Inflammatory bowel disease and cancer: The role of inflammation, immunosuppression, and cancer treatment

In patients with inflammatory bowel disease(IBD), chronic inflammation is a major risk factor for the development of gastrointestinal malignancies. The pathogenesis of colitis-associated cancer is distinct from sporadic colorectal carcinoma and the critical molecular mechanisms underlying this process have yet to be elucidated. Patients with IBD have also been shown to be at increased risk of developing extra-intestinal malignancies. Medical therapies that diminish the mucosal inflammatory response represent the foundation of treatment in IBD, and recent evidence supports their introduction earlier in the disease course. However, therapies that alter the immune system, often used for long durations, may also promote carcinogenesis. As the population of patients with IBD grows older, with longer duration of chronic inflammation and longer exposure to immunosuppression, there is an increasing risk of cancer development. Many of these patients will require cancer treatment, including chemotherapy, radiation, hormonal therapy, and surgery. Many patients will require further treatment for their IBD. This review seeks to explore the characteristics and risks of cancer in patients with IBD, and to evaluate the limited data on patients with IBD and cancer, including management of IBD after a diagnosis of cancer, the effects of cancer treatment on IBD, and the effect of IBD and medications for IBD on cancer outcomes.

Post-infectious irritable bowel syndrome

Post-infectious irritable bowel syndrome (PI-IBS) is a common disorder wherein symptoms of IBS begin after an episode of acute gastroenteritis. Published studies have reported incidence of PI-IBS to range between 5% and 32%. The mechanisms underlying the development of PI-IBS are not fully understood, but are believed to include persistent sub-clinical inflammation, changes in intestinal permeability and alteration of gut flora. Individual studies have suggested that risk factors for PI-IBS include patients' demographics, psychological disorders and the severity of enteric illness. However, PI-IBS remains a diagnosis of exclusion with no specific disease markers and, to date, no definitive therapy exists. The prognosis of PIIBS appears favorable with spontaneous and gradual resolution of symptoms in most patients.

Eosinophilic gastroenteritis:Approach to diagnosis and management

Eosinophilic gastroenteritis(EGE) is a rare and benign inflammatory disorder that predominantly affects the stomach and the small intestine.The disease is divided into three subtypes(mucosal,muscular and serosal) according to klein's classification,and its manifestations are protean,depending on the involved intestinal seg-ments and layers.Hence,accurate diagnosis of EGE poses a significant challenge to clinicians,with evidence of the following three criteria required:Suspicious clinical symptoms,histologic evidence of eosinophilic infiltration in the bowel and exclusion of other pathologies with similar findings.In this review,we designed and applied an algorithm to clarify the steps to follow for diagnosis of EGE in clinical practice.The management of EGE represents another area of debate.Prednisone remains the mainstay of treatment;however the disease is recognized as a chronic disorder and one that most frequently follows a relapsing course that requires maintenance therapy.Since prolonged steroid treatment carries of risk of serious adverse effects,other options with better safety profiles have been proposed;these include budesonide,dietary restrictions and steroid-sparing agents,such as leukotriene inhibitors,azathioprine,anti-histamines and mast-cell stabilizers.Single cases or small case series have been reported in the literature for all of these options,and we provide in this review a summary of these various therapeutic modalities,placing them within the context of our novel algorithm for EGE management according to disease severity upon presentation.

Investigation and prediction of enteral nutrition problems after percutaneous endoscopic gastrostomy

AIM:To investigate and predict enteral nutrition problems after percutaneous endoscopic gastrostomy (PEG). METHODS:We retrospectively analyzed data for 252 out of 285 patients who underwent PEG at our hospital from 1999 to 2008.Enteral nutrition problems after PEG were defined as:(1)patients who required ≥1 mo after surgery to switch to complete enteral nutrition,or who required additional parenteral alimentation continuously;or(2)patients who abandoned switching to enteral nutrition using the gastrostoma and employed other nutritional methods. We attempted to identify the predictors of problem cases by using a logistic regression analysis that examined the patients’backgrounds and the specific causes that led to their problems. RESULTS:Mean age of the patients was 75 years,and in general,their body weight was low and their overall condition was markedly poor.Blood testing revealed that patients tended to be anemic and malnourished.A total of 44 patients(17.5%)were diagnosed as having enteral nutrition problems after PEG.Major causes ofthe problems included pneumonia,acute enterocolitis (often Clostridium difficile-related),paralytic ileus and biliary tract infection.A multivariate analysis identified the following independent predictors for problem cases:(1)enteral nutrition before gastrectomy(a risk reduction factor);(2)presence of esophageal hiatal hernia;(3)past history of paralytic ileus;and(4) presence of chronic renal dysfunction. CONCLUSION:Enteral nutrition problems after PEG occurred at a comparatively high rate.Patient background analysis elucidated four predictive factors for the problem cases.

