Robotic or transanal total mesorectal excision (TaTME) approach for rectal cancer, how about both? Feasibility and outcomes from a single institution.

Laparoscopic surgery for rectal cancer is technically challenging. Robotic and transanal TME (TaTME) are both novel approaches developed to provide better visualization and dissection. We aim to combine both approaches in a hybrid procedure and evaluate the feasibility as well as patient and oncological outcomes in this study. A review of a prospectively maintained database of patients who underwent a hybrid abdominal robotic approach with TaTME for rectal cancer between January 2016 and October 2018 was undertaken. Patient demographics, tumor characteristics and surgical outcomes were recorded and analyzed. A total of 69 patients (43 males, 26 females) received this hybrid approach. Their median age was 58 years (range 35-87) with a mean BMI of 24.3 kg/m2 (range 16.4-44.2). Median distance from anal verge was 5 cm (range 2-9). The patients had a median hospital length of stay of 7 days (range 5-28). Complication rate was 17.4% (12 patients) with 3 patients (4.3%) requiring a reoperation. TME quality was optimal with all of them either complete (81.2%) or almost complete (18.8%). 65 patients (94.2%) had an R0 resection with 4 patients (5.8%) with involved circumferential resection margins (≤ 1 mm). The median number of lymph nodes harvested was 20 (range 6-37). After a median follow-up of 27.7 months (range 7-42), local recurrence was identified in 2 patients (4%). Three patients (5.2%) had distant recurrence at the 3-year mark. Hybrid robotic abdominal dissection with transanal TME for rectal cancer appears to be feasible with comparable surgical outcomes to other traditional approaches.

The multiple mediating effects of cancer threat appraisal and quality of life on the association between mindfulness and depression for colorectal cancer survivors.

OBJECTIVE: This study explored the multiple mediating effects of cancer threat appraisal, functional status, and symptom distress on the association between mindfulness and depression in colorectal cancer (CRC) patients at the transition stage after completing cancer treatments. METHODS: A total of 90 CRC survivors who received cancer treatments within 3 months participated in this cross-sectional study. The functional status and symptom distress (EORTC-C30 and EORTC CR29), dispositional mindfulness (Five Facet Mindfulness Questionnaire), cancer threat appraisal ( Constructed Meaning Scale), and depressive symptoms (Beck Depression Inventory-II scale) were collected. The mediation and moderation analyses were conducted using the PROCESS macros for SPSS. RESULTS: Survivors' dispositional mindfulness (γ = -0.49, p < 0.001) and cancer threat appraisal (γ = -0.59, p < 0.001) were significantly associated with depressive symptoms. Simple mediation analysis indicated that cancer threat appraisal mediated the relationship between dispositional mindfulness and depression (ß = -0.02, 95% CI = -0.04 to -0.001). The multiple mediated analysis identified the path between dispositional mindfulness and depression via cancer threat appraisal and colorectal symptom distress (ß = -0.01, 95% CI = -0.03 to -0.01). In the mediated moderation model, the path between dispositional mindfulness and depression via colorectal function was moderated by cancer threat appraisal (ß = -0.02, 95% CI = -0.05 to -0.004). CONCLUSIONS: The two cognitive mechanisms of reducing CRC survivors' depression are as follows: (1) dispositional mindfulness reducing the appraisal of cancer as a threat and increasing positive perceptions of CRC symptoms and (2) the cancer threat appraisal buffered the impacts of CRC's mindfulness and colorectal function on depressive symptoms. Developing mindfulness with cognitive training is recommended for improving depressive symptoms among CRC patients in the transition period.

High plasma C-terminal FGF-23 levels predict poor outcomes in patients with chronic kidney disease superimposed with acute kidney injury.

