Discovery of an orally effective double-stapled peptide for reducing ovariectomy-induced bone loss in mice

Stapled peptides with significantly enhanced pharmacological profiles have emerged as promising therapeutic molecules due to their remarkable resistance to proteolysis and performance to penetrate cells. The all-hydrocarbon peptide stapling technique has already widely adopted with great success, yielding numerous potent peptide-based molecules. Based on our prior efforts, we conceived and prepared a double-stapled peptide in this study, termed FRNC-1, which effectively attenuated the bone resorption capacity of mature osteoclasts in vitro through specific inhibition of phosphorylated GSK-3β. The double-stapled peptide FRNC-1 displayed notably improved helical contents and resistance to proteolysis than its linear form. Additionally, FRNC-1 effectively prevented osteoclast activation and improved bone density for ovariectomized (OVX) mice after intravenous injection and importantly, after oral (intragastric) administration. The double-stapled peptide FRNC-1 is the first orally effective peptide that has been validated to date as a therapeutic candidate for postmenopausal osteoporosis (PMOP).

Intracorporeal esophagojejunostomy using hemi-double-stapling technique after laparoscopic total gastrectomy in gastric cancer patients

PURPOSE: To present the feasibility and safety of Roux-en-Y esophagojejunostomy using hemi-double-stapling technique after laparoscopic total gastrectomy. METHODS: We reviewed the outcomes from 58 consecutive patients with gastric cancer who underwent laparoscopic total gastrectomy. The clinicopathological characteristics including postoperative complications were examined. RESULTS: The mean age and body mass index were 57.3 ± 9.7 years and 23.7 ± 2.6 kg/m², respectively. The mean overall total operation was 199.8 ± 57.0 minutes. Intraoperative blood loss was 81.6 ± 56.3 mL and there was no open conversion. The patients' hospital stay was a mean 9.6 ± 2 days. The mean proximal margin of the specimens was 2.7 ± 1.8 cm. There were 3 cases (5.1%) of anastomosis leakage, but all were controlled successfully by endoscopic stent. CONCLUSION: The circular HDST technique is simple and reliable without any significant demerits with respect to safety concerns or difficulty of operation.

Value of double stapling technique with curved cutter stapler in low colorectal anastomosis / 上海第二医科大学学报

Objective To evaluate the value of double stapling technique with curved cutter stapler in colorectal anastomosis,especially in low colorectal anastomosis. Methods The clinical data of 168 cases of rectal carcinomas treated with double stapling technique with curved cutter stapler were retrospectively reviewed.The intraoperative condition,postoperative complications and findings during follow up were analysed. Results During the operations,the processes of closure and anastomosis of all the patients were satisfactory,and no operative death occurred.After the operations,4 cases(2.4%) had anastomotic leakage,3 cases(1.8%) had anastomotic bleeding,and 2 cases(1.2%) had rectovaginal fistula.All the complications were cured.There was no anastomotic stricture. Conclusion Double stapling technique with curved cutter stapler may help to accomplish low colorectal anastomosis which is a difficult task for handed suture.

Double Stapling Technique in the Management of Low Rectal Carcinoma / 中国微创外科杂志

12 months in 36 patients),during the follow-up 2 patients died.Conclusions The DST is minimally invasive for the treatment of low rectal carcinoma with high rate of anus conservation,and can improve the life quality of the patients.

The double stapling technique for anus-saving in rectal cancer / 临床外科杂志

Objective To evaluate role of double stapling technique in anus-saving operations for patient with low rectal carcinoma.Method The double stapling technique was used for anus-saving in colorectal anastomosis after anterior resection in 52 patiens with rectal cancer from 1994 to 1999,and the results were evaluated.Results 2 cases were failed to close rectal.4 cases were failed to anastomose.2 cases had anastomotic fistula(3.8%).3 cases had anastomotic stenosis (5.8%).2 cases had waund infection.1 case had anastomotic bleeding.There was no operative death.Conclusion The double stapling technigue provided a safe alternative for anus-saving operation in patients with rectal cancer.

Application of double stapling technique in low anterior resection of the rectal carcinoma / 临床外科杂志

Objective To evaluate the role of double stapling technique in low rectal anastomosis that can save anus.Methods 114 patients with low rectal cancer from June 1994 to January 2002 were treated by low anterior resection of the rectal carcinoma in which the double stapling technique was used,were valuated and the experience was presented.Results Operations of all the 114 patients were successful. Complication included anastomotic fistula in 4 patients (3.5%)and anastomotic stenosis in 5 patients (4.4%) and they were healed by irrigating ?draining the wound and enlarging anus respectively.Conclusion The low anterior resection of the low rectal carcinoma which can save anus becomes safe and time-saving .

