Francis C. Nichols

High-grade esophageal dysplasia: long-term survival and quality of life after esophagectomy

BACKGROUND Esophagectomy for high-grade dysplasia in Barretts esophagus has been advocated. Although long-term survival data exist, little is known about functional outcome and quality of life in this particular subset of patients. METHODS The records of all patients who underwent esophageal resection for high-grade dysplasia from June 1991 through July 1997 were reviewed. Long-term functional outcome and quality of life were assessed using a two-part written survey. RESULTS There were 54 patients (48 men, 6 women). Median age was 64 years (range, 36 to 83 years). Ivor Lewis esophagogastrectomy was performed in 34 patients (63%), transhiatal esophagectomy in 10 (18%), extended esophagectomy in 8 (15%), and other in 2 (4%). Invasive carcinoma was found in 19 patients (35%). Five patients (9%) were stage 0, 7 (13%) stage I, 3 (6%) stage IIA, 1 (2%) stage IIB, and 3 patients (6%) stage III. There was one operative death (1.8%). Complications occurred in 31 patients (57%). Median hospitalization was 13 days (range, 11 to 44 days). Follow-up was complete in all patients and ranged from 6 months to 9 years (median, 63 months). Overall 5-year survival was 86% and did not differ significantly from a population matched for age and gender. Five-year survival for patients with only high-grade dysplasia was 96% and 68% for patients with cancer (p = 0.017). Quality of life was measured by the Medical Outcomes Study 36-Item Short-Form Health Survey. For patients with only high-grade dysplasia, the role-physical and role-emotional scores were better than for the control population (p < 0.03). For patients with cancer, the health perception score was worse than for the control population (p < 0.03). Scores measuring physical-function, social function, mental health, bodily pain, and energy/fatigue were similar. CONCLUSIONS Although perioperative morbidity is significant, surgical resection of high-grade dysplasia in Barretts esophagus provides excellent long-term survival with acceptable function and quality of life.

Empyema and bronchopleural fistula after pneumonectomy: factors affecting incidence

BACKGROUND Factors affecting the incidence of empyema and bronchopleural fistula (BPF) after pneumonectomy were analyzed. METHODS All patients who underwent pneumonectomy at the Mayo Clinic in Rochester, Minnesota, from January 1985 to September 1998 were reviewed. There were 713 patients (514 males and 199 females). Ages ranged from 12 to 86 years (median 64 years). Indication for resection was primary malignancy in 607 patients (85.1%), metastatic disease in 32 (4.5%), and benign disease in 74 (10.4%). One hundred fifteen patients (16.1%) underwent completion pneumonectomy. Factors affecting the incidence of postoperative empyema and BPF were analyzed using univariate and multivariate analysis. RESULTS Empyema was documented in 53 patients (7.5%; 95% confidence interval [CI], 5.7% to 9.7%) and a BPF in 32 (4.5%; 95% CI, 3.1% to 6.3%). Univariate analysis demonstrated that the development of empyema was adversely affected by benign disease (p = 0.0001), lower preoperative forced expiratory volume in 1 second (FEV1; p < 0.01) and diffusion capacity of lung to carbon monoxide (DLCO; p = 0.0001), lower preoperative serum hemoglobin (p = 0.05), right pneumonectomy (p = 0.0109), bronchial stump reinforcement (p = 0.007), completion pneumonectomy (p < 0.01), timing of chest tube removal (p = 0.01), and the amount of blood transfusions (p < 0.01). Similarly, the development of BPF was significantly associated with benign disease (p = 0.03), lower preoperative FEV1 (p = 0.03) and DLCO (p = 0.01), right pneumonectomy (p < 0.0001), bronchial stump reinforcement (p = 0.03), timing of chest tube removal (p = 0.004), increased intravenous fluid in the first 12 hours (p = 0.04), and blood transfusions (p = 0.04). Bronchial stump closure with staples had a protective effect against BPF compared with suture closure (p = 0.009). No risk factors were identified as being jointly significant in multivariate analysis. CONCLUSIONS Multiple perioperative factors were associated with an increased incidence of empyema and BPF after pneumonectomy. Prophylactic reinforcement of the bronchial stump with viable tissue may be indicated in those patients suspected at higher risk for either empyema or BPF.

