"What if I do nothing?" The natural history of operable cancer of the alimentary tract.

INTRODUCTION: "Natural history", or anticipated survival without treatment, is critical for patients weighing risks and benefits of cancer surgery. Current estimates concerning the natural history of cancer includes patients whose poor health precludes treatment; a cohort whose fate is likely distinctly worse than those eligible for surgery ("operable"). The study objective was to evaluate survival among patients recommended for cancer surgery but went untreated, to determine the natural history of "operable" alimentary tract cancer. METHODS: The NCDB was queried for untreated patients with clinical stage I-III esophageal, gastric, colon, and rectal cancer diagnosed between 2003 and 2009. Untreated patients who were recommended for surgery were considered "operable," while patients coded as surgically ineligible for health reasons were "inoperable." RESULTS: 5-year survival of untreated, "operable" alimentary tract cancers varied by clinical stage: esophageal cI = 10.0%, cII = 9.8%, cIII = 4.6%; gastric cI = 9.2%, cII = 5.8%, cIII = 4.3%; colon cI = 18.4%, cII = 5.0%, cIII = 10.4; and rectal cI = 17.1%, cII = 14.0%, cIII = 19.9%. At every timepoint, stage-specific survival of "operable" patients was superior to inoperable patients (p < 0.05). Additionally, median survival among "operable" patients at least doubled "inoperable" patients for each tumor. CONCLUSION: Natural history of patients with "operable" alimentary tract cancer is superior to that of "inoperable" patients. Preoperative counseling should be refined to reflect this distinction.

Long term results of lung transplantation for cystic fibrosis.

OBJECTIVES: We reviewed our experience with lung transplant for cystic fibrosis (CF) over a 10-year period to identify factors influencing long-term survival. METHODS: One hundred and twenty-three patients with CF have undergone 131 lung transplant procedures at our institution; 114 have had bilateral sequential lung transplants (DLTX) and nine have had bilateral lower lobe transplants from living donors. Three patients had retransplant for acute graft failure, and five had late retransplant for bronchiolitis obliterans syndrome (BOS). Kaplan-Meier survival was calculated for the entire cohort and for subsets at higher risk of death to determine factors predicting a better outcome. RESULTS: Actuarial survival for the entire group of DLTX CF patients was 81% at 1 year, 59% at 5 years, and 38% at 10 years. Lobar transplant was associated with a poorer survival (37.5% at 1 and 5 years). Among DLTX patients, colonization with Burkholderia cepacia was present in 22 patients and was associated with poorer outcome (1- and 5-year survival 60 and 36% in B. cepacia patients vs. 86 and 64% in non-cepacia patients). DLTX patients younger than age 20 (n=22) had a similar survival to patients age 20 or older (n=90). Being on a ventilator at the time of transplant was not associated with poorer survival (n=8). BOS affects increasing numbers of survivors with time. Five CF patients have been retransplanted due to BOS with one operative death and 1-year survival of 60%. CONCLUSIONS: DLTX has acceptable long term survival in CF adults and children with end stage disease. CF patients colonized with B. cepacia have a worse outcome but transplantation is still warranted.

Dose-escalating conformal thoracic radiation therapy with induction and concurrent carboplatin/paclitaxel in unresectable stage IIIA/B nonsmall cell lung carcinoma: a modified phase I/II trial.

