Complete response to local therapy for advanced hepatocellular carcinoma with lung metastasis: a case report

The concept of oligometastasis is widely accepted for various types of solid tumors; accordingly, better outcomes can be anticipated with aggressive local interventions. The treatment of advanced hepatocellular carcinoma (HCC) with extrahepatic metastasis is systemic therapy. However, treatment responses to systemic therapy are poor. Recently, a small number of metastatic cancers (oligometastasis) have been controlled by local therapy rather than systemic therapy. Our study reports a case of a 66-year-old male patient with advanced HCC with lung metastasis, which was treated with local therapy. There were less than four metastases in the lungs, which were treated with wedge resection, radiofrequency, and radiation therapy. He repeatedly underwent local therapy for lung oligometastasis and locoregional therapy for intrahepatic HCC rather than systemic therapy; control by local therapy was possible as his liver function was preserved with Child-Turcotte-Pugh class A.

Bowel Wall Thickness, Elasticity, Intestinal Permeability, and Inflammatory Cytokines in Patients with Cirrhosis and Ascites / 대한내과학회지

BACKGROUND/AIMS: Previous studies have reported that endotoxemia is associated with pathogenesis and complications in cirrhosis. Endotoxin stimulates the secretion of inflammatory cytokines, which contributes to the development of complications. In addition, endotoxin easily invades the gut barrier system because of the increased intestinal permeability due to portal hypertensive enteropathy. In this report, we explored changes in cytokine levels and intestinal permeability and measured the thickness and elasticity of the bowel wall using ultrasonography in cirrhotic patients.METHODS: We enrolled 40 patients with cirrhosis classified as Child-Pugh B or C and 20 healthy volunteers. Abdominal ultrasonography examinations were used to evaluate bowel wall parameters in the ascending colon and terminal ileum. Intestinal permeability was measured using dual sugar absorption tests with lactulose and mannitol. Levels of tumor necrosis factor (TNF)-α and IL-10 were determined from blood samples. We compared these outcomes between cirrhotic patients and healthy controls and between Child-Pugh B and C patients. In addition, we explored the correlation between cytokine levels, intestinal permeability ratio, and bowel wall parameters in cirrhotic patients.RESULTS: In cirrhotic patients, the ascending colon wall elasticity decreased (20.4 vs. 10.9 kPa, p = 0.048) and the terminal ileum wall thickness increased (4.2 vs. 1.9 mm, p < 0.001). The intestinal permeability ratio and levels of the cytokines TNF-α and IL-10 increased (0.219 vs. 0.017, p < 0.001; 22.47 vs. 13.48 pg/mL, p < 0.001; and 14.91 vs. 8.57 pg/mL, p = 0.019, respectively) in cirrhotic patients. However, there were no significant differences between Child-Pugh classes and no significant correlations between bowel wall parameters and intestinal permeability or cytokine levels.CONCLUSIONS: Ultrasonography revealed bowel wall thickening and decreases in elasticity; in addition, intestinal permeability and cytokine levels increased in cirrhotic patients compared with healthy controls.

Gastroenteropancreatic Neuroendocrine Tumor with Hepatic Metastasis Misdiagnosed as Hepatocellular Carcinoma / 대한내과학회지

The liver is the most common site of metastasis of neuroendocrine tumors (NETs). Gastroenteropancreatic (GEP)-NETs are rare, and the distinction between hepatocellular carcinoma (HCC) and metastatic NET can be difficult due to the similarity of their histological characteristics. Herein, we report a case of GEP-NET with hepatic metastasis, which was first misdiagnosed as HCC by liver biopsy and subsequently re-diagnosed after surgery as primary GEP-NET.

Multiple Metachronous Malignancies: One Patient with Five Primary Malignancies / 대한내과학회지

We report a case of a 73-year-old male with multiple, metachronous primary malignancies. He presented with adenocarcinoma of the stomach with transverse colon invasion followed by bladder cancer, hypopharyngeal cancer, urothelial cancer, and hepatocellular carcinoma, in that order, over 10 years. While these multiples malignancies were separate entities, they shared several etiologic factors, including smoking. To the best of our knowledge, this is the first description of five metachronous malignancies in a Korean patient.

