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A 32-year-old woman who complained of intermittent rectal bleeding prior to presentation was seen in the emergency department in an outside facility in March 2019. Medical history was non-contributory. The patient had a prior cesarean section in December 2005. There was no personal or family history of cancer. She underwent a colonoscopy in November 2019 that showed two lesions. The first measured 4×5 cm, with tumor appearance obstructing 50% of the rectal lumen, at 10 cm from the anal margin; pathology reported an infiltrating tubular adenocarcinoma. The second lesion was a 3.5 cm polyp in the middle third of the transverse colon, which was completely resected, with a pathology report showing an intramucosal tubular adenocarcinoma with free margins; this lesion did not require any other treatment.
The patient presented to our institution in December 2019, with an ECOG (Eastern Cooperative Oncology Group) of 0, and at that time reported no active bleeding. On physical examination, there were no masses palpable in the abdomen and no lesions noted on rectal and pelvic examination. An MRI of the pelvis was obtained.
Dr Sernaque: please Please describe the findings on imaging
MRI of the rectum showed a tumor, located at the level of the peritoneal reflection between the upper and middle rectum, with a cephalo-caudal diameter of 4.3 cm and 10 cm from the anal margin ( Figure 1 ), with heterogeneous signal, high signal in T2 sequence due to a mucinous component, and showing intense diffusion restriction due to its high tumor cellularity. It did not penetrate the muscular layer; lymph nodes were observed in the perirectal fat planes smaller than 1 cm.
A CT scan of the abdomen and pelvis showed that there were no distant metastases.
Dr Guevara: What would be the recommendation for the patient at this point?
This case was classified as a primary middle rectal cancer with intermediate disease without high risk factors for recurrence during clinical staging (no involved circumferential resection margin, no extravascular invasion and no cN2 or lateral lymph nodes reported on MRI). Total mesorectal excision upfront surgery was the best option for this patient with a very low local recurrence rate less than 3%. 1 2 Neoadjuvant chemoradiotherapy was considered an overtreatment for this patient because complete mesorectal excision was likely 3 with minimally invasive surgery, and because neoadjuvant treatment could have fertility consequences in this young patient.
The patient was recommended surgical treatment—anterior resection of the rectum—in April 2020, but she was diagnosed with COVID-19 with mild respiratory symptoms and the surgery was postponed. The patient underwent surgery in July 2020. Anterior resection of the rectum, assisted by laparoscopy with total excision of the mesorectum with end-to-end colorectal anastomosis was performed. Intra-operative findings were a 5 cm rectal tumor that compromised the middle and upper rectum, without serosal involvement; no suspicious lymph nodes were found, the hepatic surface appeared normal, and there were no signs of carcinomatosis. Of note, the previously documented polyp in the transverse colon had been resected at the time of colonoscopy. The duration of surgery was 210 min, and blood loss was 450 mL. After 3 days of an unremarkable post-operative period, the patient was discharged. The final pathology reported: a well-differentiated infiltrating adenocarcinoma with distal and proximal margins free of cancer, and radial margin compromised by invasive carcinoma; the tumor measured 7 cm; 66 lymph nodes were free of disease, with tumor deposits in peritumoral adipose tissue (pN1c). The final pathology report confirmed high-risk histopathological features for locoregional and systemic recurrence. The patient was categorized as a stage IIIB rectal cancer (pT3 pN1c M0). The standard treatment recommendation was for adjuvant treatment with radiotherapy and chemotherapy.
Dr Ribeiro: Based on the age of the patient and wishes for fertility, what options would you consider?
It is important to acknowledge that, up until now, no pelvic radiotherapy technique can effectively protect patient fertility without compromising their safety. In such cases, we typically recommend traditional options like oocyte and/or embryo cryopreservation to preserve the possibility of having a biological genetic child, as well as ovarian transposition to maintain gonadal hormonal production. However, it is crucial to note that, despite these interventions, none of the available options or techniques have enabled these patients to successfully carry a pregnancy to full term. Therefore, the utilization of a gestational carrier becomes necessary in order to achieve a successful pregnancy and childbirth for these individuals.
Recently uterine transposition, 4–6 has emerged as a novel potential alternative for preserving the fertility and hormonal function of these patients. In addition, it is an option that may allow for these young women to conceive naturally and spontaneously and then carry a full-term pregnancy.7 Thus, for this case, we would recommend combining different methods of fertility preservation to optimize the chances of a successful pregnancy. The first option would be embryo and oocyte cryopreservation associated with uterine transposition. Recently, the first case of a successful pregnancy and delivery after a uterine transposition was published.7
It is important to consider that, in developing countries, frequently in vitro fertilization (IVF) methods are not available. In this case, uterine transposition may be the only option these patients have to preserve their fertility.
