The prevalence of lymph node metastases in patients with T1 esophageal adenocarcinoma a retrospective review of esophagectomy specimens.

UNLABELLED: Knowledge of the risk of lymph node metastases is critical to planning therapy for T1 esophageal adenocarcinoma. This study retrospectively reviews 75 T1a and 51 T1b tumors and correlates lymph node metastases with depth of tumor invasion, tumor size, presence of lymphovascular invasion, and tumor grade. OBJECTIVES: Increasingly, patients with superficial esophageal adenocarcinoma are being treated endoscopically or with limited surgical resection techniques. Since no lymph nodes are removed with these therapies, it is critical to have a clear understanding of the risk of lymph node metastases in these patients. The aim of this study was to define the risk of lymph node metastases for intramucosal and submucosal (T1) esophageal adenocarcinoma and to analyze factors potentially associated with an increased risk of lymph node involvement. METHODS: We reanalyzed the pathology specimens of all patients that had primary esophagectomy for T1 adenocarcinoma of the distal esophagus or gastroesophageal junction from January 1985 to December 2008. The prevalence of lymph node metastases was correlated with tumor size, depth of invasion, presence of lymphovascular invasion, and degree of tumor differentiation. RESULTS: There were 126 patients, 102 men (81%) and 24 women (19%), with a mean age of 64 (± 10) years. Tumor invasion was limited to the mucosa (T1a) in 75 patients (60%), whereas submucosal invasion (T1b) was present in 51 patients (40%). Tumors that had poor differentiation, lymphovascular invasion, and size ≥2 cm were significantly more likely to be invasive into the submucosa. Lymph node metastases were rare (1.3%) with intramucosal tumors but increased significantly with submucosal tumor invasion (22%)[P = 0.0003]. Lymph node metastases were also significantly associated with poor differentiation (P = 0.0015), lymphovascular invasion (P < 0.0001), and tumor size ≥2 cm (P = 0.01). Division of the submucosa into thirds did not show a layer with a significantly decreased prevalence of node metastases. CONCLUSIONS: Adenocarcinoma invasive deeper than the muscularis mucosa is associated with a significant increase in the prevalence of lymph node metastases,and there is no "safe" level of invasion into the submucosa. Lymphovascular invasion, tumor size ≥2 cm, and poor differentiation are associated with an increased risk of submucosal invasion and lymph node metastases and should be factored into the decision for endoscopic therapy or esophagectomy

Genetic variations in angiogenesis pathway genes predict tumor recurrence in localized adenocarcinoma of the esophagus.

OBJECTIVE: The aim of this study was to determine whether the risk of systemic disease after esophagectomy could be predicted by angiogenesis-related gene polymorphisms. SUMMARY BACKGROUND DATA: Systemic tumor recurrence after curative resection continues to impose a significant problem in the management of patients with localized esophageal adenocarcinoma (EA). The identification of molecular markers of prognosis will help to better define tumor stage, indicate disease progression, identify novel therapeutic targets, and monitor response to therapy. Proteinase-activated-receptor 1 (PAR-1) and epidermal growth factor (EGF) have been shown to mediate the regulation of local and early-onset angiogenesis, and in turn may impact the process of tumor growth and disease progression. METHODS: We investigated tissue samples from 239 patients with localized EA treated with surgery alone. DNA was isolated from formalin-fixed paraffin-embedded normal esophageal tissue samples and polymorphisms were analyzed using polymerase chain reaction-restriction fragment length polymorphism and 5'-end [gamma-P] ATP-labeled polymerase chain reaction methods. RESULTS: PAR-1 -506 ins/del (adjusted P value=0.011) and EGF +61 A>G (adjusted P value=0.035) showed to be adverse prognostic markers, in both univariate and multivariable analyses. In combined analysis, grouping alleles into favorable versus nonfavorable alleles, high expression variants of PAR-1 -506 ins/del (any insertion allele) and EGF +61 A>G (A/A) were associated with a higher likelihood of developing tumor recurrence (adjusted P value<0.001). CONCLUSION: This study supports the role of functional PAR-1 and EGF polymorphisms as independent prognostic markers in localized EA and may therefore help to identify patient subgroups at high risk for tumor recurrence.

