J. Boone

First experience with robot-assisted thoracoscopic esophagolymphadenectomy for esophageal cancer.

BackgroundTransthoracic esophagectomy with extended lymph node dissection is associated with higher morbidity rates than transhiatal esophagectomy. This morbidity rate could be reduced by the use of minimally invasive techniques. The feasibility of robot-assisted thoracoscopic esophagectomy (RTE) with mediastinal lymphadenectomy was assessed prospectively.MethodsThis study investigated 21 consecutive patients with esophageal cancer who underwent RTE using the Da Vinci™ robotic system. Continuity was restored with a gastric conduit and a cervical anastomosis.ResultsA total of 18 (86%) procedures were completed thoracoscopically. The operating time for the thoracoscopic phase was 180 min (range, 120–240 min), and the median blood loss was 400 ml (range, 150–700 ml). A median of 20 (range, 9–30) lymph nodes were retrieved. The median intensive care unit stay was 4 days (range, 1–129 days), and the hospital stay was 18 days (range, 11–182 days). Pulmonary complications occurred in 10 patients (48%), and one patient (5%) died of a tracheoneoesophageal fistula.ConclusionsIn this initial experience, robot-assisted thoracoscopic esophagectomy was found to be feasible, providing an effective lymphadenectomy with low blood loss. Standardization of the technique and increased experience should reduce the complication rate, which is in the range of the rate for open transthoracic dissection.

Robot‐assisted thoracoscopic oesophagectomy for cancer

Thoracoscopic oesophagectomy was introduced to reduce the morbidity of transthoracic oesophagectomy. The aim was to assess the short‐ and mid‐term results of robot‐assisted thoracoscopic oesophagectomy for oesophageal cancer.

DIAGNOSTIC VALUE OF ROUTINE AQUEOUS CONTRAST SWALLOW EXAMINATION AFTER OESOPHAGECTOMY FOR DETECTING LEAKAGE OF THE CERVICAL OESOPHAGOGASTRIC ANASTOMOSIS

Background:  Water‐soluble contrast swallow examination is routinely carried out after oesophagectomy to detect leakage of the cervical oesophagogastric anastomosis. This study evaluated the diagnostic accuracy and clinical value.

Validation of tissue microarray technology in squamous cell carcinoma of the esophagus

Tissue microarray (TMA) technology has been developed to facilitate high-throughput immunohistochemical and in situ hybridization analysis of tissues by inserting small tissue biopsy cores into a single paraffin block. Several studies have revealed novel prognostic biomarkers in esophageal squamous cell carcinoma (ESCC) by means of TMA technology, although this technique has not yet been validated for these tumors. Because representativeness of the donor tissue cores may be a disadvantage compared to full sections, the aim of this study was to assess if TMA technology provides representative immunohistochemical results in ESCC. A TMA was constructed containing triplicate cores of 108 formalin-fixed, paraffin-embedded squamous cell carcinomas of the esophagus. The agreement in the differentiation grade and immunohistochemical staining scores of CK5/6, CK14, E-cadherin, Ki-67, and p53 between TMA cores and a subset of 64 randomly selected donor paraffin blocks was determined using kappa statistics. The concurrence between TMA cores and donor blocks was moderate for Ki-67 (κ = 0.42) and E-cadherin (κ = 0.47), substantial for differentiation grade (κ = 0.65) and CK14 (κ = 0.71), and almost perfect for p53 (κ = 0.86) and CK5/6 (κ = 0.93). TMA technology appears to be a valid method for immunohistochemical analysis of molecular markers in ESCC provided that the staining pattern in the tumor is homogeneous.

mTOR in squamous cell carcinoma of the oesophagus: a potential target for molecular therapy?

Aims: The mammalian target of rapamycin (mTOR), an important regulator of protein translation and cell proliferation, is activated in various malignancies. In a randomised controlled trial of advanced renal cell carcinoma patients, targeted therapy to mTOR by means of rapamycin analogues has been shown to significantly improve survival. An in vitro study has revealed that mTOR is activated in oesophageal squamous cell carcinoma (OSCC) cell lines and that mTOR expression is inhibited by rapamycin. The objectives of this histological study were to determine the proportion of OSCC tissues with activated mTOR (p-mTOR) expression, thereby assessing the percentage of patients with OSCC that would possibly benefit from neoadjuvant rapamycin therapy, and to identify the clinicopathological features of these potentially rapamycin-sensitive tumours. Methods: The expression of p-mTOR (Ser2448) was immunohistochemically assessed in a validated tissue microarray comprising triplicate tissue biopsy cores of 108 formalin-fixed, paraffin-embedded OSCCs. Staining results were correlated with clinicopathological data. Results: Normal oesophageal epithelium was negative for p-mTOR. Activated mTOR expression was located in the cytoplasm of oesophageal tumour cells. 26 (25%) of 105 assessable OSCCs showed tumour cells with positive staining for activated mTOR. Activated mTOR expression was associated with a lesser degree of differentiation only (p = 0.024). No correlation was detected between p-mTOR and the proliferation marker Ki-67. Conclusions: Activated mTOR can be detected in one-quarter of OSCCs. Since this subset of patients may potentially benefit from mTOR inhibiting therapy, a phase II clinical trial of neoadjuvant mTOR-inhibiting therapy in patients with OSCC may be considered.

