The role of cytotoxic T-lymphocytes in the prevention and immune surveillance of tumors— lessons from normal and immunodeficient mice

The idea of immunological surveillance against cancer has existed for nearly 100 years but as no conclusive evidence has yet been published the importance of the cellular immune defense in the detection and removal of incipient or existing tumors is still a hotly debated subject. However, in order to select a relevant immunotherapeutic strategy in the treatment of cancer, a fundamental understanding of the basic immunologic conditions under which a tumor develops and exists is a prerequisite. Therefore, a murine model was set up that we hoped would enable us to confirm or reject the theory of immunological surveillance. A large panel of methylcholanthrene induced tumors was established in T-cell immunodeficient nude mice and congenic normal mice to study the influence of the immune system on developing tumors. As nude mice developed tumors fastest and with the highest incidence, we concluded that in this model the immune system constituted a 'tumor-suppressive factor' delaying and sometimes abrogating tumor growth, i.e. performing immune surveillance. Immunogenicity of the tumors was assessed by transplantation back to normal histocompatible mice. Tumors originating from the immunodeficient nude mice turned out to be far more immunogenic than tumors from normal mice, resulting in a high rejection rate. CD8+ cytotoxic T cells were found to be indispensable for this rejection, leading to the conclusion that the cytotoxic T cells perform immune selection in normal mice, eliminating immunogenic tumor cell variants in the incipient tumor. In this review, we discuss the difficulties facing immunotherapy when conclusions are drawn from the presented observations and hypotheses.     

Granulomatous mastitis: a report of seven cases

The clinical history and histological features of seven cases of granulomatous mastitis are presented. The lesion occurs in young parous women as a tender extra-areolar breast lump. Histologically, non-caseating discrete granulomas are present, confined to breast lobules with, in three cases, coalescence of the granulomas and microabscess formation. Pathogenesis of the changes is discussed. It is thought that granulomatous mastitis is an entity morphologically distinct from duct ectasia/plasma cell mastitis and the commoner forms of granulomatous breast diseases.     

Isolated Roux loop pancreaticojejunostomy versus pancreaticogastrostomy after pancreaticoduodenectomy: a prospective randomized study

Objectives

The optimal strategy for the reconstruction of the pancreas following pancreaticoduodenectomy (PD) is still debated. The aim of this study was to compare the outcomes of isolated Roux loop pancreaticojejunostomy (IRPJ) with those of pancreaticogastrostomy (PG) after PD.

Methods

Consecutive patients submitted to PD were randomized to either method of reconstruction. The primary outcome measure was the rate of postoperative pancreatic fistula (POPF). Secondary outcomes included operative time, day to resumption of oral feeding, postoperative morbidity and mortality, and exocrine and endocrine pancreatic functions.

Results

Ninety patients treated by PD were included in the study. The median total operative time was significantly longer in the IRPJ group (320 min versus 300 min; P = 0.047). Postoperative pancreatic fistula developed in nine of 45 patients in the IRPJ group and 10 of 45 patients in the PG group (P = 0.796). Seven IRPJ patients and four PG patients had POPF of type B or C (P = 0.710). Time to resumption of oral feeding was shorter in the IRPJ group (P = 0.03). Steatorrhea at 1 year was reported in nine of 42 IRPJ patients and 18 of 41 PG patients (P = 0.029). Albumin levels at 1 year were 3.6 g/dl in the IRPJ group and 3.3 g/dl in the PG group (P = 0.001).

Conclusions

Isolated Roux loop PJ was not associated with a lower rate of POPF, but was associated with a decrease in the incidence of postoperative steatorrhea. The technique allowed for early oral feeding and the maintenance of oral feeding even if POPF developed.     