Cytomegalovirus infection in patients with active inflammatory bowel disease.

BACKGROUND: The reported prevalence of cytomegalovirus (CMV) infection with active inflammatory bowel disease (IBD) is highly variable, and whether CMV negatively impacts the clinical course is controversial. AIMS: The aim of this study was to determine the prevalence of CMV in patients with active ulcerative colitis (UC) or Crohn's disease (CD) and compare the course of disease in patients with and without CMV. METHODS: Consecutive patients with acute exacerbations of active IBD colitis had immunohistochemistry staining for CMV antigen performed on archived specimens. Clinical features were retrospectively reviewed. RESULTS: Twelve (10%) of 122 UC patients had CMV, and 0/20 patients with CD had CMV. Of 12 UC patients with CMV infection, seven were not taking steroids or immunosuppressives at their index flare. UC patients with CMV were more likely to have leukocytosis (OR = 5.3, 95% CI 1.5-18.2), require hospitalization (OR = 4.9, 95% CI 1.2-19.0), and be hospitalized > or =7 days (OR = 5.0, 95% CI 1.6-21.3) compared to patients without CMV. Of 12 UC patients with CMV, ten (83%) were treated for their index flare with steroids or 6-mercaptopurine. Only one patient (8%) was treated for CMV infection which occurred 14 months after index endoscopy. Over the 6 months after the index flare, UC patients with CMV had a higher frequency of IBD-related hospitalizations compared to patients without CMV (50 vs. 24%, P = 0.021), but none required surgery or died. CONCLUSIONS: The prevalence of CMV with active UC was 10%. Although CMV infection may be a marker of disease severity, our results suggest it does not cause severe morbidity or mortality in a general population of patients with a UC flare.

Granulomatous lobular mastitis: imaging, diagnosis, and treatment.

OBJECTIVE: Granulomatous lobular mastitis is a rare chronic inflammatory disease that has clinical and radiologic findings similar to those of breast cancer. We performed a retrospective analysis of clinical, imaging, and treatment findings in 54 women diagnosed with granulomatous lobular mastitis between January 2000 and April 2008. CONCLUSION: The imaging findings of granulomatous lobular mastitis overlap with those of malignancy. The most common presentation is a focal asymmetric density on mammography and an irregular hypoechoic mass with tubular extensions on ultrasound. Core biopsy is typically diagnostic. Once the diagnosis is established by tissue sampling, corticosteroids are the first line of treatment.

Changing concepts in the pathogenesis, evaluation, and management of solitary rectal ulcer syndrome.

The purpose of this study was to assess the impact of new technology on both the understanding of the underlying pathophysiology and treatment of solitary rectal ulcer syndrome (SRUS). This study is a retrospective review of patients with a histologic diagnosis of SRUS (1993 to 2007) complimented with a prospective database of those patients studied with defecography and dynamic pelvic MRI. Thirty patients were available for evaluation. A polyp or mass was present in 74 per cent. Ulcers were found in only 23 per cent. All 12 patients undergoing defecography demonstrated rectorectal intussusception. Dynamic MRI of the pelvis revealed pronounced anorectal redundancy and lack of mesorectosacral fixation with mild to severe pelvic floor descent in all four patients studied. Fiber with or without stool softeners was the initial treatment in all patients with resolution of symptoms in 65 per cent. One patient with refractory symptoms underwent a stapled transanal rectal resection with complete resolution of symptoms. Occult rectorectal intussusception appears to be the operant anatomic pathology in SRUS. Anorectal redundancy with lack of mesorectosacral fixation may contribute to the process. All patients should be studied with defecography and dynamic MRI. Stapled transanal rectal resection may offer a promising surgical option.

Ovarian preservation in stage I low-grade endometrial stromal sarcomas.

