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.

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.

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.

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.

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.

Association of long non-coding RNA HOTTIP with progression and prognosis in colorectal cancer.

Long non-coding RNA (lncRNA) has an important role in carcinoma progression and prognosis. However, little is known about the pathological role of lncRNA HOTTIP (HOXA transcript at the distal tip) in colorectal cancer (CRC) patients. This study attempted to investigate the association of lncRNA HOTTIP expression with progression and prognosis in CRC patients. LncRNA HOTTIP expression was measured in 156 CRC tissues and 21 adjacent non-malignant tissues using qRT-PCR. In present study, our results indicated that lncRNA HOTTIP was highly expressed in CRC compared with adjacent non-malignant tissues (P<0.001), and positively correlated with T stage (T1-2 vs. T3-4, P = 0.001), clinical stage (I-II stages vs. III-IV stages, P = 0.003), and distant metastasis (absent vs. present, P = 0.014) in CRC patients. Furthermore, we also observed that increased lncRNA HOTTIP expression was an unfavorable prognostic factor in CRC patients (P = 0.001), regardless of T stage, distant metastasis and clinical stage. Finally, overexpression of lncRNA HOTTIP was supposed to be an independent poor prognostic factor for CRC patients through multivariate analysis (P = 0.017). In conclusion, lncRNA HOTTIP overexpression maybe serves as an unfavorable prognosis predictor for CRC patients. However, a further larger sample size investigation is needed to support our results.

Modified Glasgow prognostic score is an independent prognostic factor in patients with cervical cancer undergoing chemoradiotherapy.

OBJECTIVES: There is increasing evidence that the presence of an inflammation-based prognostic score (modified Glasgow prognostic score, mGPS) could predict survival in patients with advanced cancer. The aim of this study was to investigate the prognostic value of mGPS in patients with cervical cancer. METHODS: We included 238 consecutive patients with cervical cancer in our study. The albumin and serum C-reactive protein (CRP) were measured before initiation of treatment. The relationships between the mGPS and other clinical parameters including body mass index (BMI), white blood cell count, lymphocyte, platelet, hemoglobin, total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) were analyzed. Overall survival (OS) and progression-free survival (PFS) were calculated. Significant prognostic factors were identified using univariate and multivariate analyses. RESULTS: The 5-year OS rate for all patients was 52.1% and 5-year PFS rate was 42.3%. Patients with mGPS of 0, 1 and 2 were 138, 71, 29, respectively. Higher mGPS was related to more advanced disease, including higher FIGO stage, lymph node metastases and lower lymphocyte counts, BMI and hemoglobin level. Performance status (PS), FIGO stage, lymph nodal status and mGPS were independent prognostic indicators for OS and PFS in the multivariate analysis. CONCLUSIONS: Higher mGPS is associated with advanced cervical cancer. The mGPS is an easily measurable biomarker which can be used in combination with conventional FIGO stage to predict survival in patients with cervical cancer undergoing chemoradiotherapy.

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.

[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.

[Proximal gastrectomy versus total gastrectomy for adenocarcinoma of esophagogastric junction: a meta-analysis].

OBJECTIVE: To compare the efficacy of proximal gastrectomy(PG) and total gastrectomy(TG) for adenocarcinoma of esophagogastric junction. METHODS: Clinical trials comparing PG with TG for adenocarcinoma of esophagogastric junction published from 1990 to 2012 were searched in Cochrane library, Medline, Embase and China National Knowledge Infrastructure (CNKI), Wanfang Data. Review manager 5.0 was used for meta-analysis and outcome measures included mortality and complication morbidity, as well as nutritional state. RESULTS: A total of 10 studies including 2481 patients were identified and analyzed. The results showed no significant differences in the mortality(OR=1.00, P=0.99) and complication morbidity(OR=2.14, P=0.12) between PG and TG. However, anastomotic stenosis(OR=5.40, P<0.01) and reflux esophagitis(OR=7.12, P=0.01) were more frequently observed in PG group. The nutritional state in TG group was comparable with PG group(WMD=2.09, P=0.57). CONCLUSION: TG is superior to PG in reducing the morbidity of anastomotic stenosis and reflux esophagitis.

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.

[Efficacy observation of paralleled clipping of rectal ligament in resection of rectal cancer in obese male patients].

OBJECTIVE: To investigate the approach and efficacy of dealing the rectal ligament in resection of rectal cancer in obese male patients. METHODS: A total of 92 patients (BMI>25 kg/m(2)) undergoing resection of rectal cancer from December 2008 to December 2010 in Henan Tumor hospital were assigned into 2 groups according to the surgical technique, the modified group (paralleled clipping of rectal ligament, 48 patients) and traditional group (44 patients). Operative time, intra-operational bleeding, rectal ulceration, ureteral injury, mesorectal integrity, and positive rate of lateral margin of pelvic wall were compared between two groups. RESULTS: The operative time was (66.9±99.8) min in modified group, which was significantly shorter than that in traditional group [(125.4±12.2) min, P=0.000]. Intra-operative bleeding was (160.3±27.2) ml in modified group and (150.5±28.5) ml in traditional group (P=0.093). Rectal ulceration rated were 0 and 18.2% (8/44), mesorectal disintegrity rates were 6.2% and 22.7%, pelvic infection rates were 2.1% (1/48) and 20.4 (9/44) in modified and traditional groups respectively, whose differences were all significant (all P<0.05). No ureteral injury and positive margin were found in both two groups. CONCLUSION: The approach of paralleled clipping of rectal ligament around the rectum meets the principle of TME, which is simple, safe and effective.

[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.

[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.