during treatment. However, these methods of feeding are not without associated complications. This study was carried out to assess the complications associated with percutaneous endoscopic gastrostomy tube insertion, the commonest means of providing nutrition in this patient group. Two hundred and sixty patients with successful percutaneous endoscopic gastrostomy (PEG) tube insertion were retrospectively reviewed to assess the complications of the procedure. The overall complication rate was 25 % (65 patients). Fifty-five patients (21 %) patients had minor complications. Ten patients (3.8 %) suffered a major complication, including peritonitis and major peri-PEG infection each in three patients (1.2 %), while oesophageal perforation, collection around the PEG insertion site requiring operative drainage, bleeding from the PEG insertion site and tumour seeding at the gastrostomy site were each seen in one (0.4 %) patient. Percutaneous endoscopic gastrostomy tube insertion is a useful means of providing enteral nutrition to patients with swallowing problems. Patients with head and neck cancer who are likely to develop dysphagia should be assessed promptly for PEG tube insertion before the start of radiation. Early recognition and prompt treatment of serious complications can avoid potential fatality associated with PEG tubes.
TL;DR: A meta-analysis evaluates the association between HBsAg positivity and pancreatic cancer and revealed a nonsignificant increased risk of cancer in patients with positive anti-HBc status, which could have important implications for both primary prevention and treatment of pancreaticcancer.
Abstract: Several studies have proposed an association between hepatitis B and pancreatic cancer Although the spectrum of serological tests varied between studies, hepatitis B virus (HBV) surface antigen (HBsAg) test results were consistently reported This meta-analysis evaluates the association between HBsAg positivity and pancreatic cancer A systematic literature search was performed from inception through September 2013 for English language studies using the following terms: “hepatitis B,” “HBsAg,” “pancreatic cancer,” and “pancreatic adenocarcinoma” Studies that have not reported cumulative odds ratio for the association of interest were excluded Pooled odds ratios (ORs) and corresponding 95 % confidence intervals (CI) were calculated using a random-effects model Statistical heterogeneity and publication bias were addressed using the I
2 statistic and Egger’s weighted regression statistics, respectively We included two case–control studies and one cohort study, involving 1,636 patients with pancreatic cancer The OR of developing pancreatic cancer was 150 (95 % CI 121 to 187) for individuals who were HBsAg-positive The type of study, case–control versus cohort, did not appear to influence the results Only two of the three studies reported the association between anti-HBc positivity and pancreatic cancer Our analysis revealed a nonsignificant increased risk of cancer in patients with positive anti-HBc status (OR 123, 95 % CI 095–159) No statistically significant heterogeneity or publication bias was noted HBsAg positivity is associated with an increased risk of pancreatic cancer Additional studies are needed to clearly define the association between chronic hepatitis B infection and pancreatic cancer This could have important implications for both primary prevention and treatment of pancreatic cancer