Editorial: Best Practices in Surveillance of Barrett's Esophagus.

Endoscopic surveillance in Barrett's esophagus (BE) has numerous limitations and thus provides several opportunities for improving the effectiveness of our current surveillance strategies. Several risk stratification and prediction tools have been investigated to identify patients at highest risk for progression to esophageal adenocarcinoma (EAC). Persistence of non-dysplastic BE (NDBE) has been proposed as an indicator of lower risk of progression to EAC. This editorial highlights the variable results and methodologies in studies evaluating persistence of NDBE as a risk stratification tool in the surveillance of BE patients and provides guidance for optimizing outcomes in BE patients enrolled in surveillance programs.

Risk of malignant progression in Barrett's esophagus indefinite for dysplasia.

Barrett's esophagus is a well-recognized risk factor for esophageal adenocarcinoma. The natural history of Barrett's esophagus classified as 'indefinite for dysplasia' (IND) is poorly characterized. The aim of this study is to characterize the natural history of IND by determining the rate of neoplastic progression and identifying risk factors for progression. Patients from the University of Pennsylvania Health System pathology database and Barrett's esophagus registry with a diagnosis of IND between 2000 and 2014 were identified. Exclusion criteria included: (1) prior diagnosis of low-grade dysplasia (LGD), high-grade dysplasia (HGD), or esophageal adenocarcinoma (EAC); (2) presence of LGD, HGD, or EAC at the time of diagnosis of IND; and (3) lack of follow-up endoscopy after diagnosis. Patients with neoplastic progression were classified as having either prevalent disease (LGD, HGD, or EAC on surveillance biopsy within 12 months of IND diagnosis) or incident disease (LGD, HGD, or EAC on surveillance biopsy >12 months after IND diagnosis). One hundred six patients were eligible for analysis. Of 87 patients with follow-up endoscopy and biopsies within 1 year of IND diagnosis, 7 (8%) had prevalent disease (2 LGD, 4 HGD, 1 EAC). The prevalence of LGD was 2.3%, HGD was 4.6%, and EAC was 1.1%. Importantly, four of the seven prevalent (2 LGD, 2 HGD) cases were found to have dysplasia within 6 months of IND diagnosis. No demographic or endoscopic characteristics studied were associated with prevalent disease. Of the 106 IND patients, there were 66 patients without prevalent dysplasia with >1-year follow-up. Three (4.5%) progressed (1 to LGD after 12 months, 2 to HGD after 16.5 and 28 months), yielding an incidence rate for any dysplasia of 1.4 cases/100 person-years and HGD/EAC of 0.9/100 person-years. Risk factors for incident disease were smoking (p = 0.02) and Barrett's esophagus segment length (p = 0.03). IND is associated with considerable risk of prevalent dysplasia, especially within the first 6 months after diagnosis. However, the incidence of HGD/EAC is low and similar to previous studies of IND. These data suggest that IND patients should have repeat endoscopy within 6 months with careful surveillance protocols. Longer BE length and smoking history may help predict which patients are more likely to develop dysplasia, and therefore identify patients who may warrant even closer monitoring.

Triple phase dynamic computed tomographic perfusion characteristics of spirocercosis induced esophageal nodules in non-neoplastic versus neoplastic canine cases.

