Junsheng Peng

The effects of perioperative probiotic treatment on serum zonulin concentration and subsequent postoperative infectious complications after colorectal cancer surgery: a double-center and double-blind randomized clinical trial

BACKGROUND Zonulin is a newly discovered protein that has an important role in the regulation of intestinal permeability. Our previous study showed that probiotics can decrease the rate of infectious complications in patients undergoing colectomy for colorectal cancer. OBJECTIVE The objective was to determine the effects of the perioperative administration of probiotics on serum zonulin concentrations and the subsequent effect on postoperative infectious complications in patients undergoing colorectal surgery. DESIGN A total of 150 patients with colorectal carcinoma were randomly assigned to the control group (n = 75), which received placebo, or the probiotics group (n = 75). Both the probiotics and placebo were given orally for 6 d preoperatively and 10 d postoperatively. Outcomes were measured by assessing bacterial translocation, postoperative intestinal permeability, serum zonulin concentrations, duration of postoperative pyrexia, and cumulative duration of antibiotic therapy. The postoperative infection rate, the positive rate of blood microbial DNA, and the incidence of postoperative infectious complications-including septicemia, central line infection, pneumonia, urinary tract infection, and diarrhea-were also assessed. RESULTS The infection rate was lower in the probiotics group than in the control group (P < 0.05). Probiotics decreased the serum zonulin concentration (P < 0.001), duration of postoperative pyrexia, duration of antibiotic therapy, and rate of postoperative infectious complications (all P < 0.05). The p38 mitogen-activated protein kinase signaling pathway was inhibited by probiotics. CONCLUSIONS Perioperative probiotic treatment can reduce the rate of postoperative septicemia and is associated with reduced serum zonulin concentrations in patients undergoing colectomy. We propose a clinical regulatory model that might explain this association. This trial was registered at http://www.chictr.org/en/ as ChiCTR-TRC-00000423.

Modified FOLFOX6 With or Without Radiation Versus Fluorouracil and Leucovorin With Radiation in Neoadjuvant Treatment of Locally Advanced Rectal Cancer: Initial Results of the Chinese FOWARC Multicenter, Open-Label, Randomized Three-Arm Phase III Trial

PURPOSE Total mesorectal excision with fluorouracil-based preoperative chemoradiotherapy and postoperative chemotherapy is a standard treatment of locally advanced rectal cancer. This study investigated the addition of oxaliplatin with and without preoperative radiotherapy. METHODS In this multicenter, open-label, phase III trial, we randomly assigned (1:1:1) Chinese adults (age 18 to 75 years) with locally advanced stage II/III rectal cancer to three treatments: five 2-week cycles of infusional fluorouracil (leucovorin 400 mg/m(2), fluorouracil 400 mg/m(2), and fluorouracil 2.4 g/m(2) over 48 h) plus radiotherapy (46.0 to 50.4 Gy delivered in 23 to 25 fractions during cycles 2 through 4) followed by surgery and seven cycles of infusional fluorouracil, the same treatment plus intravenous oxaliplatin 85 mg/m(2) on day 1 of each cycle (modified FOLFOX6 [mFOLFOX6]), or four to six cycles of mFOLFOX6 followed by surgery and six to eight cycles of mFOLFOX6. Random assignment was performed by using computer-generated block randomization codes. The primary end point was 3-year disease-free survival. Secondary end points of histopathologic response and toxicity are reported. RESULTS A total of 495 patients were enrolled from June 2010 to February 2015; 475 were evaluable (fluorouracil-radiotherapy, n = 155; mFOLFOX6-radiotherapy, n = 157; mFOLFOX6, n = 163). In the fluorouracil-radiotherapy, mFOLFOX6-radiotherapy, and mFOLFOX6 groups, the rate of pathologic complete response (pCR) was 14.0%, 27.5%, and 6.6%, and downstaging (ypStage 0 to 1) was achieved by 37.1%, 56.4%, and 35.5% of patients, respectively. Higher toxicity and more postoperative complications were observed in patients who received radiotherapy. CONCLUSION mFOLFOX6-based preoperative chemoradiotherapy results in a higher pCR rate than fluorouracil-based treatment. Perioperative mFOLFOX6 alone had inferior results and a lower pCR rate than chemoradiotherapy but led to a similar downstaging rate as fluorouracil-radiotherapy, with less toxicity and fewer postoperative complications.

