Neoadjuvant Chemotherapy With CAPOX Versus Chemoradiation for Locally Advanced Rectal Cancer With Uninvolved Mesorectal Fascia (CONVERT): Initial Results of a Phase III Trial.

OBJECTIVE: To compare neoadjuvant chemotherapy (nCT) with CAPOX alone versus neoadjuvant chemoradiotherapy (nCRT) with capecitabine in locally advanced rectal cancer (LARC) with uninvolved mesorectal fascia (MRF). BACKGROUND DATA: nCRT is associated with higher surgical complications, worse long-term functional outcomes, and questionable survival benefits. Comparatively, nCT alone seems a promising alternative treatment in lower-risk LARC patients with uninvolved MRF. METHODS: Patients between June 2014 and October 2020 with LARC within 12 cm from the anal verge and uninvolved MRF were randomly assigned to nCT group with 4 cycles of CAPOX (Oxaliplatin 130 mg/m2 IV day 1 and Capecitabine 1000 mg/m2 twice daily for 14 d. Repeat every 3 wk) or nCRT group with Capecitabine 825 mg/m² twice daily administered orally and concurrently with radiation therapy (50 Gy/25 fractions) for 5 days per week. The primary end point is local-regional recurrence-free survival. Here we reported the results of secondary end points: histopathologic response, surgical events, and toxicity. RESULTS: Of the 663 initially enrolled patients, 589 received the allocated treatment (nCT, n=300; nCRT, n=289). Pathologic complete response rate was 11.0% (95% CI, 7.8-15.3%) in the nCT arm and 13.8% (95% CI, 10.1-18.5%) in the nCRT arm ( P =0.33). The downstaging (ypStage 0 to 1) rate was 40.8% (95% CI, 35.1-46.7%) in the nCT arm and 45.6% (95% CI, 39.7-51.7%) in the nCRT arm ( P =0.27). nCT was associated with lower perioperative distant metastases rate (0.7% vs. 3.1%, P =0.03) and preventive ileostomy rate (52.2% vs. 63.6%, P =0.008) compared with nCRT. Four patients in the nCT arm received salvage nCRT because of local disease progression after nCT. Two patients in the nCT arm and 5 in the nCRT arm achieved complete clinical response and were treated with a nonsurgical approach. Similar results were observed in subgroup analysis. CONCLUSIONS: nCT achieved similar pCR and downstaging rates with lower incidence of perioperative distant metastasis and preventive ileostomy compared with nCRT. CAPOX could be an effective alternative to neoadjuvant therapy in LARC with uninvolved MRF. Long-term follow-up is needed to confirm these results.

Efficacy and Safety of Apatinib in Patients with Recurrent or Refractory Melanoma.

BACKGROUND: The prognosis of patients with metastatic malignant melanoma is very poor and partly due to resistance to conventional chemotherapies. The study's objectives were to assess the activity and tolerability of apatinib, an oral small molecule anti-angiogenesis inhibitor, in patients with recurrent advanced melanoma. METHODS: This was a single-arm, single-center phase II trial. The primary endpoint was progression-free survival (PFS) and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), and overall survival (OS). Eligible patients had received at least one first-line therapy for advanced melanoma and experienced recurrence. Apatinib (500 mg) was orally administered daily. RESULTS: Fifteen patients (V660E BRAF status: 2 mutation, 2 unknown, 11 wild type) were included in the analysis. The median PFS was 4.0 months. There were two major objective responses, for a 13.3% response rate. Eleven patients had stable disease, with a DCR of 86.7%. The median OS was 12.0 months. The most common treatment-related adverse events of any grade were hypertension (80.0%), mucositis oral (33.3%), hand-foot skin reaction (26.7%), and liver function abnormalities, hemorrhage, diarrhea (each 20%). The only grade ≥3 treatment-related adverse effects that occurred in 2 patients was hypertension (6.7%) and mucositis (6.7%). No treatment-related deaths occurred. CONCLUSION: Apatinib showed antitumor activity as a second- or above-line therapy in patients with malignant melanoma. The toxicity was manageable. CLINICALTRIALS.GOV IDENTIFIER: NCT03383237.

Ratiometric determination of hydrogen peroxide based on the size-dependent green and red fluorescence of CdTe quantum dots capped with 3-mercaptopropionic acid.

