Worldwide Esophageal Cancer Collaboration: pathologic staging data.

We report data-simple descriptions of patient characteristics, cancer categories, and non-risk-adjusted survival-for patients with pathologically staged cancer of the esophagus and esophagogastric junction after resection or ablation with no preoperative therapy from the Worldwide Esophageal Cancer Collaboration (WECC). Thirty-three institutions from six continents submitted de-identified data using standard definitions: demographics, comorbidities, clinical cancer categories, and all-cause mortality from first management decision. Of 13,300 patients, 5,631 had squamous cell carcinoma, 7,558 adenocarcinoma, 85 adenosquamous carcinoma, and 26 undifferentiated carcinoma. Patients were older (62 years) men (80%) with normal body mass index (51%), little weight loss (1.8 kg), 0-2 ECOG performance status (83%), and a history of smoking (70%). Cancers were pT1 (24%), pT2 (15%), pT3 (50%), pN0 (52%), pM0 (93%), and pG2-G3 (78%); most involved distal esophagus (71%). Non-risk-adjusted survival for both squamous cell carcinoma and adenocarcinoma was monotonic and distinctive across pTNM. Survival was more distinctive for adenocarcinoma than squamous cell carcinoma when pT was ordered by pN. Survival for pTis-1 adenocarcinoma was better than for squamous cell carcinoma, although monotonic and distinctive for both. WECC pathologic staging data is improved over that of the 7th edition, with more patients studied and patient and cancer variables collected. These data will be the basis for the 8th edition cancer staging manuals following risk adjustment for patient, cancer, and treatment characteristics, and should direct 9th edition data collection. However, the role of pure pathologic staging as the principal point of reference for esophageal cancer staging is waning.

Worldwide Esophageal Cancer Collaboration: clinical staging data.

To address uncertainty of whether clinical stage groupings (cTNM) for esophageal cancer share prognostic implications with pathologic groupings after esophagectomy alone (pTNM), we report data-simple descriptions of patient characteristics, cancer categories, and non-risk-adjusted survival-for clinically staged patients from the Worldwide Esophageal Cancer Collaboration (WECC). Thirty-three institutions from six continents submitted data using variables with standard definitions: demographics, comorbidities, clinical cancer categories, and all-cause mortality from first management decision. Of 22,123 clinically staged patients, 8,156 had squamous cell carcinoma, 13,814 adenocarcinoma, 116 adenosquamous carcinoma, and 37 undifferentiated carcinoma. Patients were older (62 years) men (80%) with normal body mass index (18.5-25 mg/kg2 , 47%), little weight loss (2.4 ± 7.8 kg), 0-1 ECOG performance status (67%), and history of smoking (67%). Cancers were cT1 (12%), cT2 (22%), cT3 (56%), cN0 (44%), cM0 (95%), and cG2-G3 (89%); most involved the distal esophagus (73%). Non-risk-adjusted survival for squamous cell carcinoma was not distinctive for early cT or cN; for adenocarcinoma, it was distinctive for early versus advanced cT and for cN0 versus cN+. Patients with early cancers had worse survival and those with advanced cancers better survival than expected from equivalent pathologic categories based on prior WECC pathologic data. Thus, clinical and pathologic categories do not share prognostic implications. This makes clinically based treatment decisions difficult and pre-treatment prognostication inaccurate. These data will be the basis for the 8th edition cancer staging manuals following risk adjustment for patient characteristics, cancer categories, and treatment characteristics and should direct 9th edition data collection.

Worldwide Esophageal Cancer Collaboration: neoadjuvant pathologic staging data.

To address uncertainty of whether pathologic stage groupings after neoadjuvant therapy (ypTNM) for esophageal cancer share prognostic implications with pathologic groupings after esophagectomy alone (pTNM), we report data-simple descriptions of patient characteristics, cancer categories, and non-risk-adjusted survival-for pathologically staged cancers after neoadjuvant therapy from the Worldwide Esophageal Cancer Collaboration (WECC). Thirty-three institutions from six continents submitted data using variables with standard definitions: demographics, comorbidities, clinical cancer categories, and all-cause mortality from first management decision. Of 7,773 pathologically staged neoadjuvant patients, 2,045 had squamous cell carcinoma, 5,686 adenocarcinoma, 31 adenosquamous carcinoma, and 11 undifferentiated carcinoma. Patients were older (61 years) men (83%) with normal (40%) or overweight (35%) body mass index, 0-1 Eastern Cooperative Oncology Group performance status (96%), and a history of smoking (69%). Cancers were ypT0 (20%), ypT1 (13%), ypT2 (18%), ypT3 (44%), ypN0 (55%), ypM0 (94%), and G2-G3 (72%); most involved the distal esophagus (80%). Non-risk-adjusted survival for yp categories was unequally depressed, more for earlier categories than later, compared with equivalent categories from prior WECC data for esophagectomy-alone patients. Thus, survival of patients with ypT0-2N0M0 cancers was intermediate and similar regardless of ypT; survival for ypN+ cancers was poor. Because prognoses for ypTNM and pTNM categories are dissimilar, prognostication should be based on separate ypTNM categories and groupings. These data will be the basis for the 8th edition cancer staging manuals following risk adjustment for patient, cancer, and treatment characteristics and should direct 9th edition data collection.