Complete Pathologic Response After Neoadjuvant Chemoradiotherapy for Esophageal Cancer Is Associated With Enhanced Survival

BACKGROUND Neoadjuvant chemoradiotherapy followed by esophagogastrectomy has become the standard of care for patients with locally advanced esophageal cancer. This report analyzes our experience with this treatment approach. METHODS From January 1998 through December 2003, all patients from a single institution receiving neoadjuvant chemoradiotherapy followed by esophagogastrectomy were reviewed for operative mortality, morbidity, long-term survival, and factors affecting survival. Only patients preoperatively staged with both computed tomographic scans and endoscopic ultrasound were included. RESULTS There were 162 patients (142 men, 20 women), and the median age was 61 years (range, 22 to 81 years). Histopathology was adenocarcinoma in 143 patients and squamous cell in 19. Pretreatment clinical stage was II in 28 patients (17%), III in 111 (68%), and IV (M1a) in 23 (14%). Ivor Lewis esophagogastrectomy was the most common procedure, occurring in 132 patients. Operative mortality and morbidity was 4.9% and 37%, respectively. Pathologic response was complete in 42 patients (26%), near complete in 27 (17%), partial in 88 (54%), and unresectable in 5 (3%). Five-year survival for overall, complete, near complete, and partial response patients was 34%, 55%, 27%, and 27%, respectively (p = 0.013). Patients whose lymph nodes were rendered free of cancer showed improved overall and disease-free survival compared with patients having persistently positive lymph nodes (p = 0.019). CONCLUSIONS Esophagogastrectomy after neoadjuvant chemoradiotherapy can be performed with low mortality and morbidity. Patients with complete pathologic response have significantly improved long-term survival compared with patients with near complete and partial responses. Future efforts should be directed at understanding determinants of complete responses.

Benign Liver Tumors

From a practical standpoint, the most important benign hepatic tumors are hepatocytic adenoma, focal nodular hyperplasia, cavernous hemangioma, and bile duct hamartoma. The surgeon needs to be familiar with the pathogenesis, gross and radiologic appearance, and natural history of each of these lesions to formulate an appropriate therapeutic plan.

Laparoscopic repair of large paraesophageal hiatal hernia.

BACKGROUND The objective of this study was to analyze our initial results after laparoscopic repair of large paraesophageal hiatal hernias. METHODS Between October 1997 and May 2000, 37 patients (23 women, 14 men) underwent laparoscopic repair of a large type II (pure paraesophageal) or type III (combined sliding and paraesophageal) hiatal hernia with more than 50% of the stomach herniated into the chest. Median age was 72 years (range 52 to 92 years). Data related to patient demographics, esophageal function, operative techniques, postoperative symptomatology, and complications were analyzed. RESULTS Laparoscopic hernia repair and Nissen fundoplication was possible in 35 of 37 patients (95.0%). Median hospitalization was 4 days (range 2 to 20 days). Intraoperative complications occurred in 6 patients (16.2%) and included pneumothorax in 3 patients, splenic injury in 2, and crural tear in 1. Early postoperative complications occurred in 5 patients (13.5%) and included esophageal leak in 2, severe bloating in 2, and a small bowel obstruction in 1. Two patients died within 30 days (5.4%), 1 from delayed splenic bleeding and 1 from adult respiratory distress syndrome secondary to a recurrent strangulated hiatal hernia. Follow-up was complete in 31 patients (94.0%) and ranged from 3 to 34 months (median 15 months). Twenty-seven patients (87.1%) were improved. Four patients (12.9%) required early postoperative dilatation. Recurrent paraesophageal hiatal hernia occurred in 4 patients (12.9%). Functional results were classified as excellent in 17 patients (54.9%), good in 9 (29.0%), fair in 1 (3.2%), and poor in 4 (12.9%). CONCLUSIONS Laparoscopic repair of large paraesophageal hiatal hernias is a challenging operation associated with significant morbidity and mortality. More experience, longer follow-up, and further refinement of the operative technique is indicated before it can be recommended as the standard approach.

