Monotropein Induced Apoptosis and Suppressed Cell Cycle Progression in Colorectal Cancer Cells.

OBJECTIVE: To determine whether monotropein has an anticancer effect and explore its potential mechanisms against colorectal cancer (CRC) through network pharmacology and molecular docking combined with experimental verification. METHODS: Network pharmacology and molecular docking were used to predict potential targets of monotropein against CRC. Cell counting kit assay, plate monoclonal assay and microscopic observation were used to investigate the antiproliferative effects of monotropein on CRC cells HCT116, HT29 and LoVo. Flow cytometry and scratch assay were used to analyze apoptosis and cell cycle, as well as cell migration, respectively in HCT116, HT29, and LoVo cells. Western blotting was used to detect the expression of proteins related to apoptosis, cell cycle, and cell migration, and the expression of proteins key to the Akt pathway. RESULTS: The Gene Ontology and Reactome enrichment analyses indicated that the anticancer potential of monotropein against CRC might be involved in multiple cancer-related signaling pathways. Among these pathways, RAC-beta serine/threonine-protein kinase (Akt1, Akt2), cyclin-dependent kinase 6 (CDK6), matrix metalloproteinase-9 (MMP9), epidermal growth factor receptor (EGFR), cell division control protein 42 homolog (CDC42) were shown as the potential anticancer targets of monotropein against CRC. Molecular docking suggested that monotropein may interact with the 6 targets (Akt1, Akt2, CDK6, MMP9, EGFR, CDC42). Subsequently, cell activity of HCT116, HT29 and LoVo cell lines were significantly suppressed by monotropein (P<0.05). Furthermore, our research revealed that monotropein induced cell apoptosis by inhibiting Bcl-2 and increasing Bax, induced G1-S cycle arrest in colorectal cancer by decreasing the expressions of CyclinD1, CDK4 and CDK6, inhibited cell migration by suppressing the expressions of CDC42 and MMP9 (P<0.05), and might play an anticancer role through Akt signaling pathway. CONCLUSION: Monotropein exerts its antitumor effects primarily by arresting the cell cycle, causing cell apoptosis, and inhibiting cell migration. This indicates a high potential for developing novel medication for treating CRC.

Comparison of Gut Microbiome in Human Colorectal Cancer in Paired Tumor and Adjacent Normal Tissues.

BACKGROUND: To understand the biological effect of gut microbiome on the progression of colorectal cancer (CRC), we sequenced the V3-V4 region of the 16S rRNA gene to illustrate the overall structure of microbiota in the CRC patients. METHODS: In this study, a total of 66 CRC patients were dichotomized into different groups based on the following characteristics: paired tumor and adjacent normal tissues, distal and proximal CRC segments, MMR (-) and MMR (+), different TNM staging and clinic tumor staging. RESULTS: By sequencing and comparing the microbial assemblages, our results indicated that 7 microbe genus (Fusobacterium, Faecalibacterium, Akkermansia, Ruminococcus2, Parabacteroides, Streptococcus, and f_Ruminococcaceae) were significantly different between tumor and adjacent normal tissues; and 5 microbe genus (Bacteroides, Fusobacterium, Faecalibacterium, Parabacteroides, and Ruminococcus2) were significantly different between distal and proximal CRC segments; only 2 microbe genus (f_Enterobacteriaceae and Granulicatella) were significantly different between MMR (-) and MMR (+); but there was no significant microbial difference were detected neither in the TNM staging nor in the clinic tumor staging. CONCLUSION: All these findings implied a better understanding of the alteration in the gut microbiome, which may offer new insight into diagnosing and therapying for CRC patients.

A study of using carbon nanoparticles to improve lymph nodes staging for laparoscopic-assisted radical right hemicolectomy in colon cancer.