BACKGROUND: Elevated plasma C-terminal fibroblast growth factor-23 (cFGF-23) levels are associated with higher mortality in patients with chronic kidney disease (CKD) and acute kidney injury (AKI). Our study explored the outcome forecasting accuracy of cFGF-23 in critically ill patients with CKD superimposed with AKI (ACKD). METHODS: Urine and plasma biomarkers from 149 CKD patients superimposed with AKI before dialysis were checked in this multicenter prospective observational cohort study. Endpoints were 90-day mortality and 90 days free from dialysis after hospital discharge. Associations with study endpoints were assessed using hierarchical clustering analysis, the generalized additive model, the Cox proportional hazard model, competing risk analysis, and discrimination evaluation. RESULTS: Over a median follow up of 40 days, 67 (45.0%) patients died before the 90th day after hospital discharge and 39 (26.2%) progressed to kidney failure with replacement therapy (KFRT). Hierarchical clustering analysis demonstrated that cFGF-23 levels had better predictive ability for 90-day mortality than did other biomarkers. Higher serum cFGF-23 levels were independently associated with greater risk for 90-day mortality [hazard ratio (HR): 2.5; 95% confidence interval (CI) 1.5-4.1; p < 0.001]. Moreover, adding plasma cFGF-23 to the Demirjian AKI risk score model substantially improved risk prediction for 90-day mortality than the Demirjian model alone (integrated discrimination improvement: 0.06; p < 0.05; 95% CI 0.02-0.10). The low plasma cFGF-23 group was predicted having more weaning from dialysis in surviving patients (HR = 0.53, 95% CI, 0.29-0.95, p = 0.05). CONCLUSIONS: In patients with ACKD, plasma cFGF-23 levels are an independent risk factor to forecast 90-day mortality and 90-day progression to KFRT. In combination with the clinical risk score, plasma cFGF-23 levels could substantially improve mortality risk prediction.

The Effects of Neoadjuvant Treatment on the Tumor Microenvironment in Rectal Cancer: Implications for Immune Activation and Therapy Response.

BACKGROUND: Because more than one neoadjuvant treatment is available for advanced rectal cancer, the aim of this study was to compare the differential clinical and pathologic effects of different combinations of chemoradiation regimens, treatment sequencing, and timing to surgery on patient outcomes. PATIENTS AND METHODS: Between January 2015 and October 2018, 126 newly diagnosed patients with rectal cancer with magnetic resonance imaging-based cT3-4 or N+ rectal disease for curative-intent treatment received 1 of 4 neoadjuvant regimens, followed by immediate surgery or delayed surgery. Whole post-neoadjuvant surgical specimens were assessed by 3-dimensional digital whole-tumor microarray imaging and immunostaining in pathology to analyze the global tumor pathologic regression grades, residual tumor distribution patterns, the extent of lymphovascular permeation, lymph node positivity, and the overall density of lymphocyte infiltration in the tumor microenvironment. These factors were further examined to identify possible correlations with clinical outcomes. RESULTS: Among the 4 neoadjuvant treatment groups, including 2 conventional regimens, we found a significant increase of stromal CD3+ and CD8+ immune infiltrates in the postneoadjuvant tumor microenvironment in the 3 groups with delayed surgery after different chemoradiation regimens compared with the group with immediate surgery after a short course of RT alone. Independent of neoadjuvant chemoradiation regimens, the post-induction high-intermediate-low stromal-infiltrating CD8+ T-cell densities corresponded to tumor regression grades, distant metastasis rates, and disease-free survival and were prognostic factors for the further stratification of patients with American Joint Committee on Cancer stage III rectal cancer into different risk groups after surgery. CONCLUSION: The effectiveness of induction strategies on tumor remission and disease recurrence in advanced rectal cancer was significantly correlated with an enhanced cytotoxic immune response in the tumor microenvironment.

Robotic transanal total mesorectal excision assisted by laparoscopic transabdominal approach: A preliminary twenty-case series report.

