Jayanta Chatterjee

Programmed death ligand-1 over-expression correlates with malignancy and contributes to immune regulation in ovarian cancer.

The programmed death-1 (PD-1) pathway is important in the maintenance of peripheral tolerance and homeostasis through suppression of T cell receptor signaling. As such, it is employed by many tumors as a means of immune escape. We have investigated the role of this pathway in human ovarian cancer (OC) to assess its potential role as a diagnostic and/or prognostic marker and therapeutic target, following recent clinical trial success of antibody therapy directed at this pathway. We show programmed death ligand-1 (PD-L1) expression on monocytes in the ascites and blood of patients with malignant OC is strikingly higher than those with benign/borderline disease, with no overlap in the values between these groups. We characterize the regulation of this molecule and show a role of IL-10 present in ascitic fluid. Flow cytometric analysis of T cells present in the ascites and blood showed a correlation of PD-1 expression with malignant tumors versus benign/borderline, in a similar manner to PD-L1 expression on monocytes. Finally, we demonstrate functional links between PD-L1 expression on monocytes and OC tumor cells with suppression of T cell responses. Overall, we present data based on samples obtained from women with ovarian cancer, suggesting the PD-1 pathway may be used as a reliable diagnostic marker in OC, as well as a viable target for use with PD-1/PD-L1-directed antibody immunotherapy.

Abdominal radical trachelectomy in West London

Please cite this paper as: Saso S, Ghaem‐Maghami S, Chatterjee J, Naji O, Farthing A, Mason P, McIndoe A, Hird V, Ungar L, Del Priore G, Smith J. Abdominal radical trachelectomy in West London. BJOG 2012;119:187–193.

Total laparoscopic hysterectomy for early stage endometrial cancer in obese and morbidly obese women.

This is a retrospective observational study, where we have evaluated the role of total laparoscopic hysterectomy (TLH) in obese and morbidly obese patients with early stage endometrial cancer. Our study illustrates that low conversion rates are achievable when appropriately trained surgeons undertake this procedure. All the women with high BMI were operated on laparoscopically in preference to laparotomy, unless there was an obvious contraindication such as a very large uterus or disseminated disease. We have also shown low conversation and complication rates for our patients, in particular a low rate of wound infection. This is in contrast to the high rate of wound infection and prolonged hospital stay reported for obese patients in the literature. Our study shows that TLH for endometrial cancer in obese women is feasible, safe and is likely to be cost-effective and adds to the weight of evidence for its use in this condition.

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.

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.

Risk of Ovarian Cancer Relapse Score: A Prognostic Algorithm to Predict Relapse Following Treatment for Advanced Ovarian Cancer

Objective The aim of this study was to construct a prognostic index that predicts risk of relapse in women who have completed first-line treatment for ovarian cancer (OC). Methods A database of OC cases from 2000 to 2010 was interrogated for International Federation of Gynecology and Obstetrics stage, grade and histological subtype of cancer, preoperative and posttreatment CA-125 level, presence or absence of residual disease after cytoreductive surgery and on postchemotherapy computed tomography scan, and time to progression and death. The strongest predictors of relapse were included into an algorithm, the Risk of Ovarian Cancer Relapse (ROVAR) score. Results Three hundred fifty-four cases of OC were analyzed to generate the ROVAR score. Factors selected were preoperative serum CA-125, International Federation of Gynecology and Obstetrics stage and grade of cancer, and presence of residual disease at posttreatment computed tomography scan. In the validation data set, the ROVAR score had a sensitivity and specificity of 94% and 61%, respectively. The concordance index for the validation data set was 0.91 (95% confidence interval, 0.85-0.96). The score allows patient stratification into low (<0.33), intermediate (0.34–0.67), and high (>0.67) probability of relapse. Conclusions The ROVAR score stratifies patients according to their risk of relapse following first-line treatment for OC. This can broadly facilitate the appropriate tailoring of posttreatment care and support.

Test of long‐term uterine survival after allogeneic transplantation in rabbits

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.

Immunology of Uterine Transplantation A Review

The idea of using organ transplantation to solve quality-of-life issues was first introduced a century ago, with cornea transplants and thrusted before the world again in 1998, following a controversial hand transplant. Uterus transplantation (UTn) has been proposed as another quality-of-life transplant for the cure of permanent uterine factor infertility. In order to proceed in humans, a greater appreciation of the immunological mechanisms that underlie UTn is desirable. Allogeneic UTn (animal model) was first described by 2 studies in 1969. The first and only human UTn, performed in 2000, was an early attempt with limited use of animal model experiments prior to moving onto the human setting. Since then, work using rat, mouse, ovine, goat, and nonhuman primate models has demonstrated that the uterus is a very different but manageable organ immunologically compared to other transplanted organs. Therefore, specifically exploring immunological issues relating to UTn is a valuable and necessary part of the inevitable scientific process leading to successful human UTn.

A rare sequel following cornual ectopic pregnancy: a case report.

One of the major concerns following cornual ectopic pregnancy, as shown in this case, is uterine rupture in future pregnancies. Uterine rupture has been described at 20 weeks gestation in a woman who had a cornual pregnancy treated by salpingectomy at 24 weeks, and as such it has been suggested by some experts that suturing the uterine wall to reinforce the defective area is advisable. Conversely, term deliveries have been described in patients with laparoscopic treatment of cornual pregnancies without reinforcing sutures. There is general agreement that suturing the uterine wall should be performed in cases where the cornual pregnancy sac extends into the endometrial cavity. Long-term follow-up of patients treated with cornual pregnancies with endometrial involvement may reveal the optimum treatment technique. In addition to surgical technique, patient counselling and appropriate debriefing regarding increasing interpregnancy interval is paramount in reducing maternal and fetal morbidity. Proper documentation in operative notes is vitally important for future reference.

The role of cytology and other prognostic factors in endometrial cancer

The clinical and prognostic value of positive cytology in women with endometrial cancer remains uncertain. The aim of our retrospective observational study was to determine whether in women with disease confined to the uterus, positive peritoneal cytology adversely affects disease-free (DFS) or overall survival (OS); to assess whether positive or negative cytology affects survival in women irrespective of stage and to assess whether the use of hysteroscopy or Pipelle for diagnosis affected cytology positivity rates. We have shown that median DFS and OS were almost identical for tumours confined to the uterus with and without positive peritoneal cytology. Women with tumours extending to the serosa or adnexa had a non-statistically significant shorter survival in comparison with women with stage I disease and negative cytology. Out of 59 women that had their cancer diagnosis based on a Pipelle biopsy of the endometrium, five had positive peritoneal washings. A total of 150 women had pre-treatment hysteroscopy; seven of these had positive peritoneal washings. There was no significant difference in the rates of positive cytology between these groups (4.6% vs 8.4%). In our cohort of un-staged women, positive peritoneal cytology did not adversely affect prognosis when disease was confined to the uterus.