A patient with a large recurrent pheochromocytoma demonstrating the pitfalls of diagnosis.

BACKGROUND: A 59-year-old man presented for a follow-up, 6 years after surgery for a large pheochromocytoma. He had suffered from diabetes mellitus, hypertension and abdominal pain in the right flank region. Previous postoperative follow-up did not reveal tumor recurrence. INVESTIGATION: Measurement of plasma free metanephrine and normetanephrine by high-performance liquid chromatography and radioimmunoassay; 123I-metaiodobenzylguanidine (MIBG) scintigraphy; hybrid 123I-MIBG single-photon emission CT (SPECT)-CT; MRI; testing for plasma norepinephrine and epinephrine; intraoperative ultrasonography; histological staining for chromogranin A and synaptophysin; and postoperative 18F-dihydroxyphenylalanine (DOPA) PET scan. DIAGNOSIS: Recurrent pheochromocytoma. MANAGEMENT: Laparotomy with tumor resection. Reduction of antihypertensive medications. Further follow-up by MRI, hybrid 123I-MIBG SPECT-CT and testing for plasma catecholamines and free metanephrines.

Signet-ring cell carcinoma arising in the gastric stump after duodenopancreatectomy for ductal adenocarcinoma of the pancreas: a case report.

The development of malignancy in the gastric stump following surgery for peptic ulcer disease is well recognized. There are also few reports on carcinomas occurring after surgery for malignant gastric disease. However, carcinoma of the gastric stump after duodenopancreatectomy is extremely rare. We describe what we believe to be an unusual case of signet-ring cell carcinoma of the gastric stump developing at the anastomotic site 5 years after duodenopancreatectomy for ductal adenocarcinoma of the pancreatic head. We performed remnant gastrectomy and Roux-en-Y gastrojejunostomy as a curative resection. This experience clearly underlies that g astric stump carcinoma (GSC) may mimic metastatic disease recurrence leading to diagnostic confusion after surgery for malignancy. Although an increased risk of gastric stump carcinoma after pancreatoduodenectomy for pancreatic cancer has not been established, the possibility of such a complication should be kept in mind when evaluating patients after gastric resection who present with symptoms of metastatic disease recurrence years after the primary operation. Investigations should be independent of the entity of the primary disease or its localization, since GSC may well be amenable to surgical cure as demonstrated in the presented case. Outpatient follow up results of the last four years indicated no recurrence in this case.

Does the expression of c-kit (CD117) in neuroendocrine tumors represent a target for therapy?

Neuroendocrine tumors are very heterogeneous, develop from a variety of tissues, and can be difficult to diagnose. Without the clinical manifestation of metastases, it is often difficult to characterize them as malignant. Even so-called completely (R0) resected tumors can spread clinically visible metastases within a few months after initial surgery. Treatment options for neuroendocrine tumors including pheochromocytoma are limited. Molecular targeted therapies using tyrosine kinase inhibitors might prove to be helpful in patients with these tumors. In an immunohistochemical study, we examined KIT in 26 pheochromocytomas, 8 of which were malignant (3 adrenal pheochromocytomas, 5 paragangliomas). KIT expression was found in one of these 8 malignant tumors. This 2.5-cm-large adrenal pheochromocytoma originated from a woman with neurofibromatosis type 1 and spread into spine, skull, and lung. KIT expression could be demonstrated in 5% of tumor cells. On the basis of KIT expression immunohistochemically, we treated patients with neuroendocrine (i.e., medullary thyroid cancer) and other tumors with imatinib 400 mg per day, but without efficacy after 2 months of therapy. Similar results were shown by other investigators. Therefore, monotherapy with imatinib may not be efficacious in patients with neuroendocrine tumors that express KIT. Tyrosine kinase inhibitors such as sorafenib that targets several receptors in addition to KIT may be more efficacious in treating patients with neuroendocrine tumors.

Caroli's disease: liver resection and liver transplantation. Experience in 33 patients.

