Local excision versus total mesorectal excision for rectal cancer patients with clinical complete or near-complete response after neoadjuvant chemoradiotherapy.

PURPOSE: Local excision is an effective approach for managing rectal cancer exhibiting substantial regression after neoadjuvant chemoradiotherapy. The purpose of this study is to compare the outcomes between local excision and total mesorectal excision in rectal cancer patients achieving clinical complete or near-complete response after neoadjuvant chemoradiotherapy. METHODS: This is a retrospective cohort study that includes a consecutive series of rectal cancer patients who responded well to neoadjuvant chemoradiotherapy followed by surgery. A total of 180 rectal cancer patients at a single institution during a 12-year period are included. The main outcomes include short-term outcomes, oncological outcomes, and functional outcomes between the two groups. RESULTS: A total of 180 patients were included in the study. Sixty-one (33.9%) received local excision and 119 (66.1%) received total mesorectal excision. The baseline characteristics were generally balanced between the two groups. The local excision group demonstrated a significantly shorter operative time, less blood loss, and shorter hospital stay (p < 0.001). 3-year overall survival rates were 97.5% (95% CI, 0.93-1.00) and 95.5% (95% CI, 0.91-1.00) between the two groups (p = 0.38). The local excision group exhibited significantly higher 3-year local recurrence rates 15.7% (95% CI, 0.74-0.97) vs 4.2% (95% CI, 0.92-1.00) (p = 0.017), yet lower 3-year distant metastasis rates 9.6% (95% CI, 0.82-1.00) vs 12.6% (95% CI, 0.81-0.94) (p = 0.33) and lower 3-year disease-free survival rates 76.8% (95% CI, 0.64-0.92) vs 84.7% (95% CI, 0.78-0.92) (p = 0.56) comparing with the total mesorectal excision group. The local excision group demonstrated significantly better functional outcomes compared with the total mesorectal excision group (p < 0.001). CONCLUSION: Patients who achieve either clinical complete or near-complete response after neoadjuvant chemoradiotherapy are suitable candidates for local excision. The local excision group demonstrated superior short-term and functional outcomes, and the oncological outcomes were not compromised.

Effect of Anterograde Lavage via Temporary Loop Ileostoma on the Recovery of Bowel Function in Patients Receiving Stoma Closure: A Retrospective Cohort Study.

