Rociletinib (CO-1686) enhanced the efficacy of chemotherapeutic agents in ABCG2-overexpressing cancer cells and o

Overexpression of adenosine triphosphate (ATP)-binding cassette subfamily G member 2 (ABCG2) in cancer cells is known to cause multidrug resistance (MDR), which severely limits the clinical efficacy of chemotherapy. Currently, there is no FDA-approved MDR modulator for clinical use. In this study, rociletinib (CO-1686), a mutant-selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), was found to significantly improve the efficacy of ABCG2 substrate chemotherapeutic agents in the transporter-overexpressing cancer cells and in MDR tumor xenografts in nude mice, without incurring additional toxicity. Mechanistic studies revealed that in ABCG2-overexpressing cancer cells, rociletinib inhibited ABCG2-mediated drug efflux and increased intracellular accumulation of ABCG2 probe substrates. Moreover, rociletinib, inhibited the ATPase activity, and competed with [I] iodoarylazidoprazosin (IAAP) photolabeling of ABCG2. However, ABCG2 expression at mRNA and protein levels was not altered in the ABCG2-overexpressing cells after treatment with rociletinib. In addition, rociletinib did not inhibit EGFR downstream signaling and phosphorylation of protein kinase B (AKT) and extracellular signal-regulated kinase (ERK). Our results collectively showed that rociletinib reversed ABCG2-mediated MDR by inhibiting ABCG2 efflux function, thus increasing the cellular accumulation of the transporter substrate anticancer drugs. The findings advocated the combination use of rociletinib and other chemotherapeutic drugs in cancer patients with ABCG2-overexpressing MDR tumors.

Techniques of autonomic nerve preservation in laparoscopic radical resection for rectal cancer / 中华胃肠外科杂志

Pelvic autonomic nerve is a three-dimensional structure surrounding the rectum. There are several key points related to nerve injury during laparoscopic radical resection for rectal cancer. Hypogastric nerve has close relation with the upper and middle part of the rectum. Combined with S2-S4 pelvic splanchnic nerve, hypogastric nerve forms pelvic plexus. Incorrect operation in pelvic parietal peritoneum during dissection of upper rectum will lead to nerve injury. When performing dissection of inferior mesenteric artery, bilateral nerve tracts should be pushed to posterior abdominal wall and anterior fascia of the abdominal aorta should be well protected to avoid nerve injury. Pelvic plexus fibers located lateral to the rectum of pelvic floor, as well as neurovascular bundle closed to Denonvillier's fascia, also have close relations with nerve injury. Dissection of either lateral or anterior wall of rectum should be performed behind the Denonvillier's fascia and in front of the proper fascia of rectum. Sharp dissection should be performed closed to the mesorectum to protect branches of pelvic plexus.

A comparative study of the laparoscopic appearance and anatomy of the autonomic nervous in normal males / 中华外科杂志

<p><b>OBJECTIVE</b>To further understand the anatomical basis of pelvic autonomic nerve preservation.</p><p><b>METHODS</b>Autopsy of five adult male donated cadavers was performed. Meanwhile, ten videos of laparoscopic total mesorectal excision for male mid-low rectal cancer admitted from January to June 2012 were observed and studied. Anatomical features of pelvic autonomic nerve were compared between autopsy and laparoscopic appearance.</p><p><b>RESULTS</b>Autopsy observations indicated that:the abdominal aortic plexus was situated upon the sides and front of the aorta, between the origins of the superior and inferior mesenteric arteries. The superior hypogastric plexus was a plexus of nerves situated on the the bifurcation of the abdominal aorta to sacrum; after incision of sacrum fascia was done cling to the sacrum; the pelvic splanchnic nerves and sacral splanchnic nerves were demonstrated; pelvic splanchnic nerves were splanchnic nerves that arised from ventral rami of the second, third, and often the fourth sacral nerves to provide preganglionic parasympathetic innervation to the hindgut;sacral splanchnic nerves providing postganglionic fibers, emerged from the sympathetic trunk, were then joined by the pelvic splanchnic nerves to form the inferior hypogastric plexuses which were placed lateral to the rectum.Laparoscopic observations showed that:abdominal aortic plexus and superior hypogastric plexus were unclear; at the level of sacroiliac joint, the hypogastric nerve began where the superior hypogastric plexus split into a right and left plexus, situated under the loose connective tissue, and continued inferiorly on its corresponding side of the body at the level of the 3rd sacral vertebra;left hypogastric nerve was closed to posterior of mesorectum;denonvilliers fascia was thin, reflective fascial structure, and easily removed together with mesorectum excision because of anterior loose structure.</p><p><b>CONCLUSIONS</b>Ligation of the inferior mesenteric artery at its origin is safe.Excessive dissection of the connective tissue covering the surface of the aorta should be avoided to protect the abdominal aortic plexus.Sharp dissection performed by pursuing the outer surface of the mesorectum maintaining the integrity of mesorectum, could avoid the superior hypogastric plexus and hypogastric nerves injury posteriorly, and protect the inferior hypogastric plexues while cutting lateral ligament laterally. The integrity of Denonvilliers fascia during anterior resection of rectum should be confirmed to avoid urogenitalis aparatus branches damage.</p>

