No increased risk of hepatocellular carcinoma after eradication of hepatitis C virus by direct-acting antivirals, compared with interferon-based therapy.

It is well-known that sustained virological response (SVR) by interferon (IFN)-based therapy against hepatitis C virus (HCV) infection reduced the incidence of hepatocellular carcinoma (HCC). However, whether IFN-free direct-acting antivirals reduce the risk of HCC is controversial. Therefore, this study aims to compare the incidence of HCC after the achievement of SVR between sofosbuvir combined with ledipasvir (SOF/LDV) and simeprevir with pegylated interferon plus ribavirin (Sim+IFN). Japanese patients with HCV infection (genotype 1) who achieved SVR between January 2013 and December 2014 by SOF/LDV (NCT01975675, n = 320) or Sim+IFN (000015933, n = 289) therapy in two nationwide, multicenter, phase III studies were prospectively monitored for the development of HCC by ultrasonography for 5 years after the end of treatment (EOT). No HCC was detected before the treatment. HCC was detected in 9 and 7 patients in the SOF/LDV and the Sim+IFN group in 5 years, respectively. The cumulative incidences of HCC rates 1, 3, and 5 years after EOT were similar between the two groups (1.5%, 2.7%, and 3.2% for the SOF/LDV and 1.8%, 2.8%, and 3.0% for the Sim+IFN group, respectively). No HCC was developed 3.5 years after EOT. Interestingly, a retrospective careful review of imaging taken before therapy revealed hepatic nodules in 50% of HCC patients, suggesting HCC was pre-existed before therapy. In conclusion, we could not find any differences in the incidence of HCC after the HCV eradication between the two therapeutic regimens, suggesting no enhancement of HCC development by DAA.

Relapse-Free Course in Nearly Half of Crohn's Disease Patients With Infliximab and Plant-Based Diet as First-Line Therapy: A Single-Group Trial.

Introduction Incorporation of a plant-based diet was effective in both induction and short-term relapse prevention in Crohn's disease. Ten-year long-term relapse-free rates in Crohn's disease are around 10% to 23%. Objective We investigated whether infliximab and plant-based diet as first-line therapy enhance the long-term relapse-free rate in patients with Crohn's disease. Methods This single-group, prospective study was performed in tertiary hospitals in Japan. Remission was induced in 24 consecutive newly diagnosed adult patients with Crohn's disease during hospitalization via 3 standard infliximab infusions together with a plant-based diet. Patients were instructed to continue the diet after discharge. Scheduled maintenance infliximab infusion was not used. The primary endpoint was relapse, which was defined as the appearance of symptoms resulting in the alteration of therapeutic modality. The secondary endpoints were C-reactive protein level, plant-based diet score, and surgery. Results The median follow-up period was 8.6 years. Thirteen cases were relapse-free. The relapse-free rate evaluated by Kaplan-Meier survival analysis at 1, 2, 3, and 4 years was 79%, 66%, 57%, and 52%, respectively. There was no further reduction afterward up to 10 years. The relapse-free rate with normal C-reactive protein levels at 1 to 2 and 3 to 10 years was 57% and 52%, respectively. The plant-based diet score at 20 months and 5 years was significantly higher relative to baseline (p < 0.0001). Surgical rates at 5 and 10 years were 12% and 19%, respectively. Conclusions Infliximab and plant-based diet as first-line therapy created an unprecedented relapse-free course in nearly half of patients with Crohn's disease.

High Remission Rate with Infliximab and Plant-Based Diet as First-Line (IPF) Therapy for Severe Ulcerative Colitis: Single-Group Trial.

