Chiara Boccardo1 , Marilia Bedoni3 and Oreste Gentilini2
(1)
Department of Breast Surgery, European Institute of Oncology, Milan, Italy
(2)
Department of Breast Surgery Unit, San Raffaele Hospital, Milan, Italy
(3)
Department of Anesthesia, European Institute of Oncology, Milan, Italy
Chiara Boccardo
Email: oreste.gentilini@ieo.it
Oreste Gentilini (Corresponding author)
Email: gentilini.oreste@hsr.it
Keywords
PregnancySurgeryAnesthesia
Introduction
The concurrence of cancer and pregnancy is a relatively rare problem, occurring in about 1 in 1,000 pregnancies.
Whenever a pregnant woman undergoes nonobstetric surgery, consultations among her obstetrical team, surgeon(s), anesthesiologist(s), and neonatologist(s) are important to coordinate management.
The anesthetic plan for a pregnant patient must take into account: type of surgery, underlying medical conditions (including changes of pregnancy), effects of anesthesia and surgery on both the patient and the fetus, preferences of the patient, anesthesiologist, and surgeon. Laparoscopy is not contraindicated during pregnancy, but its advantages compared to standard laparotomy should be evaluated in the specific and individual context.
Anatomic and physiologic changes related to pregnancy and concerns about the fetus may require modifications to anesthetic and surgical management.
According to the American Congress of Obstetricians and Gynecologists, some general recommendations can be pointed out [1]:
· A pregnant woman should never be denied surgery if indicated regardless of trimester.
· Surgery should be done at an institution with neonatal and pediatric services.
· An obstetrics care provider with cesarean delivery privileges should be readily available.
· A qualified team should be promptly available to interpret the fetal heart rate.
During surgery the fetus is exposed to the transplacental effects of anesthetic agents. However, patients should be made aware that commonly used anesthetics, including enflurane, barbiturates, and narcotics, have been extensively used safely in pregnancy. It is important to highlight that the risks to the fetus during surgery are not just anesthetic-related but also intraoperative complications, such as hypoxia and hypotension. Furthermore, decreased placental perfusion secondary to long-term positioning of the mother in the supine position might represent a mechanical problem during late gestational age. Additionally, postoperative problems, such as fever, infections, gastrointestinal problems, and changes in nutritional intake, thrombosis, and pulmonary embolus, could have serious adverse effects on fetal well-being.
Physiological Changes During Pregnancy and Possible Surgical Implications
Physiological changes related to pregnancy occur in virtually all systems and are caused by both hormonal and mechanical factors.
Pertinent changes in major organ systems are briefly summarized below:
Cardiovascular
Cardiac output (CO) increases by 20 % at 8 weeks and continues to rise until 30–32 weeks of gestation, at which time it plateaus at approximately 50 % above baseline. After 32 weeks of gestation and until the beginning of labor, CO remains stable.
During surgical evaluation of the gravid patient, it is important to understand the effects of the gravid uterus on cardiac output. After 20 weeks’ gestation, the uterus is at the level of the bifurcation of the great vessels (at the level of the umbilicus). In the supine position, the gravid uterus compresses the inferior vena cava, reducing venous return and thereby reducing preload and cardiac output by as much as 25–30 % [2, 3].
Pulmonary
Beginning in the first trimester, increases in tidal volume and respiratory drive (due to the stimulatory effects of progesterone) cause hyperventilation and a chronic respiratory alkalosis. Oxygen consumption increases, and the displacement of the diaphragm leads to a 20 % decrease in functional residual capacity (FRC). The surgical team needs to take into account that decreased functional residual capacity occurs as a result of compression by the gravid uterus. As a result, the mother has a lower threshold for hypoxemia and atelectasis becomes more common [4, 5].