BACKGROUND: A modified Phase I/II trial was conducted evaluating the incorporation of three-dimensional conformal radiation therapy into a strategy of sequential and concurrent carboplatin/paclitaxel in Stage III unresectable nonsmall cell lung carcinoma (NSCLC). The dose of thoracic conformal radiation therapy (TCRT) from 60 to 74 gray (Gy) was increased. Endpoints included response rate, toxicity, and survival. METHODS: Sixty-two patients with unresectable Stage III NSCLC were included. Patients received 2 cycles of induction carboplatin (area under the concentration curve [AUC], 6) and paclitaxel (225 mg/m(2) over 3 hours) every 21 days. On Day 43, concurrent TCRT and weekly (x 6) carboplatin (AUC, 2) and paclitaxel (45 mg/m(2)/3 hours) were initiated. The TCRT dose was escalated from 60 to 74 Gy in 4 cohorts (60, 66, 70, and 74 Gy). RESULTS: The response rate to induction carboplatin/paclitaxel was 40%. Eight patients (13%) progressed on the induction phase. No dose-limiting toxicity was observed during the escalation of the TCRT dose from 60 to 74 Gy. The major toxicity was esophagitis, however, only 8% developed Grade 3/4 esophagitis using Radiation Therapy Oncology Group criteria. The overall response rate was 52%. Survival rates at 1, 2, 3, and 4 years were 71%, 52%, 40%, and 36%, respectively, with a median survival of 26 months. The 1-, 2-, and 3-year progression free survival probabilities were 47%, 35%, and 29%, respectively. CONCLUSIONS: Incorporation of TCRT with sequential and concurrent carboplatin/paclitaxel is feasible, and dose escalation of TCRT to 74 Gy is possible with acceptable toxicity. Overall response and survival rates are encouraging. Both locoregional and distant failure remain problematic in this population of patients.

Blunt tracheobronchial injuries: treatment and outcomes.

BACKGROUND: Tracheobronchial injury is a recognized, yet uncommon, result of blunt trauma to the thorax. Often the diagnosis and treatment are delayed, resulting in attempted surgical repair months or even years after the injury. This report is an extensive review of the literature on tracheobronchial ruptures that examines outcomes and their association with the time from injury to diagnosis. METHODS: We reviewed all patients with blunt tracheobronchial injuries published in the literature to determine the anatomic location of the injury, mechanism of the injury, time until diagnosis and treatment, and outcome. Only patients with blunt intrathoracic tracheobronchial traumas were included. RESULTS: We identified 265 patients reported between 1873 and 1996. Motor vehicle accidents were the most frequent mechanism of injury (59%). The overall mortality among reported patients has declined from 36% before 1950 to 9% since 1970. The injury occurred within 2 cm of the carina in 76% of patients, and 43% occurred within the first 2 cm of the right main bronchus. The proximity of the injury to the carina had no detectable effect on mortality. Injuries on the right side were treated sooner but were associated with a higher mortality than left-sided injuries. No association was detected between delay in treatment and successful repair of the injury; ninety percent of patients undergoing treatment more than 1 year after injury were repaired successfully. CONCLUSIONS: This review of patients with blunt tracheobronchial injuries represents the largest cohort studied to date. These data suggest an ability to repair tracheobronchial injuries successfully many months after they occur. We are also able to assess the mortality associated with the location and side of injury, examine the time from injury until diagnosis and treatment, and evaluate treatment outcome.

Induction carboplatin/paclitaxel followed by concurrent carboplatin/paclitaxel and dose-escalating conformal thoracic radiation therapy in unresectable stage IIIA/B nonsmall cell lung carcinoma: a modified Phase I trial.

BACKGROUND: A modified Phase I trial was conducted evaluating the incorporation of 3-dimensional conformal radiation therapy (3DCRT) into a strategy of sequential and concurrent carboplatin/paclitaxel in Stage III, unresectable nonsmall cell lung carcinoma (NSCLC). In addition, dose escalation of thoracic conformal radiation therapy (TCRT) from 60 to 74 gray (Gy) was performed. Endpoints included response rate, toxicity, and survival. METHODS: Twenty-nine patients with unresectable Stage III NSCLC were included. Patients received 2 cycles of induction carboplatin (AUC 6) and paclitaxel (225 mg/m(2)/3 hours) every 21 days. On Day 43, concurrent TCRT and weekly (x6) carboplatin (AUC 2) and paclitaxel (45 mg/m(2)/3 hours) was initiated. The TCRT dose was escalated from 60 to 74 Gy in 4 cohorts. RESULTS: The response rate to induction carboplatin/paclitaxel was 52%. Three patients (10%) experienced disease progression during the induction phase. No dose-limiting toxicity was seen during the escalation of the TCRT dose from 60 to 74 Gy. The major toxicity was esophagitis, with 18% of patients developing Radiation Therapy Oncology Group Grade 3 esophagitis. The overall response rate was 70% (1 complete response and 18 partial responses). Survival rates at 1 and 2 years were 69% and 45%, with a median survival of 21 months. The 1-year progression free survival probability was 41% (95% confidence interval, 23-59%). CONCLUSIONS: Incorporation of 3DCRT with sequential and concurrent carboplatin/paclitaxel is feasible, and dose escalation of TCRT to 74 Gy is possible with acceptable toxicity. Overall response and survival rates are encouraging. Accrual is continuing in a Phase II fashion at 74 Gy with sequential and concurrent carboplatin/paclitaxel.