INTRODUCTION: About one-third of patients with severe ulcerative colitis (UC) do not respond to corticosteroid therapy and receive rescue therapy with infliximab or cyclosporine. Up to 20% of such patients fail to respond to rescue therapy and undergo colectomy. OBJECTIVE: We investigated the outcomes of infliximab and a plant-based diet (PBD) as first-line therapy for severe UC. METHODS: Patients with severe UC defined by the Truelove and Witts criteria were admitted and given standard induction therapy with infliximab (5.0 mg/kg-7.5 mg/kg) at 0, 2, and 6 weeks. Additionally, they received a PBD. The primary endpoint was remission or colectomy in the induction phase and 1 year after discharge. Secondary endpoints were changes in inflammatory markers in the induction phase and the PBD score at baseline and follow-up. A higher PBD score indicates greater adherence to a PBD. RESULTS: Infliximab and PBD as first-line therapy was administered in 17 cases. The remission rate was 76% (13/17), and the colectomy rate was 6% (1/17) in the induction phase. C-reactive protein values and the erythrocyte sedimentation rate significantly decreased at week 6 from 9.42 mg/dL to 0.33 mg/dL and from 59 to 17 mm/h, respectively (p < 0.0001). At 1-year follow-up, the cumulative relapse rate was 25%, and there were no additional colectomy cases. Mean PBD scores of 27.7 at 1 year and 23.8 at 4 years were significantly higher than baseline scores of 8.3 and 9.9, respectively (p < 0.0001 and p = 0.0391). CONCLUSION: This new first-line therapy for severe UC demonstrated a higher remission rate and lower colectomy rate than with the current modality.

Onset of Ulcerative Colitis in a Patient with Nonalcoholic Fatty Liver Disease (NAFLD): Dramatic Effect of Plant-based Diet for NAFLD.

Nonalcoholic fatty liver disease (NAFLD) develops in ulcerative colitis (UC) and Crohn's disease. However, there is scarce reporting on the onset of UC in patients with NAFLD. A 44-year-old man was diagnosed with UC and referred to us in 2019. His height was 166.0 cm, and body weight was 86.3 kg. The waist circumference was 93.7 cm (normal range <85) and triglyceride was 751 mg/dL. These findings, in addition to hypertension, resulted in a diagnosis of metabolic syndrome. HbA1c was normal. Ultrasonography disclosed severe fatty liver. Nonalcoholic fatty liver disease was diagnosed. He underwent 12 days of educational hospitalization for UC. A lacto-ovo-semi-vegetarian diet (1400 kcal/day), a kind of plant-based diet (PBD), was provided. He lost 4 kg, which was 4.6% of his base body weight. Triglyceride and total cholesterol decreased to the normal ranges. Transaminases and γ-glutamyl transpeptidase also decreased. His body weight decreased further after discharge. Follow-up ultrasonography indicated an improvement in hepatic enlargement. The shear wave velocity decreased from 1.11 to 0.88 m/s. His soft stool became normal stool by 2 months after discharge. Records of his health checkups revealed the presence of metabolic syndrome and abnormal liver function tests already in 2015. Thus, it was concluded that UC developed in a patient with NAFLD in this case. Plant-based diet has already been shown to be effective in inflammatory bowel disease (IBD). In the present case, NAFLD parameters were dramatically improved by PBD. Whether the improvement was due to weight loss per se or due to weight loss with PBD is to be clarified.

Relapse Prevention by Plant-Based Diet Incorporated into Induction Therapy for Ulcerative Colitis: A Single-Group Trial.

CONTEXT: No known previous study has focused on plant-based diet (PBD) to prevent relapse of ulcerative colitis (UC) except our previous educational hospitalization study. OBJECTIVE: To describe the relapse rate in a large case series of UC after incorporation of PBD into induction therapy. DESIGN: All patients with UC between 2003 and 2017 were admitted for induction therapy. Patients receiving educational hospitalization or treated with infliximab were excluded. A lacto-ovo-semivegetarian diet (PBD) together with medication prescribed according to UC guidelines was provided during hospitalization. MAIN OUTCOME MEASURES: The primary endpoint was relapse during follow-up. The secondary endpoint was change over time in the plant-based diet score (PBDS), which evaluated adherence to the PBD. RESULTS: Ninety-two cases were studied, of which 51 were initial episodes and 41 were relapses. Cases varied in severity (31 mild, 48 moderate, 13 severe) and extent (15 proctitis, 22 left-sided colitis, 55 extensive colitis). More severe cases existed among the relapse cases than among the initial episode cases. Cumulative relapse rates at 1- and 5-year follow-up (Kaplan-Meier analysis) were 14% and 27%, respectively, for the initial episode cases, and 36% and 53%, respectively, for relapse cases. At long-term follow-up (6 years 4 months), PBDS was significantly higher than baseline PBDS (p < 0.0001). CONCLUSION: Relapse rates in UC after induction therapy with PBD were far lower than those previously reported with conventional therapy. Adherence to PBD was significantly higher than baseline even at 6-year follow-up. We conclude PBD is effective for preventing UC relapse.(Study identification no.: UMIN000019061: Registration: www.umin.ac.jp).