Hematologic
Plasma volume increases by 50 % by 32 weeks of gestation; total red blood cell mass increases only by 20–30 %, resulting in hemodilution. Pregnancy is a procoagulant state. The concentration of clotting factors is increased and there is reduced fibrinolysis. The risk of deep vein thrombosis (DVT) is highest in the 4–6 weeks’ postpartum, and this can be considered a challenge for the surgical team for the management of thromboprophylaxis [5]. Pneumatic compression should be considered in every patient, and pharmacologic thromboprophylaxis should be determined on a case-by-case basis, taking into account the expected scope and length of the procedure and whether the woman has risk factors for venous thrombosis in addition to the pregnancy (e.g., thrombophilia, prolonged immobilization, past history of venous thrombosis, malignancy, diabetes mellitus, varicose veins, paralysis, or obesity).
Gastrointestinal
Gastroesophageal reflux occurs in 30–50 % of pregnancies, most likely related to increases in intra-abdominal pressure and to decreased lower esophageal sphincter tone during all trimesters [6].
Renal
Glomerular filtration rate (GFR) and renal blood flow rise markedly during pregnancy, resulting in a physiologic fall in the serum creatinine concentration. In pregnancy, the kidneys increase by 1 cm in size, and the ureters become physiologically dilated because of the muscle-relaxing effects of progesterone and the pressure effect of the growing uterus.
Preoperative Evaluation
Pregnant patients who require surgery should be evaluated preoperatively in the same manner as nonpregnant patients. Additional testing is not indicated in an uncomplicated pregnancy. A thorough history should document underlying medical and obstetrical conditions, and the physical examination should include detailed assessment of the airway. Laboratory and other testing should be performed as indicated by the patient’s medical problems and the proposed surgery.
Timing of Surgery
Urgently needed surgery should be performed regardless of the trimester, whereas completely elective surgery should be postponed until after delivery. There is no strong evidence of increased risk of miscarriage or teratogenesis from anesthetic agents used during early pregnancy. Because common first trimester adverse outcomes (e.g., miscarriage, vaginal bleeding, fetal structural anomalies) may be attributed to surgery and anesthesia in the absence of other obvious causes, it is prudent to minimize exposure of the fetus to surgery and medication during pregnancy, especially during organogenesis. The first trimester background miscarriage rate is approximately 8–16 % of clinically recognized pregnancies under 13 weeks of gestation, and it is 2–4 % of pregnancies between 13 and 20 weeks. Estimates of fetal deaths during surgery in the first trimester suggest that the risks are between 8 and 11 %, but in these few small reports, indications or types of surgery were not specified and the risk of fetal malformation was not increased [7]. Therefore, patients should be reassured that surgery can be performed with minimal risks which are not demonstrated to be clearly increased compared to pregnancy without surgery in terms of miscarriage and malformation. The recommendation to perform surgery during the second rather than the third trimester, whenever possible, is primarily mechanical: in the early second trimester, the uterus is still small enough to not obliterate an abdominal operative field, and the risk of preterm labor may be lower when surgery is performed during the second trimester as compared with the third trimester [8].
Preoperative Preparation for Surgery
Fasting Guidelines
Standard adult fasting guidelines are applicable to nonobstetric surgery in pregnant patients. The American Society of Anesthesiologists (ASA) recommends that patients abstain from solid food for at least 6 h prior to surgery (8 h for fried or fatty foods); clear liquids, which have a more rapid gastric transit time, may be ingested until 2 h prior to surgery.
Aspiration Risk
Preoperative medication to minimize risk from aspiration in pregnant women is felt to be a reasonable precaution by most experts, although no specific intervention has been shown to improve clinical outcome. However, this is still an area of some controversy with some authors not endorsing aspiration prophylaxis: as gastric emptying is not affected by pregnancy, it is not clear whether gastric acid secretion is altered in pregnant women or the actual risk of aspiration appears to be small [6, 9].