Traditional Chinese herbal extracts inducing autophagy as a novel approach in therapy of nonalcoholic fatty liver disease

Non-alcoholic fatty liver disease(NAFLD) is one of the leading causes of chronic liver diseases around the world due to the modern sedentary and food-abundant lifestyle, which is characterized by excessive fat accumulation in the liver related with causes other than alcohol abuse. It is widely acknowledged that insulin resistance, dysfunctional lipid metabolism, endoplasmic reticulum stress, oxidative stress, inflammation, and apoptosis/necrosis may all contribute to NAFLD. Autophagy is a protective self-digestion of intracellular organelles, including lipid droplets(lipophagy), in response to stress to maintain homeostasis. Lipophagy is another pathway for lipid degradation besides lipolysis. It is reported that impaired autophagy also contributes to NAFLD. Some studies have suggested that the histological characteristics of NAFLD(steatosis, lobular inflammation, and peri-sinusoid fibrosis) might be improved by treatment with traditional Chinese herbal extracts, while autophagy may be induced. This review will provide insights into the characteristics of autophagy in NAFLD and the related role/mechanisms of autophagy induced by traditional Chinese herbal extracts such as resveratrol, Lycium barbarum polysaccharides, dioscin, bergamot polyphenol fraction, capsaicin, and garlic-derived S-allylmercaptocysteine, which may inhibit the progression of NAFLD. Regulation of autophagy/lipophagy with traditional Chinese herbal extracts may be a novel approach for treating NAFLD, and the molecular mechanisms should be elucidated further in the near future.

Clinical features and management of primary sclerosing cholangitis

Primary sclerosing cholangitis is a chronic cholestatic liver disease characterized by inflammation and fibrosis of the bile ducts,resulting in cirrhosis and need for liver transplantation and reduced life expectancy.The majority of cases occur in young and middle-aged men,often in association with inflammatory bowel disease.The etiology of primary sclerosing cholangitis includes immune-mediated components and elements of undefined nature.No effective medical therapy has been identified.The multiple complications of primary sclerosing cholangitis include metabolic bone disease,dominant strictures,bacterial cholangitis,and malignancy,particularly cholangiocarcinoma,which is the most lethal complication of primary sclerosing cholangitis.Liver transplantation is currently the only life-extending therapeutic alternative for patients with end-stage disease,although recurrence in the allografted liver has been described.A PSC-like variant attracting attention is cholangitis marked by raised levels of the immunoglobulin G4 subclass,prominence of plasma cells within the lesions,and steroid responsiveness.

Training in endoscopic submucosal dissection

Endoscopic submucosal dissection (ESD) represents an important advancement in the therapy of early neoplastic gastrointestinal lesions by providing higher en-bloc curative resection rate with lower recurrence compared to endoscopic mucosal resection (EMR) and by sparing the involved organ and protecting patient' s quality of life. Despite these advantages ESD is associated with long procedure times and a higher rate of complications, making ESD a challenging procedure which requires advanced endoscopic skills. Thus, there has been a recognized need for structured training system for ESD to enhance trainee experience and, to reduce the risks of complications and inadequate treatment. ESD has a very flat learning curve. However, we do not have uniformly accepted benchmarks for competency. Nevertheless, it appears that, in Japan, more than 30 supervised gastric ESD procedures are required to achieve technical proficiency and minimize complications. A number of training algorithms have been pro-posed in Japan with the aim to standardize ESD training. These algorithms cannot be directly applied in the West due to substantial differences including the availability of highly qualified mentors, the type of pathology seen, choice of devices, and trainee's background. We propose a training algorithm for Western physicians which integrates both hands-on training courses, animal model work as well as visits to expert centers. No specific preceptor training programs have been yet developed but there is a consensus that these programs are important for permeation of ESD worldwide.