Simultaneous Liver and Colorectal Resections Are Safe for Synchronous Colorectal Liver Metastases

BackgroundHepatic resection (HR) is the only option offering a potential cure for patients with synchronous colorectal cancer liver metastases (SCRLM). The optimal timing of HR for SCRLM is still controversial. This study aimed to determine whether simultaneous HR is similar to staged resection regarding the morbidity and mortality rates in patients with SCRLM.MethodsFour hundred and five consecutive patients with SCRLM were treated with either simultaneous (n = 129) or staged (n = 276) HR. The postoperative complications were analyzed retrospectively according to the documented records and hepatectomy databases at the Gastrointestinal Institute.ResultsPerioperative morbidity and mortality did not differ between simultaneous resections and staged resections for selected patients with SCRLM (morbidity, 47.3% versus 54.3%; mortality, 1.5% versus 2.0%, respectively; both p > 0.05). Simultaneous liver resections of three or more segments would not increase the rate of complications compared to staged resections (56.8% and 42.4%, respectively; p = 0.119). Meanwhile, patients with simultaneous resections experienced shorter duration of surgery and postoperative hospitalization time as well as less blood loss during surgery (all p < 0.05).ConclusionsSimultaneous resections of colorectal cancer primary lesions and hepatic metastases were safe and could serve as a primary option for selected SCRLM patients.

Botulinum toxin injection versus lateral internal sphincterotomy for chronic anal fissure: a meta-analysis of randomized control trials.

BackgroundAlthough surgery is the gold standard treatment for anal fissure, the main concern remains its side effects and complications. Botulinum toxin injection and lateral internal sphincterotomy are technical options for patients suffering from chronic anal fissure. However, little is known about the efficacy of these two techniques. The aim of this meta-analysis was to compare the outcomes of botulinum toxin injection versus lateral internal sphincterotomy for chronic anal fissure.MethodsOriginal studies in English were searched from the MEDLINE database, PubMed, Web of Science, and the Cochrane Library database. Randomized control trials that compared botulinum toxin injection with lateral internal sphincterotomy were identified. Data were independently extracted for each study, and a meta-analysis was performed using fixed and random effects models.ResultsFour hundred and eighty-nine patients from seven trials met the inclusion criteria. Patients undergoing lateral internal sphincterotomy had a higher-healing and incontinence rate. No statistically significant differences were noted in total complications between botulinum toxin injection and lateral internal sphincterotomy. Patients treated with lateral internal sphincterotomy had a significantly lower recurrence rate than the patients treated with botulinum toxin injection.ConclusionsOur meta-analysis shows that lateral internal sphincterotomy was superior to botulinum toxin injection in terms of healing rate and lower recurrence rate. Botox, however, is safe associated with a lower rate of incontinence and could be used in certain situations. Further studies with a long-term follow-up are required to confirm our observations.

Neoadjuvant chemotherapy for gastric cancer: A meta‐analysis of randomized, controlled trials

Although the effect of neoadjuvant chemotherapy in gastric cancer has been extensively studied, the data of survival benefit are still controversial. The purpose of this work was to assess the effectiveness of neoadjuvant chemotherapy followed by surgery in patients with gastric cancer.

Clinicopathologic Characteristics and Outcomes of Patients with Obstructive Colorectal Cancer

PurposeThe aim of this retrospective study was to analyze the clinicopathologic characteristics and short-term and long-term outcomes of colorectal cancer patients with obstruction compared to those of non-obstructive colorectal cancer patients.MethodsBetween January 1998 and December 2005, 1,672 colorectal cancer patients undergoing operation were enrolled in this study. Patients were classified into two groups according to the presentation: patients with complete obstructive colorectal cancer (COC, n = 215) receiving emergency procedures and patients with non-obstructive colorectal cancer (NOC, n = 1,457) receiving elective procedures. The data on the clinicopathologic characteristics and short-term and long-term outcomes of patients were analyzed retrospectively.ResultsAmong 1,672 colorectal cancer patients, 215 cases presented with complete obstruction. The distribution of tumor location and size, macroscopic type, depth of invasion, liver metastasis, peritoneal carcinomatosis, and TNM stage were found to be different between the COC and NOC groups. Logistic regression analysis showed that tumor location, depth of invasion, and peritoneal carcinomatosis were independent factors associated with obstruction. Patients with obstruction had an increased risk of death by a factor of 2.251 compared to patients without obstruction. Peritoneal carcinomatosis and TNM stage were independent factors for the survival of the COC group. Obstruction, peritoneal carcinomatosis, tumor macroscopic type, and TNM stage were independent indicators for postoperative recurrence. Postoperative mortality was significantly higher in the COC group than the NOC group. The overall 5- and 10-year survival rates in the COC group were 47.8% and 42.8%, respectively, compared to 67.2% and 59.8% in the NOC group, respectively (p < 0.05). The postoperative recurrence rates were 43.1% in the COC group and 32.8% in the NOC group (p < 0.05).ConclusionsObstruction is an independent indicator for the survival and postoperative recurrence for patients with colorectal cancer. Patients in the COC group have worse overall survival with high postoperative recurrence rate compared to those in the NOC group.