Targets for molecular therapy in esophageal squamous cell carcinoma: an immunohistochemical analysis

Neoadjuvant chemotherapy may improve the outcome of esophageal cancer after esophagectomy, but is accompanied by considerable toxicity by collateral destruction of normal cells. Such side effects may be avoided by developing therapies that specifically target molecular characteristics of tumors. The aim of the present study was to determine the proportion of esophageal squamous cell carcinoma (ESCC) patients that could possibly benefit from (a combination of) currently available targeted therapies, by assessing the frequency of immunohistochemical expression of their target molecular markers in ESCC tissues. Sections from a validated tissue microarray comprising 108 ESCCs were immunohistochemically stained for Bcl-2, c-KIT, cyclo-oxygenase-2 (COX-2), cyclin D1, estrogen receptor (ER), epidermal growth factor receptor (EGFR), Her-2/neu, progesterone receptor (PR), and vascular endothelial growth factor (VEGF). VEGF, cyclin D1, EGFR, and COX-2 could be detected in 55, 42, 40, and 40%, respectively. Her-2/neu, Bcl-2, and c-KIT were detected in 12, 11, and 10% of the tumors, respectively. No nuclear expression of ER or PR was noticed. Concurrent expression of two markers was noticed in 28% of ESCCs, whereas 25% of ESCCs showed concurrent expression of three markers. The concurrent expression of two of the most frequently expressed markers (VEGF, cyclin D1, EGFR, and COX-2) ranged from 11 (COX-2 and EGFR) to 26% (cyclin D1 and VEGF). The expression of all of these four markers was seen in 5% of ESCCs. Promising targets for molecular therapy in ESCC appear to be COX-2, VEGF, EGFR, and cyclin D1, as they are frequently overexpressed. Phase II clinical studies on these molecular markers may therefore be warranted. The role for targeted therapy against ER, PR, Her-2/neu, c-KIT, or Bcl-2 in ESCC seems limited.

Reduced local immune response with continuous positive airway pressure during one-lung ventilation for oesophagectomy

BACKGROUND Transthoracic oesophagectomy requires prolonged one-lung ventilation causing systemic and local inflammatory responses. Application of continuous positive airway pressure (CPAP) to the collapsed lung potentially reduces pulmonary damage, hypoxia, and consequent inflammation. This randomized controlled trial studied the influence of CPAP applied to the collapsed right lung during thoracoscopic oesophagectomy on local and systemic inflammatory response. METHODS Broncho-alveolar lavage fluid (BALF) from the right collapsed and left ventilated lung and serum samples were obtained during surgery from 30 patients undergoing thoracolaparoscopic oesophagectomy for cancer who were randomized for one-lung ventilation with or without CPAP applied to the collapsed right lung. Concentrations of cytokines and chemokines, in BALF and serum, were determined with Luminex. RESULTS Patients from the control (no CPAP) group had significantly increased concentrations of interleukin (IL)-1α, IL-1β, IL-10, tumour necrosis factor-alpha, macrophage inflammatory protein (MIP)-1α, pulmonary and activation-regulated chemokine (PARC), and IL-8 in the collapsed (right) lung when compared with patients from the CPAP group (P<0.05). The ventilated (left) lung of the control group showed increased concentrations of monocyte chemoattractant protein (MCP)-1 and MIP-1α (P<0.05). Serum concentrations of cytokines and chemokines increased during surgery, but did not differ between the control and CPAP groups. CONCLUSIONS A significantly lower local immune response was observed during one-lung ventilation when CPAP was applied to the collapsed lung. The findings suggest a beneficial effect of CPAP on the collapsed lung during oesophagectomy with one-lung ventilation.

Robot-assisted thoracoscopic esophagectomy for a giant upper esophageal leiomyoma

