Empirical Therapy Versus Tailored Therapy of Helicobacter pylori in Korea: Results of the K-CREATE Study.

BACKGROUND: The optimal duration of regimens for tailored therapy based on genotypic resistance for clarithromycin has yet to be established. AIM: This study was a nationwide, multicenter, randomized trial comparing empirical therapy with tailored therapy based on genotypic resistance for first-line eradication of Helicobacter pylori. We also compared the eradication rates of 7- and 14-day regimens for each group. PATIENTS AND METHODS: Patients with H. pylori infection were first randomized to receive empirical or tailored therapy. Patients in each group were further randomized into 7- or 14-day regimens. Empirical therapy consisted of a triple therapy (TT) regimen (twice-daily doses of pantoprazole 40 mg, amoxicillin 1 g, and clarithromycin 500 mg) for 7 or 14 days. Tailored therapy consisted of TT of 7 or 14 days in patients without genotypic resistance. Patients with genotypic resistance were treated with bismuth quadruple therapy (BQT) regimens (twice-daily doses of pantoprazole 40 mg, three daily doses of metronidazole 500 mg, and four times daily doses of bismuth 300 mg and tetracycline 500 mg) for 7 or 14 days. A 13C-urea breath test assessed eradication rates. The primary outcome was eradication rates of each group. RESULTS: A total of 593 patients were included in the study. The eradication rates were 65.7% (201/306) in the empirical therapy group and 81.9% (235/287) in the tailored therapy group for intention-to-treat analysis (p < 0.001). In the per-protocol analysis, the eradication rates of the empirical therapy and tailored groups were 70.3% (201/286) and 85.5% (235/274) (p < 0.001), respectively. There was no difference in compliance between the two groups. The rate of adverse events was higher in the tailored group compared to the empirical group (p < 0.001). DISCUSSION: Our study confirmed that tailored therapy based on genotypic resistance was more effective than empirical therapy for H. pylori eradication in Korea. However, no significant difference was found between 7- and 14-day regimens for each group. Future studies are needed to determine the optimal duration of therapy for empirical and tailored therapy regimens.

Thirty-year Trend in Inflammatory Bowel Disease on Jeju Island, South Korea.

Background/Aims: Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is increasing in South Korea. On the other hand, there are no reports of the incidence and prevalence of IBD specific to Jeju Island, prompting the necessity of this study. Methods: In this retrospective design, the medical records of 453 patients diagnosed with IBD at Jeju National University Hospital from January 1990 to December 2019 were analyzed. Results: Of the 453 IBD subjects (165 CD, 288 UC) included, the UC: CD ratio was 1.75:1. The incidence of IBD increased continuously from 0.19/105 in 1990 to 6.39/105 in 2017 and after that decreased to 4.92/105 in 2019. The male:female ratio was 2.24:1 for CD and 1.29:1 for UC. In the CD subjects, the disease activity included remission (33.3%), mild (25.5%), moderate (30.9%), and severe (6.1%). In UC subjects, the disease activity included remission (24.0%), mild (35.4%), moderate (28.8%), and severe (6.2%). According to the Montreal classification, the cases were as follows: CD: terminal ileum (22.4%), colon (9.7%), ileocolon (66.1%), and upper gastrointestinal involvement (27.3%), and perianal fistula/abscess was present in 43.6% of subjects before or at diagnosis: UC: proctitis (43.4%), left-sided colitis (29.1%), and pancolitis (23.3%) at diagnosis. Conclusions: The incidence of IBD on Jeju Island has increased steadily for approximately 30 years but has exhibited a decline since 2017. Therefore, the incidence of IBD in Jeju is believed to have plateaued. Further study will be needed for clarification.

Gluteal and Presacral Abscess Due to Crohn's Disease with Multiple Fistulas.