Comparison of finite helical axes of normal and anatomically designed prosthetic knees.

BACKGROUND: Describing three-dimensional joint motion using the finite helical axis has an advantage in understanding unknown coupling motion in prosthetic knee joints. We aimed to examine the differences in the orientations of finite helical axis of normal and anatomically designed cruciate-retaining and posterior-stabilized prosthetic knees after total knee arthroplasty. METHODS: Ten normal, 40 cruciate-retaining prosthetic knees of 33 patients and 19 posterior-stabilized prosthetic knees of 14 patients enabling to flex > 120° were analyzed during a squatting motion with deep knee bending. The motion was recorded by a fluoroscopic imaging system, and the pose of the bone and prostheses were determined by an image registration technique. The finite helical axes were calculated using 30° window. FINDINGS: The finite helical axis in the early flexion phase of the normal knees had a greater inferior inclination (mean - 19.0° (SD 7.2°)) than those of the cruciate-retaining (mean - 1.7 (SD 5.0°)) and posterior-stabilized (mean - 2.9° (SD 5.5°)) prosthetic knees (p < 0.001), and became almost horizontal and constant in the mid to deep flexion phases. In contrast, the cruciate-retaining and posterior-stabilized prosthetic knees demonstrated slightly inclined and almost constant vertical angles throughout the all phases. INTERPRETATION: These results demonstrate that, in the normal knee, a clear coupling motion occurs during the early flexion phase. For the cruciate-retaining and posterior-stabilized prosthetic knees, an unclear coupling motion exists during all phases. These results suggest that the physiological motion is not possible to reproduce using shape-guided motion only even in an anatomically designed prosthetic knee.

Westernized Diet is the Most Ubiquitous Environmental Factor in Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD), a collective term for Crohn disease and ulcerative colitis, is a polygenic disease thought to be triggered by environmental factors. A Western or westernized lifestyle may be a major driver of the growing incidence of IBD. IBD may represent dysregulated mucosal inflammation to gut microbiota. Despite many review articles on environmental factors in IBD, no consensus exists regarding which factor contributes most to trigger the onset of IBD. Identification and recognition of major environmental factors are prerequisite for effective disease treatment and prevention. Representative environmental factors such as smoking, breastfeeding, nonsteroidal anti-inflammatory drugs, antibiotic use in childhood, oral contraceptives, and appendectomy do not correlate with disease onset in most patients with IBD. In contrast, diet appears to be important in most cases of IBD. Diets rich in animal protein (risk factor) and deficient in dietary fiber (preventive factor) are characteristic of westernized diets in affluent societies. Recent research shows that westernized diets are associated with a reduced gut microbial diversity (dysbiosis), which may result in increased susceptibility to IBD and other common chronic diseases. Plant-based diets rich in dietary fiber are associated with increased microbial diversity. Recent reports on IBD therapy that replaced westernized diets with plant-based diets achieved far better outcomes than those previously reported in the literature. We believe that westernized diet-associated gut dysbiosis is the most ubiquitous environmental factor in IBD. Adoption of this concept may have the potential to provide a better quality of life for patients with IBD.

Relapse Prevention in Ulcerative Colitis by Plant-Based Diet Through Educational Hospitalization: A Single-Group Trial.

