Guo-Zhong Ji

Should We Standardize the 1,700-Year-Old Fecal Microbiota Transplantation?

To the Editor: We reviewed the multicenter long-term follow-up study using the fecal microbiota transplantation (FMT) for recurrent Clostridium diffi cile infection by Brandt group ( 1 ). Th e study demonstrated effi cacy with 91 % primary cure rate and 98 % secondary cure rate. Th e results further showed that 97 % patients expressed willingness to undergo another FMT in the future, and 53 % stated that they would choose FMT as a fi rst-line treatment before antibiotics. We believe the transplanted feces from a healthy donor can possibly preserve 1,000 – 1,150 functional bacteria species ( 2 ) and can eventually re-establish a “ healthy ” functional microbiota in the recipient. However, we think that the effi cacy and willingness of patients are not enough to invite wider practice unless there is a standardized methodology for fecal preparation and administration. Th e concept of FMT is not new in the English literature. Brandt et al. ( 1 ) and Borody et al. ( 3 ) noted that this idea was possibly fi rst used in veterinary medicine by the Italian anatomist Fabricius Aquapendente in the 17th century. However, we report much earlier literary evidence of human fecal transplantation. During the Dong-jin dynasty in the 4th century in China, Ge Hong, a well-known traditional Chinese medicine doctor, described the use of human fecal suspension by mouth for patients who had food poisoning or severe diarrhea. Th is yielded positive results and was considered a medical miracle that brought patients back from brink of death. 2 . Qin J , Li R , Raes J et al. A human gut microbial gene catalogue established by metagenomic sequencing . Nature 2010 ; 464 : 59 – 65 . 3 . Borody TJ , Warren EF , Leis SM et al. Bacteriotherapy using fecal fl ora: toying with human motions . J Clin Gastroenterol 2004 ; 38 : 475 – 83 . 4 . Ge H (Dongjin Dynasty). Zhou Hou Bei Ji Fang . Tianjin Science & Technology Press: Tianjin , 2000 . 5 . Li S (Ming Dynasty). Ben Cao Gang Mu . Huaxia Press: Beijing , 2011 . 6 . Borody TJ , Khoruts A . Fecal microbiota transplantation and emerging applications . Nat Rev Gastroenterol Hepatol 2011 ; 9 : 88 – 96 .

Fecal microbiota transplantation for severe enterocolonic fistulizing Crohn's disease.

The concept of fecal microbiota transplantation (FMT) has been used in traditional Chinese medicine at least since the 4(th) century. Evidence from recent human studies strongly supports the link between intestinal bacteria and inflammatory bowel disease. We proposed that standardized FMT might be a promising rescue therapy for refractory inflammatory bowel disease. However, there were no reports of FMT used in patients with severe Crohns disease (CD). Here, we report the successful treatment of standardized FMT as a rescue therapy for a case of refractory CD complicated with fistula, residual Barium sulfate and formation of intraperitoneal large inflammatory mass. As far as we know, this is the first case of severe CD treated using FMT through mid-gut.

Association between body mass index and erosive esophagitis: A meta-analysis

AIM To conduct a meta-analysis to estimate the determinants of the association between erosive esophagitis (EE) and body mass index (BMI). METHODS We identified the studies using PubMed. Studies were selected for analysis based on certain inclusion and exclusion criteria. Data were extracted from each study on the basis of predefined items. Meta-analyses were performed to verify the risk factors, such as obesity and gender. RESULTS Twenty-one studies were included in this systematic review. These studies demonstrated an association between increasing BMI and the presence of EE [95% confidence interval (CI): 1.35-1.88, overweight, odds ratio (OR) = 1.60, P value homogeneity = 0.003, 95% CI: 1.65-2.55, obese, OR = 2.05, P < 0.01]. The heterogeneity disappeared by stratifying for gender. No publication bias was observed in this meta-analysis by the Egger method. CONCLUSION This analysis demonstrates a positive association between BMI and the presence of EE, especially in males. The risk seems to progressively increase with increasing weight.

A 10-Year Retrospective Analysis of Clinical Profiles, Laboratory Characteristics and Management of Pyogenic Liver Abscesses in a Chinese Hospital

Background/Aims Pyogenic liver abscess (PLA) is a serious, life threatening condition with a high mortality rate that represents a diagnostic and therapeutic challenge. The aim of this study was to collect demographic data and clinical, laboratory and microbiological characteristics of PLA patients treated between 2000 and 2010. We also aimed to collect information regarding our management experience of these cases. Methods As a retrospective review, 47 patients with PLA in a tertiary referral center were examined to determine their demographic characteristics, clinical features, and laboratory, imaging, and microbiologic findings as well as the treatment outcome. Results Cryptogenic PLA was the most frequently identified type of PLA, while benign biliary tract disease was the most frequently identifiable cause of PLA (18/47 patients; 38.3%). Leukocytosis and elevated alanine transaminase were common laboratory findings and were observed in 35 (74.5%) and 22 (46.8%) patients, respectively. Increased fibrinogen was also detected in 11 of 15 investigated cases (73.3%). Notably, infection-induced thrombocytopenia occurred in 8 patients (17%). Diabetes mellitus was associated with the occurrence of infection induced shock when compared to the non-diabetic group (p<0.05). Patients with two or more comorbid diseases had longer hospitalizations when compared to patients with one comorbid disease or those without comorbidities (p<0.001). The number of days needed to establish diagnosis was correlated with the length of hospitalization (p<0.001). The overall hospital mortality rate was 2.1% (1/47). Conclusions Characteristics of PLA patients from the past 10 years are presented. The number of days needed to establish a PLA diagnosis was correlated with the length of the hospital stay. The hospital stay of PLA patients can be further improved by early diagnosis and effective treatments during the early stages of PLA progression.

