Hydrophobic substrate binding pocket remodeling of echinocandin B deacylase based on multi-dimensional rational design.

Actinoplanes utahensis deacylase (AAC)-catalyzed deacylation of echinocandin B (ECB) is a promising method for the synthesis of anidulafungin, the newest of the echinocandin antifungal agents. However, the low activity of AAC significantly limits its practical application. In this work, we have devised a multi-dimensional rational design strategy for AAC, conducting separate analyses on the substrate-binding pocket's volume, curvature, and length. Furthermore, we quantitatively analyzed substrate properties, particularly on hydrophilic and hydrophobic. Accordingly, we tailored the linoleic acid-binding pocket of AAC to accommodate the extended long lipid chain of ECB. By fine-tuning the key residues, the resulting AAC mutants can accommodate the ECB lipid chain with a lower curvature binding pocket. The D53A/I55F/G57M/F154L/Q661L mutant (MT) displayed 331 % higher catalytic efficiency than the wild-type (WT) enzyme. The MT product conversion was 94.6 %, reaching the highest reported level. Utilizing a multi-dimensional rational design for a customized mutation strategy of the substrate-binding pocket is an effective approach to enhance the catalytic efficiency of enzymes in handling complicated substrates.

Allele-specific DNA methylation and gene expression during shoot organogenesis in tissue culture of hybrid poplar.

Plant tissue regeneration is critical for genetic transformation and genome editing techniques. During the regeneration process, changes in epigenetic modifications accompany the cell fate transition. However, how allele-specific DNA methylation in two haplotypes contributes to the transcriptional dynamics during regeneration remains elusive. Here we applied an inter-species hybrid poplar (Populus alba × P. glandulosa cv. 84 K) as a system to characterize the DNA methylation landscape during de novo shoot organogenesis at allele level. Both direct and indirect shoot organogenesis showed a reduction in genome-wide DNA methylation. At gene level, non-expressed genes were hypermethylated in comparison with expressed genes. Among the genes exhibiting significant correlations between levels of DNA methylation and gene expression, the expression patterns of 75% of genes were negatively correlated with DNA methylation in the CG context, whereas the correlation patterns in the CHH context were the reverse. The allele-biased DNA methylation was consistent during shoot organogenesis, with fewer than one-thousandth of allele-specific methylation regions shifted. Analysis of allele-specific expression revealed that there were only 1909 genes showing phase-dependent allele-biased expression in the regeneration process, among which the allele pairs with greater differences in transcription factor binding sites at promoter regions exhibited greater differences in allele expression. Our results indicated a relatively independent transcriptional regulation in two subgenomes during shoot organogenesis, which was contributed by cis-acting genomic and epigenomic variations.

Hemorrhagic Outcome of Brainstem Cavernous Malformations following Radiosurgery: Dose-Response Relationship.

INTRODUCTION: This study aimed to assess the impact of gamma knife radiosurgery on brainstem cavernous malformations (CMs). METHODS: A total of 85 patients (35 females; median age 41.0 years) who underwent gamma knife radiosurgery for brainstem CMs at our institute between 2006 and 2015 were enrolled in a prospective clinical observation trial. Risk factors for hemorrhagic outcomes were evaluated, and outcomes were compared across different margin doses. RESULTS: The pre-radiosurgery annual hemorrhage rate (AHR) was 32.3% (44 hemorrhages during 136.2 patient-years). The median planning target volume was 1.292 cc. The median margin and maximum doses were 15.0 and 29.2 Gy, respectively, with a median isodose line of 50.0%. The post-radiosurgery AHR was 2.7% (21 hemorrhages during 769.9 patient-years), with a rate of 5.5% within the first 2 years and 2.0% thereafter. The post-radiosurgery AHR for patients with margin doses of ≤13.0 Gy (n = 15), 14.0-15.0 Gy (n = 50), and ≥16.0 Gy (n = 20) was 5.4, 2.7, and 0.6%, respectively. Correspondingly, transient adverse radiation effects were observed in 6.7 (1/15), 10.0 (5/50), and 30.0% (6/20) of cases, respectively. An increased margin dose per 1 Gy (hazard ratio: 0.530, 95% CI: 0.341-0.826, p = 0.005) was identified as an independent protective factor against post-radiosurgery hemorrhage. Margin doses of ≥16.0 Gy were associated with improved hemorrhagic outcomes (hazard ratio: 0.343, 95% confidence interval [CI]: 0.157-0.749, p = 0.007), but an increased risk of adverse radiation effects (odds ratio: 3.006, 95% CI: 1.041-8.677, p = 0.042). CONCLUSION: The AHR of brainstem CMs decreased following radiosurgery, and our study revealed a significant dose-response relationship. Margin doses of 14-15 Gy were recommended. Further studies are required to validate our findings.