A uterine transposition of the uterus and adnexa to the upper abdomen was considered before the start of radiotherapy. After a medical meeting with the specialties of gynecology oncology, medical oncology, radiotherapy, surgical oncology, medical genetics and psychology, and discussing with the patient the details of the procedure, the patient consented to proceed.
Dr Ribeiro: Who is the ideal candidate for uterine transposition and what should be the pre-operative workup?
Women 40 years of age or less, with a desire to preserve fertility and carry a child, and with an indication of pelvic radiation as part of a non-gynecologic pelvic cancer (rectal cancer, pelvic sarcomas, anal cancer) are the ideal candidates. All patients considering this procedure should have a consultation with a reproductive specialist and have their ovarian reserve evaluated with anti-mullerian hormonal level. It is crucial to consider that while this approach may not be universally available, it should be taken into account for patients in appropriate situations. It is of utmost importance to provide these patients with comprehensive information about all available options, which include embryo and/or oocyte preservation, surrogacy options, as well as adoption.
In the case of young patients who develop pelvic malignancies, it is highly recommended that they undergo a thorough genetics evaluation. Patients with colorectal cancers might have Lynch syndrome, while those with certain pelvic sarcomas may have Li-Fraumeni syndrome. In patients diagnosed with these syndromes, uterine transposition may still be a viable consideration. However, further discussions are necessary regarding the potential need for future prophylactic hysterectomy and/or oophorectomy, as well as the optimal timing for such procedures.
The transposition was performed by laparoscopy in August 2020 (5 weeks after the anterior resection). During the procedure a 7 cm normal uterus was found, right and left ovaries were normal, and there were adhesions in the left retroperitoneal space. This made it difficult to dissect the left gonadal vessels at the retroperitoneal level. After ligating the uterine arteries and dissecting the gonadal blood vessels, we evaluated the perfusion of the uterus using intravenous indocyanine green and fluorescence by laparoscopy. Adequate perfusion of the uterus and cervix were confirmed (Figure 2A,B). Lastly, the cervix was anastomosed to the abdominal wall at the level of the umbilicus (Figure 2C), in order to observe the vitality of the uterus in the post-operative period, because it was the first uterine transposition that we had performed in Peru. The duration of surgery was 360 min and the blood loss was 200 mL. The patient was discharged on the third post-operative day.
Dr Ribeiro: What should be the routine follow-up for a patient who undergoes uterine transposition?
After the surgery, it is advisable to transition patients to a regular diet as soon as possible. However, efforts should be made to prevent abdominal distention, as it can lead to the stretching of the uterine vessels. If the cervix was visualized through the umbilicus during the procedure, it is possible to assess the viability of the uterus on a daily basis by direct inspection. 8
Nevertheless, there is currently no clear guidance on how to proceed if ‘non-viability’ or ‘ischemia’ are observed during these assessments. Further investigation is necessary to determine the appropriate course of action in such cases. We advise conducting a Doppler ultrasound within 2–5 days after the surgery to evaluate uterine blood flow. However, the effectiveness of Doppler ultrasound is still being investigated due to the technical difficulty some radiologists encounter in locating the ovarian vessels when the uterus is positioned higher in the abdomen. Performing the Doppler ultrasound primarily aims to establish a baseline assessment of blood flow before initiating radiation therapy. If blood flow is not detected, we recommend further evaluation using MRI to assess uterine perfusion. In cases where no blood flow is observed and there are concerns about symptomatic ischemia, a hysterectomy may be necessary. However, even in such situations, it is possible that one or both ovaries still receive adequate blood supply, allowing for a conversion of the surgery to an ovarian transposition. 8 If there are no complications, radiation therapy can commence within 7–10 days following the surgery.
The patient had regular menstrual cycles after surgery and superficial necrosis of the cervical mucosa was observed, removal of necrotic tissue was performed, and adequate epithelialization of the cervical mucosa was observed during follow-up. The patient received radiotherapy 5040 cGy in 28 sessions in in the pelvis with 3D technique (Figure 3) plus capacitabine (825 mg/m2/day) from August to October 2020. The patient tolerated treatment well.
The repositioning of the uterus and adnexae to the pelvis was considered, but fearing that this surgery could delay the systemic treatment, it was decided to perform the repositioning of the uterus at the end of systemic treatment. The patient continued with chemotherapy using the CAPOX scheme: oxaliplatin (130 mg/m2/day 1), plus capecitabine (2000 mg/m2/days 1–14) in November and December 2020. The patient did not tolerate oral capecitabine and this was discontinued after three courses of chemotherapy. The patient continued chemotherapy with the FOLFOX scheme: oxaliplatin 85 mg/m2/day 1; leucovorin 400 mg/m2/day 1; fluorouracil (5FU) 1200 mg/m2/days 1 and 2; six cycles of chemotherapy were scheduled and the patient received the FOLFOX scheme 1 course in February 2021 with adequate tolerance.
The patient was followed; we performed the repositioning of the uterus and adnexae in the pelvis by laparoscopy in March 2021 (6 months after uterine transposition, the patient had regular menses through the umbilicus each month).