Fascin and cortactin expression is correlated with a poor prognosis in hepatocellular carcinoma.

Objectives The aim of this study was to investigate the relationship between fascin and cortactin protein expression and clinicopathological parameters and survival time in patients with hepatocellular carcinoma (HCC). Methods A total of 77 specimens of HCC and seven specimens of normal liver tissues were collected. The expressions of fascin and cortactin were examined by immunohistochemical staining. The patients from whom the HCCs were taken were also followed up. In these 74 patients, Kaplan–Meier was used to assess survival outcomes. Results The data revealed that fascin and cortactin expressions were upregulated in the HCC samples. The positive expression of fascin significantly correlated with histological differentiation and metastasis. The positive expression of cortactin significantly correlated with histological differentiation, metastasis, and T stage (International Union Against Cancer). Survival time of the patients with positive fascin expression and positive cortactin expression was significantly decreased, and the median survival duration was short. Conclusion Fascin and cortactin might be important indicators of the malignancy and metastasis of liver cancer, and may have predictive value in the prognosis of HCC.

Endoscopic transpancreatic septotomy as a precutting technique for difficult bile duct cannulation

AIM To evaluate the technique of transpancreatic septotomy (TS) for cannulating inaccessible common bile ducts in endoscopic retrograde cholangiopancreatography (ERCP). METHODS Between May 2012 and April 2013, 1074 patients were referred to our department for ERCP. We excluded 15 patients with previous Billroth II gastrectomy, Roux-en-Y anastomosis, duodenal stenosis, or duodenal papilla tumor. Among 1059 patients who underwent ERCP, there were 163 patients with difficult bile duct cannulation. Pancreatic guidewire or pancreatic duct plastic stent assistance allowed for successful ERCP completion in 94 patients. We retrospectively analyzed clinical data from 69 failed patients (36 transpancreatic septotomies and 33 needle-knife sphincterotomies). RESULTS Of the 69 patients who underwent precut papillotomy, common bile duct cannulation was successfully achieved in 67. The success rates in the TS and needle knife sphincterotomy (NKS) groups were 97.2% (35/36) and 96.9% (32/33), respectively, which were not significantly different (P > 0.05). Complications occurred in 11 cases, including acute pancreatitis (n = 6), bleeding (n = 2), and cholangitis (n = 3). The total frequency of complications in the TS group was lower than that in the NKS group (8.3% vs 24.2%, P < 0.05). CONCLUSION Pancreatic guidewire or pancreatic duct plastic stent assistance improves the success rate of selective bile duct cannulation in ERCP. TS and NKS markedly improve the success rate of selective bile duct cannulation in ERCP. TS precut is safer as compared with NKS.

Fecal microbiota transplantation and prednisone for severe eosinophilic gastroenteritis

Eosinophilic gastroenteritis is a rare disease of unknown etiology. It is characterized by patchy or diffuse eosinophilic infiltration of the bowel wall to a variable depth and various gastrointestinal manifestations. We describe a case of severe eosinophilic gastroenteritis presenting as frequent bowel obstruction and diarrhea in a 35-year-old man. The patient was misdiagnosed and underwent surgery because of intestinal obstruction when he was first admitted to a local hospital. Then he was misdiagnosed as having Crohns disease in another university teaching hospital. Finally, the patient asked for further treatment from our hospital because of the on-going clinical trial for treating refractory Crohns disease by fecal microbiota transplantation. Physical examination revealed a slight distended abdomen with diffuse tenderness. Laboratory investigation showed the total number of normal leukocytes with neutrophilia as 90.5%, as well as eosinopenia, monocytopenia and lymphocytopenia. Barium radiography and sigmoidoscopy confirmed inflammatory stenosis of the sigmoid colon. We diagnosed the patient as having eosinophilic gastroenteritis by multi-examinations. The patient was treated by fecal microbiota transplantation combined with oral prednisone, and was free from gastrointestinal symptoms at the time when we reported his disease. This case highlights the importance of awareness of manifestations of a rare disease like eosinophilic gastroenteritis.

