In vivo immunization in combination with peg-interferon for chronic hepatitis B virus infection.

Only in a minority of patients with chronic hepatitis B (CHB) will treatment with interferon (IFN)-alpha or nucleoside analogues lead to sustained virological response. In vivo immunization (IVI) following virus suppression aims to optimize conditions for an effective immune response: following rapid and profound virus suppression by interferon-lamivudine combination therapy, lamivudine is withdrawn intermittently during continued interferon therapy. It is thought that withdrawal of lamivudine will lead to increased viral replication and increased antigen expression with subsequent immune stimulation. The aim of this prospective pilot study was to evaluate IVI as a therapeutic approach for CHB. Fourteen HBeAg-positive CHB patients were treated for 42 weeks with a combination of pegylated interferon-alpha 2b and lamivudine. After 12 weeks of combination therapy lamivudine was withdrawn intermittently for three consecutive periods of 4 weeks until it was permanently stopped on week 36. At the end of follow-up (week 52) all patients had remained HBeAg positive and the median viral load was similar to baseline. During the initial 12 weeks of treatment, there was a reduction of both the hepatitis B virus (HBV)-specific proliferation capacity of Th-cells and the frequencies of IFNgamma-producing cells. During the lamivudine interruption-cycle there was an inverse relation between the increase of HBV-DNA, and the decrease in proliferation capacity and frequency of IFN-gamma-producing cells. The intrahepatic fraction of CD8(+) T-cells increased during lamivudine withdrawal. In conclusion, IVI was able to transiently stimulate the HBV-specific immune responsiveness of T-cells, but the magnitude of the response was insufficient to cause a beneficial virological effect.

Human hepatic lymph nodes contain normal numbers of mature myeloid dendritic cells but few plasmacytoid dendritic cells.

We investigated whether the hyporesponsiveness of the adaptive arm of the liver immune system is related to the composition of the dendritic cell (DC) population in hepatic lymph nodes. Noninflamed human hepatic lymph nodes (LN) were obtained from multiorgan donors, inflamed hepatic LN from liver transplant recipients with autoimmune cholestatic liver diseases, and inguinal LN from kidney transplant recipients. Quantitative immunohistochemistry showed that all three types of LN contained comparable numbers of mature and immature myeloid DC, but that noninflamed and inflamed hepatic LN contained significantly fewer plasmacytoid DC as compared to inguinal LN. Likewise, DC-enriched cell preparations from hepatic LN contained relatively few plasmacytoid DC. The difference in numbers of plasmacytoid DC was confirmed in comparisons of hepatic LN and ileacal LN from the same organ-donors. Myeloid DC from hepatic LN showed similar expressions of HLA-DR, CD83, and CD86, and higher expression of CD80 compared to myeloid DC from inguinal LN. In conclusion, hepatic LN contain similar numbers of myeloid DC as muscle/skin lymph-draining LN, with no signs of immaturity, but relatively few plasmacytoid DC.

Bronchial carcinoids: a review of 60 patients.

Sixty patients with a bronchial carcinoid underwent surgical treatment. Preoperative fiberoptic bronchoscopy revealed a characteristic pink, smooth, bleeding tumor in 71.4% of the patients with a typical carcinoid and 16.7% of those with an atypical carcinoid (p less than 0.05). Eight pneumonectomies, seven bilobectomies, 34 lobectomies, three lobectomies with bronchoplasty, six bronchotomies with bronchoplasty, and two segmental resections were performed. All patients entered follow-up, and 47 were followed for more than 5 years. Ten-year survival was 89.6% for patients with a typical carcinoid and 60% for those with an atypical carcinoid. Ten-year survival was 88.1% for patients with carcinoids without lymph node involvement. All patients with lymph node involvement died within 5 years. Overall, 5 of the 8 patients having pneumonectomy died of acute cardiorespiratory failure. We conclude that a limited surgical resection with or without bronchoplasty and systematic lymphadenectomy is the procedure of choice in patients with typical carcinoids. On the other hand, atypical carcinoids are comparable to well-differentiated malignancies of the lung. Whenever possible, pneumonectomy should be avoided in favor of bronchial sleeve resection.

Sleeve lobectomy in the treatment of bronchogenic carcinoma.

From 1980 to 1985, 44 sleeve lobectomies were carried out in patients with bronchial cancer. Sixteen patients received preoperative radiotherapy. Perioperative mortality was 6.8%. There were seven anastomotic complications (three fistulae and four stenoses) and two recurrences at the anastomosis. Overall actuarial survival was 45% at four years. These results seem to suggest that sleeve lobectomy should be considered an elective rather than a compromise procedure and a viable alternative to pneumonectomy. Preoperative radiotherapy neither increases complications nor has a negative effect on outcome. It contributes towards reducing local recurrences and maximizes tissue salvage. Long-term survival is related to stage or histology, factors generally governing the survival of lung cancer operated patients, although the TNM classification is ill-suited to identifying tumors which can be resected by a sleeve lobectomy.

Primary pulmonary tumours of neurogenic origin.

Primary intrapulmonary neurogenic tumours are extremely rare. In a series of 1664 patients with pulmonary neoplasms observed during 1967-80 only four such tumours were identified (0.2%). All four patients underwent surgical excision. The histological diagnosis was benign neurilemmoma in three cases and malignant schwannoma in the fourth. The patients with neurilemmoma are alive and well four to 12 years after surgery, but the patient with malignant schwannoma died from metastatic spread of the tumour four months after surgery. No association with von Recklinghausen's disease was observed. Macroscopic and microscopic features generally lead to a correct diagnosis in benign types, but the histological diagnosis of malignant schwannoma may present some difficulties and requires the establishment of a definite origin in a nervous structure, identification of benign neurofibroma in different areas of the same tumour, and a high density of cells with appreciable pleomorphism, with mitosis and atypia. Benign tumours carry a good prognosis with little tendency to recur, but malignant schwannoma has a high invasive tendency and is associated with a low survival rate.