Featured Articles from the Annals of Gastroenterology & Hepatology

Primary Gastric T-Cell Lymphoma Not Associated with Human T-Lymphotropic Virus Type 1

Tomoaki Ito¹, Koichi Sato¹, Hiroshi Maekawa¹, Mutsumi Sakurada¹, Hajime Orita1 and Ryo Wada²

Affiliations: ¹Department of Surgery and ²Department of Pathology, Juntendo Shizuoka Hospital, Juntendo University School of Medicine, Shizuoka, Japan

Correspondence: Tomoaki Ito, Department of Surgery, Juntendo Shizuoka Hospital, Juntendo University School of Medicine, 1129 Nagaoka, Izunokuni-shi, Shizuoka 410-2295, Japan. Tel: (81)-55-948-3111; Fax: (81)-55-946-0514; e-mail: tomo-ito@k4.dion.ne.jp

ABSTRACT

Most primary gastric lymphomas are of B-cell origin, whereas a gastric T-cell lymphoma is extremely rare. We report a 73-year-old Japanese man with primary gastric T-cell lymphoma not associated with human T-lymphotropic virus type 1 (HTLV-1). In March 2009, the patient was admitted to our hospital with the chief complaint of weight loss of 6 kg over 6 months. HTLV-1 was negative by the particle agglutination (PA) method. An upper gastrointestinal endoscopy revealed a large ulcerated tumor with a partially cleaved bank at the greater curvature of the cardia. A computed tomography scanning demonstrated thickening of the gastric wall and tumor invasion into the liver and spleen; no apparent lymph node swelling was noted in the chest or abdomen. Total gastrectomy with splenectomy and partial resection of the diaphragm and liver were performed in May 2009. Hematoxylin and eosin staining of the surgical specimens showed diffuse infiltration with medium atypical lymphocytes. Immunohistochemically, the cells were positive for CD3, CD8, CD45RO, and CD30, but negative for CD4 and CD79α. Based on these histological findings, the tumor was diagnosed as a diffuse, medium type according to the Lymphoma Study Group classification and peripheral T-cell lymphoma, unspecified as per the WHO histological classification. Currently, at 17 months since diagnosis, the patient is still alive.

A Double-Blind Placebo-Controlled Assessment of Endoscopic Change and Duodenal Cox-2 Expression in Patients with Familial Adenomatous Polyposis After Treatment With a Cox-2 Inhibitor (Rofecoxib)

BACKGROUND AND AIMS

Cox-2 inhibitors have been shown to counter adenoma growth and development of malignancy of the colorectum in animals and humans. The purpose of the present study was to assess the effect of a specific Cox-2 inhibitor on duodenal adenomas in patients with familial adenomatous polyposis (FAP).

MATERIALS AND METHODS

Familial adenomatous polyposis patients (N =38) with duodenal adenomas were randomly assigned to rofecoxib (Vioxx) 25 mg or placebo in a double-blind fashion for 1 year. Endoscopy with biopsies of lesions and flat mucosa were performed before and after the treatment. Macroscopic and microscopic evaluation, immunohistochemical assessment of Cox-2 protein expression, and real-time polymerase chain reaction (PCR) analyses of COX-2 gene expression were performed. In addition, the expression of COX-2 was measured by real-time PCR in leucocytes.

RESULTS

Thirty-two patients followed the scheduled treatment for at least 9 months. The macroscopic lesions appeared unchanged after intervention, both in the treatment and placebo group. Adenomatous and normal tissue showed unchanged Cox-2 expression after treatment with rofecoxib, whereas increased staining of both adenomatous tissue and normal mucosa was shown in the placebo group. A higher concentration of Cox-2 was shown in the normal compared to adenomatous mucosa, both at baseline and after treatment. This was supported by an increased COX-2 gene expression by real-time PCR in macroscopically normal mucosa.

CONCLUSION

The reduced expression of Cox-2 in duodenal adenomatous tissue compared to normal mucosa adds to the recent findings of a great individual variation in Cox-2 expression of colorectal cancers. It may also indicate a low potential for malignancy in the duodenum of FAP patients in the Norwegian population.

