Surgical Management of Malignant Mesothelioma



Surgical Management of Malignant Mesothelioma


Joseph S. Friedberg



INTRODUCTION

Albeit the most common primary tumor of the pleura, malignant pleural mesothelioma is a very rare cancer, only several percent as common as nonsmall cell lung cancer in the United States. The tumor is most commonly linked to asbestos exposure and typically occurs several decades after exposure. Despite the relatively recent mandates to protect the public from asbestos, it is expected that the incidence of mesothelioma will continue to increase for the foreseeable future.

The natural history of mesothelioma, which is almost always unilateral, is inexorable local progression with encasement of the lung and invasion of the chest wall, diaphragm, and/or mediastinum. The majority of patients will succumb to the disease less than a year from the time of diagnosis. Although the disease has a reputation for being a purely localized tumor, at least half the patients will have occult metastases at the time of their demise. The clinical manifestations of metastases have become more commonly noted in some patients who have undergone aggressive multimodal approaches and are fortunate enough to have an extended survival.

Patients will commonly present with dyspnea secondary to a pleural effusion. Other presenting symptoms, such as weight loss or pain from chest wall invasion, are even more ominous and tend to reflect more advanced or aggressive form of the cancer. Radiographic studies may reveal only the pleural effusion and no other detectable disease. Patients with a pleural rind will commonly demonstrate a contracture of the hemithorax as a result of decrease in the size of the rib interspaces, which can be easily seen on a plain chest film.

Unless a history of asbestos exposure is offered, mesothelioma may not be immediately considered and the diagnosis will be delayed. Further delaying the diagnosis is the common event of a negative cytology on fluid withdrawn by thoracentesis. Ultimately the recurrence of the effusion or the recalcitrance of the clinical complaints to attempted interventions will, hopefully, lead the patient to a physician experienced with mesothelioma. Ideally this will be a thoracic surgeon facile in dealing with pleural diseases.

Establishing a diagnosis and simultaneously palliating the symptoms caused by the effusion can be accomplished thoracoscopically through a single 1-cm incision. If the patient is potentially a candidate for an aggressive treatment protocol, then the ideal situation is for the surgeon who would be performing the therapeutic operation to perform the diagnostic/palliative procedure. The reasons for this are twofold. The first is that mesothelioma has a propensity to seed incisions. Hence, it is often desirable to excise the biopsy incisions at the time of the thoracotomy. Consequently, if the same surgeon performs both procedures, the incisions used for the biopsy procedure can be placed in line with a potential thoracotomy, such that they could be excised as part of the thoracotomy without compromise of chest wall integrity or the need for an additional incision. In addition, the surgeon who performs both procedures can decide between pleurodesis or placement of a long-term indwelling catheter as the best route of palliation that will not interfere with future operations or therapeutic interventions.

Pemetrexed-based chemotherapy is, ostensibly, the standard of care treatment for pleural mesothelioma. Beyond this chemotherapy, essentially all treatments— including surgery—remain investigational. Nonsurgical modalities that have been used to treat this malignancy include many combinations of systemic therapy, radiation therapy, and many types of immunotherapies.

To date, however, the treatments that have met with the greatest measure of success in extending life are surgery-based multimodal treatments. Again, hobbled by the scarcity of this cancer and the small number of patients undergoing operation for this cancer, large randomized prospective trials do not exist to validate the role of surgery in treating this cancer. It is, therefore, appropriate that any patient being offered surgery for this cancer should be the focus of a multidisciplinary panel discussion to assess the options. Patients undergoing operation for mesothelioma should, in addition to standard disclosures for informed consent, be aware that surgery is not the standard of care. Furthermore, as mesothelioma remains an incurable cancer, patients should understand that although the procedure is done with “curative intent,” the realistic goal is extension of life beyond what would be anticipated with less aggressive approaches. Ideally, patients undergoing surgery for this cancer should be part of a clinical trial that will accrue data to further the field and help establish optimal treatments for future patients.

Patient selection for surgery-based treatments can vary from institution to institution, but the general principles observed by all groups are that the cancer must appear confined to one hemithorax and the patient must be at reasonable risk for the proposed procedure. Areas of controversy are typically stage-related inclusion/exclusion criteria, particularly N2 lymph nodes, and mesothelioma subtype. As a general rule, patients with nonepithelial histologies are much less likely to enjoy any significant period of remission compared to patients with epithelial subtypes. Some surgeons will have an age limit, whereas others do not. As pemetrexed-based chemotherapy is standard, essentially all surgery-based treatments will incorporate this, but whether it is given as a postoperative adjuvant, preoperative neoadjuvant, or both is also currently institution dependent. Finally use of other modalities, if any, combined with surgery, remains institution dependent.


Because microscopic disease remains after any operation for a pleural malignancy, the goal of surgery in these multimodal protocols is to achieve a macroscopic complete resection. There are two approaches toward achieving this goal, operations that take the lung or operations that spare the lung.