BACKGROUND: The aim of this study was to review and discuss our observations on 33 patients who underwent surgical treatment for Caroli's disease (CD), focusing on diagnosis, current surgical management, and long-term outcome. METHODS: Between May 1993 and June 2004, 642 liver resections and 286 liver transplantations in 252 patients were performed in our department of surgery. Thirty-three patients were referred to our center for diagnostic and therapeutic management of CD. Prior surgical interventions for hepatobiliary disorders, current diagnostic and surgical procedures, procedure-specific complications, duration of hospital stay, duration of follow-up, outpatient information, and long-term outcome were reviewed. RESULTS: Fifteen male and 18 female patients were treated in this study. Initial symptoms and signs of the disease noted in our patients included right upper quadrant pain, fever, and jaundice. In 2 of the 33 patients, we noted clinical evidence of cirrhosis followed by histologic confirmation. One patient suffered from variceal bleeding. In 26 patients, diagnoses were established by a combined endoscopic retrograde cholangiopancreatography, ultrasonography, and computed tomographic studies. The disease was localized in 25 and diffuse in 8 patients. Liver resection was carried out in 29 patients. Partial hepatectomies were performed in 27 of these 29 at our institution. Two female patients with the diffuse disease underwent orthotopic liver transplantation. Thirteen of the 31 patients who underwent surgery at our institution had an uneventful postoperative course. Fourteen patients had minor postoperative complications and responded well to medical management. Four patients had major complications that required further surgical treatment. Two patients died of complications related to postoperative hemorrhage and sepsis. Two patients with intrahepatic cholangiocarcinoma died because of primary tumor progress. One patient with cholangiocarcinoma died 1 year after a successful left hepatectomy because of metastatic disease recurrence. The long-term results of the 26 surviving patients were assessed during a mean follow-up of 3.7 years (range, 1-11 years). All 26 patients remained free of biliary symptoms or complications. In 25 patients, surgery including liver transplantation was curative. CONCLUSIONS: Partial hepatectomy for localized CD is potentially curative. In patients with diffuse CD, liver transplantation provides gratifying long-term results.

Pancreatic neuroendocrine tumor with ectopic adrenocorticotropin production upon second recurrence.

We present a 54-yr-old woman with ectopic corticotropin syndrome caused by a neuroendocrine tumor of the pancreas. At initial presentation, the patient suffered from diarrhea, heartburn, and nonspecific abdominal pain. There was no evidence of Cushing's syndrome. A neuroendocrine tumor in the head of the pancreas with metastases into peripancreatic lymph nodes was diagnosed and completely resected. Fourteen months later, abdominal computed tomography and scintigraphy with (111)In-labeled octreotide suggested relapse of the tumor. The patient again had no evidence of Cushing's syndrome. A second in toto tumor resection was performed. Another 8 months later, the patient developed forgetfulness, depressive episodes, muscle weakness, new-onset hypertension, hypokalemia, plethora, diabetes mellitus, polyuria, and weight loss. Endocrine testing suggested a source of ectopic ACTH production. An octreotide scan showed an intense uptake ventromedial of the left kidney, an area that showed a mass lateral of the superior mesenteric artery on abdominal magnetic resonance imaging. A complete pancreatectomy with splenectomy and left-sided adrenalectomy were performed. At this second relapse, this neuroendocrine tumor clinically had changed its hormonal profile. Immunohistochemically, in contrast to primary tumor and first relapse, we found strong immunostaining for ACTH in tumor cells of the second relapse and a MIB-1 index greater than 20%. To our knowledge, this is the first report describing a pancreatic neuroendocrine tumor that started to secrete ACTH de novo at the time of the second relapse after two former complete tumor resections. This case underscores the pluripotency of neuroendocrine tumor cells and the importance of keeping in mind a possible shift in hormone production during tumor evolution and progression.

Is there a place for thyroidectomy in older patients with thyrotoxic storm and cardiorespiratory failure?

