Multispectral imaging of organ viability during uterine transplantation surgery in rabbits and sheep.

Uterine transplantation surgery (UTx) has been proposed as a treatment for permanent absolute uterine factor infertility (AUFI) in the case of the congenital absence or surgical removal of the uterus. Successful surgical attachment of the organ and its associated vasculature is essential for the organ's reperfusion and long-term viability. Spectral imaging techniques have demonstrated the potential for the measurement of hemodynamics in medical applications. These involve the measurement of reflectance spectra by acquiring images of the tissue in different wavebands. Measures of tissue constituents at each pixel can then be extracted from these spectra through modeling of the light­tissue interaction. A multispectral imaging (MSI) laparoscope was used in sheep and rabbit UTx models to study short- and long-term changes in oxygen saturation following surgery. The whole organ was imaged in the donor and recipient animals in parallel with point measurements from a pulse oximeter. Imaging results confirmed the re-establishment of adequate perfusion in the transplanted organ after surgery. Cornual oxygenation trends measured with MSI are consistent with pulse oximeter readings, showing decreased StO2 immediately after anastomosis of the blood vessels. Long-term results show recovery of StO2 to preoperative levels.

Achieving an early pregnancy following allogeneic uterine transplantation in a rabbit model.

OBJECTIVE: Uterine transplantation (UTx) has been proposed as a treatment option for women diagnosed with absolute uterine factor infertility (AUFI). The goal of UTx remains achieving pregnancy and live birth of a healthy neonate following allogeneic UTx. Our aim was to assess whether fertility was possible following allogeneic uterine transplantation (UTx), when the recipient had demonstrated long-term survival and had been administered immunosuppression. STUDY DESIGN: Nine allogeneic UTx in New Zealand White rabbits were performed using a pre-determined protocol. Tacrolimus was the immunosuppressant selected. Embryos were transferred into both cornua of the sole living recipient via a mini-midline laparotomy. The pregnancy was monitored with regular reproductive profiles and serial trans-abdominal ultrasound to measure conceptus growth (gestation sac and crown rump length (CRL)). RESULTS: In the sole surviving doe a gestation sac was visualised on ultrasound from Day 9 (D9) after embryo transfer. Gestation sac diameter and CRL increased from D9 to D16 but by D18 the gestation sac had reduced in size. The fetus was no longer visible, suggesting fetal resorption had occurred. Subsequent scans on D22 and D25 did not demonstrate a gestation sac. Scheduled necropsy on D27 and histopathology confirmed evidence of a gravid uterus and presence of a gestational sac. A single episode of acute rejection occurred on D13. CONCLUSION: Pregnancy was achieved after rabbit allogeneic UTx but serial ultrasound suggested that fetal demise occurred prior to scheduled necropsy. The study represents only the third example of conception and pregnancy following an animal allogeneic UTx.

Achieving uterine auto-transplantation in a sheep model using iliac vessel anastomosis: a short-term viability study.

OBJECTIVE: To investigate, develop and evaluate anatomical, surgical and anastomotic aspects necessary for a successful uterine transplant in a large-animal model. DESIGN: Sheep model; longitudinal study involving five ewes. SETTING: Royal Veterinary College, London, UK. POPULATION: Five ewes of proven fertility. METHODS: The uterine allograft along with the internal iliacs, and uterine arterial and venous tree all intact were harvested en bloc. An end-to-side anastomosis was performed between the external iliac vessels and the internal iliac vessels of the graft using 6-0 polypropylene. Successful reperfusion of the graft was initially judged by the color shift of the uterus during reperfusion. Blood flow past the venous and arterial anastomotic sites was also ensured by visual inspection, together with pulse oximetry and multispectral imaging. MAIN OUTCOME MEASURES: Operative details (retrieval, ischemic, clamping, reperfusion and recipient hysterectomy duration); physiological profiles; gross morphology and histopathology. RESULTS: Five autotransplants were performed. One procedure was abandoned because of the inappropriate size of sheep model. Another procedure was halted because the animal suffered from respiratory failure in the immediate intra-operative period. Three transplants were completed. In those, at least two of four possible anastomoses were finished and the grafted uteri demonstrated immediate perfusion and appropriate viability 45 min post-operatively. CONCLUSIONS: Internal to external iliac vessel anastomoses are an acceptable surgical technique that should be applied in a human model to ensure adequate subsequent uterine perfusion.

