[SEPSIS IN SURGICAL PATIENT].

Epidemiological studies indicate a large incidence of sepsis in the general population. Despite advances in surgery, surgical patients with sepsis make almost one-third of all cases of sepsis. Sepsis is the leading cause of morbidity and mortality among surgical patients, with intra-abdominal infection as the main source of sepsis. According to some authors, sepsis in surgical patients is different from those in non-surgical patients because of the immune function modulation that occurs as a result of surgery and anesthesia applied; therefore, these two groups should be monitored separately. In the treatment of sepsis, the key steps are early recognition of sepsis, rapid diagnosis, and aggressive treatment that includes the choice of intervention with the least physiological insult to control the sources of infection. Emphasis should be placed on the prevention of sepsis throughout the perioperative period. In surgical septic patients, treatment is complex and requires a multidisciplinary approach.

Living donor liver transplantation for unresectable liver metastases from solid pseudo-papillary tumor of the pancreas: a case report.

Solid pseudo-papillary tumors (SPT) are rare primary tumors of the pancreas that primarily affect young women. They are of borderline malignancy, and, unlike other pancreatic malignancies, the prognosis after resection is quite good. However, metastatic disease does occur; the liver is the most common site of tumor dissemination. Herein we have reported a case of a 20-year-old woman who presented with multiple, bilateral liver metastases at 3 years after distal pancreatectomy for SPT of the body and tail of the pancreas. The patient underwent living donor liver transplantation (LDLT) and is alive and disease-free at 24 months after surgery. In this report, we discuss the treatment of liver metastases from SPT, with an emphasis on the possible role of orthotopic liver transplantation (OLT).

Orthotopic liver transplantation in a patient with acute liver failure resulting from aortic dissection.

We report a case of acute liver ischemia resulting in liver failure that occurred due to celiac trunk occlusion by an aortic dissection. A 53-year-old patient presented with clinical signs of acute abdomen. He underwent an urgent laparotomy, which revealed a splenic infarction and thrombosis of the celiac artery all the way to the porta hepatis. Imaging showed that an acute thoracoabdominal aortic dissection was present, resulting in compression of the celiac trunk. The aorta was repaired with an intervascular graft; however, an acute insufficiency of the liver ensued, and the patient was urgently transplanted. To the best of our knowledge, this is the first report of vascular compromise of the liver due to acute aortic dissection that would require liver transplantation.

Brusatol-mediated induction of leukemic cell differentiation and G(1) arrest is associated with down-regulation of c-myc.

Employing the natural product quassinoid brusatol, we currently report cellular and molecular events leading to cell death or terminal differentiation in a panel of leukemic cells. Brusatol and bruceantin exerted significant cytotoxic effects with several leukemic cell lines, but not with K562 or normal lymphocytic cells. Cell lines that were less sensitive to the cytotoxic effects of brusatol responded primarily through induction of terminal differentiation. The differentiated phenotype in cell lines derived from acute or chronic myeloid leukemias (HL-60, K562, Kasumi-1, NB4, U937, BV173) was characterized for producing superoxide and non-specific esterase, and some with up-regulation of CD13 (cluster of differentiation) and down-regulation of CD15. Chronic myeloid leukemic cell lines, K562 and BV173, and acute lymphoblastic cell lines, SUPB13 and RS4;11, were induced to differentiate along the erythrocytic pathway. Withdrawal studies showed that brusatol treatment for 48 h was sufficient to induce commitment towards terminal differentiation in HL-60, K562 and SUPB13. Reh cells did not undergo maturation. Analysis of c-MYC protein expression revealed that brusatol or bruceantin down-regulated expression to undetectable levels in cell lines that were most sensitive, based on cell death or terminal differentiation. Generally, c-myc RNA was reduced, but to a lower extent than c-MYC protein levels, indicating c-myc expression was regulated by quassinoids at the post-transcriptional level. Thus, regulation of c-myc expression may represent a critical event that leads to terminal differentiation. Since these responses are facilitated at clinically achievable concentrations, quassinoids may be of value for the management of hematological malignancies.

Pilot trial of interleukin-2 with granulocyte colony-stimulating factor for the mobilization of progenitor cells in advanced breast cancer patients undergoing high-dose chemotherapy: expansion of immune effectors within the stem-cell graft and post-stem-cell infusion.

PURPOSE: To evaluate whether administration of interleukin-2 (IL-2) with granulocyte colony-stimulating factor (G-CSF) improves mobilization of immune effector cells into the stem-cell graft of patients undergoing high-dose chemotherapy and autografting. PATIENTS AND METHODS: We performed a trial of stem-cell mobilization with IL-2 and G-CSF in advanced breast cancer patients receiving high-dose chemotherapy with cyclophosphamide, thiotepa, and carboplatin and stem cells followed by IL-2. The trial defined immune, hematologic, and clinical effects of IL-2 in this setting. RESULTS: Of 32 patients enrolled, nine received G-CSF alone for mobilization. Twenty-one of 23 patients mobilized with IL-2 plus G-CSF had stem cells collected with more mononuclear cells than those receiving G-CSF (19.3 v 10.4 x 10(8)/kg; P =.006), but fewer CD34(+) progenitor cells (6.9 v 22.0 x 10(6)/kg; P =.049). The IL-2 plus G-CSF-mobilized patients had greater numbers of activated T (CD3(+)/CD25(+)) cells (P =.009), natural killer (NK; CD56(+)) cells (P =.007), and activated NK (CD56 bright(+)) cells (P: =.039) than those patients mobilized with G-CSF. NK (P =.042) and lymphokine-activated killer (LAK) (P =.016) activity was increased in those mobilized with IL-2 + G-CSF, whereas G-CSF-mobilized patients had a decline in cytolytic activity. In the third week posttransplantation, immune reconstitution was superior in those mobilized with IL-2 plus G-CSF based on greater numbers of activated T cells (P =.003), activated NK cells (P =.04), and greater LAK activity (P =.003). The 16 of 21 IL-2 + G-CSF-mobilized patients with adequate numbers of stem cells (> 1.5 x 10(6) CD34(+) cells/kg) collected engrafted rapidly posttransplantation. CONCLUSION: The results demonstrate that G-CSF + IL-2 can enhance the number and function of antitumor effector cells in a mobilized autograft without impairing the hematologic engraftment, provided that CD34 cell counts are more than 1.5 x 10(6) cells/kg. Mobilization of CD34(+) stem cells does seem to be adversely affected. In those mobilized with IL-2 and G-CSF, post-stem-cell immune reconstitution of antitumor immune effector cells was enhanced.

