August 2022


October 2022

R.G.E. Broers (1,2), H.M.J. Werner (3,6), R-J.A.B. Mulder (6), F.H.Tijssen (2,4), B.C.T. van Bussel (2,7,8), T.T.W. van Herpt (2)
1. Department of Intensive Care Medicine, VieCuri Medical Centre, Venlo, the Netherlands, 2. Department of Intensive Care Medicine, 3. Department of Gynaecology, and 4. Department of Anaesthesiology, Maastricht UMC+, Maastricht, the Netherlands, 5. Department of Gynaecology, Laurentius Hospital Roermond, Roermond, the Netherlands, 6. GROW-School for Oncology and Reproduction, 7. Care and Public Health Research Institute (CAPHRI) and 8. Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands


R.G.E. Broers -
Case Report

Difficult decision-making in ICU patients with suspected advanced cancer: an illustrative case


Meigs syndrome is a rare clinical entity of benign origin in which a triad of ovarian tumour (usually ovarian fibroma or fibroid-like tumour), hydrothorax and ascites co-exist and raise suspicion of malignancy. Here, we report the case of a 60-year-old female presenting with a suspicion of ovarian cancer with pleural fluid and ascites, although eventually found to be of benign origin and curated after resection of the tumour. By presenting the case, we emphasise the importance of meticulously evaluating the differential diagnosis in patients with suspected advanced cancer in the absence of pathological confirmation. Moreover, we raise awareness for the complexity of evaluating which patient categories could benefit from intensive care treatment. In this specific case, with the absence of a pathological diagnosis, the option of benign cause is important to consider, even when possible malignancy interacts with a patient’s wishes for treatment.

A 60-year-old active female with a medical history of hypertension, stroke with good recovery and obstructive sleep apnoea, was referred by the community hospital with a symptomatic ovarian mass. On computerised tomography (CT), ovarian cancer was suspected, possibly with peritoneal carcinomatosis, although a benign cause could not be ruled out. She was referred to our tertiary centre in order to obtain a pathological diagnosis and for treatment. She was admitted to the operating theatre for an explorative laparotomy with removal of the adnexal mass and ovary. During the introduction of anaesthesia for the intubation procedure suffered a circulatory collapse and underwent cardiopulmonary resuscitation for two minutes. While the intensive care physician was consulted, she had a return of spontaneous circulation. The laparotomy was cancelled and she was admitted to the intensive care unit (ICU) with mechanical ventilation support. She had severe respiratory problems (saturations remained 85%) despite high mechanical ventilation support conditions (FiO2 85% / 14 PEEP) while lacking a clear underlying diagnosis or therapy for her abdominal pathology. Admission of the patient to the ICU was not disputed. However, there were also concerns about the appropriateness of further treatment.

In the month prior to her admission, she had developed complaints of abdominal bloating, dyspnoea and weight gain. On physical examination, a mass was palpable in the lower abdomen, with a significant amount of ascites. Endovaginal and abdominal ultrasound scanning showed a 12 x 18 cm multilocular mass in the pelvis and hypodense lesions in the liver, suspicious for haemangiomas. A CT scan was performed indicating a 20 cm mass near her left ovary, ascites, bilateral pleural fluid and suggestions of cancerous peritonitis with local mesenteric and omental infiltration. No suspect lymph nodes or further metastases were seen. Prior ascitic and pleural fluid cytological examinations were negative for malignant cells. However, since tumour marker CA-125 was 1347 units/ml (reference 0-35 units/ml), metastatic ovarian cancer was a realistic possibility.

Despite her relatively young age, our patient had extensively deliberated beforehand on advanced care planning. Because of negative experiences within her family, she had made the decision not to undergo major surgery, chemotherapy or cardiopulmonary resuscitation. However, she did agree to undergo removal of the adnexal mass and contralateral adnexa, in order to reduce the symptoms and confirm a working diagnosis of ovarian cancer. After counselling, she also agreed to a resuscitation policy of 24 hours around the operation, while her previous wishes remained.

In the operating theatre she received an uncomplicated epidural anaesthesia. Despite existing pleural fluid, her saturation on room air was 95% prior to surgery. The intubation procedure initially started without complications with a common sedative (propofol 2 mg/kg), analgesic (sufentanyl 0.2 µg/kg) and muscle relaxant (rocuronium 0.7 mg/kg). She had a Cormack-Lehane grade 1 intubation using a videolaryngoscope. Immediately after the correct placement of the tube, she developed haemodynamic shock and despite treatment with norepinephrine and ephedrine she lost cardiac output and hence circulation. After two minutes of basic life support there was a return of spontaneous circulation and stable
haemodynamics with vasopressors. She remained low on saturations at 85-90%, despite mechanical ventilation support (FiO2 100%/14 PEEP), an adequate tube position and bilateral breath sounds. Ultrasound in the operating theatre showed bilateral lung sliding, only a limited amount of pleural fluid but diffuse hyperechogenic aspects and Kerley-B lines, confirming pleural oedema. A transoesophageal echocardiogram ruled out cardiac failure as a cause of the oedema. A chest CT ruled out pulmonary embolism and pneumothorax, while reconfirming ascites and large amounts of pleural fluids that compressed the dorsobasal lung fields.