A ratiometric fluorescent nanoprobe is described for the detection of H2O2. It is based on the use of a mixture of green-emitting CdTe quantum dots (GQDs) and red-emitting CdTe QDs (RQDs). The two kinds of QDs have different size and different fluorescence response towards H2O2. The ratio of the emission intensities at 606 and 510 nm (under 365 nm photoexcitation) can be used as the analytical information. Even without any chemical modification of the surface of the QDs, the probe display high sensitivity and selectivity for H2O2. The fluorescence of small QDs is more effectively quenched by H2O2. Stern-Volmer analysis showed both static and dynamic quenching to occur. The probe works well in the 10~125 µM H2O2 concentration range and has a 0.3 µM detection limit (3σ/slope). Graphical abstract Schematic presentation of the ratiometric fluorescent nanoprobe composed of green-emitting and red-emitting CdTe QDs. λ, I, and k are the emission wavelength, emission intensity, and quenching/enhancement coefficient, respectively. The subscript 0 and 1 present the green-emitting and red-emitting CdTe QDs, respectively.

Aqueous synthesis of L-cysteine and mercaptopropionic acid co-capped ZnS quantum dots with dual emissions.

In this paper, L-cysteine (L-cys) and mercaptopropionic acid (MPA) co-capped ZnS quantum dots (QDs) with dual emissions have been successfully synthesized by a one-pot aqueous-phase synthesis method. The intensities of the dual emissions could be controlled by regulating the molar ratio of L-cys to MPA, and the fluorescence color also turned from blue to yellow accordingly. The relationship between the ligands and fluorescence was investigated and the results indicated that L-cys could cause two emissions and MPA improved the emission intensity. In addition, the L-cys-MPA co-capped ZnS QDs showed high photostability under UV irradiation. Therefore, the L-cys-MPA co-capped ZnS QDs, which show the dual emissions and tunable emission intensities, have great potentials for use in ratiometric fluorescence sensors and multicolor bioimaging.

Right hemicolectomy and multivisceral resection of right colon cancer: A report of 21 cases.

The long- and short-term outcomes in 21 patients with right colon cancer after right hemicolectomy and multivisceral resection surgery were investigated. Short-term therapeutic effects and long-term survival rate were retrospectively analyzed in patients with right colon cancer. These individuals underwent right hemicolectomy in combination with multivisceral resections including pancreatic head, duodenum, kidney, liver, gallbladder, and abdominal wall at the Department of General Surgery in the Henan Tumor Hospital between January 2003 and August 2014. The patients had an average age of 58.9 years (range: 39-78). Three patients had metastatic invasion only to the duodenum; meanwhile 18 patients had invasion to the duodenum and other adjacent organs. The median survival time was 41 months (95% CI: 6.972-75.028) with one death in the perioperative period. No patients lost follow-up. One-, 3-, and 5-year survival rate was 75%, 56%, and 43%, respectively. It was concluded that indications for surgery should be tightly controlled. Favorable clinical outcomes of right hemicolectomy and multivisceral resection surgery were demonstrated for patients with right colon cancer at the T4 stage.

A scoring system to predict the risk of anastomotic leakage after anterior resection for rectal cancer.

BACKGROUND: Various risk factors for anastomotic leakage after anterior resection for rectal cancer have been documented in previous studies. However, there have been no quantized studies to more accurately predict the risk of anastomotic leakage. METHODS: A total of 1,060 patients with rectal cancer who underwent anterior resection were included in the study. Potential risk factors for leakage including gender, age, body mass index (BMI), diabetes, preoperative radiotherapy, tumor size, level of anastomosis, intraoperative blood loss, concomitant resection of other organs and TNM stage were subjected to univariate analysis. Multivariate logistic regression analysis was used to identify the independent risk factors for anastomotic leakage. The scoring system was developed based on regression coefficient for each significant risk factor. RESULTS: Independent risk factors included male gender, low level of anastomosis from anal verge and high-volume intraoperative blood loss. These patients were separated into high risk, intermediate risk and low risk groups based on scores of 4-5, 2-3, and 0-1. The leakage rates of the three groups were 16.1%, 8.0%, and 1.9%, respectively (P < 0.001). CONCLUSIONS: The scoring system is effective and accurate for identifying a subgroup of patients at high risk for leakage.