TP53 codon 72 Arg/Arg polymorphism is associated with a higher risk for inflammatory bowel disease development

AIM: To investigate the association between tumor protein 53(TP53) codon 72 polymorphisms and the risk for inflammatory bowel disease(IBD) development.METHODS: Numerous genetic and epigenetic drivers have been identified for IBD including the TP53 gene. Pathogenic mutations in TP53 gene have only been reported in 50% of colorectal cancer(CRC) patients. A single nucleotide polymorphism(SNP) in the TP53 gene resulting in the presence of either arginine(Arg)or proline(Pro) or both at codon 72 was shown to alter TP53 tumor-suppressor properties. This SNP has been investigated as a risk factor for numerous cancers,including CRC. In this study we analyzed TP53 codon 72 polymorphism distribution in 461 IBD,181 primary sclerosing cholangitis patients and 62 healthy controls. Genotyping of TP53 was performed by sequencing and restriction fragment length polymorphism analysis of genomic DNA extracted from peripheral blood. RESULTS: The most frequent TP53 genotype in IBD patients was Arg/Arg occurring in 54%-64% of cases(and in only 32% of controls). Arg/Pro was the most prevalent genotype in controls(53%) and less common in patients(31%-40%). Pro/Pro frequency was not significantly different between controls and IBD patients. CONCLUSION: The data suggests that the TP53 codon 72 Arg/Arg genotype is associated with increased risk for IBD development.

Systematic review: Safety of balloon assisted enteroscopy in Crohn's disease

AIM To determine the overall and comparative risk of procedure related perforation of balloon assisted enteroscopy(BAE) in Crohn's disease(CD). METHODS Systematic review(PROSPERO #CRD42015016381) of studies reporting on CD patients undergoing BAE. Seventy-three studies reporting on 1812 patients undergoing 2340 BAEs were included. Primary outcome of interest was the overall and comparative risk of procedure related perforation of diagnostic BAE in CD. Secondary outcomes of interest were risk of procedure related perforation of diagnostic double balloon enteroscopy(DBE), risk of procedure related perforation of therapeutic BAE, efficacy of stricture dilation, and clinical utility of endoscopically assessing small bowel disease activity.RESULTS Per procedure perforation rate of diagnostic BAE in CD was 0.15%(95%CI: 0.05-0.45), which was similar to diagnostic BAE for all indications(0.11%; IRR = 1.41, 95%CI: 0.28-4.50). Per procedure perforation rate of diagnostic DBE in CD was 0.12%(95%CI: 0.03-0.44), which was similar to diagnostic DBE for all indications(0.22%; IRR = 0.54, 95%CI: 0.06-0.24). Per procedure perforation rate of therapeutic BAE in CD was 1.74%(95%CI: 0.85-3.55). Eighty-six percentof therapeutic perforations were secondary to stricture dilation. Dilation was attempted in 207 patients and 30% required surgery during median follow-up of 18 months. When diagnostic BAE assessed small bowel disease activity, changes in medical therapy resulted in endoscopic improvement in 77% of patients. CONCLUSION Diagnostic BAE in CD has a similar rate of perforation as diagnostic BAE for all indications and can be safely performed in assessment of mucosal healing.

Limited, local, extracolonic spread of mucinous appendiceal adenocarcinoma after perforation with formation of a malignant appendix-to-sigmoid fistula: Case report and literature review

A 68-year-old man presented with progressive right lower quadrant abdominal pain and tenderness without rebound tenderness, and with constipation during the prior 9 mo. Abdomino-pelvic computed tomography and magnetic resonance imaging demonstrated a dilated appendix forming a fistula to the sigmoid colon. Open laparotomy revealed a bulky abdominal tumor involving appendix, cecum, and sigmoid, and extending up to adjacent viscera, without ascites or peritoneal implants. The abdominal mass was removed en bloc, including resection of sigmoid colon, cecum(with preservation of ileocecal valve), appendix, right vas deferens, testicular vessels, and minimal amounts of anterior abdominal wall; and shaving off of small parts of the walls of the urinary bladder and small bowel. Gross and microscopic pathologic examination revealed an appendix-to-sigmoid malignant fistula secondary to perforation of mucinous adenocarcinoma of the appendix with minimal local spread(stage T4). However, the surgical margins were clear, all 13 resected lymph nodes were cancer-free, and pseudomyxoma peritonei or peritoneal implants were not present. The patient did well during 1 year of follow-up with no clinical or radiologic evidence of local recurrence, metastases, or pseudomyxoma peritonei despite presenting with extensive stage T4 cancer that was debulked without administering chemotherapy, and despite presenting with malignant appendiceal perforation. This case illustrates the non-aggressive biologic behavior of this low-grade malignancy. The fistula may have prevented free spillage of cancerous cells and consequent distant metastases by containing the appendiceal contents largely within the colon.

