Insulin-producing islet cell tumors

The types of islet cell pathology and the history and clinical course are presented for 82 patients with proven islet B-cell disease with hyperinsulinism. They form the basis for the recognition of the patient suspected of harboring this syndrome. Among laboratory tests and procedures for recognition of inappropriate hyperinsulinism, the evaluation of plasma levels of glucose (G) and immunoreactive insulin (IRI) on fasting is the most important, with calculation of the IRI/G ratio, if necessary. The determination of the concentration of basal proinsulin and C-peptide is also helpful. Suppression tests and provocative tests are used infrequently. Attempts at preoperative localization are recommended. Ultrasonography and arteriography are helpful, while transhepatic percutaneous portal venous sampling is the only procedure that can differentiate localized (solitary insulinoma) from diffuse hyperinsulinism caused by adenomatosis, hyperplasia, and nesidioblastosis (present in 18% of our patients). Intraoperative ultrasonographic localization may visualize nonpalpable tumors and exclude multiple tumors. Treatment of benign B-cell disease is primarily surgical, but a variety of drugs may be useful for temporary or more prolonged therapy.     

Localization of islet cell tumors

In summary, although similar imaging techniques are used for the localization of insulin and gastrin secreting islet cell tumors, the success rates are very different. Fortunately, the best results are obtained in the tumor for which effective medical treatment is less available, namely insulinomas, which can be found and successfully resected in over 90 per cent of patients. Both portal venous sampling and experienced intraoperative ultrasound are critical for successful surgery of small insulin-secreting tumors. Facilities without these resources should not explore patients when the conventional imaging studies are negative. Gastrinomas, on the other hand, will elude detection by even the most experienced surgeons in over 20 per cent of patients with sporadic Zollinger-Ellison syndrome in spite of positive portal venous sampling and intra-arterial secretin studies. The very small size of these tumors and their occurrence in more difficult to explore extrapancreatic sites provides the basis for this difference. However, patients with negative imaging studies and negative surgical explorations have an excellent prognosis on long-term follow-up when gastric acid hypersecretion is controlled. An annual computed tomographic scan is recommended since the appearance of a tumor would mandate surgical resection because of the significant incidence of malignancy in larger tumors. However, progression to imageable tumors has been unusual in our experience with this group of patients. There remains a small group of patients with highly malignant, rapidly metastasizing, gastrin-secreting islet cell carcinomas for whom localization is simple but of little relevance. However, locally invasive gastrinomas may often be resectable and provide prolonged remission and even cure. Aggressive surgery, supported by detailed cross-sectional and angiographic localization, has a role in this small group of patients.     

Management of nonfunctioning islet cell tumors

AIM: To more clearly define the clinical and pathological characteristics and appropriate diagnosis and treatment of nonfunctioning (NFICTs) islet cell tumors, and to review our institutional experience over the last 30 years. METHODS: The records of 43 patients confirmed to have nonfunctioning islet cell tumors of pancreas were retrospectively reviewed. Survival was estimated by the Kaplan-Meier methods and potential risk factors for survival were compared with the log-rank tests. RESULTS: The mean age was 31.63 years (range, 8 to 67 years). There were 7 men and 36 women. Twenty-eight patients had a confirmed diagnosis of nonfunctioning islet cell carcinoma (NFICC) and benign islet cell tumors were found in 15 patients. The most common symptoms in patients with NFICTs were abdominal pain (55.8%), nausea and/or vomiting (32.6%), fatigue (25.6%) and abdominal mass (23.3%). Preoperative ultrasonic and computed tomography localized the tumors in all patients. Forty-three NFICTs were distributed throughout the pancreas, with 21 located to the right of the superior mesenteric vessels, 10 in the body of the pancreas, 6 in the tail of the pancreas, and multiple tumors were found in one patient. Thirty-nine of 43 patients (91%) underwent surgical resection. Surgical treatment was curative in 30 patients (70%) and palliative in 9(21%). The resectability and curative resection rate in patients with NFICC of pancreas were 89% and 61%, respectively. The overall cumulative 5- and 10-year survival rates for patients with NFICC were 58.05% and 29.03%, respectively. Radical operation and diameter of cancer small than 10 cm were positive prognostic factors in females younger than 30 years old. Multivariate Cox regression analysis indicated that radical operation was the only independent prognostic factor, P=0.007. CONCLUSION: Nonfunctioning islet cell tumors of pancreas are found mainly in young women. The long-term results for patients undergone surgery, especially curative resection are good.     