Neoplastic transformation of Spirocerca lupi induced esophageal nodules carries a poor prognosis. Clinical, clinicopathological, endoscopic, and radiographic characteristics may be indicative of neoplastic transformation but variable sensitivity and specificity of these parameters makes their use questionable. We hypothesized that CT would be a better diagnostic modality to discriminate between non-neoplastic and neoplastic nodules. In this prospective study of 38 dogs, the appearance and perfusion characteristics of confirmed spirocercosis-induced neoplastic and non-neoplastic esophageal nodules were described using survey CT and triple phase dynamic CT angiography (CTA). Pre- and post-contrast early arterial, late arterial, and venous CTA images were evaluated. Non-neoplastic nodules were smooth and nonmineralized with a higher proportion of hypoattenuating necropurulent cavities compared to neoplastic nodules that had a more irregular surface, with 93% having mineralized foci and rarely any hypoattenuating pockets. Non-neoplastic nodules were significantly more perfused than neoplastic nodules with the difference being up to 23 Hounsfield units. The difference was most marked in the early and late arterial phases (P = 0.0005 and 0.00005, respectively). Ratios of the normal esophagus adjacent to the neoplastic and non-neoplastic nodules did not differ significantly from each other. Perfusion findings demonstrated relative hypoperfusion of the esophageal sarcomas. Findings from the current study indicated that CT characteristics of relative postcontrast hypoperfusion, combined with nodule irregularity and mineralization warrant a high level of concern for neoplastic transformation in canine spirocercosis-induced esophageal nodules.

Evaluation of hemostatic abnormalities in canine spirocercosis and its association with systemic inflammation.

BACKGROUND: Canine spirocercosis is caused by the nematode Spirocerca lupi and is characterized by esophageal fibro-inflammatory nodules that may undergo neoplastic transformation. No sensitive and specific laboratory assays other than histopathology have been reported to differentiate non-neoplastic from neoplastic disease. HYPOTHESIS/OBJECTIVES: Dogs with spirocercosis will have evidence of hypercoagulability based on thromboelastography (TEG)-derived maximal amplitude (MA); increased MA will be correlated with increased acute phase protein (APP) concentrations (C-reactive protein [CRP] and fibrinogen); increased MA and APPs will be exacerbated with neoplastic spirocercosis. ANIMALS: Thirty-nine client-owned dogs with naturally occurring spirocercosis and 15 sex-matched healthy controls. METHODS: A prospective comparative study evaluating TEG, activated partial thromboplastin time, prothrombin time, antithrombin (AT) activity, platelet count and D-dimer concentration, and APPs of dogs with non-neoplastic (n = 24) and neoplastic (n = 15) spirocercosis compared to control dogs. RESULTS: Median MA was significantly increased in the non-neoplastic group (P < .01) and neoplastic group (P < .01) compared to the controls. Both APPs were significantly increased in the neoplastic group compared to the non-neoplastic and control groups. MA was strongly correlated with fibrinogen (r = 0.85, P < .001) and CRP (r = 0.73, P < .001). An MA >76 mm provided 96% specificity and 73% sensitivity for differentiation of disease state. CONCLUSIONS AND CLINICAL IMPORTANCE: Canine spirocercosis is associated with increased TEG variables, MA and α, and decreased AT activity, which may indicate a hypercoagulable state seemingly more severe with neoplastic transformation. MA was correlated with APP in dogs with spirocercosis and can be used as an adjunctive test to support the suspicion of neoplastic transformation.

Canine spirocercosis-associated extraskeletal osteosarcoma with central nervous system metastasis.

A five-year-old male Boerboel presented for examination, collapsed for an unknown period of time. On clinical examination, multifocal subcutaneous masses and enlarged prescapular lymph nodes as well as neurological deficits that suggested a multifocal neurological syndrome were found. Fine needle aspirates of the prescapular lymph nodes revealed cells suggestive of osteosarcoma. Radiographs showed foci of mineralisation within the soft tissue masses as well as diffuse pulmonary metastasis and a caudodorsal mediastinal mass believed to be a Spirocerca lupi nodule. Computed tomography imaging, necropsy and histopathology confirmed S. lupi oesophageal neoplastic transformation (extraskeletal osteosarcoma), believed to be the primary lesion, and the majority of secondary metastasis to the brain, spine, heart, multiple muscular groups and abdominal organs. This is the first known report of extraskeletal osteosarcoma metastasis to the brain and spinal cord in a dog.

Computed tomographic and radiographic characteristics of aortic lesions in 42 dogs with spirocercosis.