Cold agglutinin disease in a patient with uterine sarcoma.

Cold agglutinin disease is a rare clinical scenario. It is usually associated with infection, drug reaction, and hematologic malignancy, such as non-Hodgkin lymphoma or lymphocytic leukemia. We report a case of cold agglutinin disease in a patient with solid-tumor uterine sarcoma. Immunological dysregulation has been proposed as the pathogenesis for this disease. We also summarize recently reported cases of cold agglutinin disease, the underlying conditions, and advances in the management of cold agglutinin disease.

Interleukin 10-induced thrombocytopenia in normal healthy adult volunteers: evidence for decreased platelet production.

Recombinant human interleukin 10 (rhuIL-10) inhibits the production of proinflammatory cytokines and has shown promise in the treatment of inflammatory bowel disease. Clinical trials have been accompanied by a reversible decline in platelet counts. We conducted a randomized, double-blinded, placebo-controlled, parallel group trial in 12 healthy volunteers to investigate the aetiology of rhuIL-10-induced thrombocytopenia. Eight volunteers received 8 microg/kg/d of rhuIL-10 subcutaneously, while four subjects received a placebo alone for 10 d. A reversible decline in the platelet counts from a mean of 275 x 10(9)/l to 164 x 10(9)/l was observed in the IL-10-treated cohort (P = 0.012). A fall in the haemoglobin mean levels was also observed in the IL-10-treated cohort from 13.7 to 11.7 g/dl (P = 0.011). No significant change was observed in the bone marrow cellularity or myeloid/erythroid ratio or in the number of megakaryocytes per high-powered field (HPF). A fall was observed in the number of megakaryocyte colony-forming units (CFU-MKs) after the administration of IL-10 compared with those receiving the placebo (P = 0.068). No difference in the change in granulocyte-macrophage CFUs (CFU-GMs), mixed lineage CFUs (CFU-GEMMs) or erythroid burst-forming units (BFU-Es) was observed when comparing the IL-10- vs. placebo-treated groups (P > 0.465). Serum cytokine levels of thrombopoietin (TPO). IL-6 and granulocyte-macrophage colony stimulating factor (GM-CSF) were not decreased following IL-10 administration. In fact, both TPO and GM-CSF appeared to be slightly increased in the serum. All subjects underwent In111-labelled platelet survival studies with liver/spleen scans to assess splenic sequestration prior to and then on day 7 of treatment. A significant reduction in splenic sequestration of platelets (P =0.012) was observed in the IL-10-treated group, but not in the placebo-treated subjects.

Organ preservation therapy for advanced-stage laryngeal carcinoma.

The standard treatment for patients with advanced laryngeal cancer remains total laryngectomy. Radiotherapy as a primary treatment modality is a reasonable alternative. Surgical salvage by total laryngectomy is an important part of the treatment plan when irradiation is used primarily to treat advanced laryngeal cancer. The value of induction and concomitant chemotherapy in laryngeal preservation protocols remains controversial. The currently accepted role for use of chemotherapy outside of research protocols is for palliation of incurable laryngeal cancers. The nonsurgical treatment of patients with advanced laryngeal cancers requires the coordinated efforts of a team with close patient follow-up in order that survival not be compromised.

Paclitaxel in advanced urothelial carcinoma: its role in patients with renal insufficiency and as salvage therapy.

PURPOSE: We evaluated the role of paclitaxel in patients with advanced urothelial carcinoma and renal insufficiency or as second line therapy for metastatic disease. MATERIALS AND METHODS: Nine patients with advanced urothelial carcinoma received 175 to 250 mg./m2. paclitaxel intravenously as a 24-hour infusion. Six patients had renal insufficiency with a median serum creatinine of 2.25 mg./dl. (range 1.9 to 3.2) and 3 with normal renal function were treated after disease progression following 1 to 2 prior chemotherapy regimens. RESULTS: Of 9 patients 5 (56%) achieved a partial response, including 4 of 6 with renal insufficiency. Toxicity was primarily hematological with 4 patients experiencing febrile neutropenia. There was no adverse impact on renal function. CONCLUSIONS: Paclitaxel as a single agent represents an effective therapeutic alternative for patients with advanced transitional cell carcinoma of the urothelium and renal insufficiency precluding cisplatin or gallium nitrate based chemotherapy. Additionally, paclitaxel appears to be effective in patients in whom prior cisplatin based therapy failed.