CONTEXT: No known published study has focused on a plant-based diet (PBD) in the treatment of ulcerative colitis (UC). OBJECTIVE: To investigate relapse prevention in UC after consumption of a PBD during educational hospitalization in Japan. DESIGN: Prospective study of patients with mild UC or UC in remission who did not need immediate treatment. A PBD and dietary guidance were provided during a two-week hospitalization. MAIN OUTCOME MEASURES: The primary end point was relapse (a flare-up that required more aggressive treatment) during the follow-up period. Kaplan-Meier analysis was used to calculate the cumulative relapse rate. Secondary end points were immediate improvement in symptoms or laboratory data during hospitalization and a chronologic change in the PBD score, which evaluated adherence to the PBD. RESULTS: Sixty cases were studied: 29 initial episode cases and 31 relapse cases. Of these, 31 involved proctitis; 7, left-sided colitis; and 22, extensive colitis. Thirty-seven patients were receiving medication; 23 were not. The median age was 34 years; median follow-up was 3 years 6 months. Eight cases relapsed during follow-up. The cumulative relapse rates at 1, 2, 3, 4, and 5 years of follow-up were 2%, 4%, 7%, 19%, and 19%, respectively. Most patients (77%) experienced some improvement such as disappearance or decrease of bloody stool during hospitalization. The short- and long-term PBD scores after the hospitalization were higher than baseline PBD scores. CONCLUSION: Relapse rates after educational hospitalization providing a PBD were far lower than those reported with medication. Educational hospitalization is effective at inducing habitual dietary changes.

Induction with Infliximab and a Plant-Based Diet as First-Line (IPF) Therapy for Crohn Disease: A Single-Group Trial.

BACKGROUND: Approximately 30% of patients with Crohn disease (CD) are unresponsive to biologics. No previous study has focused on a plant-based diet in an induction phase of CD treatment. OBJECTIVE: To investigate the remission rate of infliximab combined with a plant-based diet as first-line (IPF) therapy for CD. METHODS: This was a prospective single-group trial conducted at tertiary hospitals. Subjects included consecutive adults with a new diagnosis (n = 26), children with a new diagnosis (n = 11), and relapsing adults (n = 9) with CD who were naïve to treatment with biologics. Patients were admitted and administered a standard induction therapy with infliximab (5 mg/kg; 3 infusions at 0, 2, and 6 weeks). Additionally, they received a lacto-ovo-semivegetarian diet. The primary end point was remission, defined as the disappearance of active CD symptoms at week 6. Secondary end points were Crohn Disease Activity Index (CDAI) score, C-reactive protein (CRP) concentration, and mucosal healing. RESULTS: Two adults with a new diagnosis were withdrawn from the treatment protocol because of intestinal obstruction. The remission rates by the intention-to-treat and per-protocol analyses were 96% (44/46) and 100% (44/44), respectively. Mean CDAI score (314) on admission decreased to 63 at week 6 (p < 0.0001). Mean CRP level on admission (5.3 mg/dL) decreased to 0.2 (p < 0.0001). Mucosal healing was achieved in 46% (19/41) of cases. CONCLUSION: IPF therapy can induce remission in most patients with CD who are naïve to biologics regardless of age or whether they have a new diagnosis or relapse.

Development and Application of a Plant-Based Diet Scoring System for Japanese Patients with Inflammatory Bowel Disease.

CONTEXT: Plant-based diets (PBDs) are a healthy alternative to westernized diets. A semivegetarian diet, a PBD, has been shown to prevent a relapse in Crohn disease. However, there is no way to measure adherence to PBDs. OBJECTIVE: To develop a simple way of evaluating adherence to a PBD for Japanese patients with inflammatory bowel disease (IBD). DESIGN: PBD scores were assigned according to the frequency of consumption provided on a food-frequency questionnaire, obtained on hospitalization for 159 patients with ulcerative colitis and 70 patients with Crohn disease. Eight items considered to be preventive factors for IBD were scored positively, and 8 items considered to be IBD risk factors were scored negatively. The PBD score was calculated from the sum of plus and minus scores. Higher PBD scores indicated greater adherence to a PBD. The PBD scores were evaluated on hospitalization and 2 years after discharge for 22 patients with Crohn disease whose dietary pattern and prognosis were established. MAIN OUTCOME MEASURE: Plant-Based Diet score. RESULTS: The PBD scores differed significantly, in descending order, by dietary type: pro-Japanese diet, mixed type, and pro-westernized diet (Wilcoxon/Kruskal-Wallis test). The PBD scores in the ulcerative colitis and Crohn disease groups were 10.9 ± 9.5 and 8.2 ± 8.2, respectively. For patients with Crohn disease, those with long-term remission and normal C-reactive protein concentration were significantly more likely to have PBD scores of 25 or greater than below 25 (χ2). CONCLUSION: The PBD score is a valid assessment of PBD dietary adherence.