Uterine allotransplantation in a rabbit model using aorto-caval anastomosis: a long-term viability study.

OBJECTIVE: Uterine transplantation (UTx) has been proposed as a treatment option for women diagnosed with absolute uterine factor infertility. Allogeneic UTx has been attempted in a number of animal models, but achieving an adequate blood supply for the transplanted uterus still presents the biggest challenge. Microvascular re-anastomosis was unsuccessful in a number of animal models. The aim was to assess whether a large vessel aortic-caval vascular patch technique can bring about long-term graft survival after allogeneic UTx in a rabbit model. STUDY DESIGN: A longitudinal study involving uterine cross transplantations (n=9 donors, n=9 recipients) was performed in New Zealand white rabbits using an aortic-caval macrovascular patch harvested as part of the uterine allograft. All rabbits were allogeneic and of proven fertility, with at least one previous litter each. The end result of the donor graft harvest was a total hysterectomy transecting across the vagina and the most lateral aspects of the uterine horns together with an aortic-caval macrovascular patch (aorta, inferior vena cava, common and internal iliacs, and uterine arterial and venous tree). Tacrolimus (500 µg twice daily) was administered for immunosuppression post-transplant. The recipients were closely monitored until death or euthanasia. RESULTS: In this case series, long-term rabbit survival was 11% (n=1). Surgical survival was 56% (n=5). Three rabbits (UTx #3, #4 and #8) died intra-operatively as a result of blood aspiration, ventricular hematoma, and massive hemorrhage. Three does (#1, #2, #7 and #9) died within the first 24 h as a result of the veno-vena and anastomosis breakdown. Does #6 and #9 died secondary to pre-operative pneumonia and a pulmonary embolus, respectively. Only one rabbit survived longer than a month. CONCLUSION: Our method used a macrovascular patch technique to ensure adequate blood supply to the donor uterine graft. We have demonstrated the feasibility of uterine allotransplantation using this technique in the rabbit, but were unable to demonstrate a higher long-term survival percentage because of issues related to using a rabbit model.

Test of long-term uterine survival after allogeneic transplantation in rabbits.

AIM: To see if: (i) a large vessel aortocaval vascular patch technique may bring about long-term graft survival after allogeneic uterine transplantation (UTn) in a rabbit model; and (ii) fertility can be achieved following natural mating post-allogeneic UTn. METHODS: Allogeneic uterine cross transplantations were performed in New Zealand white rabbits using an aortocaval macrovascular patch harvested as part of the uterine allograft. Five rabbit recipients received a uterine graft from five unrelated donor rabbits. All female rabbits were unrelated and were of proven fertility with at least one previous litter each. Tacrolimus was administrated for immunosuppression post-transplant. Natural mating was attempted if long-term survival had been achieved. The main outcome measures were: (i) long-term recipient survival; (ii) long-term adequate uterine perfusion; and (iii) successful pregnancy post-UTn. RESULTS: All five recipient animals survived the surgery with satisfactory immediate postoperative recovery. Recipients 1, 2 and 4 died within the first 4 postoperative days. Both long-term survivors failed to conceive following introduction of a proven male breeder despite evidence of mating. Necropsy at 9 and 11 months showed a lack of patency of uterine cornua at the point of anastomosis, albeit a small uterus in recipient 3 and a reddish brown amorphous material at the site of the transplanted uterus in recipient 5. CONCLUSION: We have demonstrated the feasibility of uterine allotransplantation using a macrovascular patch technique, but could not demonstrate conception because of blocked cornua. To address this, we propose using embryo transfer techniques in order to achieve conception.