This is the first report of a thoracoscopic esophagectomy for a giant leiomyoma of the upper esophagus aided by a robotic system. A 37-year-old man presented with progressive dysphagia and nocturnal aspiration. Endoscopic ultrasound and CT scan of the chest revealed an upper esophageal tumor of 9 x 4 cm arising from the muscularis mucosae. A fine needle aspiration showed clustering of mesenchymal cells, confirming the diagnosis of a stromal cell tumor. A mesenchymal malignancy was suspected because the tumor was located in the upper esophagus and was arising from the muscularis mucosae, both uncommon for a leiomyoma. Moreover, tumor size, an indicator of potential malignancy if >3 cm, was 9 cm. Therefore, an esophagectomy was performed thoracoscopically with the formation of a gastric conduit via laparotomy and a hand-sewn end-to-side cervical anastomosis. The thoracoscopic phase was performed with support of the da Vincitrade mark robotic system, which allowed for an excellent 3-dimensional view and a precise dissection of the esophagus along the vital mediastinal structures. The duration of the thoracoscopic part was 115 min and that of the total procedure was 270 min. Blood loss during the thoracoscopic phase was 50 mL; total blood loss was 200 mL. The patient was ventilated for 1 day; his total intensive care stay was 2 days. He left the hospital in good condition on the 11th postoperative day. Histopathological examination combined with immunohistochemistry revealed a leiomyoma of 9.0 x 5.0 x 2.5 cm. After 3 years of follow-up, the patient is in good health.

The effect of azygos vein preservation on mediastinal lymph node harvesting in thoracic esophagolymphadenectomy

The standard surgical procedure for esophageal cancer is transthoracic esophagectomy with en bloc resection of the azygos vein, thoracic duct and mediastinal lymph nodes. To reduce morbidity of esophago-lymphadenectomy, minimally invasive techniques are increasingly being applied. In (robot-assisted) thoracoscopic esophagolymphadenectomy, the azygos vein is generally left in place, as the scopic ligation of the numerous intercostal veins is technically difficult and time-consuming. This could affect the extent of mediastinal lymph node dissection. Therefore, in this study, the effect of azygos vein preservation during thoracic esophagectomy on mediastinal lymph node harvesting was assessed. In 15 human cadavers, a right-sided thoracotomy was performed, followed by esophagectomy with mediastinal lymph node dissection after ligation of the azygos arch (representing the situation in robot-assisted thoracoscopic esophagolymphadenectomy). Subsequently, the remaining azygos vein with surrounding tissue was resected. The number of lymph nodes in both specimens was determined. A mean of 17.3 (95% Poisson CI 15.3-19.6) lymph nodes was dissected en bloc with the esophagus, and 0.67 (95% Poisson CI 0.32-1.23) around the separately resected azygos vein. The additional azygos vein resection did not add to the number of lymph nodes dissected in 60% (9/15) of cadavers. In conclusion, the extent of mediastinal lymph node dissection was not substantially affected by leaving the azygos vein in situ . Time-sparing azygos vein preservation in (robot-assisted) thoracoscopic esophagolymphadenectomy may therefore be considered justified.

The Azygos Vein: to Resect or Not?

Dear Editor, With great interest we read the article by Schroder et al. to be published in a forthcoming issue of the Journal of Gastrointestinal Surgery in which they investigated the potential value of resecting the azygos vein in transthoracic esophagectomy for esophageal cancer. During (robot-assisted) thoracoscopic esophagectomy, the trunk of the azygos vein is often preserved as the scopic ligation of the numerous intercostal veins is technically difficult and time-consuming. One may postulate that this may negatively affect the extent of lymph node harvesting or the circumferential radical (R0) resection rate. Schroder et al. have, therefore, performed a prospective evaluation on the amount of lymph nodes surrounding the azygos vein in 92 patients with esophageal cancer having undergone open transthoracic esophagectomy with two-field lymphadenectomy. Lymph nodes near the azygos vein were identified in 65% of patients and metastases in these lymph nodes were found in 8%. They, therefore, conclude that the dissection of the azygos vein should not be abandoned, irrespective of the surgical approach. A comment should be made on the design of the study. As clearly shown in Figure 2 of their article, they dissected the azygos vein with the surrounding tissues sharply from the esophagus, which is not representative for (robot-assisted) thoracoscopic esophagectomy. In (robot-assisted) thoracoscopic esophagectomy, subsequent to the ligation of the azygos arch, the mediastinal dissection of the esophagus and surrounding tissues is performed sharply along the azygos trunk. In this way, the fatty tissue in between the esophagus and the azygos vein (including the lymph nodes of stations 108 and 110) as well as the thoracic duct are included in the esophageal resected specimen and are not left in situ when the trunk of the azygos vein is preserved. The number of lymph nodes that will be left in situ with (robot-assisted) thoracoscopic esophagectomy will, therefore, be much less than stated in this article. Indeed, in our recently published cadaveric study in which we investigated an identical research question, a mean amount of only 0.67 lymph nodes were identified around the azygos vein using the thoracoscopic dissection method. Using this approach, in 60% of cadavers, no lymph nodes near the azygos vein were detected at all. With regard to the possible effect of azygos vein preservation on the radical resection rate, we can refer to our first report on 21 esophageal cancer patients having undergone robot-assisted thoracoscopic esophagectomy. The R0 resection rate of 76% in that series is similar to that of open transthoracic esophagectomy. In our opinion, it is, therefore, justified to preserve the azygos trunk during (minimally invasive) transthoracic esophagectomy.