Characterization of CD133^+ parenchymal cells in the liver:Histology and culture

AIM:To reveal the characteristics of CD133+ cells in the liver.METHODS:This study examined the histological characteristics of CD133+ cells in non-neoplastic and neoplastic liver tissues by immunostaining,and also analyzed the biological characteristics of CD133+ cells derived from human hepatocellular carcinoma(HCC) or cholangiocarcinoma cell lines.RESULTS:Immunostaining revealed constant expression of CD133 in non-neoplastic and neoplastic biliary epithelium,and these cells had the immunophenotype CD133+/CK19+/HepPar-1-.A small number of CD133+/CK19-/HepPar-1+ cells were also identified in HCC and combined hepatocellular and cholangiocarcinoma.In addition,small ductal structures,resembling the canal of Hering,partly surrounded by hepatocytes were positive for CD133.CD133 expression was observed in three HCC(HuH7,PLC5 and HepG2) and two cholangiocarcinoma cell lines(HuCCT1 and CCKS1).Fluorescence-activated cell sorting(FACS) revealed that CD133+ and CD133-cells derived from HuH7 and HuCCT1 cells similarly produced CD133+ and CD133-cells during subculture.To examine the relationship between CD133+ cells and the side population(SP) phenotype,FACS was performed using Hoechst 33342 and a monoclonal antibody against CD133.The ratios of CD133+/CD133-cells were almost identical in the SP and non-SP in HuH7.In addition,four different cellular populations(SP/CD133+,SP/CD133-,non-SP/CD133+,and non-SP/CD133-) could similarly produce CD133+ and CD133-cells during subculture.CONCLUSION:This study revealed that CD133 could be a biliary and progenitor cell marker in vivo.However,CD133 alone is not sufficient to detect tumor-initiating cells in cell lines.

psychosocial impact of irritable bowel syndrome: A brief review

Irritable bowel syndrome(IBS) is a common disorder of the gastrointestinal tract with unclear etiology and no reliable biomarker. Like other chronic and functional disorders, medical treatments for IBS are suboptimal and the overall illness burden is high. Patients with IBS report high rates of psychopathology, low quality of life, and increased suicidal ideation. These patients also miss more days of work, are less productive at work, and use many healthcare resources. However, little is known about the burden of IBS on daily functioning. The primary aim of this paper is to review the current literature on the burden of IBS and to highlight the need for further research to evaluate the impact of IBS on daily activities. This research would contribute to our existing understanding of the impact of IBS on overall quality of life and well-being.

Early apoptosis and cell death induced by ATX-S10Na(Ⅱ)-mediated photodynamic therapy are Bax- and p53-dependent in human colon cancer cells

AIM: To investigate the roles of Bax and p53 proteins in photosensitivity of human colon cancer cells by using lysosome-localizing photosensitizer, ATX-S10Na (Ⅱ).METHODS: HCT116 human colon cancer cells and Bax-null or p53-null isogenic derivatives were irradiated with a diode laser. Early apoptosis and cell death in response to photodynamic therapy were determined by MTT assays, annexin V assays, transmission electron microscopy assays, caspase assays and western blotting.RESULTS: Induction of early apoptosis and cell death was Bax- and p53-dependent. Bax and p53 were required for caspase-dependent apoptosis. The levels of anti-apoptotic Bcl-2 family proteins, Bcl-2 and Bcl-xL, were decreased in Bax- and p53-independent manner.CONCLUSION: Our results indicate that early apoptosis and cell death of human colon cancer cells induced by photodynamic therapy with lysosome-localizing photosensitizer ATX-S10Na (Ⅱ) are mediated by p53-Bax network and low levels of Bcl-2 and Bcl-xL proteins. Our results might help in formulating new therapeutic approaches in photodynamic therapy.