Comparative study of outcomes after laparoscopic versus open pancreaticoduodenectomy / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the surgical and oncological outcomes after laparoscopic pancreaticoduodenectomy (LPD), and compare its efficacy with open pancreaticoduodenectomy (OPD).</p><p><b>METHODS</b>Clinical data of 40 patients with malignant tumor undergoing pancreaticoduodenectomy between January 2012 and January 2013 in our department were retrospectively analyzed. Patients were divided into LPD and OPD group according to operative procedure. Operative time, blood loss, harvested lymph nodes, drainage on first postoperative day (POD1), first flatus day, time to liquid diet, postoperative period of fever, postoperative hospital stay, postoperative complications, and 1-year cumulative survival rate and recurrence rate were compared between the two groups.</p><p><b>RESULTS</b>There were no significant differences between the two groups in operative time, harvested lymph nodes, TNM stages, postoperative period of fever, time to drain removal, postoperative complications, 1-year cumulative survival rate and recurrence rate (all P>0.05). As compared to OPD group, LPD group showed less blood loss [(168.2±87.4) ml vs.(353.5±140.1) ml, P<0.001], drainage on POD1 [(157.7±69.7) ml vs. (289.1±197.0) ml, P=0.039], earlier flatus [(4.1±0.9) d vs. (6.6±3.4) d, P=0.024], shorter time to liquid diet [(5.8±1.3) d vs. (8.2±3.5) d, P=0.040], earlier ambulation [(3.6±1.4) d vs.(6.2±1.5) d, P<0.001], and shorter postoperative hospital stay [(17.0±2.2) d vs.(25.7±13.8) d, P=0.047].</p><p><b>CONCLUSION</b>LPD confers similar surgical and oncological outcomes and is superior to OPD in terms of decreased blood loss and rapid postoperative recovery.</p>

Anxiety and depression of liver transplant recipients and the related impact factors / 中华器官移植杂志

Objective To evaluate the anxiety and depression status of the liver transplant recipients and to investigate the related impact factors.Method Forty-two liver transplant recipients were under survey by General Information Questionnaire (GIQ),Social Support Rating Scale (SSRS),Self-rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS) before and 1,6,12,24 and 36 months after operation.Result The mean anxiety scores before and 1,6,12,24 and 36 months after operation were 37.2 ± 5.3,32.2 ± 6.2,32.1 ± 6.6,31.9± 5.1,30.1 ± 4.6 and 28.5 ± 4.1,respectively.The mean depression scores at those 6 time points were 46.7 ± 7.1,37.9 ± 10.7,36.7 ±7.9,37.1 ± 6.4,34.3 ± 5.8 and 32.1 ± 5.6,respectively.Both the anxiety and depression scores showed statistically significant difference (P＜0).001) before and after operation (all time points).Also there was statistically significant difference (P＜0.001) between post-operative month 36 and other post-operative time points.The impact factors for anxiety of liver transplant recipients were subjective supports and the utilization level of the supports.The impact factors of depression of liver transplant recipients were pre-operative depression score,objective support,subjective supports and the utilization level of the supports.Conclusion Liver transplant recipients suffer less anxiety and depression after operation.The anxiety status can be further improved from 24 to 36 months postoperation.

Effects of hyperlipidemia on postoperative complications in patients of rectal cancer, open vs laparoscopic surgery / 中华普通外科杂志