Thromboprophylaxis
During pregnancy, the increasing of vitamin K-dependent coagulation factors and decreasing of protein C and S levels result in a hypercoagulable state. This effect protects against excessive blood loss at delivery, but also increases the risk of a thromboembolic event in the postoperative period. The 2012 American College of Chest Physicians (ACCP) clinical practice guideline on prevention and treatment of thrombosis recommends mechanical or pharmacologic thromboprophylaxis for all pregnant patients undergoing surgery. For laparoscopic procedures (gynecologic or general surgical) predicted to last >45 min, the use of low molecular weight heparin is suggested as well as for patients undergoing surgery for oncological reasons; mechanical thromboprophylaxis is a reasonable alternative for shorter procedures. Oral anticoagulants (warfarin) usually are contraindicated during pregnancy because of possible teratogenic effects. Early mobilization is encouraged to minimize the risk of deep vein thrombosis [10].
Antibiotic Prophylaxis
The need for antibiotic prophylaxis depends on the specific procedure. Most drugs are safe to use during pregnancy, including most antibiotics and medications to treat common conditions such as upper respiratory tract and gastrointestinal complaints. Antibiotics that can be administered safely in pregnant women include cephalosporins, penicillins, erythromycin, azithromycin, and clindamycin. Several studies have shown that prophylactic antibiotics administered preoperatively reduce the risk of surgical site infection (SSI) in patients undergoing surgery [11].
Analgesia
The most common indication for acute narcotic analgesic therapy is for postoperative pain relief. Women who require surgery during pregnancy can be safely treated with a variety of analgesic agents for postoperative pain with relative safety for the fetus. Paracetamol is safe in pregnancy and is a first-line analgesic. Nonsteroidal anti-inflammatory drugs (NSAIDs) are generally avoided because of premature closure of the ductus arteriosus, and they can also affect the fetal kidney, causing reversible oligohydramnios. Opiates are suitable for more severe pain [12].
Prophylactic Glucocorticoids
Administration of a course of antenatal glucocorticoids 24–48 h prior to surgery between 24 and 34 weeks of gestation can reduce perinatal morbidity/mortality if preterm birth occurs. This decision depends upon the urgency of the surgery, and the obstetrician’s estimate of whether the patient is at increased risk of preterm birth because of the underlying disease or the planned procedure.
Prophylactic Tocolytics
There is no proven benefit to routine administration of prophylactic perioperative tocolytic therapy. Tocolytics are indicated for treatment of preterm labor until resolution of the underlying, self-limited condition that may have caused the contractions.
|
General principles of nonobstetric surgery in pregnant women |
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1. Provide mechanical or pharmacologic thromboprophylaxis. |
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2. Follow standard fasting recommendations; additional aspiration prophylaxis is not necessary in patients not otherwise at risk of aspiration. |
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3. A variety of analgesic agents can be used with relative safety for the fetus. |
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4. Minimize disruption of fetal homeostasis by avoiding maternal hypotension, hypoxemia, and hypercarbia or hypocarbia. |
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5. Left laterally displace the uterus in the second half of pregnancy, to reduce the risk of hypotension. |
Anesthesiologic Management
Positioning
When the pregnant patient is placed in a supine position, the gravid uterus places pressure on the inferior vena cava resulting in decreased venous return to the heart. This decrease in venous return results in significant reduction in cardiac output with concomitant maternal hypotension and decreased placental perfusion during surgery. Supine patients beyond 18–20 weeks of gestation should be positioned with a 15 % left lateral tilt, to reduce aortocaval compression. Alternatively, a wedge may be placed under her right hip.
Fetal Heart Rate Monitoring
The fetal heart rate should be documented pre- and postoperatively at all gestational ages. The American College of Obstetricians and Gynecologists has stated that the decision to use intermittent or continuous intraoperative fetal monitoring should be individualized, based on factors such as gestational age, type of surgery, and available resources. For abdominal operations, some centers use transvaginal ultrasound to monitor fetal heart rate. If adequate maternal oxygenation and uterine perfusion are maintained, the fetus usually well tolerates surgery and anesthesia [1].