Short GCG expansions in the PABP2 gene cause oculopharyngeal muscular dystrophy.

Autosomal dominant oculopharyngeal muscular dystrophy (OPMD) is an adult-onset disease with a world-wide distribution. It usually presents in the sixth decade with progressive swallowing difficulties (dysphagia), eyelid drooping (ptosis) and proximal limb weakness. Unique nuclear filament inclusions in skeletal muscle fibres are its pathological hallmark. We isolated the poly(A) binding protein 2 gene (PABP2) from a 217-kb candidate interval on chromosome 14q11 (B.B. et al., manuscript submitted). A (GCG)6 repeat encoding a polyalanine tract located at the N terminus of the protein was expanded to (GCG)8-13 in the 144 OPMD families screened. More severe phenotypes were observed in compound heterozygotes for the (GCG)9 mutation and a (GCG)7 allele that is found in 2% of the population, whereas homozygosity for the (GCG)7 allele leads to autosomal recessive OPMD. Thus the (GCG)7 allele is an example of a polymorphism which can act either as a modifier of a dominant phenotype or as a recessive mutation. Pathological expansions of the polyalanine tract may cause mutated PABP2 oligomers to accumulate as filament inclusions in nuclei.

End-stage achalasia.

Despite symptom improvement offered to achalasia patients by either pneumatic dilation or surgical myotomy, 10% to 15% of those so treated will present progressive deterioration of their esophageal function and up to 5% may eventually require an esophagectomy. The natural evolution of achalasia to its end stage as well as the timing of esophagectomy in these patients form the basis of this review. The optimal reconstruction for the decompensated resected esophagus will also be explored: gastric interposition, colon interposition, and jejunal interposition all have their respective advantages and disadvantages. Their use is examined in the exclusive context of resection for achalasia.

Vascular conditioning of the stomach before esophageal reconstruction by gastric interposition.

Gastric interposition with intrathoracic or cervical esophagogastrostomy is currently the preferred operation for reconstruction after esophagectomy. Anastomotic leaks however result from poor vascular supply to the proximal stomach. They are responsible for significant morbidity and mortality. 'Ischemic conditioning' of the interposed stomach has been proposed as a technique where the 'delay phenomenon' aims at improving the microcirculation of the gastric conduit and preventing anastomotic leakage. Experimental observations and clinical studies have been conducted to document the immediate effects and results of this approach. The aim of this work is to review the principles, pathophysiology, experimental, and clinical evidence related to vascular conditioning of the stomach prior to esophagectomy with gastric interposition and esophagogastric anastomosis. MEDLINE and PubMed were searched to identify articles related to vascular conditioning of the stomach. Cross references were added and reviewed to complete the reference list. The anatomic basis of ischemic conditioning, the prevalence of ischemic events on the gastric conduit, the methodology to assess the microcirculation before and after gastric devascularization, animal experiments, and clinical studies reported on this approach were reviewed. Ten experimental works, eleven clinical observations, four reviews, and two editorial commentaries addressing ischemic conditioning of the stomach were identified and reviewed. Experimental observations document improved microcirculation to the proximal stomach following partial gastric devascularization. Clinical reports show the feasibility and relative safety of gastric ischemic conditioning. Preliminary observations suggest potential improvements to the gastric microcirculation resulting from gastric ischemic conditioning. This approach may help prevent complications at the esophagogastric anastomosis. The actual level of evidence however cannot promote its use outside of clinical research protocols.

The Kagoshima consensus on esophageal achalasia.

Esophageal achalasia is a primary esophageal motility disorder characterized by lack of peristalsis and a lower esophageal sphincter that fails to relax appropriately in response to swallowing. This article summarizes the most salient issues in the diagnosis and management of achalasia as discussed in a symposium that took place in Kagoshima, Japan, in September 2010 under the auspices of the International Society for Diseases of the Esophagus.