Synthesis of Quercetin-Acid Esters and Its Reduction of H2 O2 -Triggered PC12 Cells Damage by Down-Regulating ROS.

Quercetin is a kind of polyphenolic flavonoid compounds which has perfect antioxidant properties. However, quercetin is not available in many situations due to its poor bioavailability. In this work, the QAEs with better solubility and even stronger antioxidant properties were synthesized, through the esterification between quercetin and the chlorinated cinnamic acid or its derivatives, whose chlorination were achieved by using SOCl2 . The protective effects of the QAEs were evaluated by the H2 O2 -induced apoptosis experiment in rat adrenal pheochromocytoma cells (PC12 cells) and its ability to remove ROS generated by oxidative stress. Compared with the original quercetin group, the QAEs groups showed much improved cell viability and capability of removing ROS, which means their higher bioavailability than the parent.

Nomogram for predicting an individual prospective hemorrhage risk in untreated brainstem cavernous malformations.

OBJECTIVE: In this study, the authors aimed to create a nomogram for precisely predicting the 5-year prospective hemorrhage risk in brainstem cavernous malformations (BSCMs). METHODS: Patients with confirmed BSCMs in a single-center prospective observational series from January 2012 to December 2016 were included in the present study for nomogram building and validation. The concordance index (C-index), calibration curves, and decision curve analysis were used to evaluate the predictive accuracy, discriminative ability, and clinical usefulness of the nomogram. Then, a nomogram-based risk stratification model for untreated BSCMs was developed. RESULTS: In total, 600 patients were included in the study; 417 patients who had been enrolled before July 2015 were divided into the training and validation cohorts, and 183 subsequently enrolled patients were used as the external validation cohort. By applying a backward stepwise procedure in the multivariable Cox model, variables, including prior hemorrhage (HR 1.69), hemorrhage on admission (HR 3.33), lesion size > 1.5 cm (HR 1.84), lesion depth (HR 2.35), crossing the axial midpoint (HR 1.94), and developmental venous anomaly (HR 2.62), were incorporated to develop a nomogram. The Harrell C-index values for a 5-year prospective hemorrhage were 0.752 (95% CI 0.687-0.816), 0.801 (95% CI 0.665-0.936), and 0.758 (95% CI 0.674-0.842) in the training, internal validation, and external validation cohorts, respectively. The nomogram performed well in terms of consistency between prediction and actual observation according to the calibration curve. The patients could be classified into three distinct (low, medium, and high) risk groups using the final score of this nomogram. CONCLUSIONS: Independent predictors of the 5-year hemorrhage risk in untreated BSCMs were selected to create the first nomogram for predicting individual prospective hemorrhage. The nomogram was able to stratify patients into different risk groups and assist in clinical decision-making.

Five-year symptomatic hemorrhage risk of untreated brainstem cavernous malformations in a prospective cohort.

Hemorrhage of brainstem cavernous malformation (CM) would cause various symptoms and severe disability. The study aimed to elaborate on the 5-year actuarial cumulative hazard of symptomatic hemorrhage. Patients diagnosed in our institute between 2009 and 2013 were prospectively registered. All clinical data were obtained, follow-up was performed, and risk factors were evaluated. Four hundred sixty-eight patients (217 female, 46.4%) were included in the study with a median follow-up duration of 79.0 months. A total of 137 prospective hemorrhages occurred in 107 patients (22.9%) during 1854.0 patient-years. Multivariate Cox analysis found age ≥ 55 years (hazard ratio (HR) 2.166, p = 0.002), DVA (HR 1.576, p = 0.026), superficial-seated location (HR 1.530, p = 0.047), and hemorrhage on admission (HR 2.419, p = 0.026) as independent risk factors for hemorrhage. The 5-year cumulative hazard of hemorrhage was 30.8% for the overall cohort, 47.8% for 60 patients with age ≥ 55 years, 43.7% for 146 patients with DVA, 37.9% for 272 patients with superficial-seated lesions, and 37.2% for 341 patients with hemorrhage on admission. As a stratified analysis, within subcohort of 341 patients with a hemorrhagic presentation, age ≥ 55 years (HR 3.005, p < 0.001), DVA (HR 1.801, p = 0.010), and superficial-seated location (HR 2.276, p = 0.001) remained independently significant. The 5-year cumulative hazard of hemorrhage was 52.0% for 119 patients with both DVA and hemorrhagic presentation. The 5-year cumulative hemorrhagic risk was 30.8% and was higher in subgroups if harboring risk factors that helped to predict potential hemorrhagic candidates and were useful for treatment decision-making.Clinical Trial Registration-URL: http://www.chictr.org.cn Unique identifier: ChiCTR-POC-17011575.

