Drug or radiation changes to the host which could affect the outcome of combined modality therapy.

In this review, the various ways are examined by which combined modality regimens can affect the host in such a manner as to modify the outcome of the therapy. These host changes are considered under the general headings of effects on (1) drug pharmacokinetics, (2) vasculature, (3) the specific immune response, (4) non-specific host defenses, particularly those mediated by macrophages, (5) general host condition, and (6) a miscellaneous category including local infection and drug-stimulated recovery of surviving cells.Where appropriate, the relative influence is examined of each of these host effects on the commonly used endpoints for assay of tumor response. In general, the assays most likely to be affected are those in which the tumor remains in situ after treatment (tumor cure, regrowth delay, and, the most limited endpoint, increase in lifespan). However, assays for cell survival by removal of the tumor soon after treatment are not entirely free from possible host effects.A possible outcome of several different host effects is a change in the metastatic frequency of the tumor. This may have little or no effect on the “therapeutic ratio” judged in terms of local effect, but could have a large influence of the overall efficacy of a particular regimen.Since host effects are likely to be rather specific to the particular model system employed, they usually represent an unwanted side-effect of the treatment which may interfere with, or alter, interpretations of the experimental data. For this reason a list of precautions in the selection and use of experimental systems is given in the results. These include measurement of tumor drug levels, use of non-immunogenic tumor/host models, and the avoidance of stress, excessive weight loss, local infection, and the use of anesthetics for animal immobilization.     

Clinical activity of sorafenib and sunitinib in renal cell carcinoma refractory to previous vascular endothelial growth factor-targeted therapy: two case reports

Sunitinib and sorafenib are multitargeted receptor tyrosine kinase inhibitors of the vascular endothelial growth factor and platelet-derived growth factor receptor families with antiangiogenic and antitumor activity in metastatic renal cell carcinoma. The utility of these agents in patients refractory to previous treatment with the other agent is unknown. We report 2 cases highlighting that efficacy of these agents is possible after failure of the other agent. Further prospective study is needed.     

The Distribution of Bone Metastases as Shown on Isotope Scanning: Proposed Modes of Spread

Bone metastases may result from arterial, retrograde venous or direct spread. Three groups of patients; with carcinoma of lung, carcinoma of breast and carcinoma of prostate, each of approximately 50 individuals were studied to examine patterns of spread in order to relate this to the mechanism of seeding. Statistically significant differences (p < 0.05) were observed in early bone spread in carcinoma of prostate (absence of skull involvement), carcinoma of lung (presences of posterior chest wall involvement) and carcinoma of breast (presence of anterior chest wall involvement). The results support retrograde venous reflux as being an important contributing mode of spread for carcinoma of prostate and local spread as being relevant in the early spread of carcinoma of lung and breast.     

Differentiated thyroid cancer in children and adolescents

Introduction: There have been only a few studies on differentiated childhood thyroid cancer (DTC) in children and adolescents. Methods: We analyzed the characteristics of DTC with respect to age, gender and histology in 114 patients under 18 years of age. In a questionnaire-based survey, data of 114 patients, aged between 3 years and 18 years, was collected from 65 clinical institutions in Germany. Characteristics of 80 females and 34 males were evaluated, and the prognostic effect of age, gender, histology, multicentric growth, tumor stage and N-status on distant metastases was tested using multivariate discriminant analysis. Between-group comparison was performed using student t-test and chi-squared test. Results: The incidence of DTC in females was higher than in males with a peak of female:male ratio at puberty, which was more pronounced in children with papillary thyroid cancer, but not with follicular thyroid cancer. Papillary thyroid cancer was associated with more advanced disease (P = 0.009), more lymph-node involvement (P = 0.007) and more distant metastases (P = 0.02) compared with follicular thyroid cancer. Multivariate analysis showed advanced tumor stage as the only significant factor (P = 0.02) associating with distant metastasis. Conclusion: It can be concluded that in children and adolescents: 1. The incidence of papillary thyroid cancer is higher in females than males, with a peak at puberty. 2. The only significant factor associated with distant metastases is the advanced tumor stage. 3. Childhood thyroid cancer is frequently associated with lymph-node involvement, distant metastases and advanced tumor stage. 4. Papillary childhood thyroid cancer is more aggressive than follicular type. Received: 31 January 1998     