Mini-loop ligation of a bleeding duodenal Dieulafoy's lesion

Two percent of gastrointestinal hemorrhages are caused by Dieulafoy's lesions, which are located in duodenum in only 15% of cases. There are no recommendations regarding the prime endoscopic treatment technique for this condition. A 61-year-old woman presented with melena without signs of hemodynamic instability. During an urgent upper endoscopy, blood oozing from the normal mucosa of the duodenum was seen and this was classified as a Dieulafoy's lesion. A mini-loop was opened at the rim of a transparent ligation chamber, at the end of the endoscope, and after aspiration of the lesion, closed and detached. Complete hemostasis was achieved without early or postponed complications. In every day clinical practice, mini-loop ligation is rarely used because of possible complications, such as site ulceration, organ perforation, re-bleeding and possible inexperience of the operator. To the best of our knowledge this is the first case of successful treatment of bleeding duodenal Dieulafoy's lesion by mini-loop ligation.

Direct-acting antiviral agents against hepatitis C virus and lipid metabolism

Hepatitis C virus(HCV) infection induces steatosis and is accompanied by multiple metabolic alterations including hyperuricemia, reversible hypocholesterolemia and insulin resistance. Total cholesterol, low-density lipoprotein-cholesterol and triglyceride levels are increased by peginterferon and ribavirin combination therapy when a sustained virologic response(SVR) is achieved in patients with HCV. Steatosis is significantly more common in patients with HCV genotype 3 but interferon-free regimens are not always effective for treating HCV genotype 3 infections. HCV infection increases fatty acid synthase levels, resulting in the accumulation of fatty acids in hepatocytes. Of note, low-density lipoprotein receptor, scavenger receptor class B type Ⅰ and Niemann-Pick C1-like 1 proteins are candidate receptors that may be involved in HCV. They are also required for the uptake of cholesterol from the external environment of hepatocytes. Among HCV-infected patients with or without human immunodeficiency virus infection, changes in serum lipid profiles are observed during interferon-free treatment and after the achievement of an SVR. It is evident that HCV affects cholesterol metabolism during interferon-free regimens. Although higher SVR rates were achieved with interferon-free treatment of HCV, special attention must also be paid to unexpected adverse events based on host metabolic changes including hyperlipidemia.

Pre-operative clinical and instrumental factors as antireflux surgery outcome predictors

Gastroesophageal reflux disease(GERD) is nowadays a highly prevalent, chronic condition, with 10% to 30% of Western populations affected by weekly symptoms. Many patients with mild reflux symptoms are treated adequately with lifestyle modifications, dietary changes, and low-dose proton pump inhibitors(PPIs). For those with refractory GERD poorly controlled with daily PPIs, numerous treatment options exist. Fundoplication is currently the most commonly performed antireflux operation for management of GERD. Outcomes described in current literature following laparoscopic fundoplication indicate that it is highly effective for treatment of GERD; early clinical studies demonstrate relief of symptoms in approximately 85%-90% of patients. However it is still unclear which factors, clinical or instrumental, are able to predict a good outcome after surgery. Virtually all demographic, esophagogastric junction anatomic conditions, as well as instrumental(such as presence of esophagitis at endoscopy, or motility patterns determined by esophageal high resolution manometry or reflux patterns determined by means of pH /impedance-pH monitoring) and clinical features(such as typical or atypical symptoms presence) of patients undergoing laparoscopic fundoplication for GERD can be factors associated with symptomatic relief. With this in mind, we sought to review studies that identified the factors that predict outcome after laparoscopic total fundoplication.

Update on the endoscopic treatments for achalasia

Achalasia is the most common primary motility disorder of the esophagus and presents as dysphagia to solids and liquids. It is characterized by impaired deglutitive relaxation of the lower esophageal sphincter. Highresolution manometry allows for definitive diagnosis and classification of achalasia, with type Ⅱ being the most responsive to therapy. Since no cure for achalasia exists, early diagnosis and treatment of the disease is critical to prevent end-stage disease. The central tenant of diagnosis is to first rule out mechanical obstruction due to stricture or malignancy, which is often accomplished by endoscopic and fluoroscopic examination. Therapeutic options include pneumatic dilation(PD), surgical myotomy, and endoscopic injection of botulinum toxin injection. Heller myotomy and PD are more efficacious than pharmacologic therapies and should be considered first-line treatment options. Per oral endoscopic myotomy(POEM) is a minimally-invasive endoscopic therapy that might be as effective as surgical myotomy when performed by a trained and experienced endoscopist, although long-term data are lacking. Overall, therapy should be individualized to each patient's clinical situation and based upon his or her risk tolerance, operative candidacy, and life expectancy. In instances of therapeutic failure or symptom recurrence re-treatment is possible and can include PD or POEM of the wall opposite the site of prior myotomy. Patients undergoing therapy for achalasia require counseling, as the goal of therapy is to improve swallowing and prevent late manifestations of the disease rather than to restore normal swallowing, which is unfortunately impossible.