The lung-sacrificing approach, extrapleural pneumonectomy, currently is the most common approach. This operation involves resection of the parietal pleural envelope en bloc with the lung, diaphragm, and pericardium. The pericardium and diaphragm are then reconstructed with prosthetic patches. This procedure has the advantages of standardized techniques/nomenclature, leaving the least amount of residual microscopic disease and, because the lung is absent, the ability to deliver fulldose adjuvant hemithoracic radiation. The obvious disadvantages are the risk and life-style consequences of pneumonectomy and the smaller pool of patients, many of whom are elderly, who are appropriate candidates for pneumonectomy.

Whereas extrapleural pneumonectomy enjoys uniformity in technique and nomenclature, lung-sparing surgery enjoys neither. Some surgeons intentionally leave behind gross disease, while others use it to achieve a macroscopic complete resection. Terms to describe this procedure include palliative pleurectomy, palliative debulking, pleurectomy, decortication, pleurectomydecortication, and radical pleurectomy. Radical pleurectomy is the term used by the author and is defined as a procedure used to achieve a macroscopic complete resection that spares the lung and, whenever possible, the phrenic nerve, and as much of the diaphragm and pericardium as possible. The advantages of radical pleurectomy are the obvious benefits of lung preservation which, compared to pneumonectomy, has the potential to translate into less operative risk resulting in more patients being eligible for surgery-based treatment, better postoperative quality of life with greater reserve, and, consequently, more treatment options when the inevitable recurrence occurs. The disadvantages include lack of standardization, unique technical challenges, the need for judgment as to when the resection is complete, inability to incorporate standard adjuvant hemithoracic radiation, and, almost certainly, more residual microscopic disease than after an extrapleural pneumonectomy.

The modalities that have been used in an adjuvant and/or neoadjuvant capacity with operation include radiation, chemotherapy, and immunotherapy. The two principle modalities that have been used as intraoperative adjuvant therapies are hyperthermic chemotherapy lavage and photodynamic therapy. Again, with the exception of pemetrexed-based chemotherapy none of these, in any combination, is considered the standard of care.

Once a patient has been reviewed in a multidisciplinary conference and has elected to pursue a surgery-based treatment while understanding and recognizing other options, we initiate an evaluation to determine if the patient is a safe and appropriate candidate from an oncologic perspective. Our preoperative safety workup includes all of the usual studies and evaluations for a major pulmonary procedure, but with special emphasis on pulmonary function, cardiac function, and nutritional status. With respect to staging, our standard noninvasive preoperative workup includes a chest computed tomographic (CT) scan, brain imaging, and a positron emission tomography (PET) scan. MRI is utilized selectively when there is a question as to the extent of diaphragmatic or mediastinal invasion. We routinely perform a bronchoscopy and outpatient laparoscopy with peritoneal lavage to rule out radiographically occult disease. If the contralateral thorax has any questionable findings, we incorporate a VATS inspection of that hemithorax at the same time. Mediastinoscopy or endobronchial ultrasound (EBUS)-guided biopsies of the mediastinal lymph nodes also is commonly performed. Until our most recent study the status of the mediastinal (N2) lymph nodes had not demonstrated significant correlation with outcome. Now that we have established that mediastinal nodal involvement is correlated with outcome, although not an exclusion criterion like contralateral chest or abdominal disease, we also incorporate mediastinal staging with EBUS as part of our invasive staging workup.


OPERATIVE TECHNIQUES


Diagnosis, Palliation of Pleural Effusion, and Invasive Staging

Occasionally, a diagnosis can be established on the basis of fluid cytology from a thoracentesis or a closed pleural biopsy. More commonly, however, a surgical biopsy is required. This is best accomplished using a thoracoscopic technique and can be performed through a single 1-cm incision. After medical clearance the patient is brought to the operating room and once general anesthesia is induced, a bronchoscopy is performed. We have, on one occasion, discovered contralateral endobronchial metastases that served as a contraindication for any aggressive treatment options. The expected appearance of the airway, in the setting of a large effusion or bulky pleural disease, is extrinsic compression. If there is a significant amount of secretions in the airway, the surgeon should plan on performing a completion toilet bronchoscopy at the conclusion of the operation in order to maximize postoperative lung expansion.


Diagnosis and Palliation for Patients Presenting with Effusion

Once the patient is turned to the lateral decubitus position, the position of the double-lumen tube or bronchial blocker is confirmed and the lung on the operative side is isolated. After preparing the skin and positioning the patient, a potential thoracotomy incision is drawn on the chest wall. It is our practice to enter the chest through a serratus-sparing thoracotomy through the sixth interspace or the bed of the resected seventh rib. Starting in the anterior axillary line and working forward as necessary, the chest is sounded with a 22-gauge needle, along the potential future incision line, until fluid is encountered. This sample is saved for microbiology stains and cultures if there is any chance that the effusion is secondary to an infectious process. Having identified a safe site for entry, a local cutaneous and intercostal block is performed with a long-acting local anesthetic and a 10-mm incision is then created. The chest is then entered through this incision and fluid is aspirated to allow visualization. The fluid is collected for cytologic evaluation in the event that lesional tissue is not confirmed on the pleural biopsies. It is our practice to send an entire suction canister of pleural effusion for this purpose.