Objective To study the effect of hyperlipidemia on postoperative complications in patients of colorectal cancer (CRC) undergoing open or laparoscopic surgery. Methods Clinical data of 382 CRC patients who received either traditional or laparoscopic operation from Mar. 2005 to Sep. 2009 were reviewed. By preoperative blood lipid levels, patients were divided into hyperlipidemia group and normal blood lipid group. Data were analyzed by Chi-square test and T test. Results In hyperlipidemia group of 201 CRC cases, volume of blood loss ( t = 11.318, P ＜ 0.01 ), time to resume oral intake( t =5.956, P ＜ 0.01 ), drainage tube removing (t = 4.781, P ＜ 0.01 ), hospital stay( t = 2.449, P ＜ 0.05 ), and incidence of wound liquefaction( x2 =3.988 ,P ＜0.05) were inferior to the other 181 cases in normal blood lipid group, while no difference was observed in operation time ( t = 0.374, P ＞ 0.05 ) and incidence of anastomotic leakage( x2 = 0.239, P ＞ 0.05 ). Patients who received laparoscopic operation had less blood loss (t=10.078 ,P ＜0.01 ), less time to resume oral intake(t =6.366,P ＜0.01 ) and earlier drainage tube removing ( t = 7.654, P ＜ 0.01 ), shorter hospital stay ( t = 4.241, P ＜ 0.01 ) and lower incidence of wound liquefaction ( x2 = 5. 203, P ＜ 0.05 ), though longer operation time ( t = 8.456, P ＜ 0.01 ) comparing with those receiving traditional operation. Among patients who received laparoscopic operation, there was no difference observed postoperatively in time to resume oral intake ( t = 0.356, P ＞ 0.05 ) and drainage tube removing (t = 0.261, P ＞ 0.05 ), and hospital stay (t = 0.248, P ＞ 0.05 ) between the hyperlipidemia group and normal blood lipid group, though the former suffered from more blood loss (t =8.784,P ＜0.01).Conclusions Hyperlipidemia impacts adversely on hemorrhage, delayed recovery and increasing rate of wound liquefaction on rectal cancer surgery. Laparoscopic surgery effectively eliminates prolonged postoperative recovery caused by hyperlipidemia.

Contrastive study on body fluid metabolism in patients with colorectal caner during laparoscopic or laparotomic surgery / 国际外科学杂志

Objective To investigate the effects of laporoscopic resection applied to colorectal cancer patients on metabolism. Methods According to patients' choice of operation, either laparoscopic-assisted (n = 22, experimental group) or open(n = 27, control group) resection of colorectal cancer was performed. The levels of electrolyte were assayed preoperatively, postoperatively and on the time of 24 hours after opera-tion. Rseults There was no significant difference in the level of electrolyte before operation between the two groups (P > 0. 05). Compared with the preoperative period, the level of serum potassium in the both groups were significantly increased after operation(P < 0. 05), and 24 hours later, the levels of electrolyte was not significantly different in both the two groups (P > 0. 05). During the postoperative period, the level of serum potassium in the experimental group was lower than the control group(P <0. 05), while the level of HCO_3~- was higher than the control group(P <0. 05), and there were no significant differences in the level of serum sodium, chloride and calcium between the two groups(P > 0. 05). Conclusions Laparoscopic-assisted re-section of colorectal cancer gives lower levels of stress responses compared to open surgery. However, it shows higher effect on the level of HCO_3~- , and must be paid more attention during operative and postopera-tive period.

Enteral and parenteral nutritional support for gastric cancer patients undergoing laparoscopic radical gastrectomy / 中华消化外科杂志

Objective To compare the effect and safety of enteral and parenteral nutritional support for gastric cancer patients undergoing laparoscopic radical gastrectomy(LRG). Methods Sixty gastric cancer patients received nutritional support after LRG at The Third Affiliated Hospital of Sun Yat-sen University from December 2007 to April 2010. All patients were randomly divided into the enteral nutrition(EN) group (n = 30)and parenteral nutrition (PN) group (n = 30) according to the random number table. Anthropometry, nutritional indexes, complications and expenses of the two groups were compared after treatment. All data were analysed by using the t test and chi-square test. Results Body mass index, triceps skin fold, mid-upper arm muscle circumference, hemoglobin levels, transferrin levels, and albumin levels were ( 16.9 ± 2.4) kg/m2, ( 10.6 ± 2.5 ) mm,(24.2 ±2.5) cm, (106 ± 15) g/L, (2.2 ±0.4) g/L and (39 ±3) g/Lin the EN group, and they were (16.6 ±2.1) kg/m2, (9.2 ± 1.3) mm, (24.0 ±3.4) cm, (102 ± 18) g/L, (2.0 ±0.4) g/L and (38 ±3) g/L in the PN group, respectively, with no significant differences between the two groups (t =0. 52, 1.72, 0.05, 0.93, 1.94,1.29, P ＞ 0.05). Prealbumin levels, nitrogen balance, time of first flatus, and daily expenses in the EN group were (0.30 ±0.10) g/L,0.8 ±0.3, (29 ± 10) hours and (210 ±30) yuan, while they were (0.25 ±0.09) g/L,0. 4 ± 0.2, (38±6) hours and ( 700 ± 50) yuan in the PN group, respectively, with a significant difference between the two groups ( t = 2. 03, 6. 08, 2. 25, 10. 38, P ＜ 0.05 ). One patient had dysbacteriosis, two were glycometabolic and two had a hepatic disorder in the EN group, while the corresponding numbers in the PN group were 9, 12 and 15 patients, respectively, with a significant difference between the two groups ( x2 =7.68, 9.32,13.87, P ＜ 0.05). Conclusions Nutritional support can promote the recovery of gastric cancer patients undergoing LRG. The efficacy of EN is superior to that of PN, and EN is the method of choice for nutritional support.