Lower oesophageal sphincter dysfunction is part of the functional abnormality in epiphrenic diverticulum.

BACKGROUND: The pathophysiology and management of epiphrenic diverticula remain controversial. This study investigated the underlying functional abnormalities and long-term results of surgical treatment. METHODS: Patients with symptoms and epiphrenic diverticula who had undergone long myotomy and Belsey Mark IV fundoplication were reviewed retrospectively. They were assessed before and after surgery by radiology, functional testing and endoscopy, and compared with a group of 40 normal volunteers. RESULTS: The study included 23 consecutive symptomatic patients who had surgery, 20 of whom had oesophageal spastic disorders. Lower oesophageal sphincter (LOS) incoordination was considered the most constant functional abnormality (P < 0.001). After operation oesophageal diameter increased, contraction pressures decreased and peristalsis was reduced. LOS resting and gradient pressures decreased (P = 0.001). Despite unchanged acid exposure values, endoscopy revealed increased mucosal damage after operation (P = 0.003). New columnar-lined metaplasia was documented in eight patients (P = 0.013). Symptoms had decreased after a median of 61 months (P = 0.001). CONCLUSION: Epiphrenic diverticulum was associated with spastic dysfunction and LOS abnormalities. A long myotomy including the LOS relieved functional obstruction and symptoms, but partial fundoplication did not prevent reflux damage.

The esophageal remnant after gastric interposition.

Gastric interposition is usually considered the reconstruction of choice following esophageal resection. However, a number of reports show that esophagectomy followed by a gastric transplant is associated with poor quality of life and significant reflux esophagitis in the esophageal remnant. The aim of this work is to review the factors affecting the mucosa of the esophageal remnant when using the stomach. A Medline was conducted. Additional references and search pathways were sourced from the references of reviewed articles. Reflux disease is considered an unavoidable consequence of esophageal resection followed by gastric interposition. Mucosal damage from acid and bile exposure in the esophageal remnant affects approximatively 50% of these patients. There is usually no correlation between symptoms and the presence of mucosal damage in the remaining esophagus. Endoscopy and endoscopic biopsies are the only reliable methods to document the status of the mucosa. When present, reflux esophagitis shows a progression from inflammation to erosions and to the development of columnar lined metaplasia. Esophageal and gastric function, gastric drainage operation, level of the anastomosis, route of reconstruction, and patients' position after the operation have all been shown to influence the severity and extent of damage in the esophageal remnant. Prevention and treatment of esophagitis in the remaining esophagus are discussed. When the stomach is used as a substitute to reconstruct the esophagus whether for malignant or benign conditions, an in vivo model of reflux diseases is created. Studies using this model may help clarify molecular and cellular events that lead to irreversible insult on the esophageal mucosa. Improvement to the reconstruction itself must be sought to favor better results with the gastric transplant.

Cricopharyngeal myotomy in the management of neurogenic and muscular dysphagia.

Oropharyngeal dysphagia results from disruption of the integrated mechanism of swallowing. Neurogenic dysphagia is caused by central nervous system disorders or by cranial nerve involvement and it may be distinguished from muscular dysphagia such as that seen mostly in oculopharyngeal muscular dystrophy (OPMD). Based on our 20-year experience in a university hospital thoracic surgery service, we describe the results of the clinical evaluation, the laboratory testing and the surgical management of a recent subgroup of patients experiencing dysphagia from neurogenic and muscular disorders.

Radionuclide esophageal transit study in detection of esophageal motor dysfunction: comparison with motility studies (manometry)

Radionuclide esophageal transit study (RETS) has been developed to assess motor function of the esophagus. The purpose of this study was to compare RETS to esophageal motility studies (EMS) in detection of motility disorders. A total of 109 consecutive patients without previous history of surgery on the esophagus underwent both RETS and EMS within one month of each other. Final diagnosis was divided into three categories: I--primary esophageal motor disorders (n = 39); II--reflux disease (n = 48); and III--non-cardiac chest pain and/or dysphagia (n = 22). Using EMS as the standard, the results of RETS were as follows: sensitivity for detection of motor dysfunction was 97%, 92%, and 77% for Groups I, II, and III, respectively, while specificity was 91% for Group II and 100% for Group III. Global sensitivity was 92% and specificity was 88%. No clinically significant motor disorders were missed by RETS. In conclusion, RETS is a useful noninvasive test for the screening of patients with symptoms thought to be of esophageal origin.