The abscess is a common complication of Crohn's disease (CD), with the perianal form more frequent than gluteal or presacral which is relatively rare. There are few case reports of gluteal abscess combined with presacral abscess caused by CD and the treatment has not been established. A 21-year-old male was admitted with right buttock and lower back pain with a duration of 3 months. He had a history of CD in the small intestine diagnosed 10 months previously. He had poor compliance and had not returned for follow-up care during the previous 6 months. Abdominopelvic CT indicated newly developed multiple abscess pockets in right gluteal region, including piriformis muscle and presacral space. Additionally, fistula tracts between small bowel loops and presacral space were observed. Patient's CD was moderate activity (273.12 on the Crohn's Disease Activity Index [CDAI]). Treatment was started with piperacillin/ tazobactam antibiotic but patient developed a fever and abscess extent was aggravated. Therefore, surgical incision and drainage was performed and 4 Penrose drains were inserted. Patient's pain and fever were resolved following surgery. Infliximab was then administered for the remaining fistulas. After the induction regimen, multiple fistula tracts improved and patient went into remission (CDAI was -0.12).

EPHB2 expression is associated with intestinal phenotype of gastric cancer and indicates better prognosis by suppressing gastric cancer migration.

The protein tyrosine kinase Ephrin type-B receptor 2 (EPHB2) belongs to one of the intestinal stem cell signature genes and plays a crucial role in maintaining the crypt-villous axis. Herein, we aimed to investigate the expression of EPHB2 during gastric carcinogenesis and evaluated its prognostic and functional significance in gastric cancer (GC). EPHB2 expression was upregulated in intestinal metaplasia and GCs compared to normal antral and fundic glands. EPHB2 mRNA levels were strongly correlated with the intestinal stem cell markers OLFM4, LGR5, and EPHB3. Notably, EPHB2 expression was significantly correlated with CDX2 expression, and in vitro studies demonstrated that CDX2 expression increased both EPHB2 transcription and protein levels. In a large cohort of GC patients, EPHB2 positivity was observed in 39% of 704 GCs and was negatively correlated with tumor differentiation, lymphovascular invasion, and tumor-node-metastasis stages. Notably, EPHB2 positivity was associated with better overall survival, and it was an independent prognostic marker in intestinal-type GCs. Overexpression of EPHB2 in GC cell lines, MKN-28 and MKN-74, reduced migration activity by suppressing phosphorylation of focal adhesion kinase, whereas no significant difference was observed in proliferation rates. Thus, we suggest that EPHB2 acts as a tumor suppressor in GCs and can be a prognostic marker in intestinal-type GCs.

Propulsive colonic contractions are mediated by inhibition-driven poststimulus responses that originate in interstitial cells of Cajal.

The peristaltic reflex is a fundamental behavior of the gastrointestinal (GI) tract in which mucosal stimulation activates propulsive contractions. The reflex occurs by stimulation of intrinsic primary afferent neurons with cell bodies in the myenteric plexus and projections to the lamina propria, distribution of information by interneurons, and activation of muscle motor neurons. The current concept is that excitatory cholinergic motor neurons are activated proximal to and inhibitory neurons are activated distal to the stimulus site. We found that atropine reduced, but did not block, colonic migrating motor complexes (CMMCs) in mouse, monkey, and human colons, suggesting a mechanism other than one activated by cholinergic neurons is involved in the generation/propagation of CMMCs. CMMCs were activated after a period of nerve stimulation in colons of each species, suggesting that the propulsive contractions of CMMCs may be due to the poststimulus excitation that follows inhibitory neural responses. Blocking nitrergic neurotransmission inhibited poststimulus excitation in muscle strips and blocked CMMCs in intact colons. Our data demonstrate that poststimulus excitation is due to increased Ca2+ transients in colonic interstitial cells of Cajal (ICC) following cessation of nitrergic, cyclic guanosine monophosphate (cGMP)-dependent inhibitory responses. The increase in Ca2+ transients after nitrergic responses activates a Ca2+-activated Cl− conductance, encoded by Ano1, in ICC. Antagonists of ANO1 channels inhibit poststimulus depolarizations in colonic muscles and CMMCs in intact colons. The poststimulus excitatory responses in ICC are linked to cGMP-inhibited cyclic adenosine monophosphate (cAMP) phosphodiesterase 3a and cAMP-dependent effects. These data suggest alternative mechanisms for generation and propagation of CMMCs in the colon.