[Clinical effects of pedicled omentum covering and wrapping the ureteral anastomosis to prevent ureteral anastomotic leakage after surgery of abdominal and pelvic tumors].

OBJECTIVE: To explore the clinical effects of pedicled omentum covering and wrapping the ureteral anastomosis to prevent ureteral anastomotic leakage after surgery of abdominal and pelvic tumors. METHODS: Clinical data of 64 patients with ureteral anastomosis after surgery of abdominal and pelvic tumors treated in our department from May 2005 to May 2012 were retrospectively analyzed. They were assigned into 2 groups. There were 23 patients of ureteral anastomosis combined with pedicled omentum surrounding and wrapping the anastomotic site (optimization group), and 41 cases of ureteral anastomosis alone (control group). The clinical data of all the 64 patients were reviewed and the therapeutic effects of the two treatment approaches were compared. RESULTS: At one week after the operation, there were 8 cases (34.8%, 8/23) with ureteral anastomotic fistula in the optimization group and 31 cases (75.6%, 31/41) in the control group (P = 0.010). In the postoperative days 1-3, the average drainage everyday from abdominal tube around the anastomotic site was 260.4 ml and 320.8 ml, respectively (P = 0.446). The average drainage volume everyday was 80.5 ml and 160.5 ml from the postoperative day 4 to day 7 (P = 0.015). The average time of removal of the peritoneal cavity drainage tube was 18.5 d in the optimization group and 32.6 d postoperatively in the control group (P = 0.015). CONCLUSIONS: Covering and wrapping the ureteral anastomosis with pedicled omentum can promote the rapid adhesion of surrounding tissues to reduce urine leakage and postoperative complications, and shorten the surgical treatment cycle.

[Common types of massive intraoperative haemorrhage, treatment philosophy and operating skills in pelvic cancer surgery].

OBJECTIVE: To explore the common types of massive intraoperative bleeding, clinical characteristics, treatment philosophy and operating skills in pelvic cancer surgery. METHODS: We treated massive intraoperative bleeding in 19 patients with pelvic cancer in our department from January 2003 to March 2012. Their clinical data were retrospectively analyzed. The clinical features of massive intraoperative bleeding were analyzed, the treatment experience and lessons were summed up, and the operating skills to manage this serious issue were analyzed. RESULTS: In this group of 19 patients, 7 cases were of presacral venous plexus bleeding, 5 cases of internal iliac vein bleeding, 6 cases of anterior sacral venous plexus and internal iliac vein bleeding, and one cases of internal and external iliac vein bleeding. Six cases of anterior sacral plexus bleeding and 4 cases of internal iliac vein bleeding were treated with suture ligation to stop the bleeding. Six cases of anterior sacral and internal iliac vein bleeding, one cases of anterior sacral vein bleeding, and one case of internal iliac vein bleeding were managed with transabdominal perineal incision or transabdominal cotton pad compression hemostasis. One case of internal and external iliac vein bleeding was treated with direct ligation of the external iliac vein and compression hemostasis of the internal iliac vein. Among the 19 patients, 18 cases had effective hemostasis. Their blood loss was 400-1500 ml, and they had a fair postoperative recovery. One patient died due to massive intraoperative bleeding of ca. 4500 ml. CONCLUSIONS: Most of the massive intraoperative bleeding during pelvic cancer surgery is from the presacral venous plexus and internal iliac vein. The operator should go along with the treatment philosophy to save the life of the patient above all, and to properly perform suture ligation or compression hemostasis according to the actual situation, and with mastered crucial operating hemostatic skills.

[The clinical application of compression hemostasis with an arc-shaped transperineal incision in front of the apex of coccyx in controlling presacral venous plexus hemorrhage during rectectomy].