Low Anterior Resection for Rectal Cancer Using Double Stapling Technique

PURPOSE: Since its introduction by Knight and Griffen in 1980, the double stapling technique has gained widespread popularity in performing the low anterior resection for the rectal cancer. But their effectiveness is not clear. The purpose of this study is to evaluate the usefulness of the low anterior resection using the double stapling technique for rectal cancer in an oncological, technical standpoints. METHODS: Perioperative and follow up data were retrospectively reviewed in all patients undergoing the low anterior resection using the double stapling technique by same surgeons for rectal cancer over a 2.5 year period. RESULTS: Thirty two rectal cancer patients had double stapling technique anastomoses. There was no postoperative mortality. Intraoperative complications including rectal wall tearing, incomplete doughnuts, misfiring and extraction related problems occurred in 9 of 32 patients (28.2%). Early and late postoperative complications occurred in 9 (28.8%) and 8 (24.9%) of 32 patients. Early anastomotic leak developed in 1 patient (3.1%) and anastomotic site bleeding developed in 2 patient (6.3%). Lately, the local recurrence occurred in 3 patients (9.3%) and anastomotic site stricture occurred in 3 patients (9.3%). CONCLUSIONS: The low anterior resection using the double stapling technique has relatively low rate of leakage, stricture, local recurrence. The double stapling technique can be performed for mid or low rectal cancer with greater safety and facility.

Clinical Review of the Double Stapling Technique for Lower Rectal Cancer

From January 1993 to December 1995, 47 patients with rectal carcinomas underwent a rectal anastomosis using the double stapling technique at the Surgical Department of Kwang-ju Christian Hospital. The major advantages of the double stapling technique for lower rectal cancer over the single stapling technique or a hand-sewn operation are as follows:1) Insertion of a purse-string suture is eliminated, and application of a linear stapler to close the distal rectum may be performed with greater ease. 2) In addition, fecal contamination and spillage of tumor cells from the rectal segment are minimized. 3) Differences in the sizes of the colons and rectums are not a concern in constructing the anastomosis. 4) The operating time is shorter. The following results were obtained by a comparison with 24 patients with rectal carcinoma who had undergone a rectal anastomosis using the double stapling technique from January 1989 to December 1992 which was reported in a previous study:1) Anastomotic stenosis was decreased from 8.3% to 4.2% because of reduced ischemia due to the double row of staples and the reduced injury due to compression of tissue between the anvil and the cartridge with experience. In addition, it resulted from reduced tension of the anastomosis due to sufficients mobilization of the proximal colon and from selection of large cartridge (33 mm). 2) Anastomotic leakage, even though the same location as the tumor and in the advanced age group, was decreased from 4.2% to 0% because the blood circulation was maintained and unnecessary tension was reduced with experience. In addition, it resulted from reinforced suture of the anastomotic site which was performed after anastomosis. 3) Systemic recurrence was the same result as that of the previous study(4.2/4.3%). 4) Local recurrence, even though at the same distal distance from the margin of the cancer, was increased from 0% to 2.1% because of advancing the pathologic stage (B2, C1>B1, B2) and increasing the poorly differentiated pathologic type.

Clinical Review of the Double Stapling Technique for Lower Rectal Cancer

From January 1993 to December 1995, 47 patients with rectal carcinomas underwent a rectal anastomosis using the double stapling technique at the Surgical Department of Kwang-ju Christian Hospital. The major advantages of the double stapling technique for lower rectal cancer over the single stapling technique or a hand-sewn operation are as follows:1) Insertion of a purse-string suture is eliminated, and application of a linear stapler to close the distal rectum may be performed with greater ease. 2) In addition, fecal contamination and spillage of tumor cells from the rectal segment are minimized. 3) Differences in the sizes of the colons and rectums are not a concern in constructing the anastomosis. 4) The operating time is shorter. The following results were obtained by a comparison with 24 patients with rectal carcinoma who had undergone a rectal anastomosis using the double stapling technique from January 1989 to December 1992 which was reported in a previous study:1) Anastomotic stenosis was decreased from 8.3% to 4.2% because of reduced ischemia due to the double row of staples and the reduced injury due to compression of tissue between the anvil and the cartridge with experience. In addition, it resulted from reduced tension of the anastomosis due to sufficients mobilization of the proximal colon and from selection of large cartridge (33 mm). 2) Anastomotic leakage, even though the same location as the tumor and in the advanced age group, was decreased from 4.2% to 0% because the blood circulation was maintained and unnecessary tension was reduced with experience. In addition, it resulted from reinforced suture of the anastomotic site which was performed after anastomosis. 3) Systemic recurrence was the same result as that of the previous study(4.2/4.3%). 4) Local recurrence, even though at the same distal distance from the margin of the cancer, was increased from 0% to 2.1% because of advancing the pathologic stage (B2, C1>B1, B2) and increasing the poorly differentiated pathologic type.

