Minimally invasive surgical staging for esophageal cancer

Background: The incidence of esophageal adenocarcinoma is increasing in the United States, and the 5-year survival rate is dismal. Preliminary data suggest that conventional imaging is inaccurate in staging esophageal cancer and could limit accurate assessment of new treatments. The objective of this study was to compare minimally invasive surgical staging (MIS) with conventional imaging for staging esophageal cancer. Methods: Patients with potentially resectable esophageal cancer were eligible. Staging by conventional methods used computed tomography (CT) scan of the chest and abdomen, and endoscopic ultrasound (EUS), whereas MIS used laparoscopy and videothoracoscopy. Conventional staging results were compared to those from MIS. Results: In 53 patients, the following stages were assigned by CT scan and EUS: carcinoma in situ (CIS; n= 1), I (n= 1), II (n= 23), III (n= 20), IV (n= 8). In 17 patients (32.1%), MIS demonstrated inaccuracies in the conventional imaging, reassigning a lower stage in 10 patients and a more advanced stage in 7 patients. Conclusions: In 32.1% of patients with esophageal cancer, MIS changed the stage originally assigned by CT scan and EUS. Therefore, MIS should be applied to evaluate the accuracy of new noninvasive imaging methods and to assess new therapies for esophageal cancer. Received: 5 April 1999/Accepted: 15 March 2000/Online publication: 12 July 2000     

Evaluation of minimally invasive surgical staging for esophageal cancer

BACKGROUND: Conventional imaging studies (computed tomography and endoscopic esophageal ultrasonography) used for preoperative evaluation of patients with esophageal cancer can be inaccurate for detection of small metastatic deposits. We evaluated the efficacy of minimally invasive surgical (MIS) staging as an additional modality for evaluation of patients with esophageal cancer. METHODS: Between December 1998 and February 2001, 33 patients with esophageal cancer were evaluated for surgical resection. Conventional imaging studies demonstrated operable disease in 31 patients and equivocal findings in 2 patients. All patients then underwent MIS staging (laparoscopy, bronchoscopy, and ultrasonography of the liver). We compared the results from surgical resection and MIS staging with those from conventional imaging. RESULTS: MIS staging altered the treatment plan in 12 (36%) of 33 patients; MIS staging upstaged 10 patients with operable disease and downstaged 2 patients with equivocal findings. MIS staging accurately determined resectability in 97% of patients compared with 61% of patients staged by conventional imaging. The specificity and negative predictive value for detection of unsuspected metastatic disease in MIS staging were 100% and 96%, respectively, compared with 91% and 65%, respectively, for conventional imaging studies. CONCLUSION: In addition to conventional imaging studies, MIS staging should be included routinely in the preoperative work-up of patients with esophageal cancer.     

腹腔镜探查判断胆囊癌可切除性的临床意义

目的 初步评价腹腔镜探查在胆囊癌外科治疗中的应用价值.方法 自2007年1月至2010年3月在上海交大医学院附属新华医院普外科及第二军医大学东方肝胆外科医院腹腔镜科收治胆囊癌患者中,选择有手术切除可能的60例患者作为腹腔镜探查组,将同期符合相同条件行剖腹探查的192例胆囊癌患者作为对照组,比较两组手术切除率、腹腔广泛转移患者的手术时间及住院时间.计量资料采用t检验,计数资料采用x2检验.结果 腹腔镜探查组60例中27例患者的肝脏和(或)腹膜有肿瘤广泛转移,中止手术;33例转行剖腹探查,发现1例肝脏多处肿瘤转移、12例侵犯门静脉主干和(或)胰头、十二指肠,无手术切除可能,中止手术;其余20例中7例行胆囊癌姑息性切除,13例行胆囊癌根治性切除术.直接行剖腹探查组192例术中发现肝脏和(或)腹膜肿瘤广泛转移的82例及侵犯门脉主干和(或)胰头31例均中止手术,姑息性切除32例,根治性切除47例.两组手术切除率、腹腔广泛转移患者的手术时间及住院时间差异有统计学意义(x2=4.328,t=8.6501,t=5.8260;P＜0.05、P＜0.01、P＜0.01).结论 腹腔镜探查有助于手术决策的制定,减少不必要的非治疗性剖腹探查,能显著提高手术切除率,可以作为胆囊癌外科治疗中的常规操作.