Manometric and radionuclide assessment of pharyngeal emptying before and after cricopharyngeal myotomy in patients with oculopharyngeal muscular dystrophy.

Fifteen patients with oculopharyngeal muscular dystrophy underwent cricopharyngeal myotomy for palliation of dysphagia. The aim of this work was to assess the effectiveness of this operation by using a radionuclide pharyngeal emptying study as a new quantitative method in addition to clinical and manometric evaluation. Radionuclide study was performed with the patient in both the upright and the supine positions after ingestion of 15 ml of water labeled with sulfur colloid 99mTc. Computerized data were acquired at 0.5 second intervals for 15 minutes and a pharyngeal time-activity curve was generated. Four quantitative parameters were evaluated: the time for pharyngeal clearance of 25%, 50%, and 75% of the ingested radioactive water and the pharyngeal stasis at 15 minutes. Manometric studies were also performed before and after cricopharyngeal myotomy. The pharyngeal clearance of 25%, 50%, and 75% of the water and pharyngeal stasis at 15 minutes were all improved by cricopharyngeal myotomy, decreasing from 1.2 to 0.9 second (p less than 0.04), 4.2 to 2 seconds (p less than 0.005), 15 to 7 seconds (p less than 0.02), and 10.3% to 6% (p less than 0.01), respectively. Both pharyngoesophageal and tracheobronchial symptoms were also significantly improved by cricopharyngeal myotomy. Manometric evaluation showed a decrease of the upper esophageal sphincter closing pressure from 60.1 mm Hg before to 28.2 mm Hg after the operation (p less than 0.001), and the resting pressure decreased from 34.4 to 15.7 mm Hg (p less than 0.0005). Cricopharyngeal myotomy significantly improves both symptoms and pharyngeal emptying in patients with oculopharyngeal muscular dystrophy.

Cricopharyngeal myotomy for neurogenic oropharyngeal dysphagia.

BACKGROUND: Forty patients (18 women, 22 men) with incapacitating oropharyngeal dysphagia of neurologic origin underwent cricopharyngeal myotomy. The subjective and objective response to myotomy was analyzed retrospectively with a mean postoperative follow-up of 48 months (range 1 to 255 months). RESULTS: Radiologic evidence of functional obstruction caused by incoordination and incomplete relaxation of the upper esophageal sphincter was significantly reduced. Manometric recordings of resting and closing pressures of the upper esophageal sphincter were also significantly altered by the myotomy. Resting pressures decreased from 65 to 18 mm Hg and closing pressures dropped from 69 to 22 mm Hg. The relaxation time and poor coordination at the level of the upper esophageal sphincter, observed in the preoperative period, persisted after the operation. Radionuclide emptying studies in which a single liquid bolus was used showed persistent hypopharyngeal stasis with a 20% retention of radioactive material at 120 seconds. Subjectively, 33 patients initially had frequent aspiration episodes. Twenty became free of symptoms after myotomy (p < 0.01) and in six others the symptoms were improved. Overall, seven patients claimed to be free of symptoms of dysphagia and no longer had pharyngo-oral or pharyngonasal regurgitations and aspirations after their operation. Twenty-three other patients had improvement in symptoms. Ten patients reported no change in symptoms. All of them either were unable to swallow voluntarily or had dysarthria when assessed before the operation. One retropharyngeal hematoma is the only postoperative complication recorded. The operative mortality was 2.5% (1/40). CONCLUSIONS: Cricopharyngeal myotomy palliates neurogenic oropharyngeal dysphagia in patients with intact oral-phase deglutition.

Results of reoperation on the upper esophageal sphincter.