Worse disease-free survival in never-smokers with ALK+ lung adenocarcinoma

Introduction: The EML4–anaplastic lymphoma kinase (ALK) translocation is a recognized oncogenic driver in non-small cell lung cancer. We investigated immunohistochemistry (IHC) screening with fluorescence in situ hybridization (FISH) confirmation for ALK detection and estimated the prevalence of ALK positivity in our patient cohort of never-smokers, together with differences in clinical outcomes and prognostic factors for patients with ALK-positive and ALK-negative tumors. Methods: We designed a three-phase study (training, validation, and testing) in 300 never-smokers with lung adenocarcinoma from the observational Mayo Clinic Lung Cancer Cohort. Tumor samples were tested using IHC and FISH, and concordance between the methods was assessed. Clinical outcomes were assessed via 5-year progression- or recurrence-free survival from diagnosis. Prognostic factors for ALK-positive tumors and metastases were also investigated. Results: ALK-positive patients were significantly (p < 0.05) younger and had higher grade tumors than ALK-negative patients. ALK positivity was 12.2% by IHC and confirmed at 8.2% of tumors by FISH, with complete concordance between IHC 3+/0 and FISH+/− assessments, respectively. Five-year risk of progression or recurrence was doubled for patients with ALK-positive compared with ALK-negative tumors; ALK-positive tumors also appeared to be associated with a higher risk of brain and liver metastases. Conclusions: Our findings suggest that ALK positivity is associated with a significantly poor outcome in nonsmoking-related adenocarcinoma and that ALK-positive tumors may be associated with an increased risk of brain and liver metastases compared with ALK-negative disease. Consequently, an unmet medical need exists in ALK-positive lung cancer patients, and effective ALK-specific therapies are needed.

Prognostic significance of lymph node metastasis found during pulmonary metastasectomy for extrapulmonary carcinoma

BACKGROUND The prognostic significance of lymph node metastasis in cancer patients is well documented. Pulmonary metastasectomy in selected patients is associated with improved survival. Little is known about the prognostic significance of lymph node metastases found during pulmonary metastasectomy for extrapulmonary carcinoma metastatic to the lung. METHODS The records of all patients who underwent pulmonary metastasectomy and complete mediastinal lymph node dissection for extrapulmonary carcinomas at our institution from November 1985 through July 1999 were reviewed. RESULTS Eight hundred eighty-three patients underwent pulmonary metastasectomy. Of these, 70 patients (7.9%) (44 men, 26 women) had concomitant complete lymphadenectomy. Median age was 64 years (range, 33 to 83 years). Median time interval between primary tumor resection and metastasectomy was 34 months (range, 0 to 188 months). Wedge excision was performed in 46 patients, lobectomy in 16, both in 7, and pneumonectomy in 1. Lymph node metastases were found in 20 patients (28.6%) and were classified as intrapulmonary or hilar (N1) in 9, mediastinal (N2) in 8, and both in 3. There were no operative deaths. Median follow-up was 6.6 years (range, 1.1 to 14.6 years). Three-year survival for patients with negative lymph nodes was 69% as compared with only 38% for those with positive lymph nodes (p < 0.001). CONCLUSIONS The presence of lymph node metastases at the time of pulmonary metastasectomy for extrapulmonary carcinoma has an adverse effect on prognosis. Complete mediastinal lymph node dissection should be considered at the time of pulmonary metastasectomy for carcinoma to improve staging and guide treatment.

Tumor response to induction chemoradiation: influence on survival after esophagectomy

OBJECTIVE Preoperative chemoradiation is becoming standard of care for locally advanced esophageal cancer. The objective of this study was to determine if the degree of pathologic response to preoperative chemoradiation could predict survival and recurrence after resection in patients with adenocarcinoma of the distal esophagus. METHODS Between January 1998 and December 2001, 366 patients underwent esophagectomy for adenocarcinoma of the esophagus; 108 (30%) had induction chemoradiation prior to surgery. The records of these 108 patients were reviewed. RESULTS Histologic examination of the resected specimens documented complete pathologic response (CR) in 24 patients (22%) and residual tumor (RT) in 84 (78%). Operative mortality was 3.7%. Follow-up was complete in all patients and ranged from 1 to 46 months (median, 11 months). Three-year survival for patients with CR was 64% as compared to 34% for patients with RT (P=0.17). Median survival for patients with CR has not yet been reached; however, median survival for patients with RT was 19 months. Three-year cancer free survival for patients with CR was 57% compared to 30% for patients with RT (P=0.03). While median survival free of recurrence for patients with CR has not yet been reached, median survival free of recurrence for patients with RT was 9 months. CONCLUSION Complete pathologic response to induction chemoradiation is associated with improved early overall and disease-free survival following esophagectomy for adenocarcinoma of the distal esophagus. Because recurrent cancer still develops in many of these patients, even after complete pathologic response, the search for the optimal treatment continues.