The patient was transferred to the ICU for further diagnosis and treatment. The working hypothesis for haemodynamic shock and respiratory problems was supported by the combination of a marginal equilibrium in an underfilled patient, some possible preload restriction after positive pressure ventilation, and a preexistent increased intra-abdominal pressure due to ascites and tumour, all drastically disturbed by induction of anaesthesia. Treatment options in the ICU included draining of pleural fluid and drainage of ascites, in particular since removal of the tumour was cancelled.
Primarily, ascites drainage was chosen, removing approximately 4 litres of ascites. Later additional pleural drainage of the right lung oedema removed 0.5 litres. Chemistry of the ascites showed an albumin of 24.9 g/l with a serum albumin of 21 g/l; thus the serum-ascites albumin gradient was 0.3 g/dl, not suggestive of portal hypertension. After drainage, respiratory support could be reduced and she was extubated the next day. The patient explained that she did not want to risk another operation, and would rather opt for repeated ascites drainage, despite the fact that the working diagnosis of ovarian cancer had not been confirmed.

After recovery from the ICU she was discharged home. She was counselled by her treating gynaecologist at our tertiary clinic and she consented again to laparotomic removal of the adnexal mass. This would be beneficial or even curative in case of a benign diagnosis. The latter was also a realistic option in view of the repeatedly negative pleural and ascitic fluid cytology for cancer. However, she developed a pulmonary embolism and surgical treatment was postponed for another six weeks. Upon admission for surgery again, for optimisation, ascites and pleural puncture and drainage were performed. Finally the planned laparotomy commenced and a normal uterus with smooth serosal surface and two normal, small ovaries were seen. Next to the left ovary, but clearly separate, a large tumour (largely cystic and thin-walled, but partly solid) measuring approximately 25 cm was seen. Clinically there was no suspicion of malignancy. Extensive inspection also showed no evidence of cancerous peritonitis. The cyst was strongly adherent to the bladder, peritoneum and round ligament. The cyst was removed and sent for pathology examination. Here the benign aspect was confirmed as a benign cystic mass with predominantly solid areas and areas of fibrosis with siderophages, consistent with minor prior bleeding. No epithelial tissue was found that would match an ovarian carcinoma. There were sporadic mitoses, not suspicious for proliferative disease. Additional immunohistochemical stains (WT-1. CD56m desmin, ASMA
and CD10) were appropriate for a fibroma fitting the diagnosis of Meigs syndrome.

A prompt recovery after surgery was seen and symptomatology related to ascites and dyspnoea disappeared immediately after surgery. The CA-125 value is not repeated in benign diagnosis. Literature describes a normalisation of tumour markers after surgery.[1-3]

Admission of patients with (suspected) advanced cancer to the ICU has long been controversial, especially among those with respiratory failure requiring mechanical ventilation, like the patient in this case. Decisions regarding whether advanced cancer patients should be admitted to the ICU are based on complex considerations, including short- and long-term prognosis, quality of life, patients’ wishes and therapeutic options to treat cancer.
The long-term survival and intensive care survival for most patients with cancer has increased over the past decades. However, the probability of life-threatening events related to therapy requiring intensive care has also increased.[4-6] Therefore, intensivists worldwide are increasingly consulted for patients with cancer. Whilst the life expectancy for cancer patients in general is increasing, the one-year mortality of cancer patients (haematological and solid) with an unplanned ICU admission is consistently high. Recent literature reports that one-third of the cancer patients surviving ICU admission died within one year after ICU admission.[4] There is limited data on the quality of life (QoL) of these patients. Only a few studies, mainly in haematological malignancies, have investigated QoL in cancer patients after ICU admission and showed mixed results.[6-8]

In this case report we describe a case of an unexpected rare benign disease with recovery after ICU admission. The case shows a few things to consider as an anaesthesiologist, gynaecologist and intensivist. First, we would like to emphasise that when evaluating patients with suspected advanced cancer, an alternative diagnosis should always be considered in the absence of pathological confirmation, especially in patients who are otherwise healthy.
Although this case concerns a rare disease (estimated 1% of all ovarian tumours), there are other patient categories when ICU admission is sometimes needed, where an uncertain diagnosis occurs more frequently. For example, in hepatobiliary surgery it remains difficult to confirm the presence of hepatic, pancreatic or proximal bile duct malignancy preoperatively and some patients may undergo surgical resection and ICU admission for suspected malignant lesions, which subsequently turn out to be benign. Despite recent advances in diagnostic imaging, 5% to 10% of the patients who underwent Whipple’s procedure had a benign disease in the final histological examination, for example.[9,10] The same applies to suspected lung cancer, as a small percentage of patients (2.5%) may undergo major pulmonary resection for unexpectedly benign pathology.[11]

In Meigs syndrome, the combination of ascites, pleural fluid and a tumour mass quickly gives the impression of a malignant disease. Additionally, in this case, the CT scan suggested peritoneal metastases and the CA-125 was elevated. Both fed the suspicion of ovarian cancer, despite negative cytology. The prognosis for ovarian cancer with peritoneal metastases (stage 3) is poor. After five-years approximately 38% of the women are alive.[12] For this reason, intensivists will be cautious about long-term admission to an ICU with invasive treatments, such as mechanical ventilation, in confirmed ovarian cancer.