Abstract：

Objective To evaluate the role of laparoscopic staging for the resectability of gallbladder cancer. Methods From Jan 2007 to Mar 2010,60 gallbladder cancer patients without of metastatic disease or main hepatic portal vessel invasion as assessed by preoperative imaging underwent staging laparoscopy for tumor resectability evaluation. Peritoneal and liver surface metastases were looked for and assessment of local spread was done if possible. Assessment was based on visual impression and biopsies were obtained routinely. T test and x2 test were used. Results At laparoscopy, 27 (45%) patients were found with disseminated disease on peritoneal cavity or the surface of liver, hence, senseless open surgery was avoided. The other 33 patients were converted to open laparotomy, among those 1 patient was found with disseminated metastasis in the liver and 12 patients with the invasion of main hepatic portal vessel,pancreatic head, duodenum did not undergo any further surgery. Finally 7 patients received surgical bypass procedure and 13 patients underwent radical resection. During the same period, 192 clinically diagnosed gallbladder cancer patients undergoing open laparotomy without laparoscopic pre-assessment served as control. Among those in control group 79 patients received radical or palliative resection. The resectability rate was significantly different between the two groups ( P ＜ 0. 05). Conclusion Staging laparoscopy in patients with gallbladder cancer is helpful in detecting liver and peritoneal metastases overlooked by preoperative imaging, avoiding unnecessary open explorations.     

Preoperative staging and assessment of resectability of pancreatic cancer

To study the accuracy of preoperative staging techniques for assessing resectability of pancreatic and ampullary adenocarcinoma, we entered 88 consecutive candidates into a prospective study of contrast-enhanced computed tomography, magnetic resonance imaging, angiography, and laparoscopy. Resectability was proved in 16 (29%) of 55 patients for the head of the pancreas, 1 (6%) of 17 for the body and tail of the pancreas, and 14 (88%) of 16 for the ampulla. The combined findings of computed tomography and angiography showed that more than 87% of pancreatic head tumors were unresectable because of vascular encasement, but neither modality sufficed alone. Small liver and peritoneal metastases were found in 15 (27%) of 55 cancers of the head of the pancreas, 11 (65%) of 17 cancers of the body and tail of the pancreas, and 1 (6%) of 16 cancers of the ampulla; computed tomography missed all but 2 of these instances of metastasis, but laparoscopy with biopsy identified 22 (96%) of 23 instances. Magnetic resonance imaging findings did not differ significantly from computed tomography and conferred no added benefit. Ninety percent of unresectable tumors were identified. Seventy-eight percent of pancreatic head cancers were resectable when all test results were negative vs 5% (2/37) when any test result was positive. This study demonstrates that accurate and efficient triage is possible for patients with cancer of the pancreas and ampulla.     

New techniques for staging esophageal cancer

Correct staging is essential for treatment selection, discussion of prognosis, and scientific communication. The CT scan has long been the essential tool for staging esophageal cancer and still remains valuable for initial screening for distant metastases. The development of endoscopic ultrasonography (EUS), with EUS fine-needle aspiration, positron emission tomography, and minimally invasive surgical staging via thoracoscopy and laparoscopy has resulted in more precise staging. These new tools will allow better definition of patient subsets that may benefit from selected therapies and clinical investigations.     

Refining esophageal cancer staging

OBJECTIVE: Cancer staging is dynamic, reflecting accrual of knowledge and experience in treatment. The objectives of this study were to assess current esophageal cancer staging and to determine whether refinements of classification and stage grouping are necessary. METHODS: From 1983 through November 2000, 480 patients underwent esophagectomy without induction therapy. Depth of tumor invasion (T), regional lymph node status (N), distant status (M), number of metastatic regional lymph nodes, and histopathologic type and grade were subjected to survival-tree analysis, multivariable Cox and hazard function analysis, and residual misclassification risk analysis. RESULTS: Inhomogenity of survival was found within and lack of distinction was found between current American Joint Committee on Cancer staging groups, supporting the need for refinement. T1 and N1 were redefined on the basis of survival differences. T1a is intramucosal cancer, T1b is submucosal cancer (P =.008), N1 is 1 or 2 metastatic regional lymph nodes, and N2 is 3 or more metastatic regional lymph nodes (P =.01). Current subclassification of M1 is not warranted (P =.9). Histopathologic type (P =.17) and grade (P =.3) minimally refined staging. Reassignment of staging groups constrained by American Joint Committee on Cancer definitions of stages 0 and IV produced less monotonic, distinctive, and homogeneous survival than free assignment of staging groups. CONCLUSIONS: Current American Joint Committee on Cancer staging of esophageal cancer is inadequate. Refinement requires redefinition of T1, N1, and M1 classifications. Stage grouping within the constraints of American Joint Committee on Cancer definitions produces less accurate prognosis than free assignment based on survival data.     