Bowel Wall Thickness, Elasticity, Intestinal Permeability, and Inflammatory Cytokines in Patients with Cirrhosis and Ascites / 대한내과학회지

BACKGROUND/AIMS@#Previous studies have reported that endotoxemia is associated with pathogenesis and complications in cirrhosis. Endotoxin stimulates the secretion of inflammatory cytokines, which contributes to the development of complications. In addition, endotoxin easily invades the gut barrier system because of the increased intestinal permeability due to portal hypertensive enteropathy. In this report, we explored changes in cytokine levels and intestinal permeability and measured the thickness and elasticity of the bowel wall using ultrasonography in cirrhotic patients.@*METHODS@#We enrolled 40 patients with cirrhosis classified as Child-Pugh B or C and 20 healthy volunteers. Abdominal ultrasonography examinations were used to evaluate bowel wall parameters in the ascending colon and terminal ileum. Intestinal permeability was measured using dual sugar absorption tests with lactulose and mannitol. Levels of tumor necrosis factor (TNF)-α and IL-10 were determined from blood samples. We compared these outcomes between cirrhotic patients and healthy controls and between Child-Pugh B and C patients. In addition, we explored the correlation between cytokine levels, intestinal permeability ratio, and bowel wall parameters in cirrhotic patients.@*RESULTS@#In cirrhotic patients, the ascending colon wall elasticity decreased (20.4 vs. 10.9 kPa, p = 0.048) and the terminal ileum wall thickness increased (4.2 vs. 1.9 mm, p < 0.001). The intestinal permeability ratio and levels of the cytokines TNF-α and IL-10 increased (0.219 vs. 0.017, p < 0.001; 22.47 vs. 13.48 pg/mL, p < 0.001; and 14.91 vs. 8.57 pg/mL, p = 0.019, respectively) in cirrhotic patients. However, there were no significant differences between Child-Pugh classes and no significant correlations between bowel wall parameters and intestinal permeability or cytokine levels.@*CONCLUSIONS@#Ultrasonography revealed bowel wall thickening and decreases in elasticity; in addition, intestinal permeability and cytokine levels increased in cirrhotic patients compared with healthy controls.

Combination Therapy of Angiotherapy, Radiation Therapy, and Radiofrequency Ablation for Pulmonary Metastasis of Hepatocellular Carcinoma Accompanied by Nontuberculous Mycobacteria

With the advances in hepatocellular carcinoma (HCC) treatment, the lung metastasis of HCC is becoming increasingly important. In treating the lung metastasis of HCC, a multidisciplinary approach can lead to better results than systemic chemotherapy alone. Here, we report on a patient who presented with pulmonary masses, while the HCC was being controlled in the abdominal cavity. The presence of nontuberculous mycobacteria was identified during the diagnosis of the pulmonary masses. The pulmonary metastases of HCC were treated with a combination of angiotherapy, radiation therapy, and radiofrequency ablation. The patient showed a satisfactory progress with this multidisciplinary localized treatment. We report the clinical progress and review the recent literature regarding the treatment of pulmonary metastasis without intrahepatic HCC herein.

Long-Term Efficacy and Safety of Partial Splenic Embolization in Hepatocellular Carcinoma Patients with Thrombocytopenia Who Underwent Transarterial Chemoembolization