OBJECTIVE: To evaluate the effect of compression hemostasis with an arc-shaped transperineal incision in front of the apex of coccyx in controlling presacral venous plexus hemorrhage during rectectomy. METHODS: From October 2002 to October 2012, 52 patients with rectal cancer received neoadjuvant radiotherapy and developed presacral venous plexus hemorrhage during rectectomy, included 36 male and 26 female cases. Their age were 36-65 years. The hemostasis time and blood loss were analyzed. RESULTS: All 52 patients achieved R0 resection. Of which 13 patients achieved suture hemostasis within 15 minutes, whereas 22 patients unsuccessfully treated within 15 minutes received compression hemostasis with an arc-shaped transperineal incision in front of the apex of coccyx. The median blood loss was (196 ± 44)ml and hospitalization time was (15.2 ± 1.7)days in this group. Additionally, 7 patients achieved suture hemostasis within 20 minutes except 4 patients who received compression hemostasis, with a median blood loss of (1016 ± 86)ml and hospitalization time of (21.7 ± 6.3)days. Other 6 patients achieved suture hemostasis within 30 minutes except 3 patients who received compression hemostasis, with a median blood loss of (2508 ± 73)ml and the hospitalization time was (28.8 ± 3.3)days. There was statistically significant difference of bleeding (F = 4289.562) and hospitalization time (F = 50.121) in 3 groups of patients (P = 0.000). CONCLUSIONS: Once intraoperative presacral venous plexus hemorrhage can't be stopped timely, compression hemostasis with an arc-shaped transperineal incision in front of the apex of coccyx is an effective alternative for the patients with rectal cancer who received neoadjuvant radiotherapy.

[Application of trans-abdominal-mediastinal drainage tube in patients with high risk of esophagogastric or esophago-jejunal anastomotic leakage].

OBJECTIVE: To evaluate the therapeutic effects of trans-abdominal-mediastinal drainage tube on the prevention of esophagogastric or esophago-jejunal anastomotic leakage. METHODS: A total of 79 patients underwent thoraco-abdominal radical resection for gastric cardia cancer, with high risk of leakage of the anatsomosis, from Aug. 2007 to Aug. 2011 were included in this study. They were assigned into 2 groups. Forty one patients had trans-abdominal-mediastinal drainage tube (improvement group) and 38 patients were without the mediastinal drainage tube (control group). The clinical data of all the 79 patients were reviewed and the therapeutic effects of the two treatment approaches were compared. RESULTS: There was anastomotic leakage in four patients of the improvement group. They were with stable vital signs and the median hospital stay was 29.3 days. There was anastomotic leakage in five cases of the contol group and all of them had high fever and chest tightness. One among those five patients had transdermal placement of thoracic drainage tube and was cured, and four among those five patients had second debridement operation, with 3 cured and one death case. Except the one death case, the median hospital stay of the control group was 53.4 days, significantly longer than that of the improvement group (P < 0.05). CONCLUSIONS: Although putting trans-abdominal-mediastinal drainage tube can not prevent the leakage of esophagogastric or esophago-jejunnal anastomosis, it can reduce the systemic inflammatory responses, death and painful suffering of the patients caused by anastomotic leakage.

[Application of an arc-shaped transperineal incision in front of the apex of coccyx during the resection of pelvic retroperitoneal tumors].

OBJECTIVE: To explore a better operative approach to resect complicated pelvic retroperitoneal tumors. METHODS: A total of 28 patients with complicated pelvic retroperitoneal tumors who received surgical resection in our hospital from 2006 to 2010 were included in this study. The surgical operation was assisted with an arc-shaped transperineal incision in front of the apex of coccyx. The operation time, intraoperative blood loss, death toll and length of hospital stay of the patients were retrospectively analyzed. RESULTS: The median operation time was 122.5 minutes. The median blood loss was 420 ml, and the median length of hospital stay of the patients was 17.5 days. There was no postoperative death in this group of patients. CONCLUSION: With the assistance of this arc-shaped transperineal incision in front of the apex of coccyx, the resection of pelvic retroperitoneal tumors can be effectively improved and the surgery risk is reduced.

[Effects of splenic flexure and sigmoid colon variation on the types of anastomosis after left colectomy].

OBJECTIVE: To explore the effects of splenic flexure and sigmoid colon variation on anastomosis after left colectomy. METHODS: The clinical data of 76 descending colon patients were collected retrospectively from March 2004 to April 2011 at our hospital. Statistical analysis was performed for the types of splenic flexure and sigmoid colon with regards to the choice of anastomosis. RESULTS: There were mesenteric type (n = 55), mobile type (n = 7) and adhesive type (n = 14) for splenic flexure. And among 61 regular types, 15 were of variable type for sigmoid colon variation. There was significant difference of anastomosis between the types of sigmoid colon variation [43 (78.2%) vs 5 (71.4%) vs 9 (64.3%), P > 0.05] while no significant difference existed between the types of splenic flexure [I type 56(91.8%) vs II type 1 (14.3%), III or IV type 0, P < 0.05]. CONCLUSION: A clinician should pay more attention to the types of sigmoid colon variation. And it helps to select the right approach of anastomosis after left colectomy.