Unique situation of hepatocellular carcinoma in Egypt: A review of epidemiology and control measures

Hepatocellular carcinoma (HCC) is the sixth most common primary malignancy worldwide, and the third most common cause of death among cancers worldwide. HCC occurs in several pre-existing conditions, including hepatitis C, hepatitis B virus, and non-alcoholic cirrhosis. Egypt used to be the country with the heaviest hepatitis C virus (HCV) burden. The relationship between HCV and HCC is an important research area. In Egypt, HCC is a significant public health problem. A possible cause for the increasing rates of detection of HCC in Egypt is the mass screening program that was carried by the government for detecting and treating HCV. A multidisciplinary approach is now widely applied to HCC management in health centers all over Egypt. Different treatment modalities are available in Egypt, with success rates comparable to global rates. The Egyptian health authorities have made the elimination of HCV from Egypt a special priority, and this approach should lead to a decrease in number of HCC cases in the near future. In this article we review the current situation of HCC in Egypt, including epidemiological aspects, relevant risk factors for HCC development, strategies, and efforts established by health authorities for the screening and prevention of both HCV and HCC in Egypt. We highlight the different modalities for HCC treatment.     

Pulmonary metastatectomy for soft tissue sarcomas: is it valuable?

BACKGROUND: A retrospective study and analysis was performed to determine the value and benefit of pulmonary metastatectomy for soft tissue sarcomas, and which factors predict prognosis following resection. METHODS: Twenty-three patients underwent resections for pulmonary metastases from a soft tissue sarcoma (STS) at King Faisal Specialist Hospital and Research Center (KFSH&RC), between January 1985 and December 1998. There were 11 male and 12 female patients. Thirteen of 23 patients (57%) had one to three metastases, and 10 (43%) had four or more metastases. A total of 41 thoracic explorations was performed for the 23 evaluable patients. Median sternotomy was used only for three patients and lateral thoracotomy was used for 20 patients as an initial surgical approach. Pulmonary resections performed included one or more wedge resections (n=16), segmentectomy (n=5), and lobectomy (n=2). No one in this series underwent pneumonectomy. The number of resected metastatic nodules ranged from one-six with average three. Eight patients (35%) received various kinds of postoperative adjuvant chemotherapy. RESULTS: The overall and disease-free survival rate post-metastatectomy at five years was 24% and 21%, respectively. Various prognostic indicators were examined to evaluate their association with improved survival. Age, sex localization of the primary site and histologic type, tumor grade, size of the resected nodules, laterality (unilateral or bilateral), types of resection, adjuvant chemotherapy, and local recurrence did not significantly affect survival. However, patient with disease free interval >6 months, and those with three or fewer metastases showed a trend toward a higher five-year overall survival (p=0.06, 0.07, respectively). CONCLUSIONS: Surgical excision of lung metastases from soft tissue sarcomas is well accepted and should be considered as a first line of treatment if preoperative evaluation indicated that complete resection of the metastases is possible. Further investigation is needed before chemotherapy can be recommended as additional therapy.     

Thyroid dysfunction after mantle irradiation of Hodgkin's disease patients

Thyroid dysfunction can develop in patients with Hodgkin's disease who are treated with mantle irradiation. During the period 1970-89, the records of 320 patients who received mantle irradiation and who had thyroid function tests (TFT) were retrospectively reviewed. The median age was 30 years (range, 7-69 years). The median mantle and thyroid dose was 36 Gy (range, 30-40 Gy) and 39.8 Gy (range, 32-65 Gy), respectively. Overall thyroid dysfunction was present in 39% of the patients. Clinical hypothyroidism was seen in 10% and biochemical hypothyroidism was noted in 25%. Hyperthyroidism was found in 4% of patients. Thyroid nodules had developed in six patients (2%), of which those in four patients were malignant. Age, sex, histological subtype, stage of disease, dose, lymphangiogram and treatment with chemotherapy were not significant factors in the development of thyroid dysfunction. The narrow dose range prevented adequate analysis of dose effect. The results indicate that the incidence of thyroid abnormalities is high enough to warrant regular TFT assessment with pre-irradiation levels and follow-up testing for life because the development of abnormalities can occur many years later. Thyroid examination should form part of the routine follow-up examination and any abnormality should be promptly investigated.     