PURPOSE: This study aimed to analyze and evaluate the feasibility of using carbon nanoparticles (CNs) to track lymph nodes (LNs) metastases in right colon tumors, especially for patients who underwent laparoscopic-assisted radical right hemicolectomy. METHOD: A total of 99 patients were enrolled in this retrospective study between November 2015 and September 2017 (control group n = 47). One day before surgery, 1 ml of CNs suspension was injected into the submucosal layer around the site of the primary lesions by colonoscopy. Then complete mesocolic excision (CME) of laparoscopic right hemicolectomy was performed. CNs-stained LNs were identified and counted from all dissected LNs after surgery. RESULTS: The dates showed that the number of total harvested LNs and the number of positive patients in the experimental group increased significantly compared with the control group (respectively, P < 0.01 and P < 0.05). The increase of positive percentage shifted some patients toward higher stage, although the total number of positive LNs changed a little bit. In addition, the duration for pathologist to dissect LNs became shorter (26.4 vs. 31.1 min, P < 0.05). CONCLUSION: Therefore, the CNs are not only a good tattoo in laparoscopic-assisted operation, but could be regarded as a better pathological evaluating tool for tumor treatment.

Complete mesocolic excision in right hemicolectomy: comparison between hand-assisted laparoscopic and open approaches.

PURPOSE: To demonstrate the feasibility, safety, and technical strategies of hand-assisted laparoscopic complete mesocolic excision (HAL-CME) and to compare oncological outcomes between HAL-CME and the open approach (O-CME) for right colon cancers. METHODS: Patients who were scheduled to undergo a right hemicolectomy were divided into HAL-CME and O-CME groups. Measured outcomes included demographic variables, perioperative parameters, and follow-up data. Demographic variables included age, sex distribution, body mass index (BMI), American Society of Anesthesiologists (ASA) physical status classification, previous abdominal surgery, tumor localization, and potential comorbidities. Perioperative parameters included incision length, operative time, blood loss, conversion rate, postoperative pain score, postoperative first passage of flatus, duration of hospital stay, total cost, number of lymph nodes retrieved, TNM classification, and postoperative complications. Follow-up data included follow-up time, use of chemotherapy, local recurrence rate, distant metastasis rate, and short-term survival rate. RESULTS: In total, 150 patients (HAL-CME, 78; O-CME, 72) were included. The groups were similar in age, sex distribution, BMI, ASA classification, history of previous abdominal surgeries, tumor localization, and potential comorbidities. Patients in the HAL-CME group had shorter incision lengths, longer operative times, less operative blood loss, lower pain scores, earlier first passage of flatus, shorter hospital stay, higher total costs, similar numbers of lymph nodes retrieved, similar TNM classifications, and a comparable incidence of postoperative complications. The 2 groups were also similar in local recurrence rate, distant metastasis rate, and short-term survival rate. CONCLUSION: The results demonstrate that the HAL-CME procedure is a safe, valid, and feasible surgical method for right hemicolon cancers.

A Modified Spontaneously Closed Defunctioning Tube Ileostomy After Anterior Resection of the Rectum for Rectal Cancer with a Low Colorectal Anastomosis.

The aim of this study is to introduce a new technique of modified spontaneously closed defunctioning tube ileostomy after anterior resection of the rectum for rectal cancer with a low colorectal anastomosis. Patients with rectal cancer who underwent anterior resection of rectum with a low colorectal anastomosis and chose a modified defunctioning tube ileostomy between March 2012 and August 2013 were retrospectively reviewed. Data on the success of the operation procedures, post-operative hospital stay, and post-operative tube ileostomy-related complications were analyzed. One hundred fifty-two patients (87 males and 65 females; 57.1 ± 17.4 years) undergoing the modified defunctioning tube ileostomy after anterior resection for rectal cancer were included. The post-operative hospital stay was 11.9 ± 3.2 days. The tube was removed on days 22.6 ± 4.1 after operation and the ileostomy wound closed spontaneously within 13.1 ± 1.9 days. Twenty-five patients felt tube-associated pain or discomfort, which was relieved after a period of adaptation and appropriate tube adjustment. Nine patients suffered from tube blockage and were treated successfully with saline irrigation. Two patients had intestinal obstruction, which was resolved with conservative treatment. Three patients developed leakage of the distal anastomosis: two were successfully treated with conservative measures and the other completely recovered after reoperation. The modified spontaneously closed defunctioning tube ileostomy appears efficacious and safe. This technique may be used to protect the distal anastomosis and simultaneously decrease the ileostomy complications, and minimize the morbidity and mortality associated with stoma takedown.