Expression profile of CD98 heavy chain and L-type amino acid transporter 1 and its prognostic significance in colorectal cancer.

L-type amino acid transporter (LAT1) is a neutral amino acid transporter, forming a heterodimer complex with the CD98 heavy chain (CD98hc). In this study, we studied the expression profiles of LAT1 and CD98hc in colorectal cancer (CRC) and its precursor lesions. Transcription levels of CD98hc and LAT1 were significantly increased in CRC compared to the matched normal mucosa. CD98hc and LAT1 expression showed no significant correlations with cancer stem cell markers and intestinal stem cell markers, whereas both had positive correlations with Wnt target genes, AXIN2, and EPHB2, suggesting an association with aberrant Wnt signaling activation. Immunohistochemical analysis revealed that CD98hc and LAT1 are not expressed in normal colonic mucosa and various benign lesions including hyperplastic polyps and sessile and traditional serrated adenomas. CD98hc and LAT1 expressions began to appear in tubular adenomas and further increased in carcinomas. Of interest, CD98hc expression decreased during lymph node metastasis. Survival analysis demonstrated that CD98hc and LAT1 have no significant prognostic effect in CRCs. In conclusion, CD98hc and LAT1 are not normally expressed in colonic mucosa and most benign lesions. Their expression began to appear in tubular adenomas and further increased during the adenoma-to-carcinoma transition. CD98hc expression decreased while metastasizing to regional lymph nodes. However, CD98hc and LAT1 expressions had no prognostic value in patients with CRC.

The Intestinal Stem Cell Marker SMOC2 Is an Independent Prognostic Marker Associated With Better Survival in Gastric Cancer.

BACKGROUND/AIM: SPARC-related modular calcium-binding protein 2 (SMOC2), a secreted matricellular protein, is reported to be involved in cancer progression such as cell cycle, angiogenesis, and invasion. In this study, we aimed to investigate the expression of SMOC2 in various gastric lesions and assessed its prognostic value in a large cohort of gastric cancer (GC) patients. PATIENTS AND METHODS: SMOC2 mRNA levels were measured by quantitative real-time PCR using 26 matched fresh-frozen GC samples. SMOC2 protein expression was determined by immunohistochemistry on tissue microarrays including 734 GC specimens and its correlations with clinicopathological features and survival were evaluated. RESULTS: The transcription level of SMOC2 was higher in GC samples compared to normal mucosa (p=0.006). Its expression levels were associated with the intestinal stem cell (ISC) marker, LGR5, but there were no correlations with EPHB2 and OLFM4 or the candidate cancer stem cell markers CD133 and CD44. SMOC2 expression was significantly increased in the intestinal metaplasia and was further increased in gastric adenomas and early gastric cancers (EGC). In total, 34% of GCs were positive for SMOC2, and SMOC2 positivity was higher in old (p=0.001) and male (p<0.001) patients, and in well-differentiated GC (p<0.001). SMOC2 expression had a negative association with perineural invasion (p<0.001) and tumor stage (p<0.001). In survival analysis, SMOC2-positive GC patients had much better clinical outcomes in overall survival rates (p<0.001) compared to SMOC2-negative GC patients. The prognostic impact of SMOC2 remained significant both in intestinal (p<0.001) and diffuse-type GC (p<0.001). Remarkably, a multivariate analysis demonstrated SMOC2 as an independent prognostic marker [hazard ratio (HR)=0.732, p=0.045] along with venous invasion (p=0.012), tumor stage (p<0.001) and CDX2 (p=0.028). CONCLUSION: Our results suggest that SMOC2 can be a prognostic marker for better clinical outcomes in GC.