Ledipasvir and sofosbuvir fixed-dose combination with and without ribavirin for 12 weeks in treatment-naive and previously treated Japanese patients with genotype 1 hepatitis C: an open-label, randomised, phase 3 trial.

BACKGROUND: Compared with other countries, patients with chronic hepatitis C infection in Japan tend to be older, have more advanced liver disease, and are more likely to have been previously treated for hepatitis C. We aimed to assess the efficacy and safety of an all-oral, fixed-dose combination of the hepatitis C virus NS5A inhibitor ledipasvir and the NS5B nucleotide polymerase inhibitor sofosbuvir with and without ribavirin for 12 weeks in treatment-naive and previously treated Japanese patients with chronic genotype 1 hepatitis C virus infection. METHODS: In this randomised, open-label study, we enrolled patients from 19 clinical Japanese centres. Patients were randomly assigned (1:1) to receive either ledipasvir (90 mg) and sofosbuvir (400 mg) or ledipasvir, sofosbuvir, and ribavirin (dosed according to the Japanese Copegus product label-ie, patients ≤60 kg received 600 mg daily, patients >60 kg to ≤80 kg received 800 mg daily, and patients >80 kg received 1000 mg daily) orally once daily for 12 weeks. After completion or early discontinuation of treatment, patients were followed up off-treatment for 24 weeks. Eligible patients were at least 20 years of age with chronic genotype 1 hepatitis C virus infection with serum hepatitis C virus RNA concentrations of at least 5 log10 IU/mL, creatinine clearance of at least 1·0 mL/s, and a platelet count of at least 50 × 10(9) per L. An interactive web response system was used to manage patient randomisation and treatment assignment. Randomisation was stratified by the presence or absence of cirrhosis for treatment-naive patients and stratified by presence or absence of cirrhosis and by previous treatment category (relapser or breakthrough, non-responder, or interferon-intolerant) for previously treated patients. Within each strata, patients were sequentially assigned to either treatment with ledipasvir-sofosbuvir or ledipasvir-sofosbuvir plus ribavirin in a 1:1 ratio with block size of 4. The primary endpoint was sustained virological response 12 weeks after completion of treatment (SVR12) assessed in all patients who were randomly assigned and received at least one dose of study drug; safety outcomes were assessed in all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT01975675. FINDINGS: Between Oct 15, 2013 and Dec 13, 2013, 341 patients were randomly assigned to treatment groups and received at least one dose of study treatment. SVR12 was achieved in all 171 (100%) patients (83 of 83 treatment naive and 88 of 88 treatment experienced) receiving ledipasvir-sofosbuvir (95% CI 98-100) and 167 (98%) of 170 patients (80 of 83 treatment naive and 87 of 87 treatment experienced) receiving ledipasvir-sofosbuvir plus ribavirin (95% CI 95-100). Of the 76 patients with baseline NS5A resistant variants, 75 (99%) achieved SVR12. Two (1·2%) of 170 patients in the ledipasvir-sofosbuvir plus ribavirin group discontinued treatment because of adverse events. The most common adverse events were nasopharyngitis (50 [29·2%] of 171), headache (12 [7·0%] of 171), and malaise (nine [5·3%] of 171) in patients receiving ledipasvir-sofosbuvir; and nasopharyngitis (40 [23·5%] of 170), anaemia (23 [13·5%] of 170), and headache in those receiving ledipasvir-sofosbuvir and ribavirin (15 [8·8%] of 170). INTERPRETATION: Although existing regimens for the treatment of hepatitis C virus are effective for many patients, medical needs remain unmet, particularly in Japan where the population with hepatitis C virus genotype 1 is generally older and treatment-experienced, with advanced liver disease. The efficacy, tolerability, and absence of drug-drug interactions of ledipasvir-sofosbuvir suggest that it could be an important option for treatment of genotype 1 hepatitis C virus in Japanese patients. FUNDING: Gilead Sciences.