Schwannoma of the colon: A case report and review of the literature.

Colonic schwannomas are rare gastrointestinal mesenchymal tumors, and only a limited number of cases has been reported. The occurrence of these tumors is less common in the large intestine than in the stomach. The present study reports a case of colonic schwannoma in a 62-year-old female patient with no specific symptoms. The patient was diagnosed with a mass in the ascending colon by colonoscopy and abdominal computed tomography scanning. A right hemicolectomy was performed. The postoperative pathological diagnosis was ascending schwannoma. This case is noteworthy as colonic schwannomas are rare and are typically treated as colon cancer. No recurrence of the lesion was observed after 24 months of follow-up.

Multi-stage resection and repair for the treatment of adult giant sacrococcygeal teratoma: A case report and literature review.

Sacrococcygeal teratoma (SCT) is a sacrococcygeal neoplasm derived from more than one primitive germ layer and is only occasionally encountered in adults. The primary treatment for all primary SCTs is surgical excision. The present study reports the case of a giant SCT in a middle-aged female with a history lasting >3 decades. Multi-staged surgical treatment was performed, including ileostomy plus tumor excision, four debridement plus flap repair procedures, and closure of the ileostomy. Follow-up showed improved quality of life without evidence of local recurrence after resection. The study also presents a brief overview of the relevant literature. To the best of our knowledge, this is the first report of multi-staged surgical treatment for giant SCT in an adult patient.

Combined right hemicolectomy and pancreaticoduodenectomy for locally advanced right hemicolon cancer.

Extracolonic invasion of the duodenum and/or pancreatic head rarely occurs in patients with right hemicolon cancer. However, when necessary, combined radical operation is a challenge to the surgeon. We reported 7 patients with locally advanced right hemicolon cancer who underwent combined right hemicolectomy (RH) and pancreaticoduodenectomy (PD) due to direct involvement of the duodenum or pancreatic head. This study included four males and three females with a mean age of 66.9+/-5.9 years. Computed tomography (CT) scans revealed right hemicolon cancer with duodenal invasion (5 patients) and pancreatic invasion (2). The mean operation time was 410+/-64 minutes and the estimated blood loss was 514+/-157 mL. After the operation, the mean postoperative hospital stay was 22.1+/-7.2 days. Five patients had postoperative complications. The mean follow-up time was 16.4+/-5.9 months. During this period, three patients died from tumor recurrence, one from postoperative complications, one from pulmonary disease, and two survived until the last scheduled follow-up. Five patients survived more than one year. Combined RH and PD for locally advanced right hemicolon cancer can be performed safely, thus providing a long-term survival rate in selected patients in a high-volume center.

Comparison of hand-assisted laparoscopy with open total colectomy for slow transit constipation: a retrospective study.

OBJECTIVE: To compare the efficacy and safety of hand-assisted laparoscopic colectomy (HALC) and open colectomy (OC) for patients with slow transit constipation (STC). METHODS: Data of patients with STC who underwent total colectomy from January 2008 to December 2012 were retrospectively reviewed after clinical evaluation and an exclusion of secondary causes. These patients were further divided into the HALC and OC groups. Patients' outcomes, including intraoperative and postoperative data on their recovery and complications were compared between the two groups. RESULTS: A total of 68 patients with STC were finally enrolled in the study, including 32 in the HALC group and 36 in the OC group. The baseline characteristics did not significantly differ between the two groups. Compared with the OC group, patients in the HALC group had a shorter length of incision, a longer operative time and less blood loss volume. There was no conversion to OC for patients undergoing HALC and no intraoperative complications in both groups. Furthermore, after operation, patients in HALC group experienced less pain (3.4 ± 0.7 vs 4.8 ± 1.0), earlier first passage of flatus (58.3 ± 6.3 h vs 73.4 ± 13.0 h), shorter length of postoperative hospital stay (8.8 ± 1.2 days vs 11.3 ± 1.7 days) but higher medical cost (RMB 33 979 ± 3 135 vs RMB 29 828 ± 3 216). The overall postoperative complications and the satisfaction in defecation were comparable in the two groups. CONCLUSION: HALC is a safe, minimally invasive and effective surgical alternative for treating STC, which is comparable to OC.