Solitary fibrous tumors of the pleura: Results of surgical treatment and long-term prognosis

OBJECTIVE We sought to define the long-term outcome of surgically treated solitary fibrous tumors of the pleura. METHODS We performed a retrospective review from December 1972 through December 2002. RESULTS There were 84 patients (39 men and 45 women) with a median age of 57 years (range, 34-83 years). Forty-six patients were symptomatic. Surgical resection included pulmonary wedge excision in 62 patients, lobectomy in 4 patients, segmentectomy in 2 patients, chest wall resection in 3 patients, isolated pleural resection in 7 patients, and chest wall resection with pulmonary wedge excision, lobectomy, or pneumonectomy in 3, 2, and 1 patients, respectively. Tumors were polypoid in 57 patients, sessile in 20 patients, and intrapulmonary in 7 patients. Histopathology was benign in 73 and malignant in 11 patients. Nine (82%) patient with malignant tumors and 37 (54%) patients with benign tumors were symptomatic (P = .11). The median tumor diameters for malignant and benign tumors were 12.0 and 4.5 cm, respectively (P = .001). Operative mortality and morbidity occurred in 3 (3.6%) and 7 (8.1%) patients, respectively. Median follow-up in survivors was 146 months (range, 23-387 months). Median survival for patients with benign and malignant tumors was 284 and 55 months, respectively, and 5-year survival was 88.9% and 45.5%, respectively (P = .0005). Eight (9.5%) patients had recurrent solitary fibrous tumors of the pleura. Recurrences were malignant in 6 and benign in 2 patients. Localized chest recurrences occurred in 3 patients, all of whom had reresection, with 2 patients again having recurrence. CONCLUSION Resection of benign solitary fibrous tumors of the pleura carries an excellent prognosis. Larger tumors are more likely to be malignant. Both benign and malignant tumors can recur. Although prolonged survival after resection of malignant tumors is possible, recurrence is common.

Barrett's esophagus: the role of laparoscopic fundoplication.

BACKGROUND To review our early operative results and endoscopic findings after laparoscopic fundoplication for Barretts esophagus (BE). METHODS From January 1995 through December 2000, 49 patients with BE (35 men and 14 women) underwent laparoscopic antireflux surgery. Median age was 54 years (range, 28 to 85 years). No patient had high-grade dysplasia; 6, however, had low-grade dysplasia. All 49 patients had gastroesophageal reflux symptoms. Heartburn was present in 41 patients (84%), dysphagia in 16 (33%), epigastric or chest pain in 9 (18%), and other symptoms in 16 (33%). A Nissen fundoplication was performed in 48 patients and a partial posterior fundoplication in 1. Forty-one patients (84%) had concomitant hiatal hernia repair. RESULTS There were no deaths. Complications occurred in 2 patients (4%). Follow-up was complete in 48 patients (98%) and ranged from 1 to 81 months (median, 29 months). Functional results were classified as excellent in 33 patients (69%), good in 9 (19%), fair in 5 (10%), and poor in 1 (2%). Thirty-three patients (67%) underwent postoperative surveillance esophagoscopy with biopsy. Nine patients (18%) had total regression of BE and 3 (6%) had a decrease in total length. In the 6 patients with preoperative low-grade dysplasia, dysplasia was not found in 4, remained unchanged in 1, and progressed to in situ adenocarcinoma in 1. CONCLUSIONS Laparoscopic fundoplication is effective in controlling symptoms in the majority of patients with BE. While disappearance of BE may occur in some patients, the possibility of developing esophageal adenocarcinoma is not eliminated by laparoscopic fundoplication. Therefore, endoscopic surveillance should continue.