High amount of dietary fiber not harmful but favorable for Crohn disease.

Current chronic diseases are a reflection of the westernized diet that features a decreased consumption of dietary fiber. Indigestible dietary fiber is metabolized by gut bacteria, including Faecalibacterium prausnitzii, to butyrate, which has a critical role in colonic homeostasis owing to a variety of functions. Dietary fiber intake has been significantly inversely associated with the risk of chronic diseases. Crohn disease (CD) is not an exception. However, even authors who reported the inverse association between dietary fiber and a risk of CD made no recommendation of dietary fiber intake to CD patients. Some correspondence was against advocating high fiber intake in CD. We initiated a semivegetarian diet (SVD), namely a lacto-ovo-vegetarian diet, for patients with inflammatory bowel disease. Our SVD contains 32.4 g of dietary fiber in 2000 kcal. There was no untoward effect of the SVD. The remission rate with combined infliximab and SVD for newly diagnosed CD patients was 100%. Maintenance of remission on SVD without scheduled maintenance therapy with biologic drugs was 92% at 2 years. These excellent short- and long-term results can be explained partly by SVD. The fecal bacterial count of F prausnitzii in patients with CD is significantly lower than in healthy controls. Diet reviews recommend plant-based diets to treat and to prevent a variety of chronic diseases. SVD belongs to plant-based diets that inevitably contain considerable amounts of dietary fiber. Our clinical experience and available data provide a rationale to recommend a high fiber intake to treat CD.

Sofosbuvir plus ribavirin in Japanese patients with chronic genotype 2 HCV infection: an open-label, phase 3 trial.

Genotype 2 hepatitis C virus (HCV) accounts for up to 30% of chronic HCV infections in Japan. The standard of care for patients with genotype 2 HCV - peginterferon and ribavirin for 24 weeks - is poorly tolerated, especially among older patients and those with advanced liver disease. We conducted a phase 3, open-label study to assess the efficacy and safety of an all-oral combination of the NS5B polymerase inhibitor sofosbuvir and ribavirin in patients with chronic genotype 2 HCV infection in Japan. We enrolled 90 treatment-naïve and 63 previously treated patients at 20 sites in Japan. All patients received sofosbuvir 400 mg plus ribavirin (weight-based dosing) for 12 weeks. The primary endpoint was sustained virologic response at 12 weeks after therapy (SVR12). Of the 153 patients enrolled and treated, 60% had HCV genotype 2a, 11% had cirrhosis, and 22% were over the aged 65 or older. Overall, 148 patients (97%) achieved SVR12. Of the 90 treatment-naïve patients, 88 (98%) achieved SVR12, and of the 63 previously treated patients, 60 (95%) achieved SVR12. The rate of SVR12 was 94% in patients with cirrhosis and in those aged 65 and older. No patients discontinued study treatment due to adverse events. The most common adverse events were nasopharyngitis, anaemia and headache. Twelve weeks of sofosbuvir and ribavirin resulted in high rates of SVR12 in treatment-naïve and previously treated patients with chronic genotype 2 HCV infection. The treatment was safe and well tolerated by patients, including the elderly and those with cirrhosis.

Crohn's disease successfully treated with infliximab in a patient receiving hemodialysis: case report and review of the literature.