Clinical staging of esophageal carcinoma. CT, EUS, and PET

CT is readily available to all patients. It is relatively inexpensive and fees are usually reimbursed. It provides exquisite anatomic detail of the chest and abdomen in patients with esophageal cancer. The only reliable use of CT in the determination of T is the exclusion of T4 tumors, which is suggested by the preservation of fat planes. Enlarged lymph nodes are suspicious for metastatic disease but require further study or tissue sampling if nodal metastases will determine treatment. Its major use is in the detection of distant metastatic disease; however, 30% to 60% of distant metastases may be radiographically occult. There is a significant learning curve for EUS staging of esophageal cancer. It is suggested that this study be performed at institutions where there is a dedicated, experienced endoscopic ultrasonographer with adequate instrumentation that allows specialty imaging and EUS-FNA. EUS is the best means of clinically determining T. The addition of EUS-FNA to routine EUS evaluation of lymph nodes allows an accuracy similar to the EUS determination of T. EUS has no purpose in assessment of non-nodal distant metastatic disease; however, the serendipitous finding of distant metastases in adjacent structures visualized during the evaluation of the primary tumor and lymph nodes has, on occasion, detected M1b disease. FDG-PET represents an advance over CT scanning in the screening for distant metastases. The major problems with FDG-PET staging of esophageal cancer is failure to detect metastatic deposits less than 1 cm in diameter and lack of anatomic definition. It is unable to determine T and has been inaccurate in the detection of lymph node metastases. Because this test is not readily available, is expensive, and is not routinely reimbursed, its use in staging esophageal cancer continues to be limited. Today, CT and EUS are the mainstays in the clinical staging of esophageal carcinoma. When possible, FDG-PET should be added to CT to improve the evaluation of non-nodal M1b disease. Results of these studies should determine the necessity for invasive staging techniques and direct their use.     

Pretreatment surgical lymph node staging predicts results of trimodality therapy in esophageal cancer

Objective: Prediction of responders to induction therapy in esophageal cancer (EC) patients is important. In this study, we evaluated the role of thoracoscopic/laparoscopic (Ts/Ls) staging in prediction of treatment response and survival in EC patients with trimodality treatment. Methods: Retrospective study of EC patients who had undergone Ts/Ls staging and received trimodality treatment at the University of Maryland Medical Center and the Baltimore Veterans Administration Hospitals from July, 1991 to December, 1999. Preoperative therapy consisted of concurrent chemotherapy (5-FU+cisplatinum) and radiotherapy. Results: Forty-four EC patients who underwent pretreatment Ts/Ls staging during the study period were able to complete concurrent chemoradiotherapy followed by surgical resection. There were 36 men and 8 women aged 40 to 77 (median age 62). Twenty-seven (61.4%) patients were found to have lymph node metastasis by surgical staging. Fourteen patients (31.8%) had a pathologic complete response. Patients with positive lymph nodes had a lower response rate than those with negative lymph nodes (14.8% vs. 58.8%, P=0.006). Other clinicopathologic features including gender, weight loss, clinical TNM stage, surgical T stage, and histology did not correlate with treatment response. Univariate analysis showed that weight loss and treatment response were important prognostic factors for disease-free survival (P=0.01 and P=0.02, respectively). Histology, surgical N stage and surgical TNM stage appeared to be associated with prognosis (P=0.067–0.097). Multivariate analysis revealed that only surgical N status and weight loss were significant prognostic factors (P=0.05, and P=0.006, respectively). Conclusions: Surgical Ts/Ls staging provides accurate evaluation of tumor spread in EC patients. Pretreatment N status was the single most important predictor of response to induction treatment as well as a reliable prognosticator of survival.     