BACKGROUND: Performing transarterial chemoembolization (TACE) is difficult with the occurrence of thrombocytopenia in cirrhotic patients with hepatocellular carcinoma (HCC). We aimed to evaluate the long-term efficacy and safety of partial splenic embolization (PSE) combined with TACE in patients with HCC with severe thrombocytopenia related to splenomegaly. METHODS: We conducted a case–control study consisting of 18 HCC patients with severe thrombocytopenia (< 50 × 109/L) who underwent PSE concurrently with TACE (PSE group) and 72 controls who underwent TACE alone (non-PSE group). RESULTS: Mean platelet counts at 1 month and 1, 3, and 5 years after concurrent PSE and TACE significantly increased compared with baseline (all P < 0.05), whereas the platelet count did not significantly increase after TACE alone. In addition, the platelet count at several time points after treatment in the PSE group was significantly higher than that in the non-PSE group, although the baseline platelet count in the PSE group was significantly lower than that in the non-PSE group. The platelet increase after PSE significantly reduced the need for platelet transfusions (P = 0.040) and enabled the subsequent TACE procedures in time (P = 0.046). The leukocyte counts and hemoglobin concentrations after concurrent PSE and TACE were also significantly increased, without deterioration of Child-Turcotte-Pugh score and unexpected side effects. CONCLUSION: PSE combined with TACE is effective in inducing and maintaining long-term thrombocytopenia improvement which reduces the need for the platelet transfusion and helps to perform initial and serial TACE, and is well-tolerated in patients with HCC and thrombocytopenia. PSE may be a promising treatment option for HCC patients with severe thrombocytopenia associated with splenomegaly who will undergo TACE.

Development and validation of a scoring system for advanced colorectal neoplasm in young Korean subjects less than age 50 years

BACKGROUND/AIMS: Colorectal cancer incidence among patients aged ≤50 years is increasing. This study aimed to develop and validate an advanced colorectal neoplasm (ACRN) screening model for young adults aged <50 years in Korea. METHODS: This retrospective cross-sectional study included 59,575 consecutive asymptomatic Koreans who underwent screening colonoscopy between 2003 and 2012 at a single comprehensive health care center. Young Adult Colorectal Screening (YCS) score was developed as an optimized risk stratification model for ACRN using multivariate analysis and was internally validated. The predictive power and diagnostic performance of YCS score was compared with those of Asia-Pacific Colorectal Screening (APCS) and Korean Colorectal Screening (KCS) scores. RESULTS: 41,702 and 17,873 subjects were randomly allocated into the derivation and validation cohorts, respectively, by examination year. ACRN prevalence was 0.9% in both cohorts. YCS score comprised sex, age, alcohol, smoking, obesity, glucose metabolism abnormality, and family history of CRC, with score ranges of 0 to 10. In the validation cohort, ACRN prevalence was 0.6% in the low-risk tier (score, 0–4), 1.5% in the moderate-risk tier (score, 5–7), and 3.4% in the high-risk tier (score, 8–10). ACRN risk increased 2.5-fold (95% confidence interval [CI], 1.8–3.4) in the moderate-risk tier and 5.8-fold (95% CI, 3.4–9.8) in the high-risk tier compared with the low-risk tier. YCS score identified better balanced accuracy (53.9%) than APCS (51.5%) and KCS (50.7%) scores and had relatively good discriminative power (area under the curve=0.660). CONCLUSIONS: YCS score based on clinical and laboratory risk factors was clinically effective and beneficial for predicting ACRN risk and targeting screening colonoscopy in adults aged <50 years.

Gastroenteropancreatic Neuroendocrine Tumor with Hepatic Metastasis Misdiagnosed as Hepatocellular Carcinoma / 대한내과학회지

The liver is the most common site of metastasis of neuroendocrine tumors (NETs). Gastroenteropancreatic (GEP)-NETs are rare, and the distinction between hepatocellular carcinoma (HCC) and metastatic NET can be difficult due to the similarity of their histological characteristics. Herein, we report a case of GEP-NET with hepatic metastasis, which was first misdiagnosed as HCC by liver biopsy and subsequently re-diagnosed after surgery as primary GEP-NET.

Multiple Metachronous Malignancies: One Patient with Five Primary Malignancies / 대한내과학회지

We report a case of a 73-year-old male with multiple, metachronous primary malignancies. He presented with adenocarcinoma of the stomach with transverse colon invasion followed by bladder cancer, hypopharyngeal cancer, urothelial cancer, and hepatocellular carcinoma, in that order, over 10 years. While these multiples malignancies were separate entities, they shared several etiologic factors, including smoking. To the best of our knowledge, this is the first description of five metachronous malignancies in a Korean patient.

