Hank C. Hill

Predictive factors associated with long-term survival in patients with neuroendocrine tumors of the pancreas

BackgroundNeuroendocrine tumors of the pancreas are rare tumors. We identified predictive factors that are associated with long-term survival (≥5 years).MethodsFifty patients with a diagnosis of neuroendocrine tumors of the pancreas were retrospectively evaluated. The following factors were evaluated for disease-specific mortality: age, sex, primary tumor location, functional status, type of primary tumor treatment, presence or absence of liver metastases, timing of liver metastases occurrence, and type of liver metastases treatment. Aggressive treatment of the liver metastases included surgery, chemoembolization, or intrahepatic arterial infusion chemotherapy.ResultsTwenty-three patients (47%) had tumor located in the head of the pancreas, and 29 patients (58%) had nonfunctioning tumor. Thirty-nine patients (78%) had liver metastases. The median follow-up for the entire group was 35 months (range, 76–206 months). The median survival for the entire group was 40 months, and the overall 1-, 2-, and 5-year survival rates were 84%, 69%, and 36%, respectively. Factors that had a significant favorable effect on survival included curative resection of the primary tumor, metachronous liver metastases, absence of liver metastases, and aggressive treatment of the liver metastases.ConclusionsDefinitive surgical resection of the primary tumor, absence of liver metastases, metachronous liver metastases, and aggressive treatment of the liver metastases were predictors of long-term survival in patients with neuroendocrine tumors of the pancreas.

High-grade dysplasia within Barrett's esophagus: Controversies regarding clinical opinions and approaches

Barretts esophagus with high-grade dysplasia is a well-known risk factor for the development of esophageal adenocarcinoma, which has become the predominant form of esophageal cancer in the United States. This review addresses four major fundamental issues that shape our treatment decisions regarding high-grade dysplasia within Barretts esophagus: (1) the poorly defined natural history of high-grade dysplasia in its progression to adenocarcinoma, (2) the potentially high morbidity and mortality of esophageal resection for high-grade dysplasia, (3) the difficulty in detecting cancer among dysplastic cells during endoscopy, and (4) the controversial role of endoscopic mucosal ablative therapy for high-grade dysplasia. Until there are more accurate surveillance methods, better biochemical or molecular markers in predicting cancerous progression, or more effective minimally invasive methods of treatment, esophagogastrectomy must be considered the standard means of managing patients with Barretts esophagus and high-grade dysplasia. Regular rigorous systematic surveillance and endoscopic mucosal ablation are alternative treatment options that are available but should be used only under strict conditions. The decision to proceed in a certain direction is quite complex and challenging and ideally requires the feedback of patients who are properly educated about the controversies surrounding this disease.

A BALB/c murine lung alveolar carcinoma used to establish a surgical spontaneous metastasis model

Line-1, a weakly immunogenic lung tumor cell line derived from the BALB/c mouse, metastasizes spontaneously to the lungs of mice following subcutaneous administration. The parameters that influence metastasis as well as the progression of metastatic lung disease following surgical resection of primary subcutaneous tumors were characterized. Histological analysis of the lungs obtained from mice bearing different size subcutaneous tumors demonstrated that >90% of the mice developed micrometastatic disease in the lungs when the tumor exceeded 650 mm3 in size. Surgical resection of subcutaneous tumors resulted in the cure of primary disease in 95% of the mice. Macroscopic tumor nodules were grossly visible in the lungs of 75% of the mice 5 weeks after surgery. Serum amyloid A level correlated with primary tumor burden and was diagnostic for the presence of metastatic disease. The efficiency of metastasis, post-surgical primary tumor recurrence and long-term survival were significantly different between BALB/c mice obtained from different suppliers. The Line-1-BALB/c surgical metastasis model provides a clinically relevant tool for the evaluation of anti-cancer therapies, especially those that are designed to target long-term suppression of minimal residual disease following surgical intervention.

Challenges of utilizing immunostains to facilitate the diagnosis and management of metastatic adenocarcinoma.

Women presenting with metastases from an unknown primary site represent a growing diagnostic challenge. Treatment is based upon the results of several diagnostic radiographic modalities that may locate the occult primary and determine the extent of metastatic tumor burden. Immunostaining represents another modality that can be used to facilitate identification and management of occult primary carcinoma. In patients who present with advanced disease, combining standard techniques with immunostaining can usually aid in determining the most effective regimen for optimal palliation and, in some cases, prolonged survival. We describe metastatic adenocarcinoma of unknown primary presenting as a pericardial effusion and coincident supraclavicular adenopathy. The patient completed the chemotherapy and had stable metastatic tumor burden with an acceptable quality of life. Two years after initial diagnosis, the patient expired because of disease progression. Although immunohistochemical staining initially suggested metastatic breast carcinoma, her clinical course confirmed a lung primary.

Localized fibrous tumors of the pleura

Localized fibrous tumor of the pleura (LFTP) is uncommon, with occasional malignant features. Six patients referred to a comprehensive cancer center were diagnosed preoperatively by computed tomography–guided biopsy. CD34 immunoreactivity supports the pathologic diagnosis of LFTP. Malignancy was confirmed in 3 of these cases. While the natural history of pleural LFTP is not well known, favorable prognostic features are pedicled growth and complete surgical resection. Tumors with necrotic or hemorrhagic areas, greater than 4 mitoses per 10 high-power fields, and invasion of adjacent structures have poor prognoses. Surgical resection with long-term clinical follow-up is the optimal therapeutic approach.

Off-Label Management of Primary and Metastatic Endobronchial Tumors With Photodynamic Therapy

Photodynamic therapy (PDT) is a US Food and Drug Administration–approved method for managing both early- and advanced-stage endobronchial non–small-cell lung carcinoma. The possibility of eradicating metastatic endobronchial lesions with PDT was offered to patients presenting with a variety of histologies. We retrospectively reviewed the treatment outcomes of primary and metastatic endobronchial tumors with the off-label and compassionate exemption use of PDT. Between 1991 and 2002, we administered PDT to 13 patients with a variety of endobronchial histologies. PDT was used either as definitive therapy or in the adjuvant setting. The most common histology was carcinoid (38%). Initial response rate to PDT was seen in 8 of 13 (61%). Five patients were treated with PDT alone, while 46% of patients had various additional treatments including brachytherapy, laser therapy, lobectomy, chemotherapy, and/or radiation therapy. Complete, partial, and nonresponders were seen in 39%, 46%, and 15%, respectively. The overall mean percentage change in endoluminal occlusion after PDT was 84%. A long-term response rate (≥12 months) was seen in 5 patients (39%). The estimated 5-year survival is 73%. Photodynamic therapy provides the option of a less morbid treatment of the management of endobronchial lesions. Patients with isolated endobronchial tumors can achieve effective treatment with PDT with or without combination therapy. The “off-label” use of PDT for the management of endobronchial tumors is a viable option that requires further investigation with prospective randomized clinical trials.