BACKGROUND: The effect of anterograde lavage in patients with rectal cancer who underwent anterior resection and plan to receive stoma closure is unclear. OBJECTIVE: This study aimed to investigate the effect of anterograde lavage on postoperative bowel function recovery in patients who underwent temporary loop ileostomy and stoma closure. DESIGN: This was a hospital-based retrospective cohort study. SETTINGS: This study was conducted at a tertiary referral center. PATIENTS: All consecutive patients who underwent anterior resection for rectal cancer and were planning to receive stoma closure from March through December 2019 were included. INTERVENTIONS: The enrolled patients were divided into 2 groups according to whether they received anterograde lavage before stoma closure. MAIN OUTCOME MEASURES: Short-term functional outcomes, including time to first passing of flatus, first defecation time, and recovery time to first meal, were compared between the groups. Secondary outcomes included length of hospital stay, total cost of hospitalization, and postoperative complications. RESULTS: A total of 222 eligible participants were included in the analysis, including 114 in the lavage group and 108 in the nonlavage group. No statistically significant differences were found in age, sex ratio, or distance between the anastomotic line and dentate line. In the lavage group, patients' time to first passing of flatus (38 vs 42 h; p = 0.006), first defecation time (42 vs 48 h; p < 0.001), recovery time to first meal (48 vs 55.5 h; p < 0.001), and length of hospital stay (5 vs 7 d; p < 0.001) were significantly shorter than those in the nonlavage group, and the total cost of hospitalization was significantly lower than that of the nonlavage group (25,000 vs 28,000 RMB; p < 0.001). No significant difference was found in the incidence of postoperative complications between the 2 groups (p = 0.067). LIMITATIONS: This study is limited by its relatively small sample size and retrospective design with single-center participants. CONCLUSIONS: Anterograde lavage before stoma closure is safe and noninvasive. For patients receiving anterior resection and planning to have stoma closure, this procedure can potentially help recover bowel function more rapidly. See Video Abstract at http://links.lww.com/DCR/C51. EFECTO DEL LAVADO ANTERGRADO MEDIANTE ILEOSTOMA TEMPORAL EN ASA SOBRE LA RECUPERACIN DE LA FUNCIN INTESTINAL EN PACIENTES QUE RECIBEN CIERRE DE ESTOMA UN ESTUDIO DE COHORTE RETROSPECTIVO: ANTECEDENTES:No está claro el efecto del lavado anterógrado en pacientes con cáncer de recto con resección anterior que planean recibir el cierre del estoma.OBJETIVO:Investigar el efecto del lavado anterógrado en la recuperación de la función intestinal posoperatoria en pacientes que se sometieron a ileostomía en asa temporal y cierre de estoma.DISEÑO:Estudio de cohorte retrospectivo basado en el hospital.AJUSTES:Centro de referencia terciario.PACIENTES:Todos los pacientes que se sometieron a una resección anterior por cáncer de recto y que planeaban recibir el cierre del estoma desde marzo hasta diciembre de 2019.INTERVENCIONES:Los pacientes inscritos se dividieron en dos grupos según si recibieron lavado anterógrado antes del cierre del estoma.PRINCIPALES MEDIDAS DE RESULTADO:Los resultados funcionales a corto plazo, incluido el tiempo de la primera evacuación de flatos, tiempo de la primera defecación y tiempo de recuperación hasta la primera comida, se compararon entre los grupos. Resultados secundarios incluyeron duración de la estancia hospitalaria, costo total de la hospitalización y complicaciones posoperatorias.RESULTADOS:Se incluyeron en el análisis un total de 222 participantes elegibles, incluidos 114 en el grupo de lavado y 108 en el grupo de no lavado. No hubo diferencias estadísticamente significativas en la edad, la proporción de sexos o la distancia entre la línea de anastomosis y la línea dentada. En el grupo de lavado, el tiempo de la primera evacuación de flatos de los pacientes (38 vs 42 h; p = 0,006), el tiempo de la primera defecación (42 vs 48 h; p < 0,001), el tiempo de recuperación hasta la primera comida (48 vs 55,5 h; p < 0,001) y la duración de la estancia hospitalaria (5 vs 7 días; p < 0,001) fueron significativamente más cortos que los del grupo de no lavado, y el costo total de la hospitalización fue significativamente menor que el del grupo de no lavado (25000 vs 28000 RMB; p < 0,001). No hubo diferencia significativa en la incidencia de complicaciones postoperatorias entre los dos grupos (p = 0,067).LIMITACIONES:Este estudio está limitado por su tamaño de muestra relativamente pequeño y su diseño retrospectivo con participantes de un solo centro.CONCLUSIONES:El lavado anterógrado antes del cierre del estoma es seguro y no invasivo. Para los pacientes que se someten a una resección anterior y planean cerrar el estoma, este procedimiento puede ayudar potencialmente a recuperar la función intestinal más rápidamente. Consulte Video Resumen en http://links.lww.com/DCR/C51. (Traducción-Dr. Francisco M. Abarca-Rendon).

LncRNA CASC21 induces HGH1 to mediate colorectal cancer cell proliferation, migration, EMT and stemness.

Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. Long non-coding RNAs (lncRNAs) have been increasingly reported to serve vital parts in malignancies including CRC. Although cancer susceptibility 21 (CASC21) has been uncovered to play a part in CRC, its mechanism still needs further explanation. Thus, our study aimed to further explore the influence and mechanism of CASC21 in CRC progression. Quantitative real-time RT-PCR and western blot were performed to detect gene expression; a series of functional assays were performed to investigate the effect of CASC21 on CRC cells; in vivo tumour growth was evaluated via the nude mice xenograft model. The results revealed that CASC21 facilitated CRC cell proliferation, migration, epithelial-mesenchymal transition (EMT) and stemness. In addition, CASC21 was co-expressed with and bound to transcription factor POU5F1B (POU class 5 homeobox 1B). CASC21 recruited POU5F1B to HGH1 promoter to activate the transcription of HGH1 homolog. Also, CASC21 served as a competitive endogenous RNA (ceRNA) to up-regulate HGH1 via endogenously sponging miR-485-5p. Moreover, HGH1 overexpression counteracted the suppression of CASC21 deficiency on CRC tumour growth. In summary, our study indicated that CASC21 enhanced the expression of HGH1 to promote the malignancy of CRC by recruiting POU5F1B and sponging miR-485-5p, suggesting a key role of CASC21 in CRC progression.