Expression profile of intestinal stem cell and cancer stem cell markers in gastric cancers with submucosal invasion.

Cancer stem cells (CSCs) are believed to be responsible for tumor growth, invasion, and metastasis. Submucosal invasion, which greatly enhances metastasis risk, is a critical step in gastric cancer (GC) progression. To identify stem cell-related markers associated with submucosal invasion and lymph node (LN) metastasis in GCs, we investigated the expression of candidate CSC markers (CD133, CD44, and ALDH1A) and intestinal stem cell (ISC) markers (EPHB2, OLFM4, and LGR5) in early GCs that manifested submucosal invasion. We discovered that EPHB2 and LGR5 expression was frequently confined to the basal area of the lamina propria (basal pattern) in mucosal cancer, and the proportion of stem cell marker-positive cells substantially increased during submucosal invasion. CD44 expression showed a focal pattern, ALDH1A was predominantly expressed diffusely, and there was no expansion of CD44 or ALDH1A expression in the submucosal cancer cells. Unexpectedly, no CSC markers showed any associations with LN metastasis, and only loss of EPHB2 expression was associated with increased LN metastasis. Treatment of RSPO2, a niche factor, along with Wnt 3a, to GC cells led to increased EPHB2 and LGR5 mRNA levels. RNA in situ hybridization confirmed specific RSPO2 expression in the smooth muscle cells of the muscularis mucosa, suggesting that RSPO2 is responsible for the increased expression of ISC markers in GC cells at the basal areas. In summary, no stem cell markers were associated with increased LN metastasis in early GCs. Conversely, isolated EPHB2 expression was associated with lower LN metastasis. EPHB2 and LGR5 showed a basal distribution pattern along with enhanced expression in submucosal invading cells in early GCs, which was induced by a niche factor, RSPO2, from the muscularis mucosa.

SMOC2, an intestinal stem cell marker, is an independent prognostic marker associated with better survival in colorectal cancers.

We aimed to investigate the expression profile of SPARC-related modular calcium-binding protein 2 (SMOC2) during colorectal cancer (CRC) progression and assess its prognostic impact in CRC patients. In our study, we showed that SMOC2 transcript level was higher in CRC samples than in normal mucosa (P = 0.017); this level was not associated with candidate cancer stem cell markers (CD44, CD166, CD133, and CD24) or intestinal stem cell markers (LGR5, ASCL2, and EPHB2) except for OLFM4 (P = 0.04). Immunohistochemical analysis showed that SMOC2-positive cells were confined to the crypt bases in the normal intestinal mucosa, hyperplastic polyps, and sessile serrated adenomas, whereas traditional serrated adenomas and conventional adenomas exhibited focal or diffuse distribution patterns. In total, 28% of 591 CRCs were positive for SMOC2, but SMOC2 positivity had negative correlations with lymphatic invasion (P = 0.002), venous invasion (P = 0.002), and tumor stage (P < 0.001). However, a positive association with nuclear ß-catenin expression was seen. Furthermore, while upregulated SMOC2 expression was maintained during the adenoma-carcinoma transition, it decreased in cancer cells at the invasive front but did not decline further during lymph node metastasis. SMOC2 positivity showed no correlations with molecular abnormalities, including microsatellite instability, CpG island methylator phenotype, and mutations of KRAS and BRAF. In addition, we showed comprehensively that SMOC2 positivity is an independent prognostic marker for better clinical outcomes in a large cohort of CRC patients (P = 0.006). In vitro studies also demonstrated that induced SMOC2 expression in DLD1 cells exerts a suppressive role in tumor growth as well as in migration, colony, and sphere formation abilities. Taken together, our results suggest SMOC2 as a candidate tumor suppressor in CRC progression.

Ten-Day Concomitant, 10-Day Sequential, and 7-Day Triple Therapy as First-Line Treatment for Helicobacter pylori Infection: A Nationwide Randomized Trial in Korea.