Early thyroidectomy is the treatment of choice for thyrotoxic storm in patients with thyroid autonomy often induced by iodine. However, older patients who are mostly affected by this condition often have underlying chronic cardiopulmonary diseases, apparently contradicting surgical intervention. The published evidence for suitable treatment strategies in these patients is limited. We report the outcome of a series of older critically ill patients who were treated by thyroidectomy because of thyrotoxic storm. We retrospectively analyzed the outcome of 10 patients (4 males, 6 females; 70 years of age, range, 54-79, Burch-Wartofsky point scale, 61; range, 40-85) with thyrotoxic storm, thyroid autonomy, and severe cardiorespiratory and renal failure with cardiac arrhythmia, coronary artery or chronic obstructive pulmonary disease, or acute inflammation. Thyroidectomy was performed for the following reasons: symptoms of thyrotoxic storm deteriorated or did not improve within 24-48 hours despite intensive medical treatment, or patients developed thionamide-induced agranulocytosis or severe thrombocytopenia. All patients with severe accompanying diseases survived thyroidectomy (early post-operative mortality, 0%). The two oldest patients died 2-3 weeks after thyroidectomy because of myocardial infarction or respiratory failure (late postoperative mortality, 20%). In contrast, in the few previous reports of patients who underwent thyroidectomy for thyrotoxic storm and severe accompanying diseases (n = 7), late postoperative mortality was 43%. The overall mortality for all reported patients including our own, who underwent thyroidectomy for thyrotoxic storm with and without severe accompanying disease (n = 49) was 10%. Our results suggest that early total thyroidectomy should be considered as the method of choice for older, chronically ill patients with thyrotoxic storm complicated by cardiorespiratory and renal failure, especially if high-dose thionamide treatment, iopanoic acid, glucocorticoids, and intensive care fail to improve the patient's conditions within 12-24 hours.

Early malignant progression of hereditary medullary thyroid cancer.

BACKGROUND: An age-related progression from C-cell hyperplasia to medullary thyroid carcinoma is associated with various germ-line mutations in the rearranged during transfection (RET) proto-oncogene that could be used to identify the optimal time for prophylactic surgery. METHODS: In this European multicenter study conducted from July 1993 to February 2001, we enrolled patients who had a RET point mutation in the germ line, were 20 years of age or younger, were asymptomatic, and had undergone total thyroidectomy after confirmation of the RET mutation. Exclusion criteria were medullary thyroid carcinomas of more than 10 mm in greatest dimension and distant metastasis. RESULTS: Altogether, 207 patients from 145 families were identified. There was a significant age-related progression from C-cell hyperplasia to medullary thyroid carcinoma and, ultimately, nodal metastasis in patients whose RET mutations were grouped according to the extracellular- and intracellular-domain codons affected and in those with the codon 634 genotype. No lymph-node metastases were noted in patients younger than 14 years of age. The age-related penetrance was unaffected by the type of amino acid substitution encoded by the various codon 634 mutations. The codon-specific differences in the age at presentation of cancer and the familial rates of concomitant adrenal and parathyroid involvement suggest that the risk of progression was based on the transforming potential of the individual RET mutation. CONCLUSIONS: These data provide initial guidelines for the timing of prophylactic thyroidectomy in asymptomatic carriers of RET gene mutations.

Splenohepatic arterial steal syndrome in liver transplantation: clinical features and management.

Well-known arterial complications after liver transplantation comprise thrombosis and major stenosis, which usually necessitate a retransplantation procedure. In our institution, in a series of 165 consecutive liver transplantations, we report the first recognized case of a splenohepatic arterial steal syndrome. This is characterized by an arterial malperfusion of the hepatic graft caused by a marked diversion of blood flow to a significantly enlarged spleen, which leads to major ischemic damage of the hepatic graft. After splenectomy the perfusion through the hepatic artery increased substantially and the graft was salvaged, with a following favorable clinical course. Splenohepatic arterial steal syndrome may ultimately result in graft loss if it is falsely diagnosed or recognized too late. A post-transplantation splenectomy represents a successful therapeutic approach; alternatively a primary arterial anastomosis to the aorta prevents the development of this condition.