Self-expanding metal stent insertion by colorectal surgeons using a two-person approach colonoscopy without fluoroscopic monitoring in the management of acute colorectal obstruction: a 14-year experience.

BACKGROUND: Placement of a self-expanding metal stent (SEMS) in patients presenting with an acute colorectal obstruction (ACO) may obviate emergency surgery (ES), potentially effectively palliating incurable tumors, acting as a bridge to surgery (BTS) in patients with operable or potentially operable tumors and achieving effective decompression of other ACO. We present our experience with SEMS insertion by colorectal surgeons without fluoroscopic monitoring for ACO especially for acute malignant colorectal obstruction (AMCO) for nearly a 14-year period (2007-2020). AIM: To explore the safety and effectiveness of SEMS insertion in the management of ACO by colorectal surgeons using a two-person approach colonoscopy without fluoroscopic monitoring. METHODS: We reviewed the medical records of patients retrospectively to identify all patients presenting to our unit with ACO especially with AMCO who had stenting carried out to achieve colonic decompression. All 434 procedures were performed by colorectal surgeons using a two-person approach colonoscopy without fluoroscopic monitoring. RESULTS: The overall technique success rate and clinic success rate by SEMS insertion were 428/434 (98.6%) and 412/434 (94.9%). The overall incidence of complications by SEMS insertion was 19/434 (4.4%). The complications included clinical perforation (6/434, 1.4%); stent migration (2/434, 0.5%), 1 of which re-stent; stent detachment (fell off) (3/434, 0.7%), none of them with re-stent; stool impaction (6/434, 1.4%), 1 of which re-stent; and abdominal or anal pain (2/434, 0.5%). There was no hemorrhage in any of the 434 patients. CONCLUSIONS: SEMS insertion is a relatively safe and effective technique for colonic decompression in dealing with ACO as either a BTS or as a palliative measure. It is also a solution to other causes of ACO such as recurrent tumor, benign diseases, or extra-luminal compression. Therefore, ES was largely avoided.

Early screening the small bowel is key to protect Peutz-Jeghers syndrome patients from surgery: a novel mutation c.243delG in STK11 gene.

BACKGROUND: Peutz-Jeghers syndrome (PJS) is a Mendelian disease, whose causative gene is STK11, mainly characterized by gastrointestinal polyposis and increased cancer risk. Clinical observation reveals intussusception in childhood are more frequent and severe than in adults, and it is difficult to prevent this knotty complication. CASE PRESENTATION: A boy without a positive family history grew oral MP after birth and developed abdominal pain and bloody stood at 7 years old. Endoscopy revealed multiple polyps within the colon and the ileum, and endoscopic polypectomy and regular surveillance protected him from severe complications and open surgeries. A heterozygous deletion in STK11, c.243delG, was detected in the proband but not in his parents. This mutation has not been documented in databases. CONCLUSIONS: We suspect a child of PJS may need a more thorough endoscopic examination including enteroscopy or capsule endoscopy to take care of small bowel when PJS related symptoms comes up.

Silencing of Proteasome 26S Subunit ATPase 2 Regulates Colorectal Cancer Cell Proliferation, Apoptosis, and Migration.

OBJECTIVE: Colorectal cancer (CRC) remains a major cause of cancer-related death worldwide. Proteasome 26S subunit ATPase 2 (PSMC2) plays vital roles in regulating cell cycle and transcription and has been confirmed to be a gene potentially associated with some human tumors. However, the expression correlation and molecular mechanism of PSMC2 in CRC are still unclear. This study aimed to investigate the role of PSMC2 in malignant behaviors in CRC. METHODS: The high protein levels of PSMC2 in CRC samples were identified by tissue microarray analysis. Lentivirus was used to silence PSMC2 in HCT116 and RKO cells; MTT and colony formation assay were performed to determine cell proliferation. Wound healing and Transwell assay were used to detect cell migration and invasion. Flow cytometry assay was applied to detect cell cycle and apoptosis. RESULT: The results showed that, among the 96 CRC patients, the expression of PSMC2 was a positive correlation with the clinicopathological features of the patients with CRC. Furthermore, the low PSMC2 expression group showed a higher survival rate than the high PSMC2 expression group. The expression levels of PSMC2 in cancer tissue were dramatically upregulated compared with adjacent normal tissues. In vitro, shPSMC2 was designed to inhibit the expression of PSMC2 in CRC cells. Compared with shCtrl, silencing of PSMC2 significantly suppressed cell proliferation, decreased single cell colony formation, enhanced apoptosis, and accelerated G2 phase and/or S phase arrest. CONCLUSION: Survival analysis indicated that high expression of PSMC2 in the CRC samples was associated with poorer survival rate than low expression of PSMC2, while the anti-tumor effect of PSMC2 silencing was also confirmed at the cellular level in vitro. Our results suggested that PSMC2 potentially worked as a regulator for CRC, and the silencing of PSMC2 may be a therapeutic strategy for CRC.