Inhibition of TRPA1 Attenuates Oxidative Stress-induced Damage After Traumatic Brain Injury via the ERK/AKT Signaling Pathway.

Neuron apoptosis is a feature of secondary injury after traumatic brain injury (TBI). Evidence implies that excess calcium (Ca2+) ions and reactive oxidative species (ROS) play critical roles in apoptosis. In reaction to increased ROS, the anti-oxidative master transcription factor, Transient receptor potential Ankyrin 1 (TRPA1) allows Ca2+ ions to enter cells. However, the effect of TBI on the expression of TRPA1 and the role of TRPA1 in TBI are unclear. In the present study, TBI in the mouse brain was simulated using the weight-drop model. The process of neuronal oxidative stress was simulated in HT22 neuronal cells by treatment with hydrogen peroxide. We found that TRPA1 was significantly upregulated in neurons at 24 h after TBI. Neuronal apoptosis was increased in the in vivo and in vitro models; however, this increase was reduced by the functional inhibition of TRPA1 in both models. After TBI, TRPA1 was upregulated via nuclear factor, erythroid 2 like 2 (Nrf2) in neurons. TRPA1-mediated neuronal apoptosis after TBI might be achieved in part through the CaMKII/AKT/ERK signaling pathway. To sum up, TBI-triggered TRPA1 upregulation in neurons is mediated by Nrf2 and the functional blockade of TRPA1 attenuates neuronal apoptosis and improves neuronal dysfunction, partially mediated through the activation of the calcium/calmodulin dependent protein kinase II (CaMKII) extracellular regulated kinase (ERK)/protein kinase B (AKT) signaling pathway. Our results suggest that functional blockade of TRPA1 might be a promising therapeutic intervention related to ROS and Nrf2 in TBI.

Neurological outcomes of untreated brainstem cavernous malformations in a prospective observational cohort and literature review.

BACKGROUND: Haemorrhages of brainstem cavernous malformations (CMs) can lead to neurological deficits, the natural history of which is uncertain. The study aimed to evaluate the neurological outcomes of untreated brainstem CMs and to identify the adverse factors associated with worsened outcomes. METHODS: From 2009 to 2015, 698 patients (321 women) with brainstem CMs were entered into the prospective cohort after excluding patients lost to follow-up (n=43). All patients were registered, clinical data were collected and scheduled follow-up was performed. RESULTS: After a median follow-up of 60.9 months, prospective haemorrhages occurred in 167 patients (23.9%). The mean modified Rankin Scale scores at enrolment and at censoring time were 1.6 and 1.2. Neurological status was improved, unchanged and worsened in 334 (47.9%), 293 (42.0%) and 71 (10.2%) patients, respectively; 233 (33.4%) recovered to normal levels. Lesions crossing the axial midpoint (relative risk (RR) 2.325, p=0.003) and developmental venous anomaly (DVA) (RR 1.776, p=0.036) were independently significantly related to worsened outcomes. The percentage of worsened outcomes was 5.3% (18 of 337) in low-risk patients (neither DVA nor crossing the axial point) and increased to 26.0% (13 of 50) in high-risk patients (with both DVA and crossing the axial point). The percentage of worsened outcomes significantly increased as the number of prospective haemorrhages increased (from 1.5% (8 of 531, if 0 prospective ictus) to 37.5% (48 of 128, if 1 ictus) and 38.5% (15 of 39, if >1 ictus)). CONCLUSIONS: The neurological outcomes of untreated brainstem CMs were improved/unchanged in majority of patients (89.8%) with a fatality rate of 1.7% in our cohort, which seemed to be favourable. Radiological features significantly predicted worsened outcomes. Our results provide evidence for clinical consultation and individualised treatment. The referral bias of our cohort was underlined.