OBJECTIVE: To examine the impact of ovarian preservation in a case-control study of women with stage I low-grade endometrial stromal sarcomas. METHODS: Patients with low-grade endometrial stromal sarcomas were identified at 5 institutions from 1976 to 2002. Cases were defined as patients who retained ovarian function; each case was matched to 2 control patients who underwent bilateral salpingo-oophorectomy (BSO). Immunostaining for estrogen and progesterone receptors was performed. Data were examined with Student t, chi(2), Cox regression, and Kaplan-Meier analyses. RESULTS: Twelve premenopausal patients with low-grade endometrial stromal sarcomas who did not undergo BSO were matched to 24 controls. Of the 36 patients in the entire cohort, disease recurred in 14 (39%). Recurrences were identified in the pelvis, abdomen, lung, or lymphatics in both cases and controls. Disease recurred in 4/12 (33%) case patients, compared with 10/24 (42%) control patients (P = .63). When case patients were compared with controls, no differences in progression-free (91.3 months versus 68.6 months, P = .44) or overall survival (median survival not yet reached versus 406 months, P = .82) were identified. This study had 13% power to detect the observed difference in median disease-free survival. After controlling for use of adjuvant therapy and BSO, older age remained the only independent poor prognostic factor for progression-free survival (P = .008). Twenty-two available tumors demonstrated positivity for both estrogen and progesterone receptors. CONCLUSION: Bilateral salpingo-oophorectomy did not appear to affect time to recurrence or overall survival. Retention of ovarian function may be an option for premenopausal women with low-grade endometrial stromal sarcomas.

Giant cell tumor of the sternum.

Primary giant cell tumors of the chest wall are extremely rare. To date, we believe that there have been no reported cases of sternal giant cell tumors in the thoracic literature. We report a case of an isolated giant cell tumor of the sternum in a 28-year-old man. The mass was resected and the sternum was reconstructed with methyl methacrylate prosthesis and bilateral pectoralis muscle advancement flaps. Excellent functional and aesthetic results were achieved.

Survival in lymph node negative adenocarcinoma of the esophagus after R0 resection with and without neoadjuvant therapy: evidence for downstaging of N status.

BACKGROUND: After esophagectomy, many patients who received neoadjuvant therapy have no evidence of lymph node involvement (N0 disease). Whether lymph nodes were initially involved and eradicated by the neoadjuvant therapy (down-staged) or if the nodes were never involved is a subject of debate. To address this issue, we compared clinical outcomes in N0 patients treated with neoadjuvant therapy with outcomes in patients treated with surgery alone. STUDY DESIGN: We reviewed records of 100 consecutive patients who underwent R0 esophagectomy for adenocarcinoma with pathologic N0 status. Seventy-five patients were treated by operation alone and 25 received neoadjuvant therapy. Tumor characteristics including length, depth, lymphovascular invasion, and degree of differentiation were compared and longterm survival was assessed by Kaplan-Meier analysis at a median of 46 months (interquartile range 26 to 77 months). RESULTS: Tumor characteristics were similar between groups. Recurrence was more common in patients who received neoadjuvant therapy compared with those treated with surgery alone (10 of 25 versus 10 of 75, p=0.0063). Patients with N0 disease after neoadjuvant therapy had a significantly worse survival than patients treated by surgery alone (49% versus 85%, p=0.005). CONCLUSIONS: Although neoadjuvant therapy may eradicate lymph node metastases, it does not result in the same outcomes as those achieved in patients with N0 disease treated with surgery alone. The poor clinical outcomes observed in N0 patients after neoadjuvant therapy suggest that they initially had node involvement and were downstaged by eradication of lymph node disease.

Differentiation of cancerous lesions in excised human breast specimens using multiband attenuation profiles from ultrasonic transmission tomography.