Genome-wide DNA methylation profiling of primary colorectal laterally spreading tumors identifies disease-specific epimutations on common pathways.

Colorectal laterally spreading tumors (LSTs) grow to extremely large size while rarely invade deeply. Also, there is a low tendency to become cancerous. We used the Illumina Human Methylation 450K array to query the main epigenetic difference of LSTs. We built a discovery cohort with 10 matched cases, and a validation cohort with 9 additional matched cases. Our results suggest that LST displays significant decrease in DNA methylation, highlighted by the discovery of 1,018 hypomethylated intergenic regions (IGRs). Comparing to classic differentially methylated probes and regions that overlap transcription starting site and CpG island, IGR-regions were associated more closely with genes involved in functional biological processes and correlated with specific histone modifications. Hypomethylated IGR regions were often annotated as tissue-specific regulatory elements for noncolon tissues and were typically epigenetically silenced in normal colon mucosa. By integration of public data, we defined the commonality and specific epigenetic signatures for adenomas, LSTs and colon adenocarcinomas. Only 435 hypermethylated differentially methylated probes (DMPs) and differentially methylated regions (DMRs) and 517 hypomethylated DMPs and DMRs were shared by the three diseases. However, our pathway-level analysis discovered that genes in four pathways were common target of epimutations in LSTs, adenomas and CRCs. More interestingly, different diseases seem to employ distinct epigenetic insult to disturb specific pathways. Between LST and adenoma, we found eight pathways including Ras signaling and Rap1 signaling pathway were commonly targeted but the epimutation patterns were opposite. Comparison between precancerous conditions and invasive states revealed the key pathways governing the progression to malignancy, including PI3K-Akt pathways.

The altered activity of P53 signaling pathway by STK11 gene mutations and its cancer phenotype in Peutz-Jeghers syndrome.

BACKGROUND: Peutz-Jeghers syndrome (PJS) is caused by mutations in serine/threonine kinase 11 (STK11) gene. The increased cancer risk has been connected to P53 pathway. METHODS: PJS probands with STK11 mutation were included in the function analysis. P53 activity elevated by STK11 mutants was investigated using dual-luciferase reporter assay in vitro after constructing expression vectors of STK11 wild type and mutants generated by site-directed substitution. The association between the P53 activity and clinicopathological factors was analysis, especially the cancer history. RESULTS: Thirteen probands with STK11 mutations were involved, and within the mutations, c.G924A was novel. P53 activity elevation caused by 6 truncating mutations were significantly lower than that of STK11 wild type (P < 0.05). Family history of cancer was observed in 5 families. Within them, P53 activity was reduced and cancer occurred before 40 in 2 families, while it was not significantly changed and cancers happened after 45 in the other 3 families. CONCLUSIONS: The affected P53 activity caused by STK11 mutations in PJS patients is significantly associated with protein truncation, while cancer risk in PJS can be elevated through pathways rather than P53 pathway. P53 activity test is probably a useful supporting method to predict cancer risk in PJS, which could be helpful in clinical practice.

Changes in gut microbiota and plasma inflammatory factors across the stages of colorectal tumorigenesis: a case-control study.

BACKGROUND: Colorectal cancer (CRC) is a common malignant gastrointestinal tumor. In China, CRC is the 5th most commonly diagnosed cancer. The vast majority of CRC cases are sporadic and evolve with the adenoma-carcinoma sequence. There is mounting evidence indicating that gut microbiota and inflammation play important roles in the development of CRC although study results are not entirely consistent. In the current study, we investigated the changes in the CRC-associated bacteria and plasma inflammatory factors and their relationships based on data from a case-control study of Han Chinese. We included 130 initially diagnosed CRC patients, 88 advanced colorectal adenoma patients (A-CRA), 62 patients with benign intestinal polyps and 130 controls. RESULTS: Fecal microbiota composition was obtained using 16S ribosomal DNA (16S rDNA) sequencing. PCOA analysis showed structural differences in microbiota among the four study groups (P = 0.001, Unweighted Unifrac). Twenty-four CRC-associated bacteria were selected by a two-step statistical method and significant correlations were observed within these microbes. CRC-associated bacteria were found to change with the degree of malignancy. Plasma C-reactive protein (CRP) and soluble tumor necrosis factor II (sTNFR-II) displayed significant differences among the four study groups and increased with adenoma-carcinoma sequence. The correlations of CRP and sTNFR-II with several CRC-associated microbes were also explored. CONCLUSIONS: CRC-associated species and plasma inflammatory factors tended to change along the adenoma-carcinoma sequence. Several CRC-associated bacteria were correlated with CRP and sTNFR-II. It is likely that gut microbiome and inflammation gradually form a microenvironment that is associated with CRC development.

