David H. Dail

Histological and anatomic changes in Barrett’s esophagus after antireflux surgery

Objective: The best treatment approach for patients with documented Barretts esophagus remains controversial. There is currently no well designed prospective study examining the effect of successful antireflux surgery on Barretts esophagus. Methods: Fourteen patients with histologically proven Barretts esophagus underwent standard antireflux surgery followed by careful endoscopic, histological, and symptomatic follow-up beginning at 2–4 wk after surgery. Pre- and postoperative symptoms, patient functional assessment scores, lower esophageal sphincter pressure, and 24-h pH studies were compared, in addition to monitoring patients for evidence of squamous re-epithelialization and dysplasia. Results: Patients demonstrated statistically significant improvement in symptoms, functional assessment scores, lower esophageal sphincter pressure, and 24-h pH assessments after antireflux surgery. Two patients had complete disappearance of short segments (2 and 3 cm) of Barretts esophagus. Ten additional patients demonstrated evidence of squamous re-epithelialization, although biopsies often showed mixed components of squamous and columnar epithelium. No patients showed progression of dysplastic change, and four patients demonstrated the disappearance of low grade dysplasia throughout the period of the study. Conclusion: Successful antireflux surgery can produce at least partial squamous re-epithelialization in Barretts metaplasia and stabilization or apparent improvement in dysplasia in some patients without the need for long term medication. Continued long term endoscopic and histologic follow-up is still required in all patients with Barretts esophagus after antireflux surgery.

Neoplasms of the Ampulla of Vater with Concurrent Pancreatic Intraductal Neoplasia: A Histological and Molecular Study

Adenoma and adenocarcinoma of the ampulla of Vater are uncommon neoplasms of the gastrointestinal tract. Only one report has analyzed the relationship between ampullary adenocarcinoma and pancreatic intraductal neoplasia (PanIN), the precursor lesion of pancreatic adenocarcinoma. An association between PanIN and ampullary adenoma has not been reported previously. Case reports have documented the progression of PanIN to invasive pancreatic adenocarcinoma. We reviewed five resected ampullary adenoma and 17 ampullary adenocarcinoma cases and evaluated the pancreas for PanIN. Pancreatic sections from 35 autopsies were reviewed as a control group. Immunohistochemistry for overexpression of p53 and COX-2 proteins was performed in selected cases, as was PCR analysis for K-ras mutations. Follow-up clinical data were obtained. All 22 ampullary neoplasms were associated with PanIN, which was high grade in two (40%) adenoma cases and seven (41%) adenocarcinoma cases. In 16 (73%) evaluable cases, PanIN extended to the pancreatic resection margin; two of which had high grade PanIN. Among the autopsy controls eight (23%) had low-grade PanIN. Seven of the 22 ampullary cases but none of the autopsy controls had coexistent pancreatitis. A smoking history was present in two of four autopsy cases in which this history was available. Overexpression of the p53 and COX-2 proteins was present in only one case of high-grade PanIN. K-ras mutations were present in four of four of the PanIN lesions evaluated, including one autopsy case. Clinical follow-up revealed no progression of PanIN to invasive carcinoma in the remnant pancreas, although the follow-up period was too short to adequately assess that risk (an average of 3.8 y for adenoma cases and 2.5 y for adenocarcinoma cases). We conclude that adenomas and carcinomas of the ampulla are associated with PanIN, and often high-grade PanIN. Although its malignant potential has not been fully established, PanIN is underreported and often unrecognized. PanIN may be analogous to colorectal adenoma in that both are prevalent in the older adult population, but few progress to carcinoma.

Metastases to and from the Lung

Because metastastic neoplasms to the lung are the most common tumor found in the lung, this chapter concentrates on this problem. At the end of the chapter, a discussion of primary lung tumors and their own metastases is included, but for contrast and comparison they are mentioned throughout the discussion of secondary tumors arriving in the lung. In autopsy studies, the lungs are involved with metastases in 20%–54%1–6 of cases of extrapulmonary malignancies, and in 15%–25%, the lung is the only site of such metastases.1 Some selected excellent reviews of the basics of metastases,7,8 their clinical, radiographic, and therapeutic details,7,9 and their presence in the lung and pleura7,9,10 are highly recommended for the interested reader.

Aspiration, Bronchial Obstruction, Bronchiectasis, and Related Disorders

The conducting airways play a pivotal role in the spectrum of pulmonary pathology, not only as conduits for injurious agents to enter the lung, but also as an anatomic compartment that is affected by a diverse array of primary or secondary bronchocentric diseases. This chapter discusses aspiration and bronchial obstruction in detail, with emphasis on the aspiration of toxic, infective, or particulate matter. Lung abscess, a frequent complication of obstruction or aspiration, is also reviewed. Both aspiration and lung abscess are reconsidered within the context of pulmonary infectious disease mainly in Chapter 8 on bacterial infections, and to some extent in the chapters on mycobacterial (Chapter 9), fungal (Chapter 10), and parasitic diseases (Chapter 14).