Multiple Hepatic Metastasis and Lymphatic Metastasis of Solid Pseudopapillary Neoplasm of Pancreas

Solid pseudo-papillary neoplasm (SPN) of pancreas is a rare epithelial neoplasm of pancreas with a low malignant potential, occurs most commonly in young females. Here, we report a rare case of woman who has severe hepatomegaly due to multiple hepatic metastases of SPN of pancreas. At the time of diagnosis, a SPN was detected at only pancreas and there was no evidence of metastasis. So, she received subtotal pancreatectomy and total splenectomy. After 2 years of follow up, multiple small hepatic metastases were presented. In spite of three times of radiofrequency ablation, the burden of hepatic metastasis has increased continuously and multiple intra-abdominal lymph nodes metastases were detected, and ascites and peripheral edema occurred. However, because of benign feature of SPN and extremely rare incidence of recurrence and metastasis, there is no specific treatment guideline for metastatic SPN. Through multidisciplinary care service, we planned to do radiotherapy followed by a transarterial chemoembolization (TACE). But the patient could not have a scheduled radiation therapy due to deterioration of liver function. So changing the strategy of treatment, followed by TACEs were done alone. Although the size of SPN is not reduced, the extent of SPN and complication of SPN (ascites, peripheral edema, abdominal pain and so on) are being controlled.

Complete cure of advanced hepatocellular carcinoma with right adrenal gland metastasis and portal vein thrombosis by multiple applications of an interdisciplinary therapy: Case report with 8-year follow up

Hepatocellular carcinoma (HCC) is the sixth most common cause of death worldwide and the main cause of primary liver cancer. The principle problem of HCC is the poor prognosis, since advanced HCC reportedly has a median survival of only 9 months. The standard therapies are sorafenib and regorafenib, but the outcomes remain unclear. We report a 60-year-old man with advanced HCC with right adrenal gland metastasis and portal vein tumor thrombosis, who showed a complete response to multiple applications of an interdisciplinary therapy.

Clinical characteristics of patients with chronic hepatitis B who developed genotypic resistance to entecavir: Real-life experience

BACKGROUND/AIMS: Clinical characteristics of patients with chronic hepatitis B (CHB) who developed genotypic resistance to entecavir (ETV) were compared to those without resistance. METHODS: Two hundred fifty eight CHB patients who underwent ETV treatment in our institution from July 2007 to May 2013 were included. RESULTS: Eight (3.1%) patients developed genotypic resistance to ETV during the follow-up period. The patterns of genotypic resistance to ETV were as follows: L180M + M204V + S202G (n=3); M204I + V173M (n=1); I169V + V173M (n=1); L180M + M204V + V173L (n=1); L180M + M204V + V173L + M250V (n=1); M204I + V214A + P237H (n=1). The cumulative occurrence rates of genotypic resistance to ETV were not significantly different between CHB patients with prior nucleos(t)tide analogues (NA) exposure (NA experienced, n=56) and NA naïve patients (n=202, P=0.823 by log rank comparison). Older age, higher baseline log10hepatitis B virus-deoxynucleic acid (log10HBV-DNA), higher log10HBV-DNA at 3, 6, 12 and 24 months after baseline, and complete virologic response (CVR, undetectable serum HBV-DNA by polymerase chain reaction 6 months after ETV treatment) were significant contributors to the development of genotypic resistance to ETV. Multivariate analyses showed higher log10HBV-DNA 6 months after baseline and absence of CVR were independent and significant contributors to the development of ETV resistance. CONCLUSIONS: Clinical characteristics of patients who developed ETV resistance were higher log10HBV-DNA 6 months after baseline and absence of CVR during the ETV treatment.

ST Elevation Myocardial Infarction in a Patient with Hereditary Hemorrhagic Telangiectasia Involving the Liver / 대한내과학회지

This is a case report of a 71-year-old woman with hereditary hemorrhagic telangiectasia (hereditary hemorrhagic telangiectasia [HHT], Osler–Weber–Rendu syndrome) involving the liver who developed ST elevation myocardial infarction and died from aggressive coronary thrombosis. HHT is an autosomal dominant hereditary disease associated with mutations of genes that regulate the endothelial surface. It has characteristic muco-cutaneous telangiectasia and other common manifestations are epistaxis, gastrointestinal bleeding, and iron-deficiency anemia. In addition, arteriovenous malformations or vascular ectases commonly occur in the pulmonary, hepatic, and cerebral circulations. Hemorrhages and thrombosis can both develop from these vascular abnormalities in HHT. Most thrombotic events are forms of venous thrombosis, such as deep vein thrombosis, while arterial thrombosis occurs infrequently. We present a case of aggressive coronary thrombosis in HHT, as a rare complication of HHT.