CXCR5+CD8+ T cells infiltrate the colorectal tumors and nearby lymph nodes, and are associated with enhanced IgG response in B cells.

Colorectal cancer is the third most prevalent cancer type worldwide and contributes to a significant percentage of cancer-related mortality. Recent studies have shown that the CXCR5+CD8+ T cells present more potent proinflammatory function than CXCR5-CD8+ T cells in chronic virus infections and in follicular lymphoma, but the role of CXCR5+CD8+ T cells in colorectal cancer is yet unclear. In this study, we demonstrated that CXCR5+CD8+ T cells were very rare in peripheral blood mononuclear cells from healthy and colorectal cancer individuals, but were significantly enriched in resected tumors and tumor-associated lymph nodes. Compared to CXCR5-CD8+ T cells, the CXCR5+CD8+ T cells demonstrated significantly higher Bcl-6 expression and lower Blimp1 expression, suggesting that CXCR5+CD8+ T cells might represent a memory CD8+ T cell subset. CXCR5+CD8+ T cells also enhanced the IgG expression by autologous B cells. Under ex vivo condition, the CXCR5+CD8+ T cells demonstrated lower degranulation, TNFα expression and IFNγ expression than CXCR5-CD8+ T cells. However, after PMA + ionomycin stimulation, the degranulation and TNFα expression by CXCR5+CD8+ T cells were significantly elevated to a level comparable with CXCR5-CD8+ T cells, whereas the IFNγ expression by PMA + ionomycin-stimulated CXCR5+CD8+ T cells were significantly higher than that by CXCR5-CD8+ T cells. Following long-term TCR-stimulation, CXCR5+CD8+ T cells demonstrated significantly more potent proliferation capacity and higher IFNγ expression than CXCR5-CD8+ T cells. TCR-stimulated CXCR5+CD8+ T cells also showed a gradual downregulation in CXCR5 expression. We further found that TCR-stimulated CXCR5+CD8+ T cells demonstrated higher granzyme B production and induced more specific lysis of autologous tumor cells than CXCR5-CD8+ T cells. Together, these data demonstrate that CXCR5+CD8+ T cells represent a significant CD8+ T cell subset in colorectal tumors and have the potential to contribute to antitumor immunity, but their specific roles require further studies in vivo.

Close and regular surveillance is key to prevent severe complications for Peutz-Jeghers syndrome patients without gastrointestinal polyps: case report of a novel STK11 mutation (c.471_472delCT) in a Chinese girl.

BACKGROUND: Peutz-Jeghers syndrome (PJS) is a Mendelian disease characterized by gastrointestinal hamartomas, mucocutaneous pigmentation (MP), and increased cancer risk. Serine/threonine kinase 11 (STK11) is the only validated causative gene in PJS. Clinical observation reveals MP and intussusception in childhood are more frequent and severe than in adults. CASE PRESENTATION: We report here a girl without a positive family history, who grew oral and fingertip MP at her age of 2 and got abdomen dull pain from 7 years old. Endoscopy revealed no obvious polyps in the stomach or the colon until 10 years old, when she received enteroscopy. Tens of polyps were resected during enteroscopy, and pathological examination confirmed them hamartomas. A heterozygous deletion in STK11, c.471_472delCT, was detected in the proband but not in her parents, which is not recorded in databases. CONCLUSION: The mutation we reported here is a novel one and a de-novo one, so our results enlarge the spectrum of STK11. We speculate close and regular endoscopy especially enteroscopy is necessary for complication prevention when the former endoscopy discovers no polyps temporarily in a child of suspect PJS.

A long-term follow-up study on the prognosis of endoscopic submucosal dissection for colorectal laterally spreading tumors.