Pituitary stalk interruption syndrome and liver changes: From clinical features to mechanisms.

Pituitary stalk interruption syndrome (PSIS) is a rare congenital abnormality characterized by thinning or disappearance of the pituitary stalk, hypoplasia of the anterior pituitary and an ectopic posterior pituitary. Although the etiology of PSIS is still unclear, gene changes and perinatal adverse events such as breech delivery may play important roles in the pathogenesis of PSIS. PSIS can cause multiple hormone deficiencies, such as growth hormone, which then cause a series of changes in the human body. On the one hand, hormone changes affect growth and development, and on the other hand, they could affect human metabolism and subsequently the liver resulting in nonalcoholic fatty liver disease (NAFLD). Under the synergistic effect of multiple mechanisms, the progression of NAFLD caused by PSIS is faster than that due to other causes. Therefore, in addition to early identification of PSIS, timely hormone replacement therapy and monitoring of relevant hormone levels, clinicians should routinely assess the liver function while managing PSIS.

Cronkhite-Canada syndrome: from clinical features to treatment.

Cronkhite-Canada syndrome (CCS) is a rare acquired polyposis with unknown etiology. To date, >500 cases have been reported worldwide. CCS is typically characterized by gastrointestinal symptoms, such as diarrhea and skin changes (e.g. alopecia, pigmentation, and nail atrophy). Endoscopic features include diffuse polyps throughout the entire gastrointestinal tract, except for the esophagus. Pathological types of polyps in CCS mainly include inflammatory, hyperplastic, hamartomatous, and adenomatous polyps. CCS can be complicated by many diseases and has a canceration tendency with a high mortality rate. Moreover, there is no uniform standard treatment for CCS. A review of the reported cases of CCS is presented herein, with the goal of improving our understanding of this disease.

Isoflavones and inflammatory bowel disease.

Isoflavones constitute a class of plant hormones including genistein, daidzein, glycitein, formononetin, biochanin A, and irilone, and the major source of human intake is soybeans. Inflammatory bowel disease (IBD) is a chronic recurrent inflammatory disease including ulcerative colitis, Crohn's disease, and indeterminate colitis, which seriously affects the quality of life of patients and has become a global health problem. Although the pathogenesis of IBD is not very clear, many factors are thought to be related to the occurrence and development of IBD such as genes, immunity, and intestinal flora. How to control IBD effectively for a long time is still a problem for gastroenterologists. Diet has an important effect on IBD. Patients with IBD should pay more attention to diet. To date, many studies have reported that isoflavones have both good and bad effects on IBD. Isoflavones have many activities such as regulating the inflammatory signal pathways and affecting intestinal barrier functions and gut flora. They can also act through estrogen receptors, as they have a similar structure to estrogen. Isoflavones are easy to get from diet for human. Whether they are valuable to be applied to the treatment of IBD is worth studying. This review summarizes the relationship between isoflavones and IBD.

Natural history of brainstem cavernous malformations: prospective hemorrhage rate and adverse factors in a consecutive prospective cohort.