Dr Ribeiro: What is the work up prior to the repositioning of the uterus in the pelvis? What are the risks outlined to the patient for that procedure?
Once uterine perfusion is confirmed as mentioned above, there is no need for additional work up besides the cancer treatment exams. During the repositioning, performing pneumoperitoneum and placing the first trocar requires special attention as adhesions are expected and the cervix is attached to the umbilicus. Once the cervix is detached from the umbilicus this incision provides a 10 mm entry point for the first trocar. 8 Adhesions caused by the transparietal sutures and omental adhesions to the uterus and adnexa are commonly seen, and nevertheless can be easily released. However, it is important to anticipate some adhesion between the gonadal vessels and the colon. This specific adhesion requires careful management to prevent injury to these vessels and ensure uterine perfusion.These adhesions are the most frequent cause that prevents the uterus from reaching the pelvis. For patients with previous rectosigmoidectomy the vagina may be attached to the colon and extra care must be taken during vaginal dissection. After removing all adhesions, the uterus and adnexa can be brought to the pelvis. Individuals who have retained the cervix within the abdominal cavity may experience the development of a mucocele or hematocele. 8 Also, the bladder may be adhered to the vaginal vault and gentle dissection is mandatory to avoid bladder injury.
During the repositioning of the uterus into the pelvic cavity, it is crucial to ensure that no rotation occurs, as this can lead to the twisting of the gonadal vessels, and venous obstruction. Additionally, one must take into account the potential risk of dehiscence of the cervicovaginal suture following uterine repositioning, once irradiation increases the risk of dehiscence, emphasizing the importance of careful consideration in these situations. Lastly, while suturing the round and broad ligament to the pelvic side wall remnants, there is a risk of injuring the external iliac vessels and the ureter. Thus, this suture should be superficial and the ureter has to be visualized.
The surgical findings were: adhesions between the bladder, upper third of the vagina and rectum in the pelvis, and adhesions of the uterus and adnexa in the upper abdominal wall. Dissection and careful release of gonadal blood vessels, uterine and adnexa with ultrasonic energy was performed. A medium malleable retractor was introduced into the vagina, which helped to dissect and separate the vagina from the bladder and rectum, then a colpotomy was made at the apex of the vagina and an anastomosis with the cervix was made using vicryl 2/0 (Figure 4). The surgery lasted 180 min, with a blood loss of 100 mL. The patient was discharged on the second post-operative day.
The patient then completed the chemotherapy FOLFOX scheme every 2 weeks for six courses, from March to July 2021, with adequate tolerance. The patient was followed with a clinical examination, MRI of the pelvis, and colonoscopy. She regained normal menstrual cycles 1 month after surgery. The patient became pregnant spontaneously in March 2022, 7 months after completing chemotherapy. She had eight prenatal evaluations with unremarkable findings until the third trimester. The patient was admitted at 36 weeks of gestation due to ruptured membranes and the ultrasounds found a single fetus with a fetal weight lower than the third percentile (severe intrauterine growth restriction) associated with oligohydramnios and fetal well-being. The patient underwent a cesarean section in October 2022. A male newborn of 2500 g was delivered with an Apgar score of 8–9. Both mother and child had an uneventful hospitalization and were discharged without complication. In March 22, 2023, the child was 5 months old and weighed 7.5 kg, and was in good health. The patient’s last oncological follow-up was in January 2023, and there was no evidence of relapse on MRI and total colonoscopy.
Dr Ribeiro: What should be the short- and long-term follow-up for a patient undergoing uterine transposition?
In general, patients are discharged on the first or second day after surgery and prescribed extended thromboprophylaxis. We strongly encourage early ambulation and an early return to normal daily activities. It is important to avoid vaginal intercourse for a period of 8 weeks following surgery, or until a clinical examination confirms the absence of vaginal dehiscence and satisfactory healing has occurred. Three months after reimplantation a transvaginal ultrasound is performed to evaluate the pelvic organs, and hormonal levels are measured. Usually, patients will have already resumed normal menses. After that, the patients have a gynecologic evaluation every 6 months for 2 years and after that they can resume their routine gynecologic schedule. In parallel, patients must keep their oncological follow-ups according to the center’s standards. We recommend that the patients wait for at least 2 years before trying to get pregnant, since the majority of the recurrences occur within this period.
It is advised to inform young women who are being considered for uterine transposition about the innovative nature of this technique and the limitations of existing literature. Additionally, all such cases should be thoroughly and thoughtfully discussed in a multidisciplinary meeting to ensure that they are genuinely suitable candidates for this procedure.
Patient consent for publication
This work was approved by the Ethics Committee from Instituto Nacional de Enfermedades Neoplasicas (Letter Nro. 041-2023-CRPI-DI-DICON/INEN).
Contributors All authors contributed equally.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Not commissioned; internally peer reviewed.