Expression of klotho and β-catenin in esophageal squamous cell carcinoma, and their clinicopathological and prognostic significance

Esophageal carcinoma is one of the most common types of cancers in the world; the molecular mechanism underlying its tumorigenesis is still not well understood. This study was aimed at investigating the expression of klotho and β-catenin in patients with esophageal squamous cell carcinoma (ESCC) and analyzing their association with clinicopathological variables and their effects on prognosis. The expression patterns of klotho and β-catenin were determined by tissue microarray and immunohistochemical technique in ESCC and normal tissues, and their correlations with clinicopathological characteristics were investigated using univariate and multivariate analysis. The serum klotho levels in 40 ESCC patients and controls were measured by sandwich enzyme-linked immunosorbent assay system (ELISA). The expression level of klotho was significantly lower in ESCC than in the adjacent noncancerous tissues (30 vs. 50%, P < 0.000), and the protein level was negative correlated with clinical staging, histological grade, lymph node metastasis, and invasion depth (P < 0.05). Whereas, the expression of β-catenin was much higher in ESCC than their corresponding normal mucosa tissues (78.3 vs. 11.5%, P < 0.000), and the level of protein correlated only with histological grade and invasion depth (P < 0.05). Correlation analysis showed the expression level of klotho inversely correlated with that of β-catenin (r = -0.214, P < 0.01). Patients with klotho-positive tumors had longer survival than those with klotho-negative tumors (P < 0.01). Cox proportional hazards model analysis demonstrated that positive expression of klotho was an important factor indicating good prognosis (hazard ratio, 0.371; 95% confidence interval, 0.201-0.685; P < 0.01). ELISA showed that the level of serum klotho was markedly higher (461.50 ± 43.30 pg/mL) than control group (239.37 ± 20.65 pg/mL) (P < 0.001). Receiver operating characteristic analysis gave a cut-off value of 327.031 of serum klotho with a sensitivity of 81.3% and specificity of 81.2% (P < 0.000). Our present study demonstrated for the first time that klotho might be a novel biomarker candidate for predicting progression and prognosis in patients with ESCC.

MYH rs3219476 and rs3219472 polymorphisms and risk of cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a rare but devastating malignancy. Up to 90% of patients presenting with CCA have no identifiable risk factors. The base excision repair (BER) pathway has a principal role in the repair of mutations caused by oxidized or reduced bases. The MutY homolog (MUTYH, MYH) is one of the key proteins in the BER pathway, but the role of MYH in the tumorigenesis of CCA is largely unknown. In this study, we investigated the influence of MYH rs3219476 and rs3219472 polymorphisms on CCA incidence. MYH genotypes were detected using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. We found that for rs3219472, compared with subjects carrying the MYH G/G genotype, those with the A/A genotype had a 2.816-fold higher risk of CCA [odds ratio (OR)=2.816, 95% confidence interval (CI)=0.992-7.999, P=0.047). For rs3219476, compared with subjects carrying the MYH T/T genotype, those with the T/G genotype had a reduced risk of CCA (OR=0.359, 95% CI=0.17-0.758, P=0.006). Our findings suggest that since significantly increased CCA risk was found in individuals with a homozygous variant genotype for rs3219472, it may be a biomarker for screening individuals at high risk of developing the disease.

Lentiviral-mediated Smad4 RNAi promotes SMMC-7721 cell migration by regulation of MMP-2, VEGF and MAPK signaling

Hepatocellular carcinoma (HCC) is a highly malignant cancer characterized by rapid progression, easy metastasis and frequent recurrence. Previous studies have shown that the Smad4 signaling pathway plays an important role in the cell growth and apoptosis of HCC. However, the effect of Smad4 signaling on the invasion and migration of HCC cells remains unclear. The present study aimed to examine the effects of the transforming growth factor (TGF)-β1-Smad4 signaling pathway on the migration of HCC cells. Lentiviral vectors expressing miRNA against Smad4 were constructed to block the expression of Smad4 in HCC cells, and transwell units were used to investigate the invasive potential of SMMC-7721 cells before and after TGF-β1 treatment. mRNA levels of matrix metalloproteinase (MMP)-2 and -9 were analyzed by reverse-transcription PCR, and concentrations of vascular endothelial growth factor (VEGF), p-JNK, p-p38 and p-Erk1/2 proteins were analyzed by Western blotting. The results indicate that TGF-β1 induced cellular invasion in the SMMC-7721 cells. These effects were almost completely blocked by the knockdown of Smad4. Reverse-transcription PCR and Western blot analysis revealed that MMP-2, VEGF, p-JNK and p-p38 were up-regulated by the silencing of Smad4, while the expression of MMP-9 and p-Erk1/2 was not affected by Smad4 silencing with or without TGF-β1 stimulation. These findings suggest that TGF-β1-induced SMMC-7721 cell invasion by the up-regulation of MMP-2 and VEGF is Smad4-dependent. The activation of MMP-2 and VEGF may be an important mechanism by which Smad4 is involved in metastasis. TGF-β1-Smad4 signaling may regulate SMMC-7721 cell migration through the activation of the MAPK pathway.