BACKGROUND AND AIMS: Colorectal laterally spreading tumors (LSTs) are divided into homogeneous (LST-G-H), nodular mixed (LST-G-M), flat elevated (LST-NG-F), and pseudodepressed (LST-NG-PD) subtypes. We hypothesized that based on the rates of advanced histology, the recurrence rates of the LST-NG-PD and LST-G-M groups may be higher than those of the other subgroups. METHODS: Endoscopic submucosal dissection (ESD) was performed in 156 patients with a total of 177 LSTs. The clinicopathological features and long-term prognosis of ESD according to specific subtype were investigated. RESULTS: LSTs were most commonly found in the rectum, and the highest percentage of rectal lesions was observed in the LST-G-M group (71.1% vs overall 55.4%, P = .032). The LST-G-M lesions were larger (60 ± 22 mm vs 40 ± 33 mm, P = .034) than the LST-G-H lesions. The LST-G-M group also demonstrated more high-grade intraepithelial neoplasias (32.2% vs 10.8%, P = .003) and submucosal carcinomas (13.6% vs 1.5%, P = .010) compared with the LST-G-H group. The LST-NG-PD group exhibited the highest incidence of submucosally invasive cancer (16.7%). The overall perforation rate was 2.3%. The perforation rate in the LST-NG group was higher than that in the LST-G group (5.7% vs 0.8%, P = .047). All recurrences (7.7%) were found by colonoscopy without any detection of cancers, and no difference was found among the subtypes. CONCLUSIONS: No significant differences were observed among subgroups with 44.4 ± 16.3 months of follow-up. Considering that all recurrences were discovered by colonoscopy and most could be cured by repeated ESD, the LSTs of all subgroups require more intensive follow-up compared with smaller adenomatous lesions.

Endoscopic submucosal dissection versus transanal local excision for rectal carcinoid: a comparative study.

AIM: The aim of this study is to compare the short-term clinical outcomes between endoscopic submucosal dissection and transanal local excision for rectal carcinoid tumors. METHODS: Between 2007 and 2012, 31 patients with rectal carcinoid underwent endoscopic submucosal dissection at our hospital. They were compared with a matched cohort of 23 patients who underwent transanal local excision for rectal carcinoid between 2007 and 2012. Short-term clinical outcomes including surgical parameters, postoperative recovery, and oncologic outcomes were compared between the two groups. RESULTS: The mean size of tumors was significantly bigger in the transanal local excision group (0.8 ± 0.2 versus 1.1 ± 0.5 cm; P = 0.018). En bloc resection was achieved for 30 patients (97 %) in the endoscopic submucosal dissection group and all the patients in the transanal local excision group. The operation time was longer in the transanal local excision than that in the endoscopic submucosal dissection group (40.0 ± 22.7 min versus 12.2 ± 5.3 min; P < 0.001). Complications in the transanal local excision group were five cases of acute retention of urine. There was no local recurrence or distant metastasis in either group during the follow-up period. CONCLUSION: For the treatment of rectal carcinoid tumors with diameter <1 cm, endoscopic submucosal dissection has better short-term clinical outcomes than transanal local excision in terms of faster recovery and possibly a lower morbidity rate. Transanal local excision may be the first therapeutic choice of scar-embedded rectal carcinoid tumors.

TSG101 Silencing Suppresses Hepatocellular Carcinoma Cell Growth by Inducing Cell Cycle Arrest and Autophagic Cell Death.

BACKGROUND: The tumor susceptibility gene 101 (TSG101) was originally identified as a tumor-suppressor gene that mediates many molecular and biological processes, such as ubiquitination, endosomal trafficking, cell survival, and virus budding, but its role in hepatocellular carcinoma (HCC) is currently unknown. MATERIAL AND METHODS: We assessed the expression of TSG101 in HCC and paracancerous tissues using qPCR. Then, we used the TSG101-specific siRNA mix to disrupt the expression of TSG101 to investigate the subsequent effect on human hepatoma-7 (Huh7) cells. Western blot was used to detect the protein expression of TSG101 and other molecules. Cell growth assay was performed using CCK8. Transwell assay was used to investigate the migration and invasion ability of Huh7 cells after transfection with of TSG101 siRNA. Flow cytometry was used to estimate the effect of TSG101 knockdown on cell cycle and apoptosis. Confocal laser scanning microscopy was used to observe the actin filaments change and the formation of autophagy. RESULTS: TSG101 was over-expressed in HCC tissues. TSG101 silence was able to suppress Huh7 cell proliferation, migration, and invasion. Furthermore, silencing of TSG101 could induce cell cycle arrest at G1 phase and inhibit the expression of cyclin A and cyclin D, while up-regulating the expression of CDK2. The mechanism might be induction of autophagic cell death and inactivation of Akt and ERK1/2. CONCLUSIONS: TSG101 plays an important role in the development of HCC and may be a target for molecular therapy.