Gd-EOB-DTPA-Enhanced MRI versus Extracellular Contrast Medium-Enhanced MRI in Differentiation of Metastatic from Benign Liver Lesions

Suitable resection of liver metastases improves survival and often leads to complete cure, especially in colorectal carcinomas. Accurate diagnosis of liver metastasis is important to assess the extent of hepatic resections. Liver metastases are often small and multiple, and intermingled with benign focal lesions, such as hemangiomas and cysts. Therefore, differentiating metastatic tumors from focal benign lesions is important.Magnetic resonance imaging (MRI) is well recognized as one of themost sensitive modalities for depicting liver metastatic tumors. Dynamic MRI using nonspecific extracellular contrast media (ECCM) has been shown to be superior to noncontrast-enhanced MRI for depicting liver metastases. Dynamic ECCM-enhanced MRI can show vascularity and interstitium of focal hepatic lesions. Gadolinium ethoxybenzyl diethylene triamine penta-acetic acid (Gd-EOB-DTPA, Primovist®, Bayer Schering Pharma, Berlin, Germany) is a hepatocyte-specific contrast medium specifically taken up in the delayed phase, thereby providing increased lesion–liver contrast not achievable with ECCM. Furthermore, Gd-EOB-DTPA can demonstrate enhancement characteristics and vascularity of liver lesions during the dynamic arterial, portal, and late phases after a bolus injection. Most liver metastases show a hypovascular pattern in the arterial–portal phase and hypointense pattern in the hepatocyte-specific phase of Gd-EOB-DTPA-enhanced MRI. Small hemangiomas, abscesses, and inflammatory pseudotumors are sometimes difficult to differentiate from metastatic tumors on MRI. This article reviews the current literature on Gd-EOB-DTPA-enhanced MRI versus ECCM-enhanced MRI in differentiating metastatic from benign liver lesions.

Evidence of Probiotic Strain Specificity Makes Extrapolation of Results Impossible From a Strain to Another, Even From the Same Species

Clinical trials show that some probiotic effects are observed with specific strains but not in control strains. The strains compared were often members of different species or even genus. There is a tendency to believe that some extrapolation of results could be possible for microorganisms of the same species, and this is especially done by some companies selling products that were not studied and using studies performed with different strains. However, several studies compared the composition, characteristics, and physiological properties of probiotic strains in comparison to very closely related strains within the same species. These studies show strain or family-specific differences. This paper will provide examples showing that related bacterial strains can differ significantly in their genotype, phenotype, and properties. The implications of this strain-specificity are that (1) for commercial products, documentation of health effects must be conducted on the specific strain contained in the product; (2) one should avoid any extrapolation of positive or negative effects between probiotic strains; (3) meta-analysis of the effect of probiotics with different active molecules should be avoided; (4) one should not call a probiotic a strain that has not been studied just on the basis that it is taxonomically related to a well-proven probiotic strain. These rules are presently frequently violated.

The Role of Cetuximab in Hepatic Resection of Metastatic Colorectal Cancer

For patients with metastatic colorectal cancer with liver-isolated metastases, complete surgical resection may be associated with long-term survival and is the treatment of choice when feasible. Fewer than 20% of patients present as candidates for potentially curative surgery. Induction chemotherapy, also called “conversion” therapy may make patients with initially unresectable disease amenable to surgery. Cetuximab is a monoclonal antibody that targets the epidermal growth factor receptor (EGFR) and increases the efficacy of systemic standard chemotherapy in wild-type KRAS patients. The addition of cetuximab to chemotherapy may increase the proportion of patients who become eligible for curative resection. It may be a reasonable option to use it in wild-type KRAS patients with liver-limited disease who need to be downstaged to resectability.

Gastroparesis: A Comprehensive Review

Gastroparesis (GP) is a multifactorial syndrome in which the predominant symptoms of abdominal pain, nausea, bloating, and early satiety occur in the face of an abnormally slow gastric emptying in the absence of a mechanical obstruction. It is most commonly idiopathic or associated with Diabetes Mellitus (DM). There is a 4:1 female to male preponderance, presumably due at least partially to hormonal causes. The differential diagnosis includes metabolic diseases, surgically- and drug-associated GP. There is a considerable overlap with postprandial distress syndrome, a distinct clinical entity that shares several of the symptoms and can be associated with decreased gastric emptying. The treatment for GP is very different in the acute and chronic settings. Acutely, replacement and correction of electrolyte, metabolic and fluid imbalances, and pain and nausea control are key elements. The chronic phase includes diet and lifestyle changes, avoidance of drugs that interfere with motility, use of gastric emptying-enhancing drugs, and careful use of analgesics and antinausea medication. In resistant and selected cases, gastric electrical stimulation may be considered. Several new drugs including newer 5HT4 agonists and Grhelin are being evaluated for future clinical use.