OBJECTIVE: Given the paucity of data on the natural history of brainstem cavernous malformations (CMs), the authors aimed to evaluate the annual hemorrhage rate and hemorrhagic risk of brainstem CMs. METHODS: Nine hundred seventy-nine patients diagnosed with brainstem CMs were referred to Beijing Tiantan Hospital from 2006 to 2015; 224 patients were excluded according to exclusion criteria, and 47 patients were lost to follow-up. Thus, this prospective observational cohort included 708 cases (324 females). All patients were registered, clinical data were recorded, and follow-up was completed. RESULTS: Six hundred ninety (97.5%) of the 708 patients had a prior hemorrhage, 514 (72.6%) had hemorrhagic presentation, and developmental venous anomaly (DVA) was observed in 241 cases (34.0%). Two hundred thirty-seven prospective hemorrhages occurred in 175 patients (24.7%) during 3400.2 total patient-years, yielding a prospective annual hemorrhage rate of 7.0% (95% CI 6.2%-7.9%), which decreased to 4.7% after the 1st year. Multivariate Cox regression analysis after adjusting for sex and age identified hemorrhagic presentation (HR 1.574, p = 0.022), DVA (HR 1.678, p = 0.001), mRS score ≥ 2 on admission (HR 1.379, p = 0.044), lesion size > 1.5 cm (HR 1.458, p = 0.026), crossing the axial midpoint (HR 1.446, p = 0.029), and superficially seated location (HR 1.307, p = 0.025) as independent adverse factors for prospective hemorrhage, but history of prior hemorrhage was not significant. The annual hemorrhage rates were 8.3% and 4.3% in patients with and without hemorrhagic presentation, respectively; the rate was 9.9%, 6.0%, and 1.0% in patients with ≥ 2, only 1, and 0 prior hemorrhages, respectively; and the rate was 9.2% in patients with both hemorrhagic presentation and focal neurological deficit on admission. CONCLUSIONS: The study reported an annual hemorrhage rate of 7.0% exclusively for brainstem CMs, which significantly increased if patients presented with both hemorrhagic presentation and focal neurological deficit (9.2%), or any other risk factor. Patients with a risk factor for hemorrhage needed close follow-up regardless of the number of prior hemorrhages. It should be noted that the referral bias in this study could have overestimated the annual hemorrhage rate. This study improved the understanding of the natural history of brainstem CMs, and the results are important for helping patients and physicians choose a suitable treatment option based on the risk factors and stratified annual rates.Clinical trial registration no.: ChiCTR-POC-17011575 (http://www.chictr.org.cn/).

Two macamide extracts relieve physical fatigue by attenuating muscle damage in mice.

BACKGROUND: Macamides, the main active components contained in maca, have attracted increasing attention due to their various bioactivities. In this study, crude macamide extract (CME) and purified macamide extract (PME) were prepared by enzyme-assisted extraction and macroporous resin separation, and the anti-fatigue effects of CME and PME were evaluated in a forced swimming model. RESULTS: The composition analysis results revealed that both CME and PME mainly contain eight kinds of macamide. Based on the results of a weight-loaded forced swimming test, compared with a control group, CME and and PME groups could prolong exhaustive swimming time, increase levels of liver glycogen (LG) and muscle glycogen (MG), accelerate fatty acid oxidation in serum to provide energy, eliminate the accumulation of blood lactic acid (BLA) and blood urea nitrogen (BUN), and decrease the serum biomarkers for muscle damage, such as lactate dehydrogenase (LDH) and creatine kinase (CK). Histological analysis also indicated that CME and PME attenuated damage to skeletal muscle and the myocardium in mice during exercise. CONCLUSION: Two macamide extracts have a beneficial effect on relieving physical fatigue by attenuating the damage of skeletal muscle and myocardium during exercise, and a better effect was observed in the PME group. © 2018 Society of Chemical Industry.

Fully Endoscope-Controlled Clipping Bilateral Middle Cerebral Artery Aneurysm Via Unilateral Supraorbital Keyhole Approach.

Clipping bilateral middle cerebral artery (bMCA) aneurysms via unilateral approach in a single-stage operation is considered as a challenge procedure. To our knowledge, there is no study in surgical management of patients with bMCA aneurysms by fully endoscope-controlled techniques. The author reported a patient with bMCA aneurysms who underwent aneurysms clipping via a unilateral supraorbital keyhole approach by endoscope-controlled microneurosurgery, and the patient had an uneventful postoperative course without neurologic impairment and complication. Furthermore, the author discussed the advantages and adaptation of endoscope-controlled clipping bMCA aneurysms via unilateral supraorbital keyhole approach.

1H NMR-based metabolic study reveals the improvements of bitter melon (Momordica charantia) on energy metabolism in diet-induced obese mouse.