Long-term effectiveness of cholecystectomy and endoscopic sphincterotomy in the management of gallstone pancreatitis.

BACKGROUND: Gallstone pancreatitis (GSP) is a common condition, accounting for 30-40 % of all pancreatitis cases. All GSP patients should undergo definitive treatment to prevent further attacks. This study aimed to investigate the long-term outcome after definitive treatment in England by cholecystectomy, endoscopic sphincterotomy (ES), or both. METHODS: Hospital episode statistics data were used to identify patients admitted for the first time with GSP between January and December 2005. These patients were followed for 18 months to identify those who underwent definitive treatment. Treatment groups then were followed until December 2010 to identify readmissions with a further GSP attack as an emergency or admissions with complications of gallstone disease. RESULTS: 5,079 patients admitted with a first bout of GSP between January and December 2005. The in-hospital mortality rate was 7.8 %. Of those who survived the initial attack, 2,511 went on to have a cholecystectomy, 419 had an ES alone, and 496 had ES followed by cholecystectomy. Recurrent pancreatitis after definitive treatment was more common among patients treated with ES (6.7 %) than among those treated with cholecystectomy (4.4 %) or ES followed by cholecystectomy (1.2 %) (p < 0.05). Admissions with other complications attributable to gallstones in patients treated with ES alone were similar to those seen in patients who had received no definitive treatment (12.2 vs. 9.4 %). CONCLUSIONS: Cholecystectomy offers better protection than ES against further bouts of pancreatitis in patients with GSP, but ES is an acceptable alternative. Interval cholecystectomy in patients treated initially with ES was the most effective method of preventing further pancreatitis, and the patients who underwent treatment by ES alone remained at risk of readmission with gallstone-related problems. Patients who have undergone ES and are fit for surgery should have a cholecystectomy.

Laparoscopic versus open repair of inguinal hernia: a longitudinal cohort study.

BACKGROUND: Traditionally, repair of an inguinal hernia has been by an open method, but laparoscopic techniques have recently been introduced and are increasing in popularity. This study aimed to compare early and late outcomes following laparoscopic and open repair of inguinal hernia. METHODS: We performed an analysis of inpatient Hospital Episode Statistics. Early-outcome criteria studied include in-hospital mortality, length of hospital stay, complications (infection, bleeding, injury to an organ, and urinary retention), and readmission. Late outcome was assessed by the need for a further inguinal hernia repair on the same side. RESULTS: Between April 2002 and April 2004 there were 125,342 patients who underwent inguinal hernia repair and were included in the analysis. They were followed until April 2009. There were no differences in postoperative stay between the laparoscopic and open groups except for the laparoscopic bilateral hernia repair patients who had a shorter stay than the open group. Infection and bleeding were more common following open repair, whilst urinary retention and injury to an organ were more frequent after laparoscopic repair. Reoperation for another inguinal hernia was more common after laparoscopic (4.0 %) than after open repair of primary inguinal hernia (2.1 %), mostly in the first year after surgery. There was no difference in reoperation rate following repair of a recurrent inguinal hernia. Consultant caseload was strongly inversely correlated with reoperation following laparoscopic but not open repair of primary inguinal hernia. CONCLUSIONS: Reoperation is more common after laparoscopic than after open repair of primary but not recurrent inguinal hernia. Surgeons with a low laparoscopic hernia repair caseload have an increased reoperation rate following laparoscopic repair of primary inguinal hernia. The increase in reoperation rate following laparoscopic repair is seen in the first year or two following the initial surgery.

Twice recurrent gallstone ileus: a case report.

INTRODUCTION: Gallstone ileus is a rare cause of bowel obstruction and results from the passage of gallstones into the bowel. CASE PRESENTATION: We present the case of an 83-year-old Caucasian woman who had three episodes of gallstone ileus, each of which was managed with simple enterotomy. This sequence is one of the first reported in the medical literature and may be seen to challenge the traditional surgical approach of enterotomy alone. CONCLUSIONS: The available evidence comparing enterotomy alone with combined enterotomy, cholecystectomy, and fistula closure in the management of gallstone ileus is reviewed. Neither approach is clearly identified as superior, but available series suggest that simple enterotomy may be safer than a combined approach and does not result in a higher rate of recurrent biliary disease.