Radiation therapy in the treatment of metastatic renal cell carcinoma

Adenocarcinoma of the kidney is an unusual tumor, both in its biological behavior and in its response to radiation treatment. Historically, these tumors have been considered to be radioresistant, and the role of radiation therapy remains questionable in the primary management of this disease. However, radiation treatment is routinely used in the palliation of metastatic lesions for relief of symptoms. Therefore we have undertaken a review of our experience in the treatment of this disease to determine the effectiveness of radiation in its palliation. From 1956 to 1981, 125 patients with metastatic lesions from hypernephroma have been treated in the Department of Radiation Therapy at Thomas Jefferson University Hospital. Most patients were referred for relief of bone pain (86), brain metastasis (12), spinal cord compression (9), and soft tissue masses (18). Total doses varied from 2000 rad to a maximum of 6000 rad. Response to treatment was evaluated on the basis of relief of symptoms, either complete, partial or no change. Our results indicate a significantly higher response rate of 65% for total doses equal to or greater than a TDF of 70, as compared to 25% for doses lower than a TDF of 70. No difference in response was observed either for bone or soft tissue metastasis or visceral disease. This leads us to believe that metastatic lesions from adenocarcinomas of the kidney should be treated to higher doses to obtain maximum response rates. Analysis of these results are presented in detail.     

The Wnt/β-catenin pathway drives increased cyclin D1 levels in lymph node metastasis in papillary thyroid cancer

We examined the expression of cyclin D1 in conjunction with β-catenin and the phosphorylated inactive form of glycogen synthase kinase 3β (GSK-3β) in benign, nonneoplastic thyroid tissue as well as papillary thyroid carcinoma primary tumors and nodal metastases. We aim to unravel the regulation of cyclin D1 and determine if this cell cycle protein is a useful biomarker for metastatic disease. It is clear that expression of cyclin D1 (P < .0001), β-catenin (P < .0001), and inactive form of GSK-3β (P < .0001) are significantly higher in papillary thyroid carcinoma primary tumors than in corresponding benign, nonneoplastic tissue thyroid specimens. Interestingly, β-catenin and cyclin D1 expressions in papillary thyroid carcinoma are correlated (P = .025), implying that β-catenin is a factor driving higher levels of cyclin D1 consistent with previous cell models linking Wnt/β-catenin signaling and cyclin D1 expression. Conversely, inactive form of GSK-3β expression does not correlate with cyclin D1 (P = .52) or β-catenin expression (P = .54). We also did not observe any relationship between tumor size and marker expression. Comparing papillary thyroid carcinoma primary tumors with or without nodal metastases, we did not see any differences in expression of inactive form of GSK-3β (P = .95), β-catenin (P = .14), or cyclin D1 (P = .46). However, in papillary thyroid carcinoma lymph node specimens, the up-regulation of cyclin D1 (P = .0083) was highly significant compared with primary tumors. pGSK-3β and β-catenin expression did not vary between primary tumors and nodal specimens. In conclusion, we have demonstrated that expression of cyclin D1 is linked to nodal metastases and that cyclin D1 levels are regulated by Wnt/β-catenin signaling. GSK pathway-mediated regulation of β-catenin or cyclin D1 expression does not appear operative in papillary thyroid carcinoma.     

Ileocolic intussusception due to intestinal metastatic melanoma. Case report and review of the literature

The small intestine is a frequent site of melanoma metastases and the most common cause of secondary intestinal tumors. Even though, its presentation with intestinal obstruction due to intussusception is very rare. We present a 47-year-old woman with a medical history of facial melanoma operated 17 years ago and recently diagnosed of cervical recurrence who complained of abdominal pain of one week duration accompanied with vomiting and abdominal distension. Computed tomography (CT) scan revealed marked distension of the small intestine with features suggesting intussusception of the distal ileum. At laparoscopic exploration a massive ileocolic intussusception was found with invagination of the last 60 cm of ileum inside the cecum and ascending colon. Surgical reduction revealed a tumor of approximately 2 cm in the distal end of the intussuscepted intestine acting as the lead point. Resection of non-viable ileum along with the tumor and end-to-end anastomosis was performed. Many other lesions of smaller size were found distantly in the proximal small bowel but were not treated. The patient had a full recovery and was discharged three days after surgery. Pathological examination showed metastatic melanoma and a positron emission tomography (PET) scan confirmed disseminated disease with brain metastasis. The patient died three months after surgery. Intestinal occlusion due to metastatic disease is a rare condition but should be taken into account particularly in patients with history of cancer. Surgical intervention with a mini-invasive laparoscopic approach is feasible. Intestinal resection and anastomosis is mandatory for either curative or palliative intentions providing a satisfactory treatment.     