Symptom Relief With Cetuximab for Patients With Metastatic Colorectal Cancer

The introduction of novel targeted therapies in the management of metastatic colorectal cancer (mCRC) has modified the natural history of this disease in the last years. New compounds with antiepidermal growth factor receptor (EGFR) or antiangiogenic activity have been progressively introduced to the clinical practice. Among these, cetuximab, a chimeric IgG1 monoclonal antibody that targets the ligandbinding domain EGFR has demonstrated antitumor activity in monotherapy or in combination with chemotherapy. Up to 80% patients with metastatic colorectal cancer have unresectable disease. Therefore, palliation is the main aim in the management of these patients. Progression-free survival (PFS) is a valid endpoint for trials in the palliative setting in mCRC. Other endpoints, frequently considered as secondary endpoints such as response rate (RR) or overall survival (OS) are also very important. However, improvement of quality of life (QoL) and appropriate symptom management are major issues in the therapeutic strategy and these are occasionally considered in some trials.

Recent retrospective data indicate that KRAS mutation status has an important role as a predictive factor for response to anti-EGFR therapy. Treatment with cetuximab in patients with KRAS mutated tumor has no benefit or might be even deleterious in combinations with oxaliplatin.

This review summarizes the most important achievements in the issue of symptomatic control and palliation induced by cetuximab therapy and provides a brief overview about the main clinical trials assessing its benefit in addition to different chemotherapy schedules and the role of KRAS mutational status as predictive factor for response.

Is Digestive Discomfort a Relevant Health Issue?

For a variety of reasons, some related to health care policy, some commercial, some scientific, the concept of digestive comfort or, more commonly, its corollary, digestive discomfort have come to be widely referred to in both the lay and medical press. Are these well defined entities? I would contend that an attempt to define digestive comfort, other than in terms of the absence of digestive discomfort, is an impossible task; the focus of this review, therefore, will be on the latter concept: digestive discomfort. The various complaints that may contribute to digestive discomfort will be discussed and their potential importance to, and impact on, the individual and society reviewed. Unfortunately, the detection of digestive discomfort, or its constituent symptoms, in the community has a limited potential to lead to the early diagnosis of serious gastrointestinal conditions or prevent their future occurrence. Furthermore, with the notable exception of heartburn and constipation, our ability to dramatically alleviate many of these symptoms is currently limited pending a more detailed understanding of their pathogenesis and the advent of specific and more effective therapies. What is needed above all is a greater understanding of what digestive discomfort means to an individual sufferer, what generates this discomfort and how we can successfully intervene.

PET/CT in GI Malignancies

The dual functional and anatomic imaging capability and its ability for whole body staging has established [¹⁸F]FDG-PET/CT as an integral part of the management of several GI malignancies. [¹⁸F]FDG-PET/CT has a proven role in the staging of esophageal cancer, detection of colorectal cancer recurrence, and in the management of GIST and certain GI lymphomas. [¹⁸F]FDG-PET/CT has shown promise in the assessment of treatment response in esophageal and colorectal cancers and in the staging of anal cancer. Limitations to the use of [¹⁸F]FDG-PET/CT for evaluation of the GI tract include the significant overlap between normal physiologic uptake and disease, false positive uptake in inflammatory processes such as inflammatory bowel disease and diverticulitis, and diffuse bowel uptake caused by certain medications such as metformin. The purpose of this review is to outline the technical issues and current evidence for the use of [¹⁸F]FDG-PET/CT in the evaluation of GI malignancies.

Stress, Intestinal Inflammation, and Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) is a highly prevalent disorder that comprises a heterogeneous group of patients suffering from chronic and recurrent abdominal pain usually associated with visceral hypersensitivity and altered bowel habit. The etiology of IBS is considered multifactorial, being psychosocial events especially life stress and gastrointestinal infections, key players in the onset, persistence, and severity of clinical manifestations. Furthermore, the common presence of low-grade inflammation and immune activation in the intestinal mucosa of certain IBS subgroups challenge the traditional assumption of IBS as a prototypic gut functional disorder and provide a plausible hypothesis linking stress and infections to IBS development. The breakdown of intestinal epithelial barrier's surveillance may represent a leading event in such a connection, as converging observations link the onset and severity of abdominal pain and visceral hypersensitivity to structural and functional abnormalities of the mucosal barrier. Consequently, intestinal barrier dysfunction might facilitate unfettered penetration of food and bacterial antigens across the epithelium to stimulate disruptive immunological responses favoring the development of mucosal inflammation. In this review, we summarize the most relevant evidences of stress-induced intestinal inflammation and discuss the most important mediators and mechanisms that have been involved.