[Hand-assisted laparoscopic surgery in radical resection of rectal cancer].

OBJECTIVE: To investigate the application experience and clinical effects of hand-assisted laparoscopic radical resection for rectal cancer. METHODS: The clinical data of 156 patients with rectal cancer treated with hand-assisted laparoscopic surgery between August 2009 and April 2011 were analyzed retrospectively. RESULTS: The operative procedures of 156 patients were completed successfully and 1 case was converted to laparotomy (0.6%). The mean operation time was (125 ± 35) minutes; the mean intraoperative blood loss was (118 ± 60) ml; the mean time of bowel function recovery was (60 ± 8) hours; the median postoperative hospital stay was (9.5 ± 2.2) days. The mean number of lymph nodes dissection was (14 ± 5). Five patients (3.2%) had postoperative complications. All the patients were followed up. There had been no local recurrence or trocar site implantation metastasis. CONCLUSION: Hand-assisted laparoscopic surgery approach for the curative resection of rectal cancer is safe and effective and has broad prospects in clinical application.

Hand-assisted laparoscopic versus open right hemicolectomy: short-term outcomes in a single institution from China.

AIM: To compare the perioperative parameters and short-term outcomes of hand-assisted laparoscopic colectomy (HALC) and open colectomy (OC) for the treatment of patients with cancer of the right hemicolon. METHODS: Patients who were scheduled to perform right hemicolectomy between August 2009 and December 2010 were randomized into either HALC or OC group. Patients were excluded if they had synchronous cancers, hepatic metastases, acute intestinal obstruction, or intestinal perforations. All the operations in the 2 groups were performed by a single surgical team. Measured outcomes included the demographic variables and perioperative parameters. The former included age, sex, body mass index, American Society of Anesthesiologists class, prior abdominal surgery, distribution of tumors, and histopathologic stage; whereas the latter included length of incision, operative time, estimated blood loss, conversion rate, number of lymph nodes retrieved, postoperative pain score, time to return of bowel function, postoperative complications, duration of hospital stay, and total cost. RESULTS: One hundred sixteen patients with cancer of the right hemicolon (HALC=59, OC=57) were recruited. The 2 groups of patients were similar in age, sex distribution, body mass index, American Society of Anesthesiologists class, and previous abdominal surgery. No significant difference was observed between the 2 groups in terms of distribution of tumors and the final histopathologic staging. HALC had a significantly shorter incision length and longer operative time than OC. Patients in the HALC group had significantly less operative blood loss, less pain and earlier passage of flatus after operation than those in the OC group. The number of lymph nodes recovered in the specimen and the overall postoperative complications was comparable in the 2 groups. The postoperative duration of hospital stay was significantly shorter in the HALC group, whereas the median overall costs in the HALC group were significantly higher than that in the OC group. CONCLUSIONS: The results from the present study demonstrate that the HALC is a valid surgical approach for cancer of the right hemicolon that retains the benefits of minimally invasive surgery. We believe that this technique is a safe, useful, and feasible method for patients with right-sided colonic cancer. If practiced more, it might be advocated as a "bridge" between traditional laparoscopic surgery and conventional open procedures.

Preventive effects of autologous bone marrow mononuclear cell implantation on intrahepatic ischemic-type biliary lesion in rabbits.

BACKGROUND: The ischemic-type biliary lesion (ITBL) is one of the most serious biliary complications of liver transplantation. This study aimed to investigate the effects of autologous bone marrow mononuclear cell (BM-MNC) implantation on neovascularization and the prevention of intrahepatic ITBL in a rabbit model. METHODS: The rabbits were divided into control, experimental model, and cell implantation groups, with 10 in each group. The model of intrahepatic ITBL was established by clamping the hepatic artery and common bile duct. Autologous BM-MNCs were isolated from the tibial plateau by density gradient centrifugation and were implanted through the common hepatic artery. Changes in such biochemical markers as aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyltranspeptidase, total bilirubin and direct bilirubin were measured. Four weeks after operation, cholangiography, histopathological manifestations, differentiation of BM-MNCs, microvessel density and the expression of vascular endothelial growth factor were assessed. RESULTS: Compared with the experimental model group, the BM-MNC implantation group showed superiority in the time to recover normal biochemistry. The microvessel density and vascular endothelial growth factor expression of the implantation group were significantly higher than those of the control and experimental model groups. The ITBL in the experimental model group was more severe than that in the implantation group and fewer new capillary blood vessels occurred around it. CONCLUSIONS: Implanted autologous BM-MNCs can differentiate into vascular endothelial cells, promote neovascularization and improve the blood supply to the ischemic bile duct, and this provides a new way to diminish or prevent intrahepatic ITBL after liver transplantation.