Tracheobronchial Tumors of the Salivary Gland Type

Tumors derived from the submucosal glands of the tracheobronchial tree are currently known as tumors of the salivary gland type. Most but not all of the tumors occurring in the major and minor salivary glands of the head and neck are known to occur in the respiratory tract. In the past, the term bronchial adenoma has been used to designate a group of slow-growing neoplasms, many of which arise from the bronchial glands of the respiratory tract. This is unfortunate since some of these so-called adenomas are in fact low-grade malignancies. Therefore, the term bronchial adenoma is to be discouraged and will not be used in this chapter.

Endogenous Mineralization, Inclusions, and Deposition Disorders

The entities discussed in this chapter are diverse. Many come under the heading of metabolic diseases, which may be congenital or acquired. Others have, or act through, an immunologic basis. A few have a single identifiable cause. Some represent a common tissue response to multiple identified causes, while others appear to have no known causes.

2G-2 Tissue-Type Imaging (TTI) of Prostate Cancer Based on Ultrasonic and Magnetic-Resonance Methods: Latest Developments

Our prostate tissue-typing studies seek to develop imaging methods that have high sensitivity and specificity for visualizing cancerous regions of the prostate to improve the effectiveness of biopsy guidance, therapy targeting, and treatment monitoring. Spectral parameters obtained from radio-frequency (RF) ultrasonic (US) echo signals acquired from biopsy regions, along with the PSA are used to train a neural-network classifier. This method produced an ROC curve area of 0.84 compared to 0.64 obtained from B-mode, image-based classification. We are investigating the integration of ultrasonic and magnetic resonance (MR) methods to further improve our prostate tissue-typing methods. To take advantage of the independent information provided by US and MR, data acquired from the two imaging modalities need to be co-registered spatially. Therefore, we are developing effective means of 3D spatial co-registration of US and MR data along with histological data used for validation

New developments in tissue-type imaging (TTI) of prostate cancer: combined ultrasonic and magnetic-resonance methods

Because current methods of imaging prostate cancer are inadequate, biopsies cannot be guided effectively and treatment cannot be planned, targeted or monitored optimally. Therefore, our research is aimed at ultrasonically characterizing cancerous prostate tissue so that we can image it more effectively and thereby provide improved means of detecting, treating, and monitoring prostate cancer. We base our characterization methods on spectrum analysis of radiofrequency (RF) ultrasonic (US) echo signals combined with clinical variables such as prostate-specific antigen (PSA). We classify parameters of US spectra (USS) using artificial neural networks (ANNs), and express classification efficacy using relative-operating- characteristic (ROC) methods. The US methods produce ROC- curve areas of 0.84 compared to 0.64 for conventional methods. We generate lookup tables (LUTs) that translate spectral parameters and clinical variables directly to pixel values in tissue-type images (TTIs) that show cancerous regions in 2- or 3- D. Based on encouraging results obtained by others using magnetic-resonance spectroscopy (MRS) for identifying cancerous prostate lesions, we are investigating means of combining MRS with USS methods to produce multimodality TTIs.

Handling of Surgical Pathology Specimens

The continuous development of new clinical, radio-logic, surgical, and pathologic techniques highlights an ever-changing practice of pathology. With reference to many locations in the body, and certainly in the lung, the pathologist is being asked to be more diagnostic with smaller and smaller samples. Immunohistochemistry and other newer techniques entering diagnostic practice may lead to a diagnosis based on only a few cells. As in electron microscopy, the challenge will be to judge whether such samples are truly representative. Pattern recognition on tissue sections is still valuable, but is being supplemented, and in part replaced, with some of these newer techniques.

Mesenchymal Tumors, Part I: Tumors of Fibrous, Fibrohistiocytic, and Muscle Origin

Tumors generally regarded as fibrous or fibrohistiocytic in nature include inflammatory pseudotumors (inflammatory myofibroblastic tumors), intrapulmonary localized fibrous tumors, cystic fibrohistiocytic tumors, cystic mesenchymal hamartomas, malignant fibrous histiocytomas, and fibrosarcomas. In recognition of their greater frequency in the pleura, localized fibrous tumors (LFTs) are primarily discussed in Chapter 43 on pleural neoplasms; in this chapter only the intrapulmonary variants of LFTs are considered. Likewise, in view of their greater frequency in younger age groups, inflammatory myofibroblastic tumors and congenital peribronchial myofibroblastic tumors are discussed in Chapter 42 on pediatric tumors.