Lower rate of colonoscopic perforation: 110,785 patients of colonoscopy performed by colorectal surgeons in a large teaching hospital in China.

BACKGROUND: Colonoscopic perforation (CP) has a low incidence rate. However, with the extensive use of colonoscopy, even low incidence rates should be evaluated to identify and address risks. Information on CP is quite limited in China. OBJECTIVE: Our study aimed to determine the frequency of CP in colonoscopies performed by surgeons at a large teaching hospital in China over a 12-year period. METHODS: A retrospective review of medical records was performed for all patients who had CPs from 1 January 2000 to 31 December 2012. Iatrogenic perforations were identified mainly by abdominal X-ray or computed tomography scan. Follow-up information of adverse events post-colonoscopy was identified from the colorectal surgery database of our hospital. Patients' demographic data, colonoscopy procedure information, location of perforation, treatment, and outcome were recorded. RESULTS: A total of 110,785 diagnostic and therapeutic colonoscopy procedures were performed (86,800 diagnostic cases and 23,985 therapeutic cases) within the 12-year study period. A total of 14 incidents (0.012%) of CP were reported (seven males and seven females), of which nine cases occurred during diagnostic colonoscopy (0.01%) and five after therapeutic colonoscopy (three polypectomy cases, one endoscopic mucosal resection, and one endoscopic mucosal dissection). Mean patient age was 67.14 years. One case of CP (7.14%) after colonoscopy polypectomy was treated using curative colonoscopy endoclips. Other patients underwent operations: six cases (46.15%) of primary repair, four cases (28.57%) of resection with anastomosis, and two cases (15.38%) of resection without anastomosis. No obvious perforation was found in one patient (7.69%). Surgeons attempted to treat one case laparoscopically but eventually resorted to open surgery. The postoperative course was uncomplicated in eight cases (57.14%) and complicated in six cases (42.86%) but without mortality. CONCLUSION: CP is a serious but rare complication of colonoscopy. A perforation risk of 0.012% was found in our study. The optimal management of CP remains controversial. Treatment for CP should be individualized according to the patient's condition, related devices, and surgical skills of endoscopists or surgeons. Selective measures such as colonoscopy without intravenous sedation and decrease of loop formation can effectively reduce rates of perforation.

Colonoscopy is the first choice for early postoperative rectal anastomotic bleeding.

BACKGROUND: Anastomotic bleeding is rare but is one of the dangerous complications, with associated morbidity and mortality, at the early stage of rectal cancer surgery. The aim of this study was to report our experiences in the treatment of this emergency condition. METHODS: We retrospectively analyzed the general characteristics, treatment and outcome of patients with severe anastomotic bleeding after undergoing rectal cancer resection with stapled anastomosis at the Department of Colorectal Surgery of Changhai Hospital (China) between January 2011 and December 2013. RESULTS: Anastomotic bleeding occurred in six out of 2,181 patients (0.3%) who underwent anterior resection with stapled anastomosis due to rectal cancer. All patients' bleeding was stopped with colonoscopic techniques. There were no anastomotic leakages or strictures in these six patients. CONCLUSIONS: Anastomotic bleeding was a very rare complication after rectal cancer resection with stapled anastomosis. Colonoscopic treatment, including electrocoagulation and clipping, were both safely and effectively used in the early postoperative period to cease persistent anastomotic bleeding.

Predictive value of preoperative routine examination for the prognosis of patients with pT2N0M0 or pT3N0M0 colorectal cancer.

