Malignant transformation of a solitary fibrous tumor of the liver and intractable hypoglycemia.

Sarcomas of the liver are rare. We report a case of intractable hypoglycemia secondary to a solitary fibrous tumor that underwent malignant transformation into a fibrosarcoma. A 70-year-old man presented with a hepatic mass and tumor-associated hypoglycemia which was resistant to medical management. Blood tests were remarkable only for elevated serum insulin-like growth factor (IGF)-2. The hypoglycemia resolved following resection of a solitary fibrous tumor surrounded by a high-grade fibrosarcoma. Real time reverse transcriptase polymerase chain reaction (RT-PCR) measured elevated levels of IGF2 mRNA in both the solitary fibrous tumor and the fibrosarcoma. Immunoblotting demonstrated a series of bands in the size range of pro-IGF2. Unfortunately, disseminated metastases developed 1 year later, concurrent with a recurrence of hypoglycemia, marked again by elevation of serum IGF2. Solitary fibrous tumors of the liver have a real risk of malignant transformation. The severity of the tumor-associated hypoglycemia may parallel the tumor burden and activity. The syndrome is the systemic effect of IGF2 secreted by the tumor. Surgery can treat the hypoglycemia syndrome and the underlying malignancy.

Postchemotherapy characteristics of hepatic colorectal metastases: remnants of uncertain malignant potential.

Accepted management for colorectal cancer (CRC) involves resection of the primary neoplasm and chemotherapy; the debate continues over the most beneficial order of these components. Preoperative chemotherapy aimed at liver metastases may result in complete pathologic response and replacement of the malignancy with scar. The McGill University liver diseases database was retrospectively reviewed. Forty-one patients receiving treatment between December 2003 and August 2004 were identified, their medical records examined, and liver histology reviewed. The histology of the remnants was linked to the appearance of the lesions on preresection imaging and to the primary colorectal neoplasms. Twenty-seven of the 41 patients (66%) received preoperative chemotherapy (oxaliplatin or irinotecan). Features of the primary neoplasm that predicted resolution of the metastases were absence of tumor budding (P = 0.04), absence of a diffusely infiltrative tumor margin (P = 0.02), and loss of expression of the DNA repair gene O6-methylguanine-DNA methyltransferase (P = 0.08). Oxaliplatin and irinotecan demonstrate beneficial effects in treating hepatic colorectal metastases and should be considered in such patients before resection. We propose the acronym RUMP to denote the remnants of uncertain malignant potential remaining. Further investigation is required to determine any correlation between the drug received and the resulting lesion.

Novel two-step resection for lesions between the middle hepatic vein and vena cava which allows the middle hepatic vein to be preserved.

Patients with bilobar colorectal cancer metastases to the liver present a unique problem in terms of resection. They sometimes require a staged approach to resection that takes advantage of the liver's ability to regenerate, as well as the newer chemotherapeutic agents (e.g., oxaloplatin, irinotecan (CPT-11), and bevacizumab) that have become available. In cases of multiple bilobar metastases, if segment IV is clear of tumor, a left lateral segmentectomy (LLS) can be performed, followed several months later by a formal right hepatectomy. The remnant liver composed of the hypertrophied segment IV is drained by the middle hepatic vein (MHV). In this context, patients with lesions between the origin of the MHV and the inferior vena cava (IVC) present a particularly difficult problem. Conventional excision would require an extended hepatectomy and division of the MHV along with either the right or left hepatic veins (RHV, LHV). This would make it impossible to continue with a formal resection of the remaining lesions in the contralateral liver without sacrificing the sole remaining hepatic vein. We present a novel two-step hepatectomy for lesions between the MHV and the IVC that allows the MHV to be preserved and all lesions to be resected.

Antithymocyte globulin induction therapy in hepatitis C-positive liver transplant recipients.

It is unclear whether antithymocyte globulin (ATG) induction therapy in hepatitis C-positive (HCV-positive) liver transplant recipients influences the risk of developing recurrent HCV disease. Multiple acute rejection episodes and high-dose steroids and/or OKT3 used to treat acute rejection increase the risk of graft loss from HCV. We studied the impact of ATG induction on graft and patient survival in HCV-positive liver transplants performed since 1990. Recipients who died or lost their grafts within 1 month of transplantation were excluded. Second, third, and fourth grafts were excluded, as were patients with stage III or IV hepatocellular carcinoma. There were 443 cadaveric liver transplants in adult recipients, of whom 142 (32%) were HCV positive. The incidence of biopsy-proven acute rejection was less in patients who received ATG induction, 34.2% (ATG induction) versus 66.6% (no ATG induction) (P

Adverse outcome of human islet-allogeneic blood interaction.

BACKGROUND: A report of inflammatory damage when islets come into contact with allogeneic blood prompted us to confirm the finding. METHODS: Fresh handpicked human islets were incubated in blood group matched, nonsensitized allogeneic blood. Destruction was quantified by assaying the supernatants for proinsulin release and by blood clot histology. The effect on global hemostasis was assessed by thromboelastography (TEG), and heparin-bonded tubing was used to assess the effect on blood cellular counts. In separate experiments, islets were incubated in allogeneic blood with heparin or Reopro (monoclonal anti-GpIIbIIIa). Islets were also incubated in serum, and cryosections were stained for C1q, C4, C3, C5b-9, immunoglobulin (Ig)M, and IgG binding using immunohistochemistry. RESULTS: Histologic assessment showed severe destruction in 37% of islets in contact with allogeneic blood versus none in controls and a sevenfold increase in proinsulin release from controls (n = 6)(P < 0.005). TEG (n = 11) showed accelerated coagulation in the presence of islets (P < 0.001). Analysis of blood cellular counts (n = 3) showed consumption of platelets, neutrophils, and monocytes in the presence of islets (P < 0.001). Inhibition of coagulation with heparin (n = 3) or inhibition of platelet aggregation with Reopro (n = 3), separately or together (n = 3), did not make a substantial improvement in the destruction in terms of histology or proinsulin release. Immunohistochemical staining (n = 4) revealed C1q, C4, C3, and C5b-9 deposition along with IgG binding. IgM binding was weak if anything. CONCLUSION: This study confirms and extends the finding that human islet-allogeneic blood interaction results in significant destruction of islet tissue with activation of the coagulation cascade and platelet, neutrophil, and monocyte consumption. There was evidence for activation of complement by the classical pathway along with IgG binding.