[Direct dissection of urogenital diaphragm in abdominoperineal resection].

OBJECTIVE: To compare the clinical outcomes of two operative approaches of perineal dissection in rectal carcinoma undergoing abdominoperineal resection. METHODS: A randomized controlled trial was conducted in a total of 126 patients with rectal cancer undergoing the Miles operation from June 2007 to June 2011 at Henan Provincial Cancer Hospital. They were divided into 2 groups. One group (Group A) underwent a direct dissection of urogenital diaphragm while another group (Group B) received the traditional operative method. And the duration of perineal surgery, rupture of rectum or tumor, urethral injury and the post-operative rate of perineal hemorrhage were compared between 2 groups. RESULTS: Group A had a shorter duration of perineal surgery ((16 ± 5) min vs (23 ± 5) min, P = 0.032). And the differences were significant statistically. However the rupture of rectum or tumor, urethral injury and the post-operative rate of perineal hemorrhage were equivalent for two groups (1 vs 5, 2 vs 5, 0 vs 1, 1 vs 3, all P > 0.05). CONCLUSION: A direct dissection of urogenital diaphragm offers more clinical advantages over the traditional operative method in abdominoperineal resection.

Prognostic Value of the post-operative Red Blood Cell Distribution Width in rectal cancer patients with neoadjuvant chemoradiation followed surgery.

Purposes Several studies have reported that elevated red  cell distribution width (RDW) is related to poor prognosis in several cancers; however, the prognostic significance of perioperative RDW in rectal cancer patients which received neoadjuvant chemoradiation therapy (NACRT) is unclear. Methods A total of 120 rectal cancer patients who received NACRT followed surgery were retrospectively reviewed from Affiliated Cancer Hospital of Zhengzhou University between 2013 to 2015. Data for peripheral blood tests prior to the initiation of NACRT，before surgery and first chemotherapy after surgery were collected，respectively. The optimal cutoff values of RDW was determined by ROC analysis, respectively. The relationship between RDW and the prognosis of patients was evaluated by, respectively. Results The post-operative RDWHigh (≥15.55) patients had significantly worse five-year overall survival (OS, P=0.001) and disease-free survival (DFS, P=0.001) than the post-operative RDWLow (<15.55) patients, respectively. Whereas high pre-operative RDW  (≥16.45) was the only marker correlated with worse DFS (P=0.005) than the pre-operative RDWLow (<16.45)patients, no relationship was found between pre-RDW and prognosis(OS, P=0.069; DFS, P=0.133). Multivariate analysis showed post-operative RDW had better predictive value than pre-RDW and pre-operative RDW. Conclusion Post-operative RDW might be a useful prognostic indicator in rectal cancer patients received neoadjuvant chemoradiation.

Cu-Mn codoped ZnS quantum dots-based ratiometric fluorescent sensor for folic acid.

In the design of new fluorescent sensors, exploration of new materials with excellent properties and smart designs is of continuing interest. Herein, we designed a dual-emission ratiometric fluorescent sensor by doping ZnS quantum dots (QDs) with Cu2+ and Mn2+ ions. The codoped ZnS QDs with two separated dopant emissions were used as ratiometric fluorescent sensors for folic acid (FA). With addition of FA, the Cu dopant emission was quenched while the Mn dopant emission was enhanced. The fluorescence intensity ratios versus the FA concentrations could be fitted to a linear regression equation ranging from 0.01 to 5 µM (R2 = 0.995) and the detection limit was calculated to be 6 nM. Thus, this method generated ratiometric fluorescence signals for quantitative detection of FA. To understand the specific fluorescence response of the sensors for FA, the sensing mechanism was proposed based on electron transfer between QDs and FA. Additionally, the sensors were successfully applied to the determination of FA in spiked samples and recoveries were ranged from 95.5 to 102.2%. Therefore, the sensors show high sensitivity and selectivity for FA and the proposed method has good potential for extension to the detection of other biological molecules after further development.