A 5 mm 30 degree thoracoscope is then introduced and the hemithorax is inspected. A small suction or blunt laparoscopic instrument can then be placed in through the same incision, alongside the thoracoscope, and loculations are disrupted and any remaining fluid is aspirated. Mediastinoscopy, or any other narrow, biopsy forceps are then introduced. The 30 degree angle allows the surgeon to maneuver the scope and the biopsy forceps without interference. In early-stage mesothelioma visual inspection within the chest may reveal only an injected-appearing pleura, in which case extensive parietal pleural biopsies are performed. More advanced stages will reveal popular or nodular lesions that will eventually coalesce into plaques coating the chest wall, lung, diaphragm, and mediastinum. It is critically important to never violate the visceral pleura or a persistent
air leak can result. All biopsies should be taken from the parietal pleura. Biopsy specimens need to be sent to the pathologist for frozen section analysis and “lesional tissue” needs to be confirmed along with a sufficient quantity of specimen for the pathologist to run all additional tests required to render a final diagnosis. Although most diagnoses are currently made on the basis of morphology and the immunohistochemical profile, some institutions may still elect to perform electron microscopy that may require special handling of the specimen and this should be discussed with the pathologist. This is occasionally required when patients are having repeat biopsies for previous nondiagnostic surgical biopsies. Molecular or genetic analysis of biopsy specimens may also be undertaken in order to definitively establish a diagnosis.

At the conclusion of the specimen sampling, palliation of the effusion should be considered. If, based on the proposed treatment plan, the patient is going to have another procedure in the near future, or if the lung fails to fully expand, then a cuffed, silicone pleural catheter with a valve should be placed with the intent for this to remain in place on a chronic basis to deal with recurrent effusion. If the treatment plan does not anticipate further surgery, or the operative surgeon desires obliteration of the pleural space, then a chemical pleurodesis should be performed. One critical error is to instill talc into a chest cavity where visceral pleural-parietal-pleural apposition does not occur. In this setting, with entrapped lung, a residual pleural space will remain. If it gets infected, it can be very difficult to treat and if talc, a permanent foreign body, is in the chest cavity, this can spiral into an incurable empyema that will be the direct cause of the patient’s death. If the patient will be a candidate for a surgery-based treatment, then the tube should be brought out in the same incision line, close enough to the VATS port that it can be incorporated in an excision at the time of thoracotomy. If the patient is not going to be a candidate or wishes not to have further surgery, then the tube should be brought out along the anterior axillary line at the level of the costophrenic recess. This will allow for better drainage. In either case, the tube should be directed posteriorly, to drain fluid at the diaphragm, and then extend to the end of this length paraspinally in a cephalad direction. The single VATS incision is then closed with absorbable sutures in a watertight manner. Depending upon the patient, this procedure may be performed on an outpatient basis. Commonly, however, these patients are best served by staying in the hospital overnight such that they can receive training on how to drain their tube in addition to determining an effective paincontrol regimen. Finally, it is often valuable to obtain a CT scan following drainage of the fluid with the tube on suction. This will give the best indication of whether or not the disease appears to be a true pleural cancer or if there are pulmonary nodules more suggestive of metastatic disease. Often these nodules will not be visible on the preoperative CT scan because of the presence of fluid and lung compression.


Diagnosis for Patients Presenting with a Pleural Rind

If a patient has a thick pleural rind, then the diagnosis can be obtained without entering the pleural space. Based on the CT scan, a spot along a potential future thoracotomy incision is selected where there appears to be significant pleural tumor thickness. Under general anesthesia, the area is infiltrated with local anesthetic. Depending upon the thickness of the soft tissue between the skin and the target, the incision can be as small as 1 cm or may need to extend to 3 to 4 cm. The soft tissue is incised and the dissection is carried into the underlying interspace where a hard, white mass will be encountered. Using a scalpel, or a biopsy forceps, specimens are harvested. Great care needs to be taken to avoid full-thickness penetration of the tumor and violation of the underlying visceral pleura. Again, it is imperative to confirm the presence of lesional tissue. It would be the exception to have a free pleural space, in the presence of bulky pleural disease and the absence of an effusion, so there is unlikely to be a role for video thoracoscopy in these cases. If additional tissue is required, it is best to harvest tumor along the interspace rather than risk deeper biopsies that may enter the lung. Once the pathologist has confirmed the presence of lesional tissue and a sufficient quantity of specimen to establish a diagnosis has been obtained, the incision is closed after irrigating with sterile water or saline. With the incision filled with liquid, the area is observed during several breaths to assure that the fluid does not drain into the chest. This would indicate the presence of pleural patency and may require placement of a chest tube. The anesthesia team is then requested to deliver a prolonged Valsalva maneuver and the site is inspected for bubbles. If it appears that the lung has been entered, a soft drainage tube should be placed in the bed of the incision and treated like a chest tube. If there are no bubbles and the fluid level is static, then the incision can be closed in layers without any drainage.

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Jun 15, 2016 | Posted by in CARDIAC SURGERY | Comments Off on Surgical Management of Malignant Mesothelioma

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