Autoimmune pancreatitis: report of two cases and literature review.

BACKGROUND: Autoimmune pancreatitis (AIP) is a unique chronic inflammation of the pancreas in which autoimmune mechanisms are involved in the pathogenesis. It is characterized by clinical, histopathological, radiographic, serologic and therapeutic features. Since it was first described in 1995, increasing numbers of AIP patients have been diagnosed. METHODS: In this study, the data from 2 patients with AIP who had elevation of serum immunoglobulin G, positive autoantibody, swelling of the pancreas and narrowing of the main pancreatic duct on imaging were analyzed retrospectively. RESULTS: With the initial diagnosis of AIP, both patients underwent regular prednisone therapy, which was initiated at a dose of 40 mg per day with a tapering schedule of 5 mg every 2 weeks. The patients responded very well to treatment with prednisone. CONCLUSIONS: AIP is a relatively new disease entity. Although it is diagnosed by distinct characteristics of the clinical, radiologic, histopathologic, and serologic findings, many questions require further clarification, including its relationship to other autoimmune diseases and misdiagnosis as pancreaticobiliary malignancies.

Giant hepatobiliary cystadenoma in a male with obvious convex papillate.

Hepatobiliary cystadenoma is an uncommon lesion that is most often found in middle-aged women and difficult to diagnose preoperatively. Here, we report a case of giant hepatobiliary cystadenoma in a male patient with obvious convex papillate. On the basis of imaging examinations, the patient was diagnosed as hepatobiliary cystadenoma prior to operation. Left hepatectomy was performed and the patient was symptom-free during a 6-mo follow-up period, suggesting that imaging examination is the major diagnostic method of hepatobiliary cystadenoma, and operation is its best treatment modality.

Targeted IL-24 gene therapy inhibits cancer recurrence after liver tumor resection by inducing tumor cell apoptosis in nude mice.

BACKGROUND: Interleukin-24 (IL-24) is a novel candidate tumor suppressor that induces tumor cell apoptosis experimentally in a variety of human malignant cells including liver cancer cells. The present study was conducted to investigate the potential effect of recombinant adeno-associated virus (rAAV)-mediated IL-24 gene therapy on tumor recurrence and metastasis by inducing tumor cell apoptosis in a hepatocellular carcinoma (HCC) model in nude mice. METHODS: We established a recurrent and metastatic HCC model in nude mice and constructed an rAAV vector carrying alpha-fetoprotein (AFP) promoter for expressing the IL-24 gene (rAVV/AFP/IL-24). The vector was administered by regional injection (liver incisal margin). AFP was detected by radiation immunoassay. Histological evaluation of tumor recurrence and metastasis was performed for the liver and lung. The effect of tumor cell apoptosis was confirmed by TUNEL analysis. RESULTS: IL-24 gene therapy prevented tumor recurrence and metastasis, as evidenced by marked decreases in the number of metastatic tumor nodules and tumor volume in the liver and lung. At the same time, serum AFP concentration decreased markedly in the IL-24 group compared with the control or rAAV groups (P<0.05). IL-24 gene therapy inhibited tumor recurrence and metastasis as evidenced by the induction of tumor cell apoptosis. CONCLUSION: The results demonstrated that targeted IL-24 gene therapy was effective in the prevention of postoperative recurrence and metastasis in an HCC nude mice model by induction of tumor cells apoptosis with potential minimum tumor burden.

Indocyanine green clearance test and model for end-stage liver disease score of patients with liver cirrhosis.