The fetal heart rate typically displays reduced variability with induction of general anesthesia, presumably by anesthetizing the brainstem center that modulates intrinsic cardiac automaticity.
Traditional teaching in the setting of fetal bradycardia, tachycardia, or repetitive decelerations, is to optimize uteroplacental oxygen delivery and blood flow (by minimizing aortocaval compression), to maintain maternal hyperoxia and normocarbia (by appropriate ventilation and adjustment of FiO2), and to correct hypovolemia and hypotension (if present, with fluids, blood, and/or vasopressors). These measures are recommended and may have some benefit [13].
Type of Anesthetic
The anesthetic plan for a pregnant patient must take into account:
· Type of surgery
· Underlying medical conditions (including changes of pregnancy)
· Effects of anesthesia and surgery on both the patient and the fetus
· Preferences of the patient, anesthesiologist, and surgeon
There are no studies showing differences in neonatal outcome (teratogenicity or preterm delivery) based on type of anesthetic; however, concerns regarding fetal drug exposure, maternal intubation, and maternal aspiration lead to a preference for regional anesthesia when possible. However, most non-obstetrical surgery in pregnancy is abdominal (laparotomy or laparoscopy), so the majority of cases are performed under general anesthesia.
The most common medications used during monitored anesthesia care) are propofol for sedation, fentanyl as an analgesic, and midazolam as an anxiolytic, administered in small incremental doses.
Sedation is generally minimized due to concerns related to the administration of sedative drugs during pregnancy:
· Sedation-induced hypoventilation may cause respiratory acidosis, with deleterious effects on placental circulation.
· Aspiration may occur during deep sedation, due to decreased gastroesophageal sphincter tone in pregnancy.
· Patients often request that drugs which may affect the fetus be avoided.
Induction of anesthesia through preoxygenation is critical during any stage of pregnancy. Although many clinicians continue the historic practice of rapid sequence intubation (RSI) in all pregnant patients, the incidence of aspiration at induction of anesthesia during pregnancy is low, and there is no evidence that RSI improves clinical outcome. However, it may be reasonable to manage pregnant patients who have not followed fasting guidelines or are felt to be at high risk of aspiration for other reasons, in the same manner as nonpregnant patients are at risk of aspiration. A healthy, fully preoxygenated nonpregnant woman will decrease her saturation level from 100 % to less than 90 % in approximately 9 min of apnea; it takes only 3 min for a term-pregnant patient to reach the same degree of desaturation and approximately 90 s in a morbidly obese pregnant patient [14].
Intubation during pregnancy has the same considerations as intubation at delivery. Most experts recommend rapid sequence intubation with cricoid pressure in all pregnant patients, due to concern that decreased lower esophageal sphincter tone leads to increased risk of regurgitation [15].
In all patients, the goal of hemodynamic and fluid management is to maintain perfusion and oxygenation to critical organs; during pregnancy, this includes fetal homeostasis, which relies on maternal blood pressure and oxygenation. Hypovolemia, drugs, neuraxial blockade, or aortocaval compression can cause hypotension, leading to a decrease in uteroplacental perfusion.
Anesthetic agents have minimal direct effects on uterine blood flow; however, many anesthetic agents have direct cardio-depressant or vasodilatory effects leading to hypotension and thus may indirectly lower uterine blood flow. The lower limit for acceptable maternal blood pressure is not known and is patient dependent; in the experience of one author and colleagues with fetal monitoring during nonobstetric surgery in the second trimester, the fetal heart rate remained in an acceptable range with maternal systolic blood pressure below 90 mmHg, with adequate inhalation anesthesia [16].