There is limited information in the use of antitumor necrosis factor α, infliximab, in patients on hemodialysis. In Crohn's disease (CD), only 3 cases are reported.A 76-year-old man on hemodialysis for renal failure caused by immunoglobulin A nephropathy developed diarrhea and abdominal pains. A marked edema was observed in the pretibia and ankle. An increase of C-reactive protein (CRP) and erythrocyte sedimentation rate, hypoalbuminemia, hypocholesterolemia, and moderate anemia was found. Ultrasonography and computed tomography (CT) found wall thickness in the left colon. Sigmoidoscopy revealed multiple ulcers in the sigmoid colon and noncaseating epithelioid granuloma was found in the biopsy specimen. Barium enema study exhibited collar button signs and longitudinal ulcers in the left colon.A severe form of CD was diagnosed. Metronidazole seemed to decrease CRP but was ineffective in ameliorating diarrhea. Infliximab rather than steroid hormone was chosen for the treatment. Standard induction therapy with infliximab was initiated. Symptoms rapidly improved then disappeared. CD activity index decreased from 747 to a remission level of 134 after 2 infusions of infliximab. Scheduled maintenance infliximab therapy was administered after the induction therapy. Ultrasonography and CT showed a disappearance of the wall thickness of the colon. Adverse reactions were not observed.Infliximab was effective and safe in a patient with CD on hemodialysis. Our case has added additional literature in accordance with previous reports supporting infliximab as effective and safe in patients on hemodialysis.

Endoscopic mucosal resection using a cap-fitted panendoscope and endoscopic submucosal dissection as optimal endoscopic procedures for superficial esophageal carcinoma.

BACKGROUND: Endoscopic mucosal resection using a cap-fitted panendoscope (EMRC) and an endoscopic submucosal dissection (ESD) are increasingly performed to treat superficial esophageal carcinoma (SEC). As an endoscopic procedure appropriate for en bloc complete resection, ESD requires a much higher level of skill and experience than EMRC. METHODS: This retrospective study reviewed 127 SECs in 112 patients treated by EMRC or ESD from January 1997 to September 2009. RESULTS: For lesions 10 mm in diameter or smaller, EMRC and ESD had equivalent en bloc resection rates with tumor-free margins (en bloc + R0 resection rates). For lesions 11 mm in diameter or larger, however, the rate was significantly higher in the ESD group than in the EMRC group (p < 0.01). The mean procedure time was significantly longer in the ESD group than in the EMRC group (p < 0.01) regardless of lesion size. No significant difference was found in esophageal perforation rate between the EMRC and ESD groups. Severe esophageal stricture developed after EMRC of eight lesions (14.3%) and after ESD of six lesions (8.5%). For patients with a mucosal defect involving more than three-fourths of the esophageal circumference, the incidence of severe esophageal stricture after procedure was significantly higher in the EMRC group than in the ESD group (p < 0.05). The overall local recurrence rate was 3.1% (4/127) during an average follow-up period of 39 months (range, 8-123 months). All local recurrences were detected as superficial cancers after EMRC and then treated endoscopically. CONCLUSIONS: For lesions 10 mm in diameter or smaller, EMRC was found to be optimal. For lesions 11 mm in diameter or larger, however, ESD was superior to EMRC in efficacy as assessed by the en bloc + R0 resection rate. Furthermore, ESD was advantageous in preventing stricture formation. The operating endoscopist should carefully select EMRC or ESD according to lesion size.

Mechanical stretch induces matrix metalloproteinase 1 production in human hepatic stellate cells.

In increasing portal blood flow, hepatic stellate cells (HSC) may be lengthened in response to mechanical stretch stimulation and their function may be changed. However, little is known about the influence of mechanical stretch on hepatic stellate cells. We examined production of matrix metalloproteinases (MMP), tissue inhibitors of metalloproteinases (TIMP), and extracellular matrix by hepatic stellate cells to investigate the relationship between mechanical stretch and hepatic fibrosis. LI90 cells, human hepatic stellate cells, were stretched cyclically using the Flexer cell strain unit. Concentrations of MMP1, MMP2, TIMP1, TIMP2, type I collagen C-telopeptide (1CTP), procollagen III propeptide (PIIIP), and hyaluronic acid in culture supernatants were determined. MMP1, MMP2, and TIMP1 mRNA expression was measured by reverse transcription-polymerase chain reaction (RT-PCR). In stretched LI90 cells, concentration of MMP1 showed an increase relative to unstretched cells, but concentrations of MMP2, TIMPl, and TIMP2 showed a decrease. MMP1/TIMP1 ratio and MMP1 mRNA expression showed an increase in stretched cells. Our finding suggested that in the early phase of portal hypertension, hepatic stellate cells increase production of MMPl and decrease production of TIMP1 and TIMP2, activated by mechanical stretch.