In this case there was an additional dilemma, which made the patient's treatment considerations complex. She had clearly indicated that she did not want major surgery or invasive treatment, such as chemotherapy. Also, her consent for resuscitation was only valid during anaesthesia and surgery. It was therefore plausible that a long intensive treatment on the ICU with mechanical ventilation would not comply with her wishes. However, a malignant cause of the ovarian mass was not confirmed and a benign cause was also a realistic option. Initial admission of this patient to the ICU was not disputed. However, the case illustrates many considerations when making decisions in critical illness, when data are incomplete. The patient wished for the most conservative treatment possible, it would thus have been an option not to perform ascites and pleural drainage and to discuss palliative management with her family if the respiratory failure did not improve. Acting in the best interest of the patient may create a conflict for different healthcare providers because of their perspective and interpretation of the situation. It must be sufficiently clear that the patient has made a well-considered decision, knowing that there is a chance of a benign disease. Additionally, real autonomy for the patient is only achieved when the other Principles of Health Care Ethics - non-maleficence, beneficence and distributive justice - are also discussed.[13] Non-maleficence and beneficence motivates healthcare providers to pursue a realistic solution for their patients while also refraining from doing harm. It puts the benefits of the treatment in perspective with the pain and suffering of the patient, which can also be caused by invasive treatment like ICU admission and mechanical ventilation.
In this case, at ICU admission when many variables were still unclear, we decided, after multidisciplinary consultation and in agreement with patient’s family, that further treatment with mechanical ventilation and pleural and ascites drainage still respected the patient's autonomy and was in line with her uncertain diagnosis.

We describe a rare gynaecological abnormality with a challenging clinical diagnosis and a favourable prognosis. Moreover, we attempt to show that the decision as to which patients can benefit from ICU admission remains a complex and multifactorial one, often based on limited information. There is significant uncertainty in outcomes after admission to the ICU and meaningful survivorship after intensive care is difficult to predict. Therefore, decisions regarding provision of organ support should be made with the involvement of
multidisciplinary teams. The possibility of a benign abnormality, even when possible malignancy interacts with patients’ wishes for treatment, is important to consider.

Demons-Meigs syndrome
Meigs syndrome (also known as Demons-Meigs syndrome) is a rare clinical presentation characterised by the clinical triad of benign ovarian tumour, hydrothorax and ascites, which should resolve completely after tumour resection. The latter which should resolve completely after tumour resection.[4-5] Patients usually present with dyspnoea, pelvic mass with or without abdominal tenderness and distension, and/or weight loss. Meigs syndrome, however, is a diagnosis of exclusion, only after ovarian carcinoma is ruled out.

Meigs syndrome occurs in 1% of all surgically removed ovarian tumours. It is mostly associated with ovarian fibroma, (fibro)thecoma or granulosa cell or Brenner tumours).[1-3] Abdominal tumours other than the benign tumours included in the definition of Meigs syndrome, with the same clinical triad, are called pseudo-Meigs syndrome. Those tumours could be benign or malignant.[1]

Meigs syndrome is extremely rare in women younger than 30 years. The syndrome is much more common in postmenopausal women, especially around 50 years, and its peak incidence is in women in their seventh decade.[1-3]

The pathophysiology of ascites and pleural effusion in Meigs syndrome is not well understood. Meigs theorised that ascites is due to the pressure of the tumour on the abdominal lymphatics, and the ascitic fluid then transferred via trans-diaphragmatic lymphatic channels into the pleural space.[14,15]

Alternatively, irritation of the peritoneal surfaces by a hard, solid ovarian tumour could stimulate peritoneal fluid production as well as release of inflammatory cytokines. The pleural fluid tends to be right sided in a majority (~60-70%) of cases for unknown reasons.[15]

Even though the pleural fluid is an exudate in most patients with Meigs syndrome, there have been reports of transudative effusions. Similarly, the peritoneal serum ascites albumin gradient is generally >1.1 g/dl, also fitting with portal hypertension.[15]

Pericardial effusion is not included in the definition of Meigs syndrome. However, there have been case reports in patients with unexplained persistent pericardial effusion, which resolved after the resection of a benign ovarian tumour. Elevation of serum CA 125 is common. The possible cause of the increased CA 125 is expression of this antigen by the tumour and mesothelial cells of the peritoneum. Mechanical stimulation by a tumour or an increase in peritoneal pressure due to ascites would induce expression of this antigen, which is also seen in liver cirrhosis.[15,16]

Meigs syndrome is a benign condition, and surgical removal results in a definite cure. The pleural effusion and ascites will resolve permanently once the patient’s tumour is resected. The life expectancy postoperatively is equivalent to that of the general population.[3,14,16]


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