Mechanical ventilation should be adjusted to maintain the normal physiological chronic respiratory alkalosis of pregnancy. The PaCO2 to ET CO2 gradient decreases during pregnancy; thus, the goal for end-tidal carbon dioxide pressure (ET CO2) is around 30 mmHg. Because CO2 crosses the placenta relatively easily, higher levels of maternal CO2 may lead to acidosis and myocardial depression in the fetus; very low maternal CO2 and severe respiratory alkalosis (PaCO2 less than 23 mmHg and pH higher than 7.5) caused by maternal hyperventilation can compromise uterine blood flow and fetal oxygenation.
Laparoscopy Versus Laparotomy During Pregnancy
When laparoscopic techniques were initially described, pregnancy was considered a contraindication to laparoscopy. Effects of CO2 pneumoperitoneum on venous return and cardiac output, uterine perfusion, and fetal acid-base status were unknown. Laparoscopy was safely used in several series to evaluate pregnant patients for ectopic pregnancy. Those patients with an intrauterine pregnancy had no increase in fetal loss or observed negative effect on long-term outcome [20].
Major concerns of laparoscopy during pregnancy include injury to the uterus, decreased uterine blood flow, fetal acidosis, and preterm labor from increased intra-abdominal pressure. During the second trimester, the uterus is no longer contained within the pelvis. There has been much debate regarding abdominal access in the pregnant patient with preferences toward either a Hasson technique or Veress needle. The concern for the use of the Veress needle has largely been based on concerns for injury to the uterus or other intra-abdominal organs. Because the intra-abdominal domain is altered during the second and third trimesters, initially accessing the abdomen via a subcostal approach has been recommended [17, 18].
Trocar placement in the pregnant patient does not differ radically from placement in the nonpregnant patient early in pregnancy. Later in pregnancy, the camera port must be placed in a supraumbilical location, and the remaining ports are placed under direct camera visualization. The gravid uterus enlarges superiorly; adjustments in trocar placement must be made to avoid uterine injury and to improve visualization. An angled scope may aid in viewing over or around the uterus. The uterus should be manipulated as little as possible.
Decreased uterine blood flow from pneumoperitoneum remains theoretical because significant changes in intra-abdominal pressure occur normally during pregnancy with maternal Valsalva maneuvers. The risk for pneumoperitoneum may also be less than the risk for direct uterine manipulation that occurs with laparotomy. Fetal respiratory acidosis with subsequent fetal hypertension and tachycardia were observed in a pregnant sheep model but were reversed by maintaining maternal respiratory alkalosis. Additionally, in the small series comparing laparoscopy and open techniques, no significant difference in preterm labor or delivery-related side effects was observed. Some authors have recommended intra-abdominal insufflation pressures be maintained at less than 12 mmHg to avoid worsening pulmonary physiology in gravid women [19].
A laparotomy is more likely to interfere with pregnancy than an extraabdominal surgical procedure. Surgery for abdominal malignancies becomes increasingly difficult as the uterus enlarges. Access is impaired and an oncologically optimum resection is technically more difficult. The uterus might need retraction, but care is essential to avoid impairment of placental flow or placental separation. Major abdominal and pelvic surgery during pregnancy should be undertaken with the close cooperation of a multidisciplinary team involving an obstetrician, a neonatologist, and skilled anesthetists. Fetal monitoring during surgery, if feasible, is invaluable, and expert opinions on pharmacological suppression of a threatened miscarriage or premature labor are crucial. Treatments to improve fetal lung maturity should be administered prophylactically where surgery carries a risk of precipitating premature delivery.
Potentially, laparoscopic surgery in the pregnant patient should result in the proven advantages of laparoscopy seen in the nonpregnant patient: decreased pain, earlier return of gastrointestinal function, earlier ambulation, decreased hospital stay, and faster return to routine activity. In addition, a decreased rate of premature delivery due to decreased uterine manipulation, decreased fetal depression secondary to decreased narcotic usage, and a lower rate of incisional hernias may be seen in the pregnant patient [20].
The following table compares main advantages and disadvantages between laparoscopy and open approach (Table 3.1).