OBJECTIVE: Reoperation on the upper esophageal sphincter is infrequent. We reviewed our experience in patients who underwent reoperation on the upper esophageal sphincter. METHODS: This is a retrospective report of accumulative series from 2 separate institutions. RESULTS: From September 1, 1976, to February 28, 1997, 37 patients underwent reoperation on the upper esophageal sphincter for recurrent or persistent obstructive symptoms. There were 29 men and 8 women. The median age was 69 years (range, 38-87 years). The original indication for the operation was a pharyngoesophageal (Zenker's) diverticulum in 33 patients (89.2%), oculopharyngeal dystrophy in 3 patients (8.1%), and muscular dystrophy in 1 patient (2.7%). One prior upper esophageal sphincter operation had been performed in 26 patients (70.3%), two operations in 9 patients (24. 3%), and three operations in 2 patients (5.4%). All patients were symptomatic; 35 patients (94.6%) had dysphagia; 23 patients (62.2%) had regurgitation; and 12 patients (32.4%) had episodes of aspiration. Thirty of the patients (91.0%) with Zenker's diverticulum were found to have a recurrent or persistent diverticulum at reoperation. A diverticulectomy and cricopharyngeal myotomy were performed in 23 patients (62.2%); cricopharyngeal myotomy alone, in 7 patients (18.9%); diverticulopexy and cricopharyngeal myotomy, in 6 patients (16.2%); and diverticulectomy alone, in 1 patient (2.7%). There were no operative deaths. Complications developed in 10 patients (27.0%). Follow-up was complete in 34 patients (91.9%) and ranged from 2 to 149 months (median, 39 mo). Thirty-two patients (94.1%) were improved. Functional results were classified as excellent in 26 patients (76. 5%), good in 2 patients (5.9%), fair in 4 patients (11.7%), and poor in 2 patients (5.9%). CONCLUSIONS: Reoperation for patients who have persistent or recurrent symptoms after an operation on the upper esophageal sphincter is associated with acceptable morbidity and mortality rates. Resolution of symptoms occurs in most patients.

Physiologic response to cricopharyngeal myotomy and diverticulum suspension.

Ten patients who had a cricopharyngeal myotomy and diverticulum suspension for pharyngoesophageal diverticulum have been studied clinically, radiologically, and manometrically. There were no deaths or morbidity and all patients have achieved marked improvement of their symptoms. Before operation all patients but one had low resting tone in the upper esophageal sphincter and all patients had normal relaxation of the sphincter upon swallowing. The coordination of pharyngeal contraction and sphincter relaxation was normal in six patients and abnormal in four patients. After operations the only change was an increase in resting tone in seven patients, and there was no change in three patients. We conclude that cricopharyngeal myotomy and diverticulum suspension constitute an effective form of treatment for pharyngoesophageal diverticulum.

Motor function of the esophagus after repair of esophageal atresia and tracheoesophageal fistula.

Eleven patients with previous esophageal atresia repair (TEF) underwent esophageal motility studies and were compared to 10 normal patients. The upper sphincters (UES) in the two groups did not differ in resting pressure, contraction pressure, or coordination. UES relaxation, was 100% in normal patients and 83+/-8% in the TEF patients (p less than 0.05). In the proximal esophagus, 100% of the TEF group showed a normal peristaltic wave, coupled with an abnormal nonperistaltic wave. The normal group did not show this type of contraction. In the middle esophagus, the mean peak pressure of 30.5+/-2.0 mm Hg was greater in controls than the 14.6+/-1.0 in the TEF group (p less than 0.001). Coordination was observed in 97+/-1% of the controls, while present in only 27+/-4% of the TEF patients (p less than 0.001). In the distal 10 cm of esophagus, peak contraction pressures were 43.3+/-1.6 in controls and 21.3+/-1.1 in the TEF group (p less than 0.001). Coordination was 94+/-1% in normal subjects and 66+/-4% in the TEF patients (p less than 0.001). The resting pressure in TEF patients was significantly higher at all three esophageal levels (proximal, mid, distal) than in normal patients. In both groups lower esophageal sphincter function did not show any significant difference, except for closing pressure, which was significantly higher in controls (39.9+/-6.8 mm Hg) than in the TEF groups (21.3+/-3.0 mm Hg) (p less than 0.02). These studies suggest that marked motility abnormalities occur in the repaired esophagus after atresia. These abnormalities are distinctly different from other motor disorders of the esophagus.

Malignant tracheoesophageal fistula.

Malignant tracheoesophageal fistula occurs infrequently in patients with esophageal and lung cancer. However, the occurrence of this entity is very distressing for the patient since it leads to rapid deterioration and death due to overwhelming pulmonary infection. A review of cases reported in the recent world literature is presented. The only effective treatment is to exclude the fistula from the alimentary tract. This may be achieved by intubation or operation. Intubation is probably associated with a lower mortality but is less certain to control the fistula. Single-stage operative exclusion and bypass is preferred under ideal circumstances. However, the patient's condition may dictate that a two-stage operation be performed--first, operative exclusion of the fistula and then, if the patient's respiratory and nutritional state improves sufficiently, restoration of alimentary continuity at a later date.

Spontaneous chylothorax associated with primary lymphedema and a lymphangioma malformation.

Spontaneous chylothorax associated with primary lymphedema is an exceedingly rare clinical entity. We report a case of chylothorax in a 38-year-old woman with a history of primary lymphedema of the right leg and an inguinal lymphangioma. Pathophysiology, diagnosis, treatment, as well as literature review are presented.