Beliefs among pulmonologists and thoracic surgeons in the therapeutic approach to non-small cell lung cancer.

STUDY OBJECTIVES: The physicians who initially evaluate patients with non-small cell lung cancer (NSCLC) strongly impact the course of therapy. Their beliefs in treatment and prognosis may contribute to practices of variable quality and appropriateness. We sought to better describe beliefs among pulmonologists and thoracic surgeons who were selected for guiding early therapy and referrals in patients with NSCLC. DESIGN: Mail questionnaire focusing on survival estimates, treatment perceptions, and referral patterns. PARTICIPANTS: Twelve hundred pulmonologists and 800 thoracic surgeons who were clinically active members of the American College of Chest Physicians. MEASUREMENTS AND RESULTS: Response rates of 50% for pulmonologists and 52% for thoracic surgeons were obtained after two mailings. Five-year survival estimates for patients with resected stage I NSCLC revealed that 30% of respondents overestimated survival rates and 18% underestimated survival rates. The underestimation of survival rate was found among more respondents who are practicing pulmonology than thoracic surgery (22% vs 10% [corrected], respectively), who were trained before 1980 than after 1980 (29% vs 10% [corrected], respectively), and who were seeing < 10 lung cancer patients annually than those who were seeing > 25 (31% vs 0.14%, respectively). Beliefs in the survival benefit of adjuvant chemotherapy or of radiation in stage I-IIIA disease divided respondents within both specialties. Chemotherapy plus radiation vs radiation alone in unresectable stage IIIA-B NSCLC was viewed as benefiting survival less often by physicians seeing < 10 lung cancer patients annually rather than > 25 (57% vs 77% [corrected], respectively) and by physicians underestimating rather than correctly estimating survival in early-stage disease (58% vs 72% [corrected], respectively). Chemotherapy was believed to confer survival benefits in patients with stage IV disease by one third of respondents. CONCLUSIONS: Certain physician characteristics, particularly the length of time since training and NSCLC patient volume, are associated with beliefs not conclusively supported in the medical literature or with opinions inconsistent within and between specialties.

Inadequacy of computed tomography in assessing patients with esophageal carcinoma after induction chemoradiotherapy.

BACKGROUND: Induction chemoradiotherapy followed by surgery may improve survival of patients with esophageal carcinoma. Computed tomography (CT) has been used to evaluate the tumor response after completing induction chemoradiotherapy. The authors examined the ability of CT to evaluate the pathologic tumor response to induction therapy and to stage the tumor correctly. METHODS: Preinduction and postinduction chemoradiotherapy CT scans were reviewed retrospectively for 50 patients enrolled in a protocol of induction chemoradiotherapy followed by surgery. All studies were performed on third-generation or fourth-generation scanners. Radiographic response was determined using Eastern Cooperative Oncology Group solid tumor response criteria for bidimensional measurable disease. This was compared with the pathologic tumor response. CT-tumor (T) classification using the modified Tio scale was compared with the pathologic T classification. RESULTS: CT-T classification did not correlate with the pathologic stage (P = 0.09) or the pathologic tumor response (P = 0.22). The postinduction chemoradiotherapy CT accurately staged the T classification in 42% of patients but overstaged 36% of patients and understaged 20% of patients. CT had a sensitivity of 65%, a specificity of 33%, a positive predictive value of 58%, and a negative predictive value of 41% in evaluating the pathologic tumor response. CONCLUSIONS: CT is a poor diagnostic study tool for determining the pathologic tumor response or the pathologic disease stage after induction chemoradiotherapy in patients with esophageal carcinoma.