BACKGROUND: Laparoscopy-assisted robotic transanal total mesorectal excision is a novel surgical technique for rectal cancer resection. Compared to prior DaVinci Si system case series, this case series is the first to report robotic taTME assisted by laparoscopy (r-taTME) in which the "transanal team" operates via the DaVinci Xi system. As a result, we aim to delineate and discuss preliminary findings from our robotic taTME experiences. METHODS: A total of twenty patients (twelve males) who underwent robotic taTME assisted by laparoscopy (r-taTME) between January 2016 and November 2016 at a single institution were documented. Surgical outcomes, including complications, pathological outcomes, and short-term results, were then retrospectively analyzed. RESULTS: All patients underwent r-taTME via a two-team approach. The "abdominal team" operated via a single port method (ileostomy site), while the "transanal team" operated via the DaVinci Xi system. The mean patient age was 56.7 ± 14.3 years (range 31-79), and the mean distance from tumor to anal verge was 6.0 ± 2.7 cm (range 2-10). The mean estimated intraoperative blood loss was 88 ± 107 ml (range 30-500), and circular stapling was utilized to restore continuity in 80% of study patients. The overall postoperative complication rate was 35%, and the mean distal margin length was 3.1 ± 1.3 cm. There were three patients who had a circumferential margin (CRM) involved by cancer cells (≤1 mm). CONCLUSION: Our preliminary series report demonstrates that utilization of r-taTME assisted by laparoscopy is safe and feasible. Development of a novel transanal approach that allows single-port access alongside a multi-arm robotic system may increase the convenience and efficiency of future operation.

Transanal total mesorectal excision for rectal cancer: hype or new hope?

Rectal cancer has always posed surgical challenges to the colorectal surgeon. The quality of the total mesorectal excision (TME) performed is key in determining local disease control. Unlike the great success in adoption of laparoscopic surgery in colon cancer treatment, studies comparing laparoscopy to open rectal surgery all revealed noninferiority was not achieved. Transanal TME (taTME) is the latest advanced technique pioneered to tackle difficult pelvic dissections. The evolution of taTME surgery in recent years was explored in this review. The outcomes to date on the latest literatures are reviewed, included complications, functional outcomes, oncological results and future clinical researches. taTME, while definitely still in its early stages of development, has steadily accumulated safety and feasibility data. It not only provides a better solution to an old problem that colorectal surgeons have been attempting to tackle for quite some time, but also appears to be quite promising in terms of outcomes on numerous fronts. With structured training models, and proctored clinical application, alongside design and implementation of international-scale large multicenter randomized clinical trials, one can only hope that taTME and its innovations will not only open a new era for colorectal surgery, but also for even more surgical disease pathologies.

Transanal Total Mesorectal Excision Versus Laparoscopic Surgery for Rectal Cancer Receiving Neoadjuvant Chemoradiation: A Matched Case-Control Study.

BACKGROUND: Neoadjuvant chemoradiation therapy (nCRT) has been indicated for locally advanced rectal cancer. While utilization of laparoscopy in rectal cancer surgery has been popular in recent years, tumors receiving nCRT is still a surgical challenge. Transanal total mesorectal excision (TaTME) has emerged as a focused area of laparoscopic surgery that is becoming an increasingly acceptable approach in the field of rectal surgery. METHODS: Between December 2013 and April 2015, a total of 50 patients (38 males) with post-nCRT middle or lower rectal cancer who then underwent TaTME at two separate institutions were prospectively documented. Overall, 100 matched control cohorts who received conventional laparoscopic rectal surgery (LapTME) were simultaneously retrieved from a prospectively registered database. Four parameters of sex, age, clinical stage, and American Society of Anesthesiologists (ASA) score were matched for surgical outcomes, and short-term oncological results, including complications and pathological outcomes, were analyzed. RESULTS: Both the TaTME and LapTME groups received 5-fluorouracil-based chemotherapy and 5 weeks of long-course radiation therapy. Mean operative time for the TaTME group was 182.1 ± 55.4 min (156.6 ± 37.8 min in two-team-approach cases) and 178.7 ± 34.8 min for the LapTME group. The TaTME group yielded longer distal margin lengths. No significant differences were observed in blood loss, intraoperative complication rate, conversion rate, anastomosis type, and free circumferential margin rate. CONCLUSION: This matched case-control study demonstrated that TaTME is safe and feasible. Compared with LapTME, TaTME not only achieves identical circumferential margin status without compromising other operative and quality parameters but also benefits patients by achieving a longer distal margin. Thus, TaTME has the potential to become an option in managing irradiated rectal cancer.