The Therapeutic Role of Ursodeoxycholic Acid in Digestive Diseases

Ursodeoxycholic acid (UDCA) makes up a small portion of the naturally occurring bile acid pool in humans, and the drug is effective in several diseases. The mechanism of action involves the displacement of more toxic endogenous bile acids, direct protection of hepatocytes against apoptosis, and stimulation of endogenous secretion of bile to alleviate cholestasis. The use of UDCA has been studied extensively in primary biliary cirrhosis and cholelithiasis and there is evidence for its use in both diseases. There is also evidence against the use of UDCA in primary sclerosing cholangitis (PSC). Several potential uses of UDCA warrant further investigation after initial studies have shown promise including treatment for microlithiasis, intrahepatic cholestasis of pregnancy, total parenteral nutrition, chemoprophylaxis of colorectal cancer in patients with ulcerative colitis and PSC, viral hepatitis, and in bone marrow transplantation. Ursodeoxycholic acid is generally well tolerated with few adverse events, though minor weight gain is a common side effect.

Familial Pancreatic Cancer

Pancreatic cancer is an extraordinarily deadly disease with a median survival of a few months after diagnosis. Studies over the past three decades have shown that 10% of patients with pancreatic ductal adenocarcinoma have a family history of the disease. A number of distinct genetic syndromes are associated with a greater risk of pancreatic cancer. These include familial atypical multiple mole melanoma, Peutz–Jeghers syndrome, hereditary nonpolyposis colorectal cancer, familial adenomatous polyposis, hereditary breast ovarian cancer, and hereditary pancreatitis. These syndromes arise as a result of germline mutations in a cancer-causing gene. Different national registries were created in order to identify and develop new approaches in screening high-risk individuals for precancerous pancreatic lesions. The study of these individuals has increased our understanding of the pathogenesis of this lethal disease and can be used to improve the diagnosis of more common “sporadic” forms of pancreatic cancer.

Interventional Radiology in the Management of Hepatocellular Carcinoma in Liver Cirrhosis

Liver cirrhosis represents the final stage in the spectrum of chronic liver disease and constitutes an important healthcare burden worldwide because of its high morbidity and mortality. Management of hepatocellular carcinoma (HCC) in cirrhotic patients is often challenging because of the presence of underlying liver disease. Image-guided diagnosis and intervention has a crucial role in the surveillance, diagnosis, treatment, and post-treatment follow-up of HCC in these patients. Image-guided biopsy has a dual role, which comprises of non-targeted liver biopsy for diagnosis and staging of cirrhosis and targeted biopsy of nodules suspicious for HCC. Surgical resection and transplantation are deemed curative therapies for treatment of HCC in cirrhosis while percutaneous image-guided ablative techniques are often used to treat patients with non-resectable and non-transplantable disease, as a bridge to transplantation, or with palliative intent. Radiofrequency ablation (RFA) is among the most effective percutaneous ablative technique while ethanol injection is an effective alternative to RFA in treatment of HCCs smaller than 2 cm. Transarterial chemoembolization (TACE) offers a non-curative or palliative therapy for nonsurgical patients with large or multifocal HCC without vascular invasion or extrahepatic disease and prolongs survival in comparison to standard supportive care. There has been an emerging trend to combine TACE with ethanol injection or RFA to reduce recurrence and improve survival in patients with HCC. In this review article we discuss the key concepts in the oncological management of cirrhotic patients from the perspective of the interventional radiologist.

Review on the Treatment of Eosinophilic Esophagitis in Adults

Eosinophilic esophagitis (EoE) is a clinicopathologic disease characterized by abnormal eosinophilic infiltration in the esophagus with associated symptoms including dysphagia, strictures, and food impaction. While esophageal eosinophilic infiltration was historically attributed to gastroesophageal reflux disease (GERD), recognition of an association between EoE and allergies has emerged. As such, therapeutic strategies have focused on allergen avoidance and treatment of eosinophil-derived inflammation. The mainstays of therapy include dietary modification, systemic steroids, topical steroids, proton pump inhibitors, leukotriene receptor antagonist, immunomodulating agents, and endoscopic dilation. However, few randomized controlled studies assessing these modalities are available. Further treatment endpoints, long-term prognosis, and the role of maintenance therapy in EoE remains unclear. This review will focus on the efficacy of current and emerging treatment strategies for adult patients with EoE.

Advances in Biliary Imaging: CT and MR Cholangiography

The purpose of this article is to review different imaging techniques for assessment of the hepatobiliary system with a focus on magnetic resonance imaging (MRI) and computed tomography (CT), to describe imaging acquisition and postprocessing techniques, and to illustrate some clinical indications. MRI as well as CT allow a comprehensive and noninvasive evaluation of the liver parenchyma, periductal tissue, and bile ducts. More recently developed hepatocyte-specific contrast agents are still in the process of evaluation for contrast-enhanced MR cholangiography. Future applications may include the grading of liver function and the diagnosis of sphincter of Oddi dysfunction.