Background/Aims: This nationwide, multicenter prospective randomized controlled trial aimed to compare the efficacy and safety of 10-day concomitant therapy (CT) and 10-day sequential therapy (ST) with 7-day clarithromycin-containing triple therapy (TT) as first-line treatment for Helicobacter pylori infection in the Korean population. Methods: Patients with H. pylori infection were assigned randomly to 7d-TT (lansoprazole 30 mg, amoxicillin 1 g, and clarithromycin 500 mg twice daily for 7 days), 10d-ST (lansoprazole 30 mg and amoxicillin 1 g twice daily for the first 5 days, followed by lansoprazole 30 mg, clarithromycin 500 mg, and metronidazole 500 mg twice daily for the remaining 5 days), or 10d-CT (lansoprazole 30 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg twice daily for 10 days). The primary endpoint was eradication rate by intention-to-treat (ITT) and per-protocol (PP) analyses. Results: A total of 1,141 patients were included. The 10d-CT protocol achieved a markedly higher eradication rate than the 7d-TT protocol in both the ITT (81.2% vs 63.9%) and PP analyses (90.6% vs 71.4%). The eradication rate of the 10d-ST protocol was superior to that of the 7d-TT protocol (76.3% vs 63.9%, ITT analysis; 85.0% vs 71.4%, PP analysis). No significant differences in adherence or serious side effects were found among the three treatment arms. Conclusions: The 10d-CT and 10d-ST regimens were superior to the 7d-TT regimen as standard first-line treatment in Korea.

[Esophageal Foreign Body: Treatment and Complications].

The most common cause of esophageal foreign bodies in adults is meat in Western countries and fish bones in Asian countries, including Korea. Although most ingested foreign bodies pass spontaneously through the esophagus without any clinical sequelae, some sharp foreign bodies, such as fish bones embedded in the esophagus, require treatment. Endoscopic management is the first choice in the treatment of esophageal foreign bodies because it is quite safe and effective. Major complications occur as a result of esophageal perforation; in particular, sharp foreign bodies, such as fish bones, are more likely to cause perforation. Complications include mediastinitis, paraesophageal abscess, pneumomediastinum, subcutaneous emphysema, pneumothorax, tracheoesophagal fistula, aortoesophageal fistula, aspiration, and asphyxia. Unnecessary delays should be avoided in endoscopic intervention for esophageal foreign bodies to prevent complications.

Endoscopic Submucosal Dissection of Early Gastric Cancer in Patients with Liver Cirrhosis.

BACKGROUND AND OBJECTIVES: Endoscopic submucosal dissection (ESD) has become widely accepted method for treating early gastric cancer (EGC), but little is known about its role in patients with liver cirrhosis (LC). The aims of this study were to evaluate the outcomes of ESD in treating EGC in patients with LC. METHODS: The multicenter retrospective study identified 43 patients with chronic hepatitis B (CHB)-related cirrhosis undergoing ESD for treating EGC. The patients (LC group) were subdivided into two groups based on their Child-Pugh classification (CP-class): 32 with CP-class A (LC-A) and 11 with CP-class B (LC-B). The patients were compared to 47 non-cirrhotic CHB patients who underwent ESD (CHB group). Eight patients had a past history of hepatocellular carcinoma (HCC) prior to ESD, but no patients had viable HCC when ESD was performed. RESULTS: Procedural outcomes (en bloc, lateral/basal margins resection) and post-procedural complications (bleeding or perforation) did not differ significantly between the LC and CHB groups or between the LC-A and LC-B groups. No patients experienced worsening of the Child-Pugh score 1 month after ESD compared with the baseline score. During a median observation period of 66 months, the recurrence rates of gastric cancers were similar between the LC and CHB groups (5-year recurrence rates: 2.4 vs. 2.3%, p = 0.925), and all recurrent gastric cancers were completely resected by additional ESD. The overall mortality rate was increased in the LC group (5-year mortality rates: 17.9 vs. 5.7%, p = 0.034), and 8 of 10 deaths were attributed to liver-related diseases (such as HCC, complications of portal hypertension, hepatic failure). CONCLUSIONS: ESD is feasible in patients with EGC and comorbid LC, even those with CP-class B cirrhosis. Their prognosis depends on LC-related diseases and not recurrent EGC.