Utility of tumor markers in determining resectability of pancreatic cancer

HYPOTHESIS: Despite advances in preoperative radiologic imaging, a significant fraction of potentially resectable pancreatic cancers are found to be unresectable at laparotomy. We tested the hypothesis that preoperative serum levels of CA19-9 (cancer antigen) and carcinoembryonic antigen will identify patients with unresectable pancreatic cancer despite radiologic staging demonstrating resectable disease. DESIGN AND SETTING: Academic tertiary care referral center. PATIENTS: From March 1, 1996, to July 31, 2002, 125 patients were identified who underwent surgical exploration for potentially resectable pancreatic cancer based on a preoperative computed tomographic scan; in 89 of them a preoperative tumor marker had been measured. MAIN OUTCOME MEASURES: Preoperative tumor markers (CA19-9 and carcinoembryonic antigen) were correlated with extent of disease at exploration. As CA19-9 is excreted in the biliary system, CA19-9 adjusted for the degree of hyperbilirubinemia was determined and analyzed. RESULTS: Of the 89 patients, 40 (45%) had localized disease and underwent resection, 25 (28%) had locally advanced (unresectable) disease, and 24 (27%) had metastatic disease. The mean adjusted CA19-9 level was significantly lower in those with localized disease than those with locally advanced (63 vs 592; P =.003) or metastatic (63 vs 1387; P<.001) disease. When a threshold adjusted CA19-9 level of 150 was used, the positive predictive value for determination of unresectable disease was 88%. Carcinoembryonic antigen level was not correlated with extent of disease. CONCLUSIONS: Among the patients with resectable pancreatic cancer based on preoperative imaging studies, those with abnormally high serum levels of CA19-9 may have unresectable disease. These patients may benefit from additional staging modalities such as diagnostic laparoscopy to avoid unnecessary laparotomy.     

Surgical staging of esophageal cancer

The rising incidence of adenocarcinoma of the esophagus and the poor overall 5-year survival using current treatment regimens make it essential that clinical trials continue to search for more effective regimens for specific stages of esophageal cancer. It is clear from work in non-small cell lung cancer that clinical efficacy for platinum-based chemotherapeutic regimens has shown promise only in specific subsets of patients, such as those with stage IIIa tumors, but no benefit at all for earlier stages. In lung cancer, mediastinoscopy has been shown to be the most accurate method to stage locoregional lymph nodes and is considered to be the gold standard for clinical trials. In esophageal cancer, accurate surgical staging of all locoregional lymph nodes is more complex and may involve abdominal, thoracic, and cervical areas. Molecular evidence of lymph node involvement in esophageal cancer suggests that even histologically negative nodes may harbor micrometastases in a significant number of cases. Laparoscopy and thoracoscopy now offer a more accurate alternative to conventional staging of esophageal cancer. For distal esophageal cancers near the gastroesophageal junction, laparoscopic staging alone may suffice in most cases. Associated costs and the requirement for a surgical procedure should encourage the continued evaluation of new noninvasive modalities and the further evolution of endoscopic ultrasound. Currently, we recommend the application of minimally invasive surgical staging to assess new noninvasive technologies, such as PET scanning, and for use in clinical trials until the definitive approach to staging esophageal cancer is established. We are currently participating in an ongoing multicenter study of thoracoscopic and laparoscopic staging for esophageal cancer.     

Thoracoscopic and laparoscopic staging for esophageal cancer

Accurate pretreatment staging for patients with esophageal cancer (EC) is becoming increasingly important in the evaluation and comparison of different treatment modalities. Noninvasive staging methods are imperfect in detecting lymph node metastasis in patients with EC. Surgical staging with the thoracoscopic/laparoscopic (Ts/Ls) technique may provide accurate staging information that is useful for evaluating and comparing the results of clinical trials of preoperative chemotherapy and radiotherapy. It can be used to confirm or exclude suspicious distant metastasis found by other staging methods. Pretreatment (lymph node) biopsies obtained by Ts/Ls staging allow further molecular biologic analysis to detect occult lymph node metastasis for more accurate lymph node staging. Since 1992, we have used Ts/Ls staging for EC in 111 patients. We found that Ts/Ls is a promising method for staging lymph nodes in EC patients. A recent study showed that pretreatment surgical lymph node staging can predict response and survival for EC patients receiving trimodality treatment (ie, radiation, chemotherapy, and surgery). The information obtained with surgical staging now offers us the opportunity to optimize therapy to specific patient groups based on the extent of disease at the time of initial presentation. Nevertheless, unlike the practice of mediastinoscopy in lung cancer patients, Ts/Ls staging in EC patients remains an academic interest rather than a clinical practice. The concept of accurate pretreatment staging of EC remains to be realized and accepted in the clinical community.     

TNM staging and assessment of resectability of pancreatic cancer by laparoscopic ultrasonography