The role of surgery in the combined management of small cell bronchial carcinoma

Even after the introduction of modern chemotherapeutic regimens and radiotherapeutic approaches in the treatment of small cell bronchial carcinoma (SCLC), the results are still disillusioning. Long-term remissions are rare even in patients with limited disease. We review 66 patients with SCLC (limited disease) which we treated either by single therapies (chemotherapy, radiotherapy, surgery n = 16), or by different combinations of the possible therapeutic measures. Favorable results were achieved by a comprehensive treatment including operation, chemotherapy and prophylactic cranial and local irradiation: 11 of 15 patients survived 3 to 97 months after the onset of therapy, 4 of those more than 24 months. Based on our own experience and the results of other authors we feel that surgical resection should be again included as an essential part of treatment: tumor resection is the rational primary therapeutic approach for cases without lymph node metastases in the mediastinum and for tumors of uncertain histological type. If there is evidence of lymph node involvement in the mediastinum (N2), surgery should be performed after a remission has been successfully induced by chemotherapy (so-called adjuvant surgery).     

Non-islet origin of pancreatic islet cell tumors

The histogenesis of pancreatic islet cell tumors was investigated by morphological identification of putative precursor lesions in pancreatic tissue from patients with multiple endocrine neoplasia type 1 (MEN1), tissue microdissection, and genetic analysis. MEN1 mutation and absence of the MEN1 wild-type allele in different precursor lesions strongly suggest that pancreatic islet cell tumors are derived from the ductal/acinar system but not from pancreatic islet tissue. Pluripotent cells within the exocrine pancreas appear capable of formation into small atypical accumulations of MEN1-deficient cells with both exocrine and endocrine phenotype. The findings suggest presence of multiple developmental aberrations in MEN1 pancreas that potentially serve as precursor material for neuroendocrine tumors.     

Diagnosis and staging of islet cell tumors of the pancreas

Pancreatic endocrine tumors arise from the amine precursor uptake and decarboxylation (APUD) cells of the pancreas and behave in a different fashion both biologically and clinically from pancreatic adenocarcinoma. Gastrinomas and insulinomas are the two most common pancreatic endocrine tumors. Unlike pancreatic adenocarcinoma, in which tumor stage, resectability, and prognosis are determined by the tumor, nodes, and metastasis (TNM) classification, the prognosis of pancreatic endocrine tumors is determined by the presence of liver but not regional lymph node metastasis. This review focuses predominantly on the different diagnostic tools available to the clinician and the relative merits of each modality. The sensitivities of computed tomography, magnetic resonance imaging, somatostatin receptor scintigraphy, endoscopic ultrasound, and angiography with venous sampling for diagnosing islet cell tumors are compared. A diagnostic algorithm for the management of these tumors is provided at the end of the discussion.     