Primary squamous cell carcinoma of the liver: a case report

Primary squamous cell carcinoma (SCC) of the liver is very rare, and few cases have been reported in Korea. Primary SCC of the liver is known to be associated with hepatic cysts and intrahepatic stones. A 71-year-old male was admitted to our hospital, and a abdominal computed tomography scan revealed a 10 × 6 cm mass in the liver. Analysis of a biopsy sample suggested SCC, and so our team performed a thorough workup to find the primary lesion, which was revealed hepatoma as a pure primary SCC of the liver with multiple distant metastases. The patient was treated with one cycle of radiotherapy, transferred to another hospital for hospice care, and then died 1 month after discharge.

The prevalence and clinical characteristics of anemia in Korean patients with inflammatory bowel disease

BACKGROUND/AIMS: Quality of life is closely related to anemia in patients with inflammatory bowel disease (IBD). Several studies have reported on anemia in patients with IBD in Western countries. This study investigated the prevalence and clinical characteristics of anemia in Korean patients with IBD. METHODS: We reviewed the medical records of 92 patients with ulcerative colitis (UC) and 76 patients with Crohn's disease (CD) who were followed regularly at a single tertiary medical center in Korea between January 2003 and December 2012. Hemoglobin (Hb) thresholds used to define anemia were <13.0 g/dL in men and <12.0 g/dL in women according to the World Health Organization criteria. We chose the lowest Hb level in each year as a representative value because Hb levels changed at each examination and anemia was associated with disease deterioration. The relationship between clinical variables and lowest Hb level was assessed. RESULTS: The prevalence of anemia was 36.3% in patients with UC and 41.6% in patients with CD. Anemia in patients with CD was associated with hospital admission, 5-aminosalicylate (5-ASA) and infliximab treatment in men. Anemia in patients with UC was associated with hospital admission, oral steroid use, thiopurine and infliximab treatment in men. CONCLUSIONS: The prevalence of anemia in Korean patients with IBD was comparable to that of patients in Western countries. Anemia was associated with male patients with CD who were admitted to the hospital and received medications including 5-ASA and infliximab, and men with UC who were admitted to the hospital and received medications including oral steroids, thiopurine and infliximab.

Comparison of the clinical outcomes between antiviral-naïve patients treated with entecavir and lamivudine-resistant patients receiving adefovir add-on lamivudine combination treatment

BACKGROUND/AIMS: To analyze the effects of preexisting lamivudine (LAM) resistance and applying antiviral treatment (adefovir [ADV] add-on LAM combination treatment) on long-term treatment outcomes, and comparing the clinical outcomes of antiviral-naïve chronic hepatitis B patients receiving entecavir (ETV) monotherapy. METHODS: This study enrolled 73 antiviral-naïve patients who received 0.5-mg ETV as an initial therapy and 54 patients who received ADV add-on LAM combination treatment as a rescue therapy from July 2006 to July 2010. RESULTS: During 24-month treatments, the decreases in serum log10HBV-DNA values (copies/mL) were significantly greater in the antiviral-naïve patients treated with ETV than the patients receiving ADV add-on LAM combination treatment. The biochemical response rates for alanine aminotransferase normalization at 6 months (ETV) and 12 months (ADV add-on LAM) were 90.4% (66/73) and 77.8% (42/54), respectively (P=0.048). A Kaplan-Meier analysis indicated that the rates of serologic response, viral breakthrough, and emergence of genotypic resistance did not differ significantly between the two patient groups. There were also no significant intergroup differences in the rates of disease progression (PD) and new development of hepatocellular carcinoma (HCC). CONCLUSION: The long-term clinical outcomes of antiviral-naïve patients treated with ETV and LAM-resistant patients receiving ADV add-on LAM combination treatment were comparable in terms of the emergence of HCC and disease progression.