Obstructive jaundice due to a rare periampullary tumor

Gangliocytic paraganglioma is a rare neuroendocrine tumor predominantly arising in the second part of the duodenum with rare local recurrence or metastasis to regional lymph nodes.A 92-year-old female presented with obstructive jaundice.On exam she had pale conjunctiva and icteric sclera.Abdominal examination revealed tenderness in the upper abdomen.Laboratory data was consistent with obstructive jaundice.Computed tomography of the abdomen revealed a dilated gall bladder and a common bile duct(CBD)with no evidence of liver lesions or pancreatic head mass.Endoscopic ultrasonography revealed a 1 cm isoechoic submucosal nodule at the periampullary area,dilated CBD(9 mm),a prominent pancreatic duct(4.1 mm)and a hydropic gall bladder with no stones.Endoscopic retrograde cholangiopancreaticography was performed to relieve obstruction and showed a 1 cm periampullary mass which underwent an en-bloc snare resection.Histopathology analyses with immunohistochemical stains were positive for cytokeratin,synaptophysin,S-100 protein,neuron specific enolase and negative for actin and desmin consistent with periampullary gangliocytic paraganglioma.Periampullary gangliocytic paraganglioma is a rare benign tumor of the small bowel.Common presentation includes abdominal pain and obstructive jaundice which should be included in differential diagnosis of obstructive jaundice.Endoscopic resection is a curative therapy in the absence of local invasion or distant metastasis.

Characteristics of Clostridium difficile infection in patients hospitalized with myelodysplastic syndrome or acute myelogenous leukemia

AIM To evaluate factors associated with Clostridium difficile infection (CDI) and outcomes of CDI in the myelodysplastic syndrome(MDS) and acute myeloid leukemia (AML) population.METHODS After IRB approval,all MDS/AML patients hospitalized at the University of Maryland Greenebaum Comprehensive Cancer Center between August 2011 and December 2013 were identified.Medical charts were reviewed for demographics,clinical information,development of CDI,complications of CDI,and mortality.Patients with CDI,defined as having a positive stool PCR done for clinical suspicion of CDI,were compared to those without CDI in order to identify predictors of disease.A t-test was used for comparison of continuous variables and chisquare or Fisher's exact tests were used for categorical variables,as appropriate.RESULTS Two hundred and twenty-three patients (60.1% male,mean age 61.3 years,13% MDS,87% AML) had 594 unique hospitalizations during the study period.Thirtyfour patients (15.2%) were diagnosed with CDI.Factors significantly associated with CDI included lower albumin at time of hospitalization (P < 0.0001),prior diagnosis of CDI (P < 0.0001),receipt of cytarabine-based chemotherapy (P = 0.015),total days of neutropenia (P = 0.014),and total days of hospitalization (P = 0.005).Gender (P = 0.10),age (P = 0.77),proton-pump inhibitor use (P = 0.73),receipt of antibiotics (P = 0.66),and receipt of DNA hypomethylating agent-based chemotherapy (P = 0.92) were not significantly associated with CDI.CONCLUSION CDI is common in the MDS/AML population.Factors significantly associated with CDI in this population include low albumin,prior CDI,use of cytarabine-based chemotherapy,and prolonged neutropenia.In this study,we have identified a subset of patients in which prophylaxis studies could be targeted.

Malignant peritoneal mesothelioma presenting umbilical hernia and Sister Mary Joseph's nodule

Malignant peritoneal mesothelioma is a rare aggres-sive tumor of the peritoneum. An increasing number of malignant mesothelioma cases have been reported in recent years. We report here a very rare case of malignant peritoneal mesothelioma with both umbilical hernia and umbilical metastasis which is also called Sister Mary Joseph's nodule. We performed laparoscopy which showed specific laparoscopic findings, and the pathological findings of the biopsy specimen led to the diagnosis. This case was associated with umbilical her-nia which could be induced by massive ascites. A newly developed abdominal hernia should be noted as a primary symptom of malignant peritoneal mesothelioma, as shown in the present case.