Spirocerca lupi is a common cause of vomiting, regurgitation, and sudden death in dogs that live in tropical or subtropical regions. Sudden death due to aortic rupture may occur with no preceding clinical signs. The purpose of this prospective study was to compare radiographic and computed tomographic (CT) characteristics of aortic lesions in a cohort of 42 dogs with endoscopically confirmed spirocercosis. Dorsoventral and right lateral recumbent thoracic radiographic findings were compared with pre- and postcontrast thoracic CT findings. Aortic mineralization was detected using CT in 18/42 dogs (43%). Three dogs had faint diffuse aortic wall mineralization. Using CT as the reference standard, radiographs had a sensitivity and specificity of 6% and 96%, respectively, for detecting aortic mineralization. A total of 20 aortic aneurysms were detected using CT in 15/42 dogs (36%). Using CT as the reference standard, radiographs had a sensitivity and specificity of 86% and 56%, respectively, for detecting aortic aneurysms. Respiratory motion, aortic displacement by esophageal masses and Spirocerca nodules adjacent to the aorta mimicked aneurysm formation on radiographs. Aortic thrombi were seen in two dogs in postcontrast CT images. Findings from this study indicated that aortic mineralization and aneurysm formation are common in dogs with spirocercosis. Findings also supported the use of pre- and postcontrast CT as effective methods for detecting and characterizing these lesions.

Plasma IL-8 concentrations are increased in dogs with spirocercosis.

The nematode Spirocerca lupi (S. lupi) induces sarcoma in the dog oesophagus in about 25% of cases. The aim of this study was to compare the differences in the cytokine milieu between dogs with neoplastic (n=29) and non-neoplastic disease (n=49) and age- and gender-matched healthy controls (n=25). We measured IL-2, IL-4, IL-6, IL-8, IL-10, IL-18, GM-CSF and MCP-1 in a specific canine multiplex immunoassay kit. Cytokine concentrations were compared between the different groups using the Kruskal-Wallis test followed by Dunn's test. Only IL-8 and IL-18 showed significant differences in their plasma concentration among the three groups. Kruskal-Wallis test revealed a significant (p=0.001) difference in IL-8 concentration between the neoplastic group (634pg/ml), the non-neoplastic (429 pg/ml) and the control groups (150 pg/ml). Post-test analysis revealed a significance difference between the two S. lupi groups and the control group (p<0.01). The highest IL-18 concentration was found in the non-neoplastic group (53 pg/ml), followed by the control group (46 pg/ml) and finally the neoplastic group (33 pg/ml). IL-18 concentrations were significantly higher in the non-neoplastic group than in the neoplastic group (p=0.05). The increased IL-8 in the spirocercosis groups is consistent with the neutrophilic infiltrate in spirocercosis lesions and in those of other inflammatory-induced neoplasias such as Barret's oesophagus and Helicobacter gastritis. IL-18 showed negative regulatory effect in several worm infections and it is possible that it plays the same role in spirocercosis, allowing the worm to evade the host response and to induce neoplastic transformation.

Serum acute phase proteins in dogs with symptomatic esophageal spirocercosis.

Canine spirocercosis (CS) is a helminthic infection caused by the nematode Spirocerca lupi. The clinical hallmark of the disease is esophageal dysphagia due to parasite-induced esophageal nodules. Currently, there is limited information on the involvement of serum acute phase proteins (APPs) in the symptomatic CS. The objective of this study was to investigate whether C-reactive protein (CRP), serum amyloid A (SAA), haptoglobin (Hp) and albumin are involved in CS, and if their concentrations measured on admission reflect the severity of benign esophageal lesions. Nineteen dogs with spontaneous symptomatic esophageal spirocercosis and 7 clinically healthy dogs were studied retrospectively. The most consistently increased APP in the symptomatic dogs was Hp (95% of the dogs), followed by CRP (68%). The SAA concentrations were infrequently increased (5% of the dogs), while albumin concentrations were decreased in 58% of the affected dogs. The dogs with spirocercosis had significantly higher median concentrations of Hp (p=0.0001) and CRP (p=0.02) compared to healthy dogs. Median albumin concentrations did not differ between the two groups of dogs. The median concentrations of Hp, CRP and albumin did not differ significantly between the dogs having a single or multiple esophageal nodules. The results of this study indicate that in symptomatic CS, Hp and CRP are significantly and consistently increased, while SAA and albumin may be of limited value as diagnostic markers. No association was established between the concentrations of Hp, CRP and albumin measured on admission and the number of esophageal nodules.