OBJECTIVE: This study examines the tissue differentiation capability of the recently developed high-resolution ultrasonic transmission tomography (HUTT) system in the context of differentiating between benign and malignant tissue types in mastectomy specimens. METHODS: Eight mastectomy patients provided breast specimens with benign and malignant lesions. The specimens were scanned by the HUTT system with a pair of either 8- or 4-MHz transducers. Multiband HUTT images over the frequency range from 2 to 10 MHz provide characteristic profiles of frequency-dependent attenuation, termed "multiband profiles," at individual pixels. These features are classified through a novel algorithm of "segment-wise classification" that identifies the disjoint segments of various tissue types and subsequently classifies them into respective diagnostic categories using a measure of proximity to the respective multiband profile templates that have been previously obtained from reference data. RESULTS: We preformed intraspecimen and interspecimen analyses of 108 slices from 8 mastectomy specimens for which "ground truth" was provided by pathology reports. The average performance indices for 2-way classification (malignant versus nonmalignant tissue) in these intraspecimen (interspecimen) specimen studies were found to be sensitivity of 81.9% (89.6%), specificity of 92.9% (92.1%), and accuracy of 89.2% (89.4%), whereas the indices for the 3-way classification were moderately lower. CONCLUSIONS: The results have shown the potential of the HUTT technology for reliable differentiation of cancerous lesions from benign changes and normal tissue in mastectomy specimens using frequency-dependent ultrasound attenuation profiles.

Concordance of histopathologic and cytologic grading in musculoskeletal sarcomas: can grades obtained from analysis of the fine-needle aspirates serve as the basis for therapeutic decisions?

BACKGROUND: Utilization of fine-needle aspiration (FNA) for the diagnosis of musculoskeletal lesions has been de-emphasized by many clinicians because of concerns regarding the technique's ability to supply all information necessary for prognostication and appropriate selection of therapy. Paramount among the concerns is the belief that FNA is incapable of supplying precise subtyping and grading in many cases. Secondary concerns regarding the use of FNA involve its perceived inability to supply adequate tissue for ancillary studies including immunohistochemistry and molecular diagnostic analysis. The authors investigated the ability of FNA to accurately subtype and grade a series of 107 primary sarcomas of the musculoskeletal system. METHODS: The files of the Departments of Pathology at Duke University Medical Center and the University of California at Los Angeles and the private consultation files of one of the authors were searched for all fine-needle aspirates of sarcomas arising within the musculoskeletal system. A total of 107 cases were obtained and reviewed by three board-certified cytopathologists. Each cytopathologist independently assigned subtype when possible and generated a grade for each of the sarcomas. Corresponding surgical material was available for 77 cases. The surgical material was re-reviewed for accuracy of diagnosis and assignment of grade independently of the cytologic examination. Correlation of cytologic grade with histopathologic grade was made and analyzed by the kappa test. In addition, agreement on grade between cytopathologists was analyzed, and accuracy of histologic subtype prediction by cytologic analysis was studied. RESULTS: Most of the sarcomas were cytologically graded as Grade 1 or 2 but were assigned a histologic grade of 2 or 3. Cytopathologist A graded 93% of the sarcomas as either Grade 1 or 2, cytopathologist B graded 89% of cases as Grade 1 or 2, and cytopathologist C graded 94% of cases as Grade 1 or 2. Histologic evaluation demonstrated 82% of cases to be Grade 2 or 3. Correlation of cytologic and surgical grade varied among the observers. Cytopathologist A showed the highest degree of correlation between cytologic and surgical grade with an r value of 0.5. The corresponding r values for cytopathologists B and C were 0.46 and 0.41, respectively. Correlation between cytologic and surgical grade was significant for all three observers (P < 0.001). Only nuclear grade showed a consistent correlation in predicting final surgical pathology grade. Cellularity, mitotic rate, and the presence of necrosis were not statistically significant for predicting histopathologic grade. Accurate exact subtyping by cytologic examination was achieved in approximately 55% of cases. Prediction of histopathologic subtype by cytologic analysis was most successful when a distinctive stroma was present or high-grade features indicative of malignant fibrous histiocytoma were observed. There was little agreement as to histopathologic type as predicated by cytology for low-grade spindle cell sarcomas. CONCLUSIONS: Although there was a statistically significant correlation between cytologically assigned grade and final histopathologic grade, statistical analysis revealed only a moderate correlation between the two with an overall r value of approximately 0.57. Cytologic analysis tended to undergrade in comparison to final histopathologic grading. Only analysis of nuclear atypia showed good correlation with final surgical grade. Fine-needle aspiration was only moderately successful at predicting histopathologic subtype for musculoskeletal sarcomas in this series.