Single-center comparative study of laparoscopic versus open colorectal surgery: a 2-year experience.

AIM: To examine the change in practice from open to laparoscopic practice in our local trust, a national training colorectal unit. METHODS: Retrospective comprehensive review of clinical case notes of all colorectal resections between October 2007 and October 2009. Patients were identified through clinical coding and data were analyzed using SPSS. RESULTS: Comparison of 113 open versus 103 laparoscopic colorectal surgeries for various indications and short-term outcomes was made. There was an expected overall increase in the laparoscopic colorectal resections. The mean age was 73 years for open and 68 years for laparoscopic surgeries. There was no significant difference between the 2 groups with respect to age, sex, and the American Society of Anaesthesiologists. Of the 103 patients who were initially treated with laparoscopy-assisted colectomy, 12 (11.7%) were shifted to open procedures. Perioperative recovery was faster in the laparoscopic-surgery group than in the open-colectomy group, as reflected by a shorter hospital stay (median, 8 vs. 13 d). The overall complication rate was significantly less in the laparoscopy-assisted colectomy group than in the open-colectomy group (33% vs. 46%, P=0.05). CONCLUSIONS: Our local hospital practices support the many benefits of laparoscopic colorectal surgery. Substantial improvements in rates of hospital stay and wound infection were noted, hence shifting our practice safely in a district general hospital.

Gangrenous cholecystitis in an asymptomatic patient found during an elective laparoscopic cholecystectomy: a case report.

INTRODUCTION: Gangrenous cholecystitis is a severe complication of acute cholecystitis. We present an unusual case of gangrenous cholecystitis which was totally asymptomatic, with normal pre-operative parameters, and was discovered incidentally during a laparoscopic cholecystectomy. We have not found any similar cases in the published literature. CASE PRESENTATION: A 79-year-old British Caucasian man presented initially with acute cholecystitis which responded to conservative management. After six weeks he was asymptomatic and had normal blood parameters. An elective laparoscopic cholecystectomy was performed and our patient was found to have a totally gangrenous gall bladder. CONCLUSION: It is important to keep a high index of suspicion for the diagnosis of gangrenous cholecystitis in order to avoid potentially serious complications.

Uterine allotranspiantation in the rabbit model using a macrovascular patch technique.

The uterus and its blood supply en bloc were successfully harvested with an aortic-caval macrovascular patch in animal and human cadaveric models. The objective of this study was to assess the technical feasibility of uterine allotransplantation in the rabbit. Six uterine allotransplants were performed. This involved harvesting the uterine allograft with an aortic-caval vascular patch en bloc in the donor. After 1 hour of cold ischemic storage, the uterine allograft was transplanted to the recipient using an aortic-aortal cava-caval end to side anastomosis. Our 6 rabbit recipients surgically survived the procedure. After postmortem and histological analyses in the short term, all of the uteri appeared viable with no evidence of graft vessel thromboses. Postoperative complications included limb paraplegia, pulmonary emboli, and intraperitoneal hemorrhage. The feasibility of uterine allotransplantation using a macrovascular patch, in anatomical and surgical terms, has been proven. Further research will lead to a successful program of fertility restoration.

Pelvic vascular prospects for uterine transplantation.

While developing the technique of abdominal radical trachelectomy for conservative cervical cancer management, the vascular supply of the uterus was thoroughly examined. This was a prelude to study the possibility of uterine transplantation where initial concerns were about how uterine artery anastomosis might be achieved and the subsequent function of these vessels in pregnancy. In experiment 1, the uterine arteries in two sows were divided and reanastomosed. At 6 weeks, all sows including control were inseminated. After weaning 3 months after delivery, the sows were killed, and postmortem studies were undertaken. Successful reanastomoses of the uterine arteries were accomplished in both study sows. After insemination, pregnancy proceeded uneventfully, and both sows farrowed normally with average litter sizes. Histopathology of the uterine arteries revealed minimal intimal fibrosis across all anastomotic sites. Uterine artery anastomosis in the porcine model is feasible with subsequent normal vascular function in pregnancy of the anastomosed vessels.