Ophthalmologic manifestations in patients with inflammatory bowel disease.

BACKGROUND/AIMS: Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), has been reported to have various ophthalmologic manifestations. The aim of this study was to evaluate the prevalence of ophthalmologic manifestations associated with IBD in Korea. METHODS: Sixty-one patients were examined between May 2013 and October 2014. We performed complete ophthalmologic examinations. RESULTS: Findings included 36 patients with CD and 25 with UC. The mean age of the patients was 34±16 years and disease duration was 45.3±23.9 months. Ophthalmologic manifestations were positive in 44 cases. Primary complication was diagnosed in 5 cases, as follows; iritis in 2 cases, episcleritis in one case, iritis with optic neuritis in 1 case, and serous retinal detachment in 1 case, without secondary complications. The most common coincidental complication was dry eye syndrome (DES), in 35 patients (57.4%). The prevalence of DES in the control group was 21.3%. The proportion of DES in patients with IBD was significantly higher than in the control group (P=0.002). CONCLUSIONS: Ophthalmologic manifestations were high (72.1%) in IBD patients. Clinically significant primary ocular inflammation occurred in 8.2% of patients. The most common complication was DES. There was a higher rate of DES in patients with IBD compared to the control group. Evaluation of the eye should be a routine component in patients with IBD.

Endoscopic Ultrasound-Guided Perirectal Abscess Drainage without Drainage Catheter: A Case Series.

A perirectal abscess is a relatively common disease entity that occurs as a postsurgical complication or as a result of various medical conditions. Endoscopic ultrasound (EUS)-guided drainage was recently described as a promising alternative treatment. Previous reports have recommended placement of a drainage catheter through the anus for irrigation, which is inconvenient to the patient and carries a risk of accidental dislodgement. We report four cases of perirectal abscess that were successfully treated with only one or two 7 F double pigtail plastic stent placements and without a drainage catheter for irrigation.

A Case of Taenia asiatica Infection Diagnosed by Colonoscopy.

A case of Taenia asiatica infection detected by small bowel series and colonoscopy is described. The patient was a 42-year-old Korean man accompanied by discharge of movable proglottids via anus. He used to eat raw pig liver but seldom ate beef. Small bowel series radiologic examinations showed flat tape-like filling defects on the ileum. By colonoscopy, a moving flat tapeworm was observed from the terminal ileum to the ascending colon. The tapeworm was identified as T. asiatica by mitochondrial DNA sequencing. The patient was prescribed with a single oral dose (16 mg/kg) of praziquantel.

Efficacy of Levofloxacin-Based Third-Line Therapy for the Eradication of Helicobacter pylori in Peptic Ulcer Disease.

BACKGROUND/AIMS: The resistance rate of Helicobacter pylori is gradually increasing. We aimed to evaluate the efficacy of levofloxacin-based third-line H. pylori eradication in peptic ulcer disease. METHODS: Between 2002 and 2014, 110 patients in 14 medical centers received levofloxacin-based third-line H. pylori eradication therapy for peptic ulcer disease. Of these, 88 were included in the study; 21 were excluded because of lack of follow-up and one was excluded for poor compliance. Their eradication rates, treatment regimens and durations, and types of peptic ulcers were analyzed. RESULTS: The overall eradiation rate was 71.6%. The adherence rate was 80.0%. All except one received a proton-pump inhibitor, amoxicillin, and levofloxacin. One received a proton-pump inhibitor, amoxicillin, levofloxacin, and clarithromycin, and the eradication was successful. Thirty-one were administered the therapy for 7 days, 25 for 10 days, and 32 for 14 days. No significant differences were observed in the eradication rates between the three groups (7-days, 80.6% vs 10-days, 64.0% vs 14-days, 68.8%, p=0.353). Additionally, no differences were found in the eradiation rates according to the type of peptic ulcer (gastric ulcer, 73.2% vs duodenal/gastroduodenal ulcer, 68.8%, p=0.655). CONCLUSIONS: Levofloxacin-based third-line H. pylori eradication showed efficacy similar to that of previously reported first/second-line therapies.