Rescue therapy with adefovir in decompensated liver cirrhosis patients with lamivudine-resistant hepatitis B virus

BACKGROUND/AIMS: Adefovir dipivoxil (ADV) is a nucleotide analogue that is effective against lamivudine-resistant hepatitis B virus (HBV). The aim of this study was to determine the long-term clinical outcomes after ADV rescue therapy in decompensated patients infected with lamivudine-resistant HBV. METHODS: In total, 128 patients with a decompensated state and lamivudine-resistant HBV were treated with ADV at a dosage of 10 mg/day for a median of 33 months in this multicenter cohort study. RESULTS: Following ADV treatment, 86 (72.3%) of 119 patients experienced a decrease in Child-Pugh score of at least 2 points, and the overall end-stage liver disease score decreased from 16+/-5 to 14+/-10 (mean +/- SD, P or =2 points; P=0.001) and high mortality following ADV rescue therapy (P=0.012). CONCLUSIONS: Three years of ADV treatment was effective and safe in decompensated patients with lamivudine-resistant HBV.

Insufficient Knowledge of Korean Gastroenterologists Regarding the Vaccination of Patients with Inflammatory Bowel Disease

BACKGROUND/AIMS: There is an increased risk for inflammatory bowel disease (IBD) patients to develop infections due to the use of immunomodulators and biologics. Several infections are preventable by immunizations. This study investigated the knowledge and awareness of Korean gastroenterologists regarding the vaccination of patients with IBD. METHODS: A self-reported questionnaire was sent by e-mail to the faculty members of tertiary hospitals. Gastroenterologists were asked ten questions regarding the immunization of patients with IBD. A total of 56 gastroenterologists completed the questionnaire. RESULTS: A majority of gastroenterologists (>60%) had rarely or never recorded an immunization history from their patients with IBD. Moreover, 50% to 70% of the gastroenterologists did not know that live vaccines should be avoided in immunosuppressed patients. The most commonly mentioned resistance to vaccinations was "the lack of concern and knowledge regarding vaccination." Gastroenterologists more frequently asked about the immunization history of influenza, pneumococcal, hepatitis A, and hepatitis B vaccines and recommended these vaccines more often than others. CONCLUSIONS: Korean gastroenterologists' awareness and knowledge regarding the vaccination of patients with IBD were very poor. Intensive educational programs on immunization guidelines directed toward gastroenterologists who care for patients with IBD are required to ensure that these patients receive the necessary vaccinations.

Correlation between Adenoma Detection Rate and Advanced Adenoma Detection Rate / 대한소화기학회지

BACKGROUND/AIMS: Adenoma detection rate (ADR) is widely used as an index of colonoscopy quality management. Although advanced adenomas can be found less frequently than non-advanced adenomas, advanced adenomas have a higher clinical significance during screening for colorectal cancer. The aim of this study was to investigate the correlation between advanced and non-advanced ADR among colonoscopists. METHODS: This study is an observational study of a cohort of patients undergoing screening colonoscopy between 2009 and 2010. We collected the data on patients' characteristics and colonoscopic findings. The detection rates of adenoma and advanced adenoma were calculated. Logistic regression was used to determine the effects of variables on advanced adenoma detection, and spearman's rank-order correlation was used to evaluate the relationship between advanced ADR and ADR. RESULTS: A total of 561 patients underwent screening colonoscopy by 18 experienced colonoscopists. Most colonoscopists had adequate (>20%) ADRs. Logistic regression showed that increased patient age (OR 1.07 per 1 year increase, 95% CI 1.009-1.133, p=0.023) and male gender (OR 1.860, 95% CI 0.764-4.529, p=0.171) were associated with advanced ADR. When colonoscopists were divided into two groups on the basis of advanced ADR of 5%, ADR was also significantly higher in the group having higher level of advanced ADR. However, there was no correlation between advanced ADR and ADR among colonoscopists as an individual. CONCLUSIONS: Colonoscopists' advanced ADRs were independent of their ADRs, indicating that advanced ADR could be quite low even among colonoscopists with acceptable ADRs. Thus, there seems to be a limitation in using ADR as an adequate index of colonoscopy quality management.