Laparoscopic Adrenalectomy for Isolated Adrenal Metastasis

Background Use of laparoscopy for isolated adrenal metastases is controversial. The aims of this study were to characterize patients with isolated adrenal metastases; compare operative characteristics of the laparoscopic adrenalectomy (LA) versus open adrenalectomy (OA) approach; and compare long-term oncological and surgical outcomes. Methods Our adrenal resection database (1995–2006) identified 63 OA and 31 LA cases done for isolated adrenal metastases. Subset analysis was performed for all patients from isolated lung metastases (n = 39) and for all tumors smaller than 4.5 cm (n = 49). Results Overall, local recurrence was 17%, median survival 30 months and 5-year estimated survival 31%. The only independent predictor of survival for all (n = 94) was adrenal tumor size less than 4.5 cm (P = 0.01). When comparing LA with OA, no differences in local recurrence, margin status, disease-free interval or overall survival were observed for the entire group, or for patients with metastases only from lung cancer (n = 39) or for those with tumors smaller than 4.5 cm (n = 49). LA provided significantly shorter operative time (175 vs 208 min, P = 0.04), lower estimated blood loss (EBL) (106 vs 749 cc, P < 0.0001), shorter length of hospital stay (2.8 vs 8.0 days, P < 0.0001) and fewer total complications (P < 0.0001). Conclusions LA is equivalent to OA in terms of margin status, local recurrence, disease-free interval and overall survival. LA for metastatic adrenal lesions is safe, with equivalent long-term oncological outcomes providing the additional benefits of a minimally invasive technique. LA can be recommended as an appropriate initial approach for isolated adrenal metastases.     

经皮冷冻治疗结直肠癌肝转移

背景：结直肠癌肝转移的手术切除率低,其他疗法效果亦欠佳。目的：探讨经皮冷冻治疗结直肠癌肝转移的疗效和安全性。方法：于超声或CT引导下,对326例不能手术切除的结直肠癌肝转移患者行经皮冷冻治疗,术后定期随访。结果：326例患者共接受526次经皮冷冻治疗。治疗后3个月,基线CEA水平升高者中77．6％降至正常范围。280例接受CT随访者中,冷冻病灶完全反应（CR）者14．6％,部分反应（PR）41．1％,稳定（SD）24.3％,进展（PD）20．0％。中位随访期为36食月（7—62个月）,复发率为41．7％。全部病例中位存活期为29个月（3～62个月）。治疗后第1、2、3、4、5年存活率分别为78％、62％、41％、34％和23％：肿瘤直径≤3cm、肝右叶肿瘤、冷冻前CEA≤10μg／L、冷冻后原先升高的CEA降至正常、冷冻治疗2～3次和冷冻后行经导管肝动脉化学栓塞（TACE）治疗者存活率较高。严重并发症发生率为5．2％。结论：经皮冷冻治疗结直肠癌肝转移安全、有效,可作为肿瘤不能手术切除者的替代治疗手段。     

Assessment of epidermal growth factor receptor (EGFR) expression in primary colorectal carcinomas and their related metastases on tissue sections and tissue microarray

Metastatic colorectal carcinomas (CRC) resistant to chemotherapy may benefit from targeting monoclonal therapy cetuximab when they express the epidermal growth factor receptor (EGFR). Because of its clinical implications, we studied EGFR expression by immunohistochemistry on tissue sections of primary CRC (n=32) and their related metastases (n=53). A tissue microarray (TMA) was generated from the same paraffin blocks to determine whether this technique could be used for EGFR screening in CRC. On tissue sections, 84% of the primary CRC and 94% of the metastases were EGFR-positive. When matched, they showed a concordant EGFR-positive status in 78% of the cases. Moreover, staining intensity and extent of EGFR-positive cells in the primary CRC correlated with those observed in the synchronous metastases. On TMA, 65% of the primary CRC, 66% of the metastases, and 43% of the matched primary CRC metastases were EGFR-positive. There was no concordant EGFR status between the primary and the metastatic sites. A strong discrepancy of EGFR status was noted between TMA and tissue sections. In conclusion, EGFR expression measured in tissue sections from primary CRC and their related metastases was found to be similar and frequent, but it was significantly underestimated by the TMA technique.