The Korean Gastric Cancer Cohort Study: Study Protocol and Brief Results of a Large-Scale Prospective Cohort Study.

PURPOSE: This study aimed to establish a large-scale database of patients with gastric cancer to facilitate the development of a national-cancer management system and a comprehensive cancer control policy. MATERIALS AND METHODS: An observational prospective cohort study on gastric cancer was initiated in 2010. A total of 14 cancer centers throughout the country and 152 researchers were involved in this study. Patient enrollment began in January 2011, and data regarding clinicopathological characteristics, life style-related factors, quality of life, as well as diet diaries were collected. RESULTS: In total, 4,963 patients were enrolled until December 2014, and approximately 5% of all Korean patients with gastric cancer annually were included. The mean age was 58.2±11.5 years, and 68.2% were men. The number of patients in each stage was as follows: 3,394 patients (68.4%) were in stage IA/B; 514 patients (10.4%), in stage IIA/B; 469 patients (9.5%), in stage IIIA/B/C; and 127 patients (2.6%), in stage IV. Surgical treatment was performed in 3,958 patients (79.8%), endoscopic resection was performed in 700 patients (14.1%), and 167 patients (3.4%) received palliative chemotherapy. The response rate for the questionnaire on the quality of life was 95%; however, diet diaries were only collected for 27% of patients. CONCLUSIONS: To provide comprehensive information on gastric cancer for patients, physicians, and government officials, a large-scale database of Korean patients with gastric cancer was established. Based on the findings of this cohort study, an effective cancer management system and national cancer control policy could be developed.

Regression of esophageal varices and splenomegaly in two patients with hepatitis-C-related liver cirrhosis after interferon and ribavirin combination therapy.

Some recent studies have found regression of liver cirrhosis after antiviral therapy in patients with hepatitis C virus (HCV)-related liver cirrhosis, but there have been no reports of complete regression of esophageal varices after interferon/peg-interferon and ribavirin combination therapy. We describe two cases of complete regression of esophageal varices and splenomegaly after interferon-alpha and ribavirin combination therapy in patients with HCV-related liver cirrhosis. Esophageal varices and splenomegaly regressed after 3 and 8 years of sustained virologic responses in cases 1 and 2, respectively. To our knowledge, this is the first study demonstrating that complications of liver cirrhosis, such as esophageal varices and splenomegaly, can regress after antiviral therapy in patients with HCV-related liver cirrhosis.

Oroesophageal Fish Bone Foreign Body.

Fish bone foreign body (FFB) is the most frequent food-associated foreign body (FB) in adults, especially in Asia, versus meat in Western countries. The esophageal sphincter is the most common lodging site. Esophageal FB disease tends to occur more frequently in men than in women. The first diagnostic method is laryngoscopic examination. Because simple radiography of the neck has low sensitivity, if perforation or severe complications requiring surgery are expected, computed tomography should be used. The risk factors associated with poor prognosis are long time lapse after FB involvement, bone type, and longer FB (>3 cm). Bleeding and perforation are more common in FFB disease than in other FB diseases. Esophageal FB disease requires urgent treatment within 24 hours. However, FFB disease needs emergent treatment, preferably within 2 hours, and definitely within 6 hours. Esophageal FFB disease usually occurs at the physiological stricture of the esophagus. The aortic arch eminence is the second physiological stricture. If the FB penetrates the esophageal wall, a life-threatening aortoesophageal fistula can develop. Therefore, it is better to consult a thoracic surgeon prior to endoscopic removal.