CONTEXT: Obesity can be ameliorated by some natural products such as polyphenol, flavones and saponin. As a typical medicinal plant, Momordica charantia L. (Cucurbitaceae) (bitter melon, BM) contains these natural chemicals and reduces diet-induced obesity in mice. OBJECTIVE: This study evaluates the metabolic effects of dietary BM supplement, investigates a global metabolic profile and determines associated perturbations in metabolic pathways. MATERIALS AND METHODS: Male C57BL/6 mice were fed with low-fat diet (LFD), high-fat diet (HFD) and HFD supplemented with 5% BM based on 37.6 g/kg body weight in average for 12 weeks, respectively. Then energy metabolism was quantified using PhenoMaster/LabMaster. The spectroscopy of urine was acquired by nuclear magnetic resonance and latent biomarkers were identified. Pattern recognition analysis was used to discriminate associated metabolic profiles. RESULTS: Dietary BM supplement reduced body weight gain (-0.15-fold, p < 0.01) and blood glucose levels (-0.19-fold, p < 0.01) in HFD-fed mice. Meanwhile, the levels of energy metabolism were enhanced (0.08-0.11-fold, p < 0.01). According to pattern recognition analysis, dietary BM supplement changed metabolic profiles in HFD-fed mice and the modified profiles were similar to those in LFD-fed mice. Finally, the mapping of metabolic pathways showed that dietary BM supplement primarily affected glucose metabolism-associated pathways. DISCUSSION AND CONCLUSION: The results indicated that BM improves weight loss in diet-induced obesity and elevate energy expenditure in HFD-fed mice. The pattern recognition with metabolic study may be used as a noninvasive detection method to assess the effects of dietary BM supplement on mouse energy metabolism.

Comparison of prediction models for blood brain barrier permeability and analysis of the molecular descriptors.

To develop an in silico model for predicting blood brain barrier (BBB) permeability, and evaluate whether incorporation of two new biological descriptors, high affinity P-glycoprotein substrate probability (HAPSP) and plasma protein binding ratio (PPBR), could result in a better model, four different multiple linear regression (MLR) models have been constructed and compared with each other. The optimized model demonstrated predictive ability and simplicity, not only suitable for passive but also for active transport. Moreover, the molecular descriptors used here are discussed.

Oncological outcomes of transanal local excision for high risk T(1) rectal cancers.

AIM: To evaluate the oncological outcomes of transanal local excision and the need for immediate conventional reoperation in the treatment of patients with high risk T(1) rectal cancers. METHODS: Twenty five high risk T(1) rectal cancers treated by transanal local excision at the Guangdong General Hospital were analyzed retrospectively. Twelve patients received transanal local excision and 13 patients underwent subsequent immediate surgical rescue after transanal local excision within 4 wk. Differences in the local recurrence rates and 5-year overall survival rates between the two groups were analyzed. The prognostic value of immediate conventional reoperation for high risk T(1) rectal cancers was also evaluated. RESULTS: The median follow-up period was 62 mo. The local recurrence rates after transanal local excision for high risk T(1) rectal cancer were 50%. By immediate conventional reoperation, the local recurrence rates were significantly reduced to 7.7%. The difference between these two groups was statistically significant (P = 0.030). Kaplan-Meier survival analysis showed a trend for decreased 5-year overall survival rates for patients treated by transanal local excision compared with immediate conventional reoperation (63% vs 89%). CONCLUSION: Transanal local excision cannot be considered sufficient treatment for patients with high risk T(1) rectal cancers. Immediate conventional reoperation should be performed if the pathology of the local excision is high risk.

[Efficacy analysis of transanal local excision in low rectal cancer:report of 40 cases].

OBJECTIVE: To explore the indication and efficacy of transanal local excision for low rectal cancer. METHODS: A total of 40 consecutive patients undergoing transanal local excision of low rectal cancer were analyzed retrospectively. RESULTS: The mean operative time was 50 (30-85) minutes. The mean intraoperative blood loss was 40 (10-100) ml. The mean hospital stay was 5 (2-10) days. The local recurrence rate was 20.0% (8/40). The 5-year survival rate was 90.0%. Local recurrence rate was 17.9% (5/28 cases) for T1, and 25.0% (3/12) for T2 lesions. However, the difference between the two groups was not statistically significant (P=0.61). Local recurrence rate was significantly lower for moderate differentiated than that for well-differentiated cancer [12.9% (4/31) vs. 44.4% (4/9), P=0.037]. Tumor diameter less than 3 cm was associated with a significantly lower local recurrence rate as compared to the counterparts (10.7% vs. 41.7%, P=0.03). No significant correlations were found between local recurrence and other variables including tumor location (P=0.93), tumor classification (P=0.53), and method of surgical excision (P=0.41). CONCLUSIONS: Indications for transanal local excision of low rectal cancer include T1 and T2 tumors with well differentiation and the diameter less than 3 cm. Clinical outcome may be favorable if patients are carefully selected for transanal local excision.