Lung transplantation for cystic fibrosis: effective and durable therapy in a high-risk group.

BACKGROUND: The purpose of this study was to review our experience with lung transplantation in patients with end-stage cystic fibrosis. METHODS: Eight-two patients with cystic fibrosis have undergone bilateral lung transplantation (n=76) or bilateral lower lobe transplantation (n=6) since October 1990. RESULTS: Actuarial survival for the entire cohort is 79% at 1 year and 57% at 5 years. The development of bronchiolitis obliterans syndrome is the leading cause of death after the first year. Freedom from bronchiolitis obliterans syndrome is 84% at 1 year and 51% at 3 years. Pulmonary function tests improve dramatically in recipients. There was no association between death within 1 year and recipient age, weight, graft ischemic time, cytomegalovirus seronegativity, or the presence of pan-resistant organisms. Similarly, there was no association between the development of bronchiolitis obliterans syndrome within 2 years and ischemic time, number of rejection episodes, cytomegalovirus seronegativity, or the presence of panresistant organisms. CONCLUSIONS: Despite their poor nutritional status and the presence of multiply resistant organisms, patients with cystic fibrosis can undergo bilateral lung transplantation with acceptable morbidity and mortality.

Multicenter VATS experience with mediastinal tumors.

BACKGROUND: The use of video-assisted thoracic surgery for diagnosis and treatment of mediastinal tumors in a multiinstitution patient population is not well understood. METHODS: We studied 48 cases from Cancer and Leukemia Group B thoracic surgeons. Of 21 men and 27 women, aged 41 +/- 16 years, 22 patients were asymptomatic. In the others, 92% of tumor-related symptoms improved or resolved after treatment. Five tumors involved the anterior compartment, 19 the middle, and 24 the posterior compartment. Diagnoses were typical for each compartment but also included uncommon problems such as superior vena cava hemangioma and a histoplasmosis cyst causing hoarseness. Of the lesions, a biopsy of 12 was done without excision and the rest were excised completely. Fifteen were cystic and 10 were malignant (8 biopsy only). Maximal dimensions were 5.2 +/- 3.3 cm. RESULTS: Operations were briefer for 24 posterior (93 +/- 41 min) than 5 anterior (195 +/- 46 min, p < 0.01) or 19 middle mediastinal tumors (170 +/- 78 min, p < 0.01). Although 96% had vital mediastinal relations, only six open conversions were performed because of bleeding (n = 3), large size, impaired exposure, or rib attachments, and no patient had morbidity beyond that expected for the thoracotomy. Postoperative stay was shorter for the nonconversion group (3.2 +/- 2.8 versus 5.5 +/- 2.1 days, p = 0.05), as was chest tube duration (1.7 +/- 1.4 days versus 3.2 +/- 1.9 days, p = 0.03). There were no postoperative deaths or major complications, but 7 patients had minor complications. During a mean of 20 months of surveillance (range, 1 to 52 months), one cyst recurred (asymptomatic) as did one sarcoma that was excised. CONCLUSIONS: Video-assisted thoracic surgery is a safe technique for benign mediastinal tumors, typically those in the middle and posterior mediastinum.

Pancoast tumors of the lung.

Pancoast or superior pulmonary sulcus tumors are uncommon primary bronchogenic carcinomas that produce a characteristic clinical syndrome of upper extremity pain and Horner's syndrome. Treatment of patients with this malignancy has traditionally involved irradiation alone or preoperative irradiation followed by resection. Recent advances in the management of Pancoast tumors include the importance of mediastinoscopy in staging the tumor before treatment begins. A complete resection should be accomplished including a lobectomy whenever possible. The current treatment protocol involves induction chemoradiotherapy followed by surgery.

Induction chemoradiotherapy followed by esophagectomy in patients with carcinoma of the esophagus.