Serum C-reactive protein concentration in benign and malignant canine spirocercosis.

BACKGROUND: Spirocerca lupi is a nematode of canids that forms a nodule in the esophagus that can undergo neoplastic transformation. C-reactive protein (CRP) is a major acute phase protein in the dog that has been used for treatment, monitoring, and prognostication in inflammatory and neoplastic disease. HYPOTHESIS/OBJECTIVES: The objectives of this study were to determine if serum CRP concentration (1) is increased in canine spirocercosis, (2) can be used to determine neoplastic transformation, and (3) can be used to monitor response to treatment in benign spirocercosis. ANIMALS: Forty-two dogs naturally infected with S. lupi and 21 control dogs. METHODS: A retrospective study was performed. The infected cases were divided into benign (n = 28) or malignant (n = 14) spirocercosis. CRP was performed on all of the spirocercosis and control cases at presentation. Statistical analysis was done by the one-way analysis of variance and Student's t-test. RESULTS: The mean CRP concentration in the benign cases was 60.4 ± 48.0 mg/L and that of the malignant cases was 76.5 ± 44.8 mg/L; both values were significantly higher (P < .001) than those of the control group where the mean was 13.4 ± 17.9 mg/L. The mean CRP concentration for the convalescent sera in the benign group was lower than the pretreatment concentrations (P= .01). CONCLUSION AND CLINICAL IMPORTANCE: CRP cannot be used to differentiate between benign and malignant spirocercosis. There is a decrease in CRP concentration in dogs with benign spirocercosis once treatment has commenced. Serial CRP measurement can be used to monitor response to treatment in benign spirocercosis.

Imaging diagnosis--spinal cord chondrosarcoma associated with spirocercosis in a dog.

A 7-year-old neutered female Boerboel cross was examined for progressive left pelvic limb lameness. There was no left patellar reflex but the remaining pelvic limb reflexes were hyperreflexic. Radiographically, there was a poorly mineralized opacity occupying the intervertebral foramen at LA-L5. On computed tomography images there was a hyperattenuating intramedullary lesion at LA-L5 that continued caudally, lateralized to the left and became extramedullary, terminating at L5-L6. In addition, well marginated, hyperattenuating lesions were noted at two muscular sites. The dog underwent euthanasia and a caudal esophageal mass was found at post mortem examination. The tumors in the spinal cord, the esophagus, and the skeletal muscles were diagnosed histologically as low-grade chondrosarcoma undergoing endochondral ossification. Spirocerca lupi-induced esophageal chondrosarcoma was believed to be the primary site from which the other, presumably metastatic, lesions originated.

Spirocercosis-associated esophageal sarcomas in dogs. A retrospective study of 17 cases (1997-2003).