BACKGROUND: In recent years, the incidence of colorectal cancer (CRC) has been increasing. With the popularization of endoscopic technology, a number of early CRC has been diagnosed. However, despite current treatment methods, some patients with early CRC still experience postoperative recurrence and metastasis. AIM: To search for indicators associated with early CRC recurrence and metastasis to identify high-risk populations. METHODS: A total of 513 patients with pT2N0M0 or pT3N0M0 CRC were retrospectively enrolled in this study. Results of blood routine test, liver and kidney function tests and tumor markers were collected before surgery. Patients were followed up through disease-specific database and telephone interviews. Tumor recurrence, metastasis or death were used as the end point of study to find the risk factors and predictive value related to early CRC recurrence and metastasis. RESULTS: We comprehensively compared the predictive value of preoperative blood routine, blood biochemistry and tumor markers for disease-free survival (DFS) and overall survival (OS) of CRC. Cox multivariate analysis demonstrated that low platelet count was significantly associated with poor DFS [hazard ratio (HR) = 0.995, 95% confidence interval (CI): 0.991-0.999, P = 0.015], while serum carcinoembryonic antigen (CEA) level (HR = 1.008, 95%CI: 1.001-1.016, P = 0.027) and serum total cholesterol level (HR = 1.538, 95%CI: 1.026-2.305, P = 0.037) were independent risk factors for OS. The cutoff value of serum CEA level for predicting OS was 2.74 ng/mL. Although the OS of CRC patients with serum CEA higher than the cutoff value was worse than those with lower CEA level, the difference between the two groups was not statistically significant (P = 0.075). CONCLUSION: For patients with T2N0M0 or T3N0M0 CRC, preoperative platelet count was a protective factor for DFS, while serum CEA level was an independent risk factor for OS. Given that these measures are easier to detect and more acceptable to patients, they may have broader applications.

Regulator of G protein signaling 16 restrains apoptosis in colorectal cancer through disrupting TRAF6-TAB2-TAK1-JNK/p38 MAPK signaling.

Colorectal cancer (CRC) remains a major global cause of cancer-related mortality, lacking effective biomarkers and therapeutic targets. Revealing the critical pathogenic factors of CRC and the underlying mechanisms would offer potential therapeutic strategies for clinical application. G protein signaling (RGS) protein family modulators play essential role within regulating downstream signaling of GPCR receptors, with function in cancers unclear. Our study focused on the expression patterns of RGS proteins in CRC, identifying Regulator of G protein signaling 16 (RGS16) as a prospective diagnostic and therapeutic target. Analyzing 899 CRC tissues revealed elevated RGS16 levels, correlating with clinicopathological features and CRC prognosis by immunohistochemistry (IHC) combined with microarray. We confirmed the elevated RGS16 protein level in CRC, and found that patients with RGS16-high tumors exhibited decreased disease-specific survival (DSS) and disease-free survival (DFS) compared to those with low RGS16 expression. Functional assays demonstrated that RGS16 promoted the CRC progression, knockdown of RGS16 led to significantly increased apoptosis rates of CRC in vitro and in vivo. Notably, we also confirmed these phenotypes of RGS16 in organoids originated from resected primary human CRC tissues. Mechanistically, RGS16 restrained JNK/P38-mediated apoptosis in CRC cells through disrupting the recruitment of TAB2/TAK1 to TRAF6. This study provides insights into addressing the challenges posed by CRC, offering avenues for clinical translation.

Red and processed meat intake and risk of colorectal adenomas: a meta-analysis of observational studies.

Inconsistent results regarding the association between red and processed meat intake and the risk of colorectal adenoma (CRA), the precursor of colorectal cancer (CRC), have been reported. To provide a quantitative assessment of this association, we summarized the evidence from observational studies. Relevant studies were identified in MEDLINE and EMBASE until December 31, 2011. Summary relative risks (SRRs) with 95% confidence intervals (CIs) were pooled with a random-effects model. Between-study heterogeneity was assessed using the Cochran's Q and I(2) statistics. A total of 21 studies (16 case-control studies and five cohort/nested case-control studies) were included in this meta-analysis. The SRRs of CRA were 1.36 (95% CI = 1.17-1.58) for every 100 g/day increase in red meat intake, and 1.24 (95% CI = 1.12-1.36) for the highest versus the lowest level of red meat intake. Nonlinear dose-response meta-analysis indicated that CRA risk increased approximately linearly with increasing intake of red meat up to ~ 90 g/day, where the curve reached its plateau. Subgrouped analyses revealed that the increased risk of CRA with intake of red meat was independent of geographic locations, design and confounders. The SRRs of CRA was 1.28 (95% CI = 1.03-1.60) for per 50 g/day increase in processed meat intake, and 1.17 (95% CI = 1.08-1.26) for the highest versus the lowest level of processed meat intake. Increased intake of red and processed meat is associated with significantly increased risk of CRA.