BACKGROUND: Induction chemoradiotherapy followed by esophagectomy may provide results superior to those of single-modality treatment in patients with esophageal cancer. The purpose of this study was to review our experience with this approach for esophageal cancer. METHODS: From 1988 to 1996, 166 consecutive patients with esophageal cancer were evaluated; 66 entered a protocol of chemotherapy (5-fluorouracil, cisplatin) concurrent with radiation (45 Gy) followed by esophagectomy. Fifty-four patients completed the protocol. RESULTS: Toxicity associated with induction chemoradiotherapy was minimal. The actuarial survival at 12, 24, and 36 months was 59%, 42%, and 32%, respectively. The pathologic complete response (pCR) rate was 41%, with 12-, 24-, and 36-month survivals of 77%, 50%, and 45%, whereas non-pCR patients had survivals of 46%, 35%, and 23%. The difference in survival between pCR and non-pCR patients was not significant (p = 0.13), but the difference in recurrence-free survival was significant (p = 0.007). CONCLUSIONS: This well-tolerated protocol resulted in a high pCR. Trimodality treatment for esophageal cancer may provide long-term survival in some patients regardless of their pCR status.

Immediate postgadolinium spoiled gradient-echo MRI for evaluating the abdominal aorta in the setting of abdominal MR examination.

To assess the reproducibility and image quality of immediate postgadolinium chelate spoiled gradient-echo MRI in demonstrating disease of the abdominal aorta. All patients (27 patients: 21 men, 6 women) with substantial disease of the abdominal aorta, who underwent abdominal MR examinations at 1.5 T between 1991 and 1995, were entered in the study. Patients were referred for evaluation of suspected aortic disease (14 patients) or other abdominal diseases (13 patients). Three experienced investigators manually measured luminal and external aortic wall diameters and rated image quality, definition of inner and outer walls, extent of disease, and presence of other abdominal abnormalities, in an independent fashion. A cardiovascular surgeon then rated all studies to determine whether clinical management could be based on the MR findings alone. There was 98 to 99% agreement in measurements of luminal and external wall diameter between the three investigators. Overall image quality was rated as good in 77.8 to 88.9% of patients. A total of 31 additional nonaortic abdominal abnormalities were detected by all observers. The cardiovascular surgeon rated 25 of 27 studies as adequate to determine clinical management based on MR findings alone. Immediate postgadolinium spoiled gradient-echo MRI is a reproducible technique for the demonstration of abdominal aortic disease and possesses good image quality. Advantages of this technique include simultaneous evaluation of other nonvascular diseases of the abdomen, short examination time, and easy implementation as part of routine abdominal MRI scanning protocol.

IIB or not IIB: the current question in staging non-small cell lung cancer.

It has been suggested that T3/N0-1/M0 non-small cell lung cancer should be classified as stage IIB rather than IIIA. This is the result of a widespread perception that the survival of patients with T3/N0-1 lung cancers greatly exceeds that of patients with stage IIIA (N2) lung cancers. This perception is based primarily on the survival of T3/N0-1 patients who have chest wall involvement. However, the T3 classification also includes tumors that involve mediastinal structures, the main stem bronchus <2 cm from the carina, and the brachial plexus as seen in Pancoast tumors. Survival for each of these T3 categories is examined in this articles and found to be somewhat different. The available data show that patients with T3/N0-1 tumors involving the chest wall have a good prognosis after resection, whereas patients with central T3/N0-1 tumors (mediastinal or main stem bronchial involvement) have a prognosis similar to that of patients with resected IIIA (N2) tumors. If a new classification of T3/N0-1 tumors as stage IIB is to be adopted, it will be important for future studies to document which type of T3 tumor is being discussed.

Pancoast (superior sulcus) tumors.

Primary carcinomas arising in the apex of the lung (Pancoast tumors) have attracted attention because of the characteristic syndrome that is produced by local extension into the chest wall and the brachial plexus. This article reviews the history of the treatment of this disease, the natural history of untreated patients, and the diagnosis of Pancoast tumors. The published data on results, prognostic factors, and technical aspects of treatment with combined irradiation and operation are examined, as well as those pertaining to treatment with irradiation alone.

Invasive carcinoid tumor of the heart.

Carcinoid tumors have been described in almost every organ and may affect virtually every body system. Cardiac involvement manifesting as right-sided valvular disease is characteristic of the carcinoid syndrome; however, direct myocardial involvement is unusual. We present a case of an invasive carcinoid tumor whose primary manifestation was myocardial invasion.