Identification of cancer-associated proteins by proteomics and downregulation of β-tropomyosin expression in colorectal adenoma and cancer

Elucidating the molecular mechanism underlying the development of adenoma, the major precursor lesion of colorectal cancer (CRC), would provide a basis for early detection, prevention as well as treatment of CRC. Using the highly sensitive 2‐D DIGE method coupled with MS, we identified 24 differentially expressed proteins in adenoma tissues compared with matched normal colonic mucosa and CRC tissues. Fifteen proteins were downregulated and three proteins were upregulated in adenoma tissues when compared with individual‐matched normal colonic mucosa. Five proteins were downregulated, while one protein was upregulated in adenoma tissues when compared with matched CRC tissues. A protein, β‐tropomyosin (TM‐β), recently suggested to be a biomarker of esophageal squamous carcinoma, was downregulated in both adenoma and CRC tissues. Additionally, the reduction in the level of TM‐β in adenoma and CRC tissues was further validated by Western blotting (p<0.05) and RT‐PCR (p<0.001). Our findings suggest that downregulation of TM‐β is involved in the early development of CRC and that differentially expressed proteins might serve as potential biomarkers for detection of CRC.

Ligasure versus stapled hemorrhoidectomy in the treatment of hemorrhoids: a meta-analysis of randomized control trials.

The aim of this meta-analysis was to compare the outcomes of Ligasure hemorrhoidectomy and stapled hemorrhoidectomy for prolapsed hemorrhoids. Original studies in any language were searched from MEDLINE database, PubMed, Web of science and the Cochrane Library database, and Wangfang database. Randomized control trials that compared Ligasure hemorrhoidectomy with stapled hemorrhoidectomy were identified. Data were extracted independently for each study, and a meta-analysis was performed using fixed and random-effects models. Five trials including 397 patients met the inclusion criteria. Patients treated with Ligasure had a significantly shorter operative time compared with patients who underwent stapler techniques. The recurrence rate was higher in patients who underwent stapled hemorrhoidectomy. No statistically significant differences were observed in postoperative bleeding, urinary retention, difficult defecating, anal fissure, anal stenosis, incontinence, postoperative pain, return to normal activities, and hospital stay. Our meta-analysis shows that Ligasure is an effective instrument for hemorrhoidectomy, which results in shorter operation time and lower recurrence rate.

Epigenetic Inactivation and Tumor-Suppressor Behavior of NGFR in Human Colorectal Cancer

The nerve growth factor receptor (NGFR/p75) is a potential tumor suppressor, but its role in colorectal cancer is unknown. Here, the hypermethylation status, biologic function, and clinical relevance were determined for p75NGFR in colorectal cancer. The methylation status and expression of p75NGFR were assessed in colorectal cancer cell lines and clinical tissues by bisulfite genomic sequencing (BGS), qRT-PCR, and immunoblot assay. Methylation of p75NGFR was frequently found in colorectal cancer, leading to its silencing or downregulation, and it was effectively restored by a demethylation agent. The overexpression of p75NGFR in multiple colorectal cancer cell model systems significantly inhibited cell proliferation (concomitant with G1-phase arrest), invasion, and colony formation and induced cell apoptosis. In contrast, p75NGFR knockdown significantly promoted proliferative and invasive phenotypes. Importantly, p75NGFR methylation was observed in the majority of primary colorectal cancer specimens and was associated with histologic grade and preoperative serum CA19-9 levels. Multivariate analysis indicated that patients who lack p75NGFR have reduced overall survival (64% vs. 75%, P = 0.028) and disease-free survival (61% vs. 72%, P = 0.034) compared with p75NGFR-positive patients. In conclusion, p75NGFR is predominantly silenced or downregulated in colorectal cancer, and its biologic activities are consistent with it being a relevant tumor suppressor. Implications: p75NGFR is a candidate tumor suppressor and has independent prognostic potential in colorectal cancer. Mol Cancer Res; 13(1); 107–19. ©2014 AACR.

Levels of human replication factor C4, a clamp loader, correlate with tumor progression and predict the prognosis for colorectal cancer

BackgroundHuman replication factor C4 (RFC4) is involved in DNA replication as a clamp loader and is aberrantly regulated across a range of cancers. The current study aimed to investigate the function of RFC4 in colorectal cancer (CRC).MethodsThe mRNA levels of RFC4 were assessed in 30 paired primary CRC tissues and matched normal colonic tissues by quantitative PCR. The protein expression levels of RFC4 were evaluated by western blotting (n = 16) and immunohistochemistry (IHC; n = 49), respectively. Clinicopathological features and survival data were correlated with the expression of RFC4 by IHC analysis in a tissue microarray comprising 331 surgically resected CRC. The impact of RFC4 on cell proliferation and the cell cycle was assessed using CRC cell lines.ResultsRFC4 expression was significantly increased in CRC specimens as compared to adjacent normal colonic tissues (P <0.05). High levels of RFC4, determined on a tissue microarray, were significantly associated with differentiation, an advanced stage by the Tumor-Node-Metastasis (TNM) staging system, and a poor prognosis, as compared to low levels of expression (P <0.05). However, in multivariate analysis, RFC4 was not an independent predictor of poor survival for CRC. In vitro studies, the loss of RFC4 suppressed CRC cell proliferation and induced S-phase cell cycle arrest.ConclusionRFC4 is frequently overexpressed in CRC, and is associated with tumor progression and worse survival outcome. This might be attributed to the regulation of CRC cell proliferation and cell cycle arrest by RFC4.