Table 3.1
Advantages and disadvantages of the use of laparoscopy instead of laparotomy in pregnancy
|
Advantages |
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Decreased fetal depression secondary to decreased narcotic requirement |
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Lower rates of wound infections and incisional hernias |
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Diminished postoperative maternal hypoventilation |
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Decreased manipulation of the uterus |
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Faster recovery with early return-to-normal function |
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Decreased risk for ileus |
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Disadvantages |
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Possible uterine injury during trocar placement |
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Decreased uterine blood flow |
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Preterm labor risk secondary to the increased intra-abdominal pressure |
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Increased risk of fetal acidosis and unknown effects of CO2 pneumoperitoneum |
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Decreased visualization with gravid uterus |
The Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) drew up recommendations on laparoscopic surgery during pregnancy that are briefly summarized in the following table [20]:
|
SAGES guidelines for the use of laparoscopy during pregnancy |
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1. Obstetric consultation is obtained preoperatively. |
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2. When possible, operative intervention is deferred until the second trimester, when fetal risk is lowest. |
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3. Pneumoperitoneum enhances lower extremity venous stasis already present in the gravid patient, and pregnancy induces a hypercoagulable state. Therefore, pneumatic compression devices are used whenever possible. |
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4. Fetal and uterine status, as well as maternal end-tidal CO2 and arterial blood gases, needs to be monitored. |
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5. The uterus needs to be protected with a lead shield if intraoperative cholangiography is a possibility. Fluoroscopy is used selectively. |
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6. Given the enlarged gravid uterus, abdominal access is attained using an open technique. |
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7. Dependent positioning is used to shift the uterus off the inferior vena cava. |
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8. Pneumoperitoneum pressures are minimized to 8–12 mmHg and not allowed to exceed 15 m. |
Surgical Complications and Pregnancy
Estimates of fetal deaths during surgery in the first trimester suggest that the risks are in the region of 8–11 % on the basis of a few small reports—which do not specify indications or type of surgery—with no increase in the risks of fetal malformation. Risks to the fetus during surgery are not just anesthetic-related, but also include intraoperative complications, such as hypoxia and hypotension [21].
Furthermore, decreased placental perfusions secondary to long-term positioning of the mother in the supine position is a mechanical problem in late pregnancy.
Additionally, postoperative problems, such as fever, infections, gastrointestinal problems and changes in nutritional intake, thrombosis, and pulmonary embolus, could have serious adverse effects on fetal well-being. Anxieties about anesthesia during pregnancy are probably greater than the actual risks. A background risk of a 15 % spontaneous abortion rate might not be appreciated, and therefore, any miscarriage might be blamed on the surgery or anesthesia.
However, a large analysis by Van Carsten et al. on 215 patients showed that surgery alone has the lowest complication rate compared to radiant therapy and chemotherapy (6.1 % VS 39.4 % VS 33.3 %) suggesting that surgery during pregnancy is preferable than other treatment modality [22].
Conclusions
Management of pregnant women with cancer has changed in the last decades. This change is due to the improvement of knowledge of the pathophysiology of pregnancy and of monitoring systems. Therefore, if before pregnancy was considered a “risk factor” for the well-being of the patient and the termination rate was higher, now pregnant patients can be operated safely.
Obviously the patient should be carefully evaluated in the preoperative setting to avoid any risk, and all the maneuvers for the protection of the fetus must be implemented. A multidisciplinary consultation is mandatory to minimize any kind of complication.
Many studies have been published and report less complication rate compared to chemotherapy or radiotherapy.
The choice regarding the surgical approach (laparotomy vs. laparoscopy) has changed too. In fact, the laparoscopic approach has proven to be feasible and complication rates are comparable to open surgery. In addition, post-op recovery has proven to be more favorable in terms of reduction of hospitalization and better control of postoperative pain. Therefore, in the absence of contraindications, we recommend the use of laparoscopy.
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