One hundred consecutive thymectomies for myasthenia gravis.

BACKGROUND: Between June 1997 and November 1993, 100 consecutive thymectomies for myasthenia gravis were performed at University of North Carolina Hospitals in Chapel Hill. METHODS: A consistent, planned protocol involving preoperative, intraoperative, and postoperative care was followed. All thymectomies were performed through a median sternotomy with removal of all visible thymus and perithymic fat in the anterior mediastinum. RESULTS: There was no perioperative mortality or longterm morbidity. Mean postoperative hospital stay was 6.3 days (range, 3 to 18 days). Ninety-six percent of the patients were extubated the day of the operation, and all patients were extubated within 24 hours. Mean postoperative intensive care unit stay was 1.2 days (range, 1 to 4 days). After a mean follow-up of 65 months (range, 1 to 199 months), 78% of all patients are improved by at least one modified Osserman classification when their current status is compared with their worst preoperative disease severity. In fact, 69% of patients with mild disease preoperatively (class I, II, or III maximal severity) are in pharmacologic remission (asymptomatic without regular medication), whereas 29% of patients with severe disease (class IV or V) are in remission (p = 0.0001). CONCLUSIONS: Our programmatic approach to thymectomy through a sternotomy has shown minimal morbidity and mortality. It is beneficial to myasthenics at both ends of the age and severity spectrum.

Wegener's granulomatosis mimicking a sternal abscess.

Bone destruction as a manifestation of Wegener's granulomatosis has been reported, but these cases were limited to the head and face. We present a case in which a sternal abscess was the initial manifestation of Wegener's granulomatosis. We believe this is the first reported case of bone destruction due to Wegener's occurring in a location other than the head and face.

Single-stage replacement of the entire thoracic aorta via transverse thoracosternotomy.

The transverse thoracosternotomy provides excellent exposure for repair of lesions involving the entire thoracic aorta. This approach has been made more feasible by other recent technical advances, such as retrograde perfusion of the brain during circulatory arrest, allowing single-stage replacement of the ascending and descending aorta and aortic arch. The two cases presented here illustrate the use of these advancements in the treatment of extensive aneurysms of the thoracic aorta.

Concurrent radiation therapy and chemotherapy followed by esophagectomy for localized esophageal carcinoma.

PURPOSE: A prospective study was performed to determine the outcome of patients with esophageal cancer who received preoperative radiation therapy and chemotherapy followed by esophagectomy, and to determine the role of preresection esophagogastroduodenoscopy (EGD) in predicting the patients in whom surgery could possibly be omitted, and the impact of surgery on survival. MATERIALS AND METHODS: Thirty-five patients with localized carcinoma of the esophagus received concurrent external-beam radiotherapy and chemotherapy followed by esophagectomy. Patients received 45 Gy in 25 fractions. Chemotherapy consisted of continuous infusion fluorouracil (5-FU; 1,000 mg/m2/d) on days 1 through 4 and 29 through 32 and cisplatin (100 mg/m2) on day 1. Patients underwent an Ivor-Lewis esophagectomy 18 to 33 days after completion of radiotherapy. RESULTS: Eighty percent of the patients had squamous cell carcinoma and 20% had adenocarcinoma. In addition, 51% had a pathologic complete response (CR). Twenty-two of the 35 underwent a preresection EGD before resection. Seventeen of the 22 (77%) had negative pathology from the preresection EGD, but seven of the 17 (41%) had residual tumor at surgery. The median survival and disease-free survival rates for all patients were 25.8 months and 32.8 months, respectively. Eighteen patients (51%) had no tumor at resection. The median survival for these patients was 36.8 months; the median disease-free survival time has not been reached. The median survival and disease-free survival rate for the patients with residual tumor in the surgical specimen were 12.9 months and 10.8 months, respectively. CONCLUSION: Preresection EGD is not reliable for determining the presence of residual disease or the patients in whom surgery could be omitted. Twenty-five percent of the patients with residual tumor in the resected surgical specimen were long-term survivors; this suggests a benefit from esophagectomy after concurrent radiotherapy and chemotherapy.