The evolving practice of hybrid natural orifice transluminal endoscopic surgery (NOTES) for rectal cancer.

BACKGROUND: Natural orifice transluminal endoscopic surgery (NOTES) has emerged as the area of focus in laparoscopic surgery. Hybrid NOTES (hNOTES) has some potential advantages for treating rectal cancer. METHODS: Between May 2013 and November 2013, a total of 20 patients (11 males) who received hNOTES at two institutes participating in the study were documented and reviewed. Surgical outcomes, including complications and pathological outcomes, were analyzed. RESULTS: The mean age of patients was 57.8 ± 10.1 years (range 34-78). Eleven patients received preoperative neoadjuvant chemoradiotherapy, with the mean distance between tumor and anal verge being 5.9 ± 1.7 cm (mean 2-8). The mean estimated intraoperative blood loss was 68 ± 106 ml (range 30-500), with one case converted to open procedure due to uncontrolled bleeding. Eight cases underwent simultaneous two-team approach. The mean operative time was 200.8 ± 47.7 min (range 110-285). Circular stapling was performed for 14 cases (70 %) as the anastomosis, and protective stoma performed for 17 cases (85 %). The overall postoperative complication rate was 25 %. Two cases (10 %) develop pelvic abscess due to leakage, which were controlled by medical treatments. The distal and circumferential margins were all free of tumor cells, and the mean distal margin length was 2.4 ± 0.98 cm (range 0.5-4). CONCLUSIONS: Hybrid NOTES for rectal cancer is safe and feasible. Rapid experience-building accelerates its evolution, as reflected here by the high stapling rate and the idea of a two-team approach. It has the potential to become an option of treating rectal cancers.

Probing the binding kinetics of proinflammatory cytokine-antibody interactions using dual color fluorescence cross correlation spectroscopy.

Dual color fluorescence cross correlation spectroscopy (FCCS) was used to investigate quantitatively the binding kinetics of tumor necrosis factor (TNFα) with TNFα antibody (anti-TNFα) following fluorescent labeling. Through the analysis of the auto correlation curves of fluorescence correlation spectroscopy (FCS), diffusion coefficients of 100.06 ± 4.9 µm(2) s(-1) and 48.96 ± 2.52 µm(2) s(-1) for Alexa488-TNFα and Atto647N-anti-TNFα were obtained. In addition, the calculated hydrodynamic diameters of the Alexa488-TNFα and Atto647N-anti-TNFα were approximately 4.89 ± 0.24 nm and 9.99 ± 0.52 nm, respectively, which agrees with the values of 5.20 ± 1.23 nm and 9.28 ± 0.86 nm for the native TNFα and the anti-TNFα as determined from dynamic light scattering measurements. For the binding kinetics, association (k(on)) and dissociation (k(off)) rate constants were (1.13 ± 0.08) × 10(4) M(-1) s(-1) and (1.53 ± 0.19) × 10(-3) s(-1) while the corresponding dissociation constant (K(d)) at 25 °C was (1.36 ± 0.10) × 10(-7) M. We believe this is the first report on the binding kinetics for TNFα-antibody recognition in the homogeneous phase. Using this technology, we have shown that controlled experiments can be performed to gain insight into molecular mechanisms involved in the immune response.

Enhanced chemotherapy of cancer using pH-sensitive mesoporous silica nanoparticles to antagonize P-glycoprotein-mediated drug resistance.