Tumor vascular signals in renal masses: detection with Doppler US

The vascularity of 49 renal masses (26 malignant and 23 benign lesions) was investigated with duplex Doppler ultrasound. Doppler signals obtained at the margins of renal masses were defined as "tumor signals" when the Doppler-shifted frequency of the lesion exceeded the frequency shift in the ipsilateral main renal artery. These exceeded 2.5 kHz with a 3-MHz insonating frequency. Among the 26 renal masses that subsequently proved to be malignant, tumor signals were obtained in 15 of 18 (83%) untreated renal cell carcinomas, in three of four Wilms tumors, and in two patients with metastases to the kidney, but not in the one patient with lymphoma. None of the 23 benign renal masses demonstrated tumor signals. Tumor vascularity in malignant lesions gives rise to abnormal, high-velocity, Doppler-shifted signals that can help in the differential diagnosis of renal masses.     

Initial experience of the High-Density Grid catheter in patients undergoing catheter ablation for atrial fibrillation

Purpose

A significant proportion of patients undergoing catheter ablation for atrial fibrillation (AF) experience arrhythmia recurrence. This is mostly due to pulmonary vein reconnection (PVR). Whether mapping using High-Density Wave (HDW) technology is superior to standard bipolar (SB) configuration at detecting PVR is unknown. We aimed to evaluate the efficacy of HDW technology compared to SB mapping in identifying PVR.

Methods

High-Density (HD) multipolar Grid catheters were used to create left atrial geometries and voltage maps in 36 patients undergoing catheter ablation for AF (either due to recurrence of an atrial arrhythmia from previous AF ablation or de novo AF ablation). Nineteen SB maps were also created and compared. Ablation was performed until pulmonary vein isolation was achieved.

Results

Median time of mapping with HDW was 22.3 [IQR: 8.2] min. The number of points collected with HDW (13299.6±1362.8 vs 6952.8±841.9, p<0.001) and used (2337.3±158.0 vs 1727.5±163.8, p<0.001) was significantly higher compared to SB. Moreover, HDW was able to identify more sleeves (16 for right and 8 for left veins), where these were confirmed electrically silent by SB, with significantly increased PVR sleeve size as identified by HDW (p<0.001 for both right and left veins). Importantly, with the use of HDW, the ablation strategy changed in 23 patients (64% of targeted veins) with a significantly increased number of lesions required as compared to SB for right (p=0.005) and left veins (p=0.003).

Conclusion

HDW technology is superior to SB in detecting pulmonary vein reconnections. This could potentially result into a significant change in ablation strategy and possibly to increased success rate following pulmonary vein isolation.

     

Addition of dextrose 3.5% to intrathecal sufentanil for labour analgesia reduces pruritus

PURPOSE: To determine whether the addition of a low concentration (3.5%) of dextrose would minimize pruritus while maintaining the quality of analgesia. METHODS: In a double blind study 48 parturients in early labour were randomized to one of two study groups: dextrose (Dex, n = 24; 10 microg sufentanil in dextrose 3.5%), or normal saline (NS, n = 24; 10 microg sufentanil in normal saline). Parturients received the study drug as the intrathecal injection of the combined spinal-epidural (CSE) technique for labour analgesia. Duration and degree of analgesia were measured until epidural analgesia was initiated or delivery of the baby. The intensity and distribution (above T6, T6-L1, and below L1) of pruritus were measured at five minute intervals during first 25 min after injection. RESULTS: Quality and duration of analgesia did not differ between groups, but the overall incidence of pruritus was less in the Dex group (88% vs 42%, P = 0.001). Within each region, the incidence of pruritus was less in the Dex group. In patients who had pruritus, for the Dex group, the incidence of pruritus in the upper region (>T6) was lower than the NS group. There was no difference in the lower regions. CONCLUSION: The addition of dextrose 3.5% to intrathecal sufentanil reduced the incidence of pruritus without affecting the duration or quality of analgesia in parturients in early labour. The distribution of pruritus in the Dex group was limited to below T6 suggesting that pruritus to intrathecal sufentanil is mediated at the spinal level.