Seventeen client-owned dogs diagnosed with spirocercosis-associated esophageal sarcomas were retrospectively reviewed. The most common clinical signs noticed were vomiting and/or regurgitation (94%), lethargy and depression (59%), pyrexia and anorexia (41% each). Leukocytosis (82%) and microcytic hypochromic anemia (30%) were the most common hematological abnormalities. Caudal thoracic masses were demonstrated on survey radiographs of 13/15 of the dogs and thoracic spondylitis was detected in 12/15 dogs. Spirocerca lupi eggs were detected in 2/8 patients and worms were demonstrated on 1/11 at necropsy. Ten cases underwent surgical attempt to remove the tumors. In six of them partial esophagectomy (PE) was performed and all of them survived the immediate postoperative hospitalization. Five of the cases that underwent PE also received chemotherapy after surgery (doxorubicin (Adriamycin, Upjohn)) with an average survival time of 267 days. The histopathological results of the esophageal tumors were osteosarcoma (9), fibrosarcoma (5) and undifferentiated sarcoma (1). In areas endemic to spirocercosis, regurgitation or vomiting in dogs and microcytic hypochromic anemia and neutrophilia warrant ruling out esophageal sarcomas. Proper surgical treatment could prolong the dogs' lifespan for months, and improve their quality of life.

Early esophageal cancer: radiologic estimation of invasion into the muscularis mucosae.

BACKGROUND: Lymph node metastasis in squamous cell carcinoma of the esophagus is rare, and the cancer remains in the lamina propria mucosae. In cases with cancer invading the muscularis mucosae (MM), the incidence of lymph node metastasis is approximately 7%. For endoscopic treatment of mucosal cancer, it is necessary to diagnose cancer invasion into the MM. The aim of this study was to estimate cancer invasion into the MM by esophagography. METHODS: One hundred ten lesions of the slightly depressed type were classified into two groups: in group A, cancer was confined to the lamina propria mucosae; in group B, the cancer invaded the MM or slightly into the submucosa. Radiologic findings of each group were studied. RESULTS: In group A, 69% of 70 lesions showed mild depression and a smooth or undulated surface. Thickened folds were noticed in only 3%. In group B, 83% of 40 lesions showed mild or moderate depression with well-defined granules. Thickened folds were evident in 78%. In the differentiation between groups, the accuracy rates of each finding of moderate depression, well-defined granules, and thickened folds were 85%, 73%, and 90%, respectively. The overall diagnostic accuracy rate was 90%. CONCLUSION: Esophagography is useful for estimation of cancer invasion into the MM and, hence, the decision to apply endoscopic treatment to mucosal cancer.

Resections of the upper aerodigestive tract for locally invasive thyroid cancer.

BACKGROUND: In view of the indolent nature of most cancers of the thyroid, particularly of the papillary and follicular variety, the decision to remove a segment of the upper aerodigestive tract when the cancer is either close to or invading this area is a difficult one. It was felt relevant to review the experience at the M.D. Anderson Hospital to see when such resections were necessary, how they were repaired, and the survival rates. PATIENTS AND METHODS: Of the 1,098 patients with cancers of the thyroid treated surgically at M.D. Anderson Cancer Center from 1954 to 1993, 46 underwent resections of some portion of the upper aerodigestive tract for invasive cancer. These included 35 patients who had histories of prior surgical treatment with or without radiation or radioactive iodine therapy. The operations included 27 total and 5 partial laryngectomies, 1 circumferential and 13 partial resections of the trachea, and 5 circumferential and 10 partial esophagectomies. Several patients had combinations of these procedures. Details of the repairs are provided. Postoperative radiation or radioactive iodine treatment was administered when indicated. RESULTS: Local recurrence was infrequent. Most deaths occurred from either pulmonary metastasis or causes other than the cancer. The 5-year survival rate for all patients exceeded 50%. More than 70% of patients with papillary and follicular cancers survived for 5 years, and some for up to 30 years. CONCLUSIONS: Although it cannot be stated with any degree of certainty if a resection of a portion of the upper aerodigestive tract should be done at the time of the initial surgical procedure, it is apparent that there are some situations in which the resection should be done because of severe local problems A variety of methods of repair are available, and the survival rate is greater than 50% for all such procedures, with those having the papillary and follicular variety surviving for 5 years in more than 70% of cases. Patients can exist with severe local problems for a number of years and it is sometimes the patient who decides when the resection should be done.