Multidrug resistance (MDR) is the major clinical obstacle in the management of cancer by chemotherapy. Overexpression of ATP-dependent efflux transporter P-glycoprotein (PGP) is a key factor contributing to multidrug resistance of cancer cells. The purpose of the present study was to use the endosomal pH-sensitive MSN (mesoporous silica nanoparticles; MSN-Hydrazone-Dox) for controlled release of doxorubicin (Dox) in an attempt to overcome the PGP-mediated MDR. In vitro cell culture studies indicate that uptake of MSN-Hydrazone-Dox by the human uterine sarcoma MES-SA/Dox-resistant tumor (MES-SA/Dx-5) cell occurs through endocytosis, thus bypassing the efflux pump resistance. This improves the efficacy of the drug and leads to significant cytotoxicity and DNA fragmentation evidenced by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and DNA laddering assays. In vivo studies show that the intratumor injection of MSN-Hydrazone-Dox induces significant apoptosis of MES-SA/Dox-resistant cancer cells. This is validated by active caspase-3 immunohistochemical analysis. However, MSN-Hydrazone, without doxorubicin conjugation, cannot induce apoptosis in vitro and in vivo. In conclusion, both in vitro and in vivo studies show that MSN could serve as an efficient nanocarrier entering cell avidly via endocytosis, thus bypassing the PGP efflux pump to compromise the PGP-mediated MDR. MSN-Hydrazone-Dox could further respond to endosomal acidic pH to release doxorubicin in a sustained manner. Besides the cell study, this is the first report that successfully shows the therapeutic efficacy of using MSN against MDR cancer in vivo.

Is it appropriate to apply the enhanced recovery program to patients undergoing laparoscopic rectal surgery?

BACKGROUND: The laparoscopic approach has played a key role in the successful application of the enhanced recovery program (ERP) in perioperative care for postoperative colon surgery patients. Reports of applying ERP in laparoscopic rectal surgery are rare, and the feasibility of doing so has yet to be solidly evaluated. The goal of this study was to evaluate whether it is appropriate to use ERP on patients who undergo rectal surgery via the laparoscopic approach and to further investigate potential factors that may affect the results of this practice modality. METHODS: Between December 2007 and July 2009, 80 eligible patients (35 women) with a median age of 60 (range, 28-82) years were enrolled. All patients received elective laparoscopic rectal surgery due to malignant or benign rectal lesions. Forty-nine percent of patients received preoperative neoadjuvant chemoradiotherapy (CCRT), because their clinical stage was beyond T3N0 or TanyN(+). The ERP used in this study was modified from a similar protocol used for patients receiving laparoscopic colectomy at the same institution. RESULTS: Sixty-five percent of patients in the study received a sphincter-preserving procedure, whereas 15 other patients underwent abdominoperineal resection (APR). The median operative time was 160 min. The conversion rate of laparoscopic surgery was 7.5%, and the combined intraoperative and postoperative complication rate was 13.8%. Forty-two patients (52.5% of the study pool) received complete postoperative recovery courses as prescribed by ERP. CONCLUSIONS: Our preliminary results of applying ERP to patients receiving laparoscopic rectal surgery showed a success rate of 52.5%. The failure of ERP among these patients was related to low rectal lesion locations (below 7 cm AAV) and surgery-related complications. ERP for laparoscopic rectal surgery is feasible but is not advised for all cases requiring laparoscopic rectal surgery.

Influence of pneumoperitoneum on tumor growth and pattern of intra-abdominal tumor spreading: in vivo study of a murine model.