Non-functioning islet cell tumors of the pancreas--a multicentric clinical study in Taiwan

BACKGROUND/AIMS: Islet cell tumors of the pancreas are rare. Functioning tumors are characterized by the symptoms induced by the hormones they secrete. The clinical behaviors of non-functioning tumors are quite different. In this retrospective study, we scrutinized 16 patients with non-functioning islet cell tumor in three tertiary university hospitals in Taiwan during a 20-year period. METHODOLOGY: There were 12 women and 4 men with a mean age of 47 years. Body-weight loss, abdominal pain and palpable mass were the most frequent symptoms. RESULTS: The mean size of these tumors was 8.9 cm in diameter. Ten tumors were located at the tail of pancreas, the other 6 located at the head. Except for hyperbilirubinemia in 2 patients, none of the patients with non-functioning islet cell tumor showed abnormalities of laboratory data including serum tumor markers. Preoperative detection of these tumors by imaging modalities was not difficult due to the large size of the tumors. However, differentiation with functioning tumor or ductal cell carcinoma required clinical and imaging correlation. Fourteen tumors were malignant including 8 with regional lymph nodes involvement, 3 with locally microscopic invasion, 2 with hepatic metastasis and 2 with nearby organ invasion. CONCLUSIONS: Even with its malignant behavior, non-functioning islet cell tumor still possessed a good prognosis after adequate surgical removal in comparison with a higher mortality rate of ductal carcinoma of the pancreas.     

Systemic and regional therapy of advanced islet cell tumors

Asymptomatic patients with islet cell tumors should be observed every 3 to 6 months. Once symptomatic, many therapeutic choices exist. First choice would be symptomatic management resulting in minimum side effects. More aggressive approaches include systemic therapy with cytotoxic or biologic agents. Vascular occlusion provides useful palliation of liver metastases.     

The role of surgery in clinical management of patients with metastatic papillary renal cell carcinoma

Objectives

Patients with metastatic papillary renal cell carcinoma (RCC) show special clinical behavior compared to patients with other histologic subtypes of RCC. This study aimed to assess the relevance of surgical and systemic options used in treatment of these patients prior to the recent era of targeted therapies.

Methods

Retrospectively, we assessed clinical data of 61 patients with metastatic papillary RCC who were treated at eight centers in Germany.

Results

Median follow-up was 20 (range 1–114) months and median age at time of diagnosis was 62 (range 24–85) years. Men were affected predominantly (50/61; 82%). Twenty-one patients (34%) showed metastases at time of diagnosis. In the remaining 40 patients, median time to development of metastases was 30.4 (range 3–143; mean 16.5) months. Sites of metastases were lung (37; 61%), bone (24; 38%), liver (20; 33%), lymph nodes (24; 38%), and local recurrence (17; 28%). Others sites of disease were brain metastases (6 patients/10%), peritoneal carcinosis (5 patients/8%), and others. A surgical approach with potentially curative intention was performed primarily in 11 patients (18%). 31 patients received an immuno- (interferon-α ± interleukin-2) or immunochemotherapy as first line treatment for metastatic disease. Overall, 42/61 patients (69%) received systemic therapy. Supportive care only was performed in 12 patients (20%) because of poor performance status. Median overall survival after diagnosis of metastatic disease was longer than 48 months in patients with tumor resection (n = 11) compared to 13.0 ± 4.3 months 95% CI 4.5–21.5 (n = 42) months in patients without surgical approach.

Conclusions

Complete resection of metastases represents a valid option in management of patients with relapsing or metastatic papillary RCC.     

The current role of thoracic surgery in tuberculosis management

Although tuberculosis is mainly managed medically today, thoracic surgery continues to play a key role in its diagnosis and treatment in selected subgroups of patients. In certain scenarios such as multi-drug-resistant tuberculosis, advanced tuberculous empyema and symptomatic bronchial stenosis, modern thoracic surgery may represent the only effective means of management in selected patients. Advances in thoracic surgery in recent years, in particular the use of Video-Assisted Thoracic Surgery, not only reduce postoperative morbidity for individual patients, but may potentially allow a wider range of tuberculosis patients to benefit from surgery. Respiratory physicians and thoracic surgeons should continue to work together to ensure that tuberculosis patients who may benefit from surgery are identified for prompt and effective intervention.     