Inequity of upper gastrointestinal cancer distribution and survival with socioeconomic deprivation: a population-based study.

BACKGROUND: It is postulated that patients with upper gastrointestinal cancers from affluent classes have better survival outcomes than those from deprived backgrounds. We aimed to analyze the incidence, mortality, and survival trends of esophageal, gastric, and pancreatic cancers in West Midlands, England, from 1986 to 2000 in terms of socioeconomic deprivation. METHODS: A well-validated demographic score, the Townsend Band, was employed as a measure of socioeconomic status. Data were collated from a cancer registry database; the individuals were allocated to 1 of 5 Townsend bands by using the postcodes at diagnosis. Relative survival rates were calculated by using stratified actuarial life tables, regression trend analysis at 1 and 5 years was performed, and the P value was derived from a t test statistic. RESULTS: An increase in esophageal cancer incidence was more marked in the affluent categories (127%), compared with the deprived categories (57%). Gastric cancer incidence fell preferentially by 31% and 47% in the most-deprived men and women, respectively, but remained relatively unchanged in the affluent groups. A marginal overall decrease in pancreatic cancer incidence masked preferential increases in the most-affluent men (39%) and women (41%). Small increases in 1- and 5-year survival were noted in affluent subgroups, with the 1-year survival advantage for esophageal cancer achieving significant levels in the most-affluent categories (P = .05). CONCLUSIONS: The esophageal cancer incidence increased preferentially in the affluent groups but with a marginally better survival rate. The gastric cancer incidence decreased noticeably in the most-deprived groups, suggesting that improvements in hygiene with consequent reduction in Helicobacter pylori primarily could be responsible. Pancreatic cancer trends were unrelated to social deprivation and warrant further studies.

Possibilities for fertility restoration: a new surgical technique.

Previously published work concluded that uterine artery microvascular anastomosis in the porcine model was feasible with subsequent normal vascular function in pregnancy. of the anastomosed vessels. The objective of this study was to assess the feasibility of uterine autotransplantation in a porcine model using microvascular anastomoses. Eight large white/landrace sows of proven fertility were used. A supracervical hysterectomy with or without bilateral salpingo-oophorectomy (BSO) was performed. After 1 hour of cold storage in a transplant solution, the specimen was reintroduced and followed by stepwise vascular reanastomosis. Objective perfusion index measurements suggested adequate uterine perfusion after transplantation. Postoperatively, sow 1 survived to 3 months with no signs of oestrus, and sows 2, 6, and 8 were killed on days 6, 33, and 54, respectively, for pelvic infection. Histopathology of the uterine grafts revealed gradual vessel thromboses. Microvascular reanastomosis is feasible, however, unsuccessful in uterine autotransplantation because of gradual vessel thromboses. The porcine model is highly susceptible to postoperative infection.

Is it feasible to use a large vessel patch with a uterine allograft en bloc for uterine transplantation?

Uterine auto-transplantation in the porcine model using a microvascular anastomotic technique failed because of gradual vessel thromboses. A macrovascular patch harvest with the uterus en bloc is probably less likely to undergo vessel thrombosis. The objective of this study was to assess the feasibility of an aortic/inferior vena caval vascular patch harvest with the uterus en bloc for uterine cross-transplantation purposes. A preserved human cadaver and freshly killed porcine and rabbit cadaveric models were used. The infrarenal aorta, inferior vena cava, common and internal iliac vessels and the uterine arterial and venous tree together with the uterus en bloc were successfully harvested intact as a large vessel patch and graft in both animal and human models. A macrovascular patch for uterine cross-transplantation is technically easy and feasible to harvest en bloc with the uterus in fresh cadaveric donors. This technique precludes live donors and makes cadaveric organ donation essential.