BACKGROUND/AIMS: The employment of laparoscopy in the treatment of locally advanced colorectal cancer is still questioned by many surgeons, mainly due to the fear of spreading tumors by the laparoscopic procedure. However, it is still unknown whether laparoscopy is actually associated with increased tumor dissemination, especially for those with tumor invasion through the serosa. The main purpose of this study is to investigate the effect of pneumoperitoneum on the intra-abdominal tumor growth and spreading of colon cancer cells by an animal study of murine model. METHODOLOGY: Under anesthesia, 10(6) tumor cells (CT26) were inoculated into the lower abdominal cavity of BALB/c mice by a mini-laparotomy. The mice were randomized to undergo pneumoperitoneum with CO2 (n=10), helium (n=10), or to act as controls (n=10). Pneumoperitoneum was established over 20 min at a pressure of 10cm H2O. The distribution pattern and the weight of peritoneal tumor growth of each mouse were recorded and analyzed at 15 days after surgery. RESULTS: The mean ratios of the tumor mass over the total body weight of the mice were 0.77+/-1.13% (control group), 4.30+/-0.86% (CO2 pneumoperitoneum), and 2.17+/-0.88% (helium pneumoperi-toneum). The mean tumor weight ratio (3.23+/-1.38%) of the pneumoperitoneal group was 4 times larger than that of the control group (p<0.001). Regarding the use of different insufflation gases over tumor growth, CO2 accelerates tumor growth more significantly than helium (p<0.001). Intraabdominal distribution (p=0.047) and diaphragm spreading (p<0.001) were significantly greater in the pneumoperitoneum group than the control group. CONCLUSIONS: The results of this animal study imply that presence of a pneumoperitoneum enhances the implantation and growth of free intraperitoneal malignant colon cancer cells in this in vivo mouse model. The results of the current study suggest that insufflation during pneumoperitoneum may play an important role in the development of peritoneal dissemination when there are free tumor cells in the intra-abdominal cavity, and the effect of using CO2 might be greater than that of using helium.

Gene cloning and characterization of a novel recombinant antifungal chitinase from papaya (Carica papaya).

A chitinase cDNA clone (CpCHI, 1002 bp) was isolated from papaya fruit, which encoded a 275 amino acid protein containing a 28 amino acid signal peptide in the N-terminal end. The predicted molecular mass of the mature protein was 26.2 kDa, and its pI value was 6.32. On the basis of its amino acid sequence homology with other plant chitinases, it was classified as a class IV chitinase. An active recombinant CpCHI enzyme was overexpressed in Escherichia coli. The purified recombinant papaya chitinase showed an optimal reaction temperature at 30 degrees C and a broad optimal pH ranging from 5.0 to 9.0. The recombinant enzyme was quite stable, retaining >64% activity for 3 weeks at 30 degrees C. The spore germination of Alternaria brassicicola could be completely inhibited by a 76 nM level of recombinant CpCHI. Recombinant CpCHI also showed antibacterial activity in which 50% of E. coli was inhibited by a 2.5 microM concentration of the enzyme.

Thermal Inactivation of Listeria monocytogenes in Chicken Gravy.

Heat resistance of Listeria monocytogenes strains V7 and Scott A in chicken gravy and changes in heat resistance during refrigerated storage were studied. After chicken gravy was made, it was cooled to 40°C, inoculated with 105 CFU L. monocytogenes per ml of gravy, and then stored at 7°C for 10 d. Gravy was heated at 50, 55, 60, and 65°C immediately after inoculation and after 1, 3, 5, and 10 d of refrigerated storage. The D values for strains Scott A and V7 in gravy heated at 50°C at day 0 were 119 and 195 min and at day 10 they were 115 and 119 min, respectively, whereas at 65°C comparable values at day 0 were 0.48 and 0.19 min and at day 10 they were 0.014 and 0.007 min. Heat resistance (expressed as D values) was greater at day 0 than at the end of refrigerated storage. The z values ranged from 3.41 to 6.10°C and were highest at the early stages of chill storage and then decreased at the later stages. Strain V7 was more heat resistant than Scott A at 50°C. Strain Scott A always had a higher z value than did strain V7 at the same storage interval. A heat treatment greater than the 4-D process recommended by the U.S. Department of Agriculture was required to inactivate the large numbers of L. monocytogenes that developed in chicken gravy during refrigerated storage.