The evolving role of radical surgery in the management of regionally advanced transitional cell carcinoma of the bladder

The management of muscle-invasive transitional cell carcinoma (TCC) of the bladder continues to evolve. The standard treatment for patients presenting with clinical stage T2-4aN0M0 bladder cancer remains radical cystectomy. However, the management of patients who present with more advanced disease on clinical evaluation, such as unresectable pelvic tumor (T4b) or regional pelvic lymph node metastases (N+) remains unclear. In addition, the intraoperative management of unsuspected pelvic adenopathy identified during exploration of a planned radical cystectomy, continues to generate controversy. The following discussion relates to the evolving attitudes towards the role of surgery in the treatment of advanced bladder cancer.     

Pancreatic islet cell survival following islet isolation: the role of cellular interactions in the pancreas.

The purpose of this study was to characterize the trophic effect of pancreatic duct cells on the islets of Langerhans. Ductal epithelium and islets were isolated from hamster pancreata. In addition, duct-conditioned medium (DCM) was prepared from primary duct cultures that had been passaged twice to remove other cellular elements. Three experimental groups were then established: Group 1, 100 islets alone; Group 2, 100 islets+80 duct fragments; and Group 3, 100 islets in 25% DCM. All tissues were embedded in rat tail collagen for up to 12 days and the influence of pancreatic ductal epithelium on islet cell survival was examined. By day 12, 20.6+/-3. 0% (S.E.M.) of the islets cultured alone developed central necrosis, compared with 6.7+/-2.0% of the islets co-cultured with ducts and 5.6+/-1.5% of the islets cultured in DCM (P<0.05). The presence of apoptotic cell death was determined by a TdT-mediated dUTP-biotin nick end labelling (TUNEL) assay and by a specific cell death ELISA. DNA fragmentation in islets cultured alone was significantly increased compared with islets cultured either in the presence of duct epithelium or in DCM (P<0.05). More than 80% of TUNEL-positive cells were situated in the inner 80% of the islet area, suggesting that most were beta-cells. DCM was analysed for known growth factors. The presence of a large amount of IGF-II (34 ng/ml) and a much smaller quantity of nerve growth factor (4 ng/ml) was identified. When the apoptosis studies were repeated to compare islets alone, islets+DCM and islets+IGF-II, the cell death ELISA indicated that IGF-II produced the same beneficial result as DCM when compared with islets cultured alone. We conclude that pancreatic ductal epithelium promotes islet cell survival. This effect appears to be mediated in a paracrine manner by the release of IGF-II from cells in the ductal epithelium.     

Tailored imaging of islet cell tumors of the pancreas amidst increasing options

Pancreatic islet cell tumors are neuroendocrine tumors, which can produce hormones and can arise as part of multiple endocrine neoplasia type 1 or von-Hippel-Lindau-disease, two genetically well-defined hereditary cancer syndromes. Currently, technical innovation improves conventional and specific molecular imaging techniques. To organize the heterogeneous results described for the imaging of these tumors, we distinguished three indications (1) imaging of a patient with hormone hypersecretion, (2) search for a pancreatic primary in case of proven neuroendocrine cancer of unknown primary, and (3) screening of asymptomatic mutation carriers. We searched for publications on imaging of islet cell tumors between 1995 and January 2010 and defined a Level of Evidence (LOE) for the applicability of each technique. For each technique, data were analyzed in a Forest plot and arranged per imaging indication and tumor subtype. LOEs are weak for all imaging techniques. Analyses indicate a prominent role for endoscopic ultrasound for all three indications.     

The contribution of ultrasonography and computed tomography in the diagnosis of nonfunctioning islet cell tumors of the pancreas

The personal series of 12 nonfunctioning islet cell tumors (NFIT) of the pancreas is reported. The ultrasound and computed tomography features of NFIT are analyzed, and a few signs are identified that may be useful in the differential diagnosis vs ductal carcinoma. The necessity to complete the diagnostic work up by means of fine needle aspiration biopsy and cytologic smears is also emphasized.