BACKGROUND: The indocyanine green (ICG) clearance test (clearance rate (K) and retention rate at 15 minutes (R15)) is a sensitive indicator to evaluate liver function. The model for end-stage liver disease (MELD) score has emerged as a useful tool for estimating the mortality of patients awaiting liver transplantation and has recently been validated on patients with liver diseases of various etiologies and severity. In this study, we investigated the correlation between the ICG clearance test and MELD score of patients with liver cirrhosis. METHODS: From June 2007 to March 2008, 52 patients with liver cirrhosis admitted to our center were classified into Child-Pugh class A (8 patients), B (14) and C (30). The ICG clearance test (K value and R15) was performed by ICG pulse spectrophotometry (DDG-3300K), and the MELD scores of patients were calculated. RESULTS: As the Child-Pugh classification of liver function gradually deteriorated, the K value decreased, while R15 and MELD score increased. There were significant statistical differences in K value, R15 and MELD score in patients with different Child-Pugh classifications. Significant correlations were found between the parameters of the ICG clearance test (K value and R15) and MELD score. A negative correlation was observed between K value and MELD score (r=-0.892, P<0.05), while a positive correlation was observed between R15 and MELD score (r=0.804, P<0.05). CONCLUSIONS: The ICG clearance test and MELD score are good parameters for evaluating liver function. Moreover, K value and R15 have significant correlations with MELD score, especially the K value, which may be a convenient and appropriate indicator to evaluate liver function of patients with liver cirrhosis.

Establishment of an animal model of ischemic type intrahepatic biliary lesion in rabbits.

AIM: To explore a method to establish an animal model of ischemic type intrahepatic biliary lesion in rabbits. METHODS: Forty Japanese white rabbits of clean grade were divided randomly into four groups (10 rabbits per group) including sham operation (SO) group, and artery-bile obstruction (ABO)-1 h group, ABO-2 h group and ABO-3 h group. All the rabbits in this study underwent the same initial surgical procedure in which the liver was prepared as for graft removal during liver transplantation. Subsequently in the SO group, no additional vascular intervention was performed, while in groups ABO-1 h, ABO-2 h and ABO-3 h, the animals underwent combined clamping of the hepatic artery and common bile duct with microvascular clips for 1, 2 and 3 h, respectively. After the scheduled occlusion time, the clip was removed to recover blood supply. The animals were killed 4 wk after operation. The survival rate, liver function, cholangiography and histopathological manifestation of the rabbits in each group were observed. RESULTS: The survival rate was 100% in groups SO, ABO-1 h and ABO-2 h, while it was 60% in group ABO-3 h. At each observation time, the change degree of the indexes of liver function was proportional to the clamping time (ABO-3 h > ABO-2 h > ABO-1 h > SO, P < 0.05). Cholangiographical and histopathologic manifestations both showed that intrahepatic biliary lesion aggravated proportionally with the increase of the clamping time. CONCLUSION: An animal model of ischemic type intrahepatic biliary lesion in rabbits is successfully established, which may provide a reliable technique for basic and clinical research into the etiology, development and prophylaxis of ischemic type intrahepatic biliary lesion after liver transplantation.

Laparoscopic cystogastrostomy for the treatment of pancreatic pseudocysts: a case report.

Pancreatic pseudocysts (PPs) are collections of pancreatic secretions that are lined by fibrous tissues and may contain necrotic debris or blood. The interventions including percutaneous, endoscopic or surgical approaches are based on the size, location, symptoms and complications of a pseudocyst. With the availability of advanced imaging systems and cameras, better hemostatic equipments and excellent laparoscopic techniques, most pseudocysts can be found and managed by laparoscopy. We describe a case of a 30-year-old male patient with a pancreatic pseudocyst amenable to laparoscopic cystogastrostomy. An incision was made through the anterior gastric wall to expose the posterior gastric wall in close contact with the pseudocyst using an ultrasonically activated scalpel. Then, another incision was made for cystogastrostomy to obtain complete and unobstructed drainage. The patient recovered well after operation and was symptom-free during a 6-mo follow-up, suggesting that laparoscopic cystogastrostomy is a safe and effective alternative to open cystogastrostomy for minimally invasive management of PPs.