[Clinical efficacy comparison between laparoscopy and open radical resection for 191 advanced colorectal cancer patients].

OBJECTIVE: To evaluate the feasibility, the radicalness and efficacy of laparoscopy for advanced colorectal cancer. METHODS: From June 2006 to December 2007, laparoscopic surgery and open radical resection were performed in 191 cases of colorectal cancer. The curative effect and clinical data were collected and analyzed. RESULTS: The patients were randomized to two groups, 98 patients underwent laparoscopic surgery and 93 open operation. Five cases(5.1%) were converted to open surgery in laparoscopic surgery group. The average intraoperative blood loss of open surgery group was(279.5+/-189.4) ml, while that of laparoscopic surgery group was(87.2+/-27.1) ml, the difference between the two groups was statistically significant(P=0.011). Within postoperative 48 hours, the intestinal function and early mobile physical activity were restored in 37.8% (37/98) and 30.6% (30/98) patients of laparoscopic surgery group, while in 6.5%(6/93, P=0.000) and 3.2% (3/93, P=0.000) patients of open surgery group, the differences between two groups were statistically significant. The average hospital stay of laparoscopic surgery group was (8.9+/-5.9) d, whereas open surgery group(12.1+/-7.6) d, the difference was statistically significant(P=0.036). No significant differences were found between the two groups in gender, age, tumor location, resection range of surgery, TNM staging, post-operative complication and lymph node harvest(P>0.05). CONCLUSIONS: Laparoscopic surgery is feasible for the patients with advanced colorectal cancer. The radicalness of laparoscopic surgery is similar to that of open surgery, and laparoscopic surgery can provide less intraoperative blood loss, better intestinal function restoration, early mobile physical activity and shorter hospital stay.

Risk factors for local recurrence of middle and lower rectal carcinoma after curative resection.

AIM: To explore the risk factors for local recurrence of middle and lower rectal carcinoma after curative resection. METHODS: Specimens of middle and lower rectal carcinoma from 56 patients who received curative resection at the Department of General Surgery of Guangdong Provincial People's Hospital were studied. A large slice technique was used to detect mesorectal metastasis and evaluate circumferential resection margin status. The relations between clinicopathologic characteristics, mesorectal metastasis and circumferential resection margin status were identified in patients with local recurrence of middle and lower rectal carcinoma. RESULTS: Local recurrence of middle and lower rectal carcinoma after curative resection occurred in 7 of the 56 patients (12.5%), and was significantly associated with family history (c2=3.929, P=0.047), high CEA level (c2=4.964, P=0.026), cancerous perforation (c2=8.503, P=0.004), tumor differentiation (c2=9.315, P=0.009) and vessel cancerous emboli (c2=11.879, P=0.001). In contrast, no significant correlation was found between local recurrence of rectal carcinoma and other variables such as age (c2=0.506, P=0.477), gender (c2=0.102, c2=0.749), tumor diameter (c2=0.421, P=0.516), tumor infiltration (c2=5.052, P=0.168), depth of tumor invasion (c2=4.588, P=0.101), lymph node metastases (c2=3.688, P=0.055) and TNM staging system (c2=3.765, P=0.152). The local recurrence rate of middle and lower rectal carcinoma was 33.3% (4/12) in patients with positive circumferential resection margin and 6.8% (3/44) in those with negative circumferential resection margin. There was a significant difference between the two groups (c2=6.061, P=0.014). Local recurrence of rectal carcinoma occurred in 6 of 36 patients (16.7%) with mesorectal metastasis, and in 1 of 20 patients (5.0%) without mesorectal metastasis. However, there was no significant difference between the two groups (c2=1.600, P=0.206). CONCLUSION: Family history, high CEA level, cancerous perforation, tumor differentiation, vessel cancerous emboli and circumferential resection margin status are the significant risk factors for local recurrence of middle and lower rectal carcinoma after curative resection. Local recurrence may be more frequent in patients with mesorectal metastasis than in patients without mesorectal metastasis.