Double Stapling Technique in Low Anterior Resection for Rectal Cancer

The double stapling technique has become an established reconstruction method for patients undergoing low anterior resection. We have used a modification of the conventional technique in which the lower rectal segment is closed with a linear stapler (TA-55) and the anastomosis is performed by using the circular EEA(CEEA) instrument across the linear staple line of the double stapling technique. The aim of this study was to evaluate the prophylactic effect of a loop ileostomy preventing anastomotic leakage. Stapled colorectal anastomosis and stapled coloanal anastomosis in 60 patients forms the basis for the report. The sixty patients were treated by using the double stapling technique either with or without a loop ileostomy. This review presents the advantages and disadvantages of a loop ileostomy for coloanal anastomosis. Postoperative anastomotic leakage in the double stapling technique group occurred in 5 (10.6%)cases of the total 31 cases while in the double stapling technique with loop ileostomy group, it allowed 1(3.4%) of the total 29 cases. This study suggests that the double stapling technique with a loop ileostomy is more effective than the double stapling technique without a loop ileostomy in preventing anastomotic leakage. The addition of a loop ileostomy to protect the low anastomosis might also be expected to influence anastomotic healing.

Clinical application of double stapling technique in anus-preserving operation of low and middle rectal cancer / 中国现代普通外科进展

Objective:To study the clinical application and postoperative complication of double stapling technique (DST) in anus-preserving operation of low and middle rectal cancer. Method:From April 2002 to April 2006, clinical data of 75 cases with low and middle rectal cancer were analyzed retrospectively. Of those 32 cases used DST underwent sphincter-reserving operation(SPO),regard as study group;and 43 cases used SST received SPO, as control group. Clinical pathologic parameters、 postoperative complication and tumor recurrence were compared between the two groups. Results:Operation of all the 75 patients was successful without operative mortality. In DST group patients, defecation function was different from SST group after postoperative 3 and 6 months (P

A Simple Technique for Complete Removal of the TA Staple Line in Double Stapling Anastomosis of Rectal Cancer

Complete removal of the TA staple line in double stapling anastomosis was conducted in thirty one consecutive patients who underwent curative resection of rectal cancer(group A) and the results were compared to those for twenty one consecutive patients who did not undergo complete removal of the TA staple line(group B). There was no leakage in the patients who had the TA staple line completely removed, but there were anastomotic leaks in three patients who did not have it completely removed, (p=0.054). A diverting ileostomy was performed for two patient in group A, seven patients in group B(p=0.04). The distal resection margin of all patients of both groups showed negative results for tumor cell. There were no pelvic complications in either group. Two wound complications were seen in group A; one in group B. Stenosis of the anastomosis line occurred in one patient in group A and group B. Local recurrence around the anastomosis line occurred in one patient in group A, two in group B. Complete removal of the TA staple line in double stapling anastomosis appears to be superior to the usual double stapling technique.

Application of indigenous staplers for anus-preservation and postoperative target chemotherapy in low-situated rectal cancer / 解放军医学杂志

Objective To evaluate the effects of indigenous staplers on anus-preservation,and postoperative target chemotherapy to prevent local recurrence and distant metastasis of low-situated rectal cancer.Methods 284 patients with low-situated rectal cancer hospitalized during Jan.1990 to Dec.2004 in the Second Affiliated Hospital of PLA General Hospital were treated surgically with indigenous staplers for anus-preservation,interoperative implantation of iliac artery pump and postoperative target infusion chemotherapy.They were followed up for 2~8 years.The clinical data including the result of anus-preservation,local recurrence rate,distant metastasis rate and long-term survival rate were retrospectively analyzed.Results All the 284 patients received anus-preservation operation with successful result.Among them 282 cases(99.3%) undervent the operation once,and the remaining two(0.7%) were operated on twice with success.Control of defecation was good in 247 cases(87.0%),anastomotic fistula occurred in 2 cases(0.7%),stanosis of anastomosis occurred in 1 case(0.4%),and bleeding from anastomotic site occurred in 1 case(0.4%).The follow-up data were completely collected from 236 cases(83.1%).The 1-,3-,5-year local recurrence was found in 2 cases(0.8%),6 cases(2.5%) and 8 cases(3.2%),respectively.The 1-,3-,5-year distant metastasis was found in 11 cases(4.7%),22 cases(9.3%) and 10 cases(4.3%),respectively.The 1-,3-,5-year overall survival rate were 97.0%(229/236),86.0%(203/236) and 65.3%(154/236),respectively.Conclusion The use of indigenous staplers is safe and dependable in operation for anus-preservation in low-situated rectal cancer.Postoperative target chemotherapy may decrease the local recurrence rate and distant metastasis rate,and raise the long-term survival rate as well.