Background: Laparoscopic ultrasonography (LUS) is an imaging modality that combines laparoscopy and ultrasonography. The purpose of this prospective blinded study was to evaluate the TNM stage and assessment of resectability by LUS in patients with pancreatic cancer. Methods: Of the 71 consecutive patients admitted to our department, 36 were excluded from the study, mainly due to evident signs of metastatic disease or another condition that would preclude surgery. Thus, a total of 35 patients were enrolled in the study. All patients underwent abdominal CT scan, ultrasonography, endoscopic ultrasonography (EUS), diagnostic laparoscopy, and LUS. Histopathologic examination was considered to be the final evaluation for LUS in all but three patients, where EUS was used as the reference. Results: The accuracy of LUS in T staging was 29/33 (80%); in N staging it was 22/34 (76%); in M staging, it was 23/34 (68%); and in overall TNM staging, it was 23/34 (68%). In assessment of nonresectability, distant metastases, and lymph node metastases, the sensitivity was 0.86, 0.43 and 0.67, respectively, for LUS alone. Combining the information gleaned from laparoscopy and LUS, the accuracy in finding nonresectable tumors was 89%. Conclusions: Diagnostic laparoscopy with LUS is highly accurate in TNM staging and assessment of resectability of pancreatic cancer and should be considered an important modality in the assessment algorithm. Received: 6 July 1998/Accepted: 13 October 1998     

Value of chest CT scans for predicting surgical resectability of lung cancer

In order to find out the correlation between chest CT scanning and operative finding, a series of 102 patients with lung cancer were analysed. Lobectomy was performed in 88 cases and exploration in 14 cases because the lesion infiltrated the ipsilateral mediastinal lymph nodes. The operations confirmed that there were 28 cases with mediastinal pleural invasion of carcinoma, 20 cases with spread to the chest wall or pleura, 43 cases with enlarged mediastinal lymph nodes (greater than or equal to 1.0cm) and 37 cases with microscopic metastasis. The preoperative chest CT of these patients showed that the carcinoma involved mediastinum and pleura in 25 and 16 cases respectively, and the enlarged mediastinal lymph nodes were present in 37 cases besides 6 cases of pseudonegative shadow. The sensitivity of metastatic mediastinal lymph nodes diagnosed by chest CT was 86%, specificity 89.3%, and accuracy 88%. We believe that the chest CT scanning is valuable in diagnosis of lung cancer and prediction of surgical resectability of the lesion.     

Robot-assisted surgical staging for ovarian cancer in pregnant women

The use of the da Vinci Surgical System is becoming popular among surgeons as it allows more control than the standard laparoscopic approach, with comparable benefits and risks. The use of the da Vinci Surgical System during pregnancy was reported earlier and showed to be as safe as laparoscopy. The use of the da Vinci Surgical System in ovarian cancer during pregnancy has not been reported before. To our knowledge, this is the first report of robot-assisted surgical staging for presumed early ovarian cancer. Two women aged 29 and 39 underwent laparotomy for ovarian cystectomy, for presumed benign pathology; the final pathology showed ovarian malignancy. Both patients were referred to a tertiary center and meanwhile became pregnant, and decided to keep the pregnancy. The staging was achieved using robot-assisted surgery in mid-trimester. The use of the da Vinci Surgical System during pregnancy is feasible and safe at mid-trimester. More robot-assisted surgeries during pregnancy will be needed before final recommendations can be made.     

Molecular staging of lung and esophageal cancer

In both esophageal and NSCLC, the TNM stage at diagnosis remains the most important determinant of survival. Significant research to investigate the biology of NSCLC and esophageal carcinoma is ongoing, and the roles of proto-oncogenes, tumor suppressor genes, angiogenic factors, extracellular matrix proteases, and adhesion molecules are being elucidated. While evidence is accumulating that various markers are involved in NSCLC and esophageal tumor virulence, the current studies are compromised by small sample sizes, heterogeneous populations, and variations in techniques. Large prospective studies with homogenous groups designed to evaluate the role of these various markers should clarify their potential involvement in NSCLC and esophageal cancer. Identification of occult micrometastases in lymph nodes and bone marrow using immunohistochemical techniques and rt-PCR is intriguing. These techniques are promising as a method to more accurately stage patients, and therefore to predict outcomes and to determine therapies. Perhaps the most promising area of research is the development of novel drugs whose mechanism of action targets the pathways of various molecular markers. Molecular biologic substaging offers an opportunity to individualize a chemotherapeutic regimen based on the molecular profile of the tumor, thus providing the potential for improved outcomes with less morbidity in patients with both NSCLC and esophageal cancer.     

Modern surgical staging of lung cancer

The estimation of the extension of a lung cancer is actually made according to the rules of TNM system. On the basis of the reports of 100 patients who underwent thoracotomy and were staged according to this system after hystological examination of resected specimen (pTNM), the authors consider some not yet clear aspects of this staging. In particular they underline the wide difference between clinical and post-histological staging; the high rate of nodal involvement, if the surgeon always perform a radical excision of the lymph nodes; the further need of accuracy for the data N2 and T3; the role of the anatomo-pathologist for the correct staging pTNM.