1. Introduction and Overview. 2. Detecting Influential Observations and Outliers. 3. Detecting and Assessing Collinearity. 4. Applications and Remedies. 5. Research Issues and Directions for Extensions. Bibliography. Author Index. Subject Index.

Regression Diagnostics: Identifying Influential Data and Sources of Collinearity

Objective To examine trends in outcomes of patients undergoing resection at a single tertiary care referral center over a 16-year period. Background Data Hepatic resection is considered the treatment of choice in selected patients with colorectal metastasis confined to the liver. Although a variety of retrospective studies have demonstrated improvements in short-term outcomes in recent years, changes in long-term survival over time are less well-established. Methods Data from 226 consecutive patients undergoing potentially curative liver resection for colorectal metastases between 1984 and 1999 were analyzed. Actuarial survival rates related to prognostic determinants were analyzed using the log-rank test. Results The median survival for the entire cohort was 46 months, with 5- and 10-year survival rates of 40% and 26% respectively. Ninety-three patients operated on between 1984 and 1992 were found to have an overall survival of 31% at 5 years, compared to 58% for the 133 patients operated on during the more recent period (1993-1999). Both overall and disease-free survival were significantly better in the recent time period compared with the earlier period on both univariate and multivariate analyses. Other independent factors associated with improved survival included number of metastatic tumors ≤ 3, negative resection margin, and CEA < 100. Comparisons were made between time periods for a variety of patient, tumor and treatment-related factors. Among all parameters studied, only resection type (anatomical versus nonanatomical), use of intraoperative ultrasonography, and perioperative chemotherapy administration differed between the early and recent time periods. Conclusions Long-term survival following liver resection for colorectal metastases has improved significantly in recent years at our institution. Although the reasons for this survival trend are not clear, contributing factors may include the use of newer preoperative and intraoperative imaging, increased use of chemotherapy, and salvage surgical therapy.

Trends in long-term survival following liver resection for hepatic colorectal metastases.

reatment of postoperative pain is provided for humanitarian reasons and to alleviate nocicepT tion-induced responses, such as the endocrine metabolic response to surgery, autonomic reflexes with adverse effects on organ function, reflexes leading to muscle spasm, and other undesirable results (1). During the last decade there has been a virtual explosion in our knowledge of basic pain physiology (2,3), but the implications for clinical practice have been less substantial. The explanation for the discrepancy between the fast progress in basic pain pathophysiology and the rather slow advances in providing optimal postoperative pain treatment may be several, but one important factor may be that more than 95% of the literature on postoperative pain treatment has considered unimodal treatment. We have emphasized previously that total or optimal pain relief allowing normal function can not be achieved by a single drug or method without major strain on equipment and surveillance systems or without significant side effects (4). Therefore, we have recommended combined analgesic regimens (balanced analgesia) or a multimodal approach to the treatment of postoperative pain (4). The rationale for this strategy is achievement of sufficient analgesia due to additive or synergistic effects between different analgesics, with concomitant reduction of side effects, due to resulting lower doses of analgesics and differences in side-effect profiles. We summarize here the existing knowledge concerning the efficacy of analgesic combination therapy from postoperative pain studies. The effects on postoperative outcome are not included, because of lack of sufficient studies. We also exclude obstetric and pediatric pain, which may represent special pain entities and solutions for treatment, although they obviously share many of the problems of general postoperative pain. Primary emphasis will be placed on moderate and severe pain and the use of and need for

The value of "multimodal" or "balanced analgesia" in postoperative pain treatment.

Immunosuppression may contribute to the progression of cancer. In this study we assessed the structural and functional status of T cells from tumor specimens obtained from patients with early stage non-small cell lung cancer and late-stage ovarian cancer. Although some groups have described structural alterations in the TCR in patients with other malignancies, we did not observe decreased expression of the CD3zeta subunit in the tumor-associated T cells. However, increased percentages of CD4(+)CD25(+) T cells were observed in the non-small cell lung cancer tumor-infiltrating lymphocytes and ovarian cancer tumor-associated lymphocytes. Furthermore, these CD4(+)CD25(+) T cells were found to secrete transforming growth factor-beta, consistent with the phenotype of regulatory T cells. Despite a generalized expression of lymphocyte activation markers in the tumor-associated T-cell populations, the CD8(+) T cells expressed low levels of CD25. To determine whether expression of CD25 could be restored on the CD8 cells, tumor-associated T cells were stimulated with anti-CD3 and anti-CD28 monoclonal antibodies. After stimulation, nearly all of the CD8 T cells expressed CD25. Furthermore, despite the low levels of interleukin 2, IFN-gamma, and tumor necrosis factor-alpha secretion by the tumor-associated and peripheral blood T cells at baseline, stimulation with anti-CD3 and anti-CD28 monoclonal antibodies significantly increased the fraction of cells producing these cytokines. Thus, tumor-associated T cells from patients with early and late-stage epithelial tumors contain increased proportions of CD4(+)CD25(+) T cells that secrete the immunosuppressive cytokine transforming growth factor-beta. Furthermore, our results are consistent with previous reports showing impaired expression of CD25 on CD8(+) T cells in cancer patients. Finally, increased lymphocyte costimulation provided by triggering the CD28 receptor is able to increase CD25 expression and cytokine secretion in tumor-associated T cells. These observations provide evidence for the contribution of regulatory T cells to immune dysfunction in cancer patients.

https://cancerres.aacrjournals.org/content/canres/61/12/4766.full.pdf

Regulatory CD4+CD25+ T Cells in Tumors from Patients with Early-Stage Non-Small Cell Lung Cancer and Late-Stage Ovarian Cancer

Objective: To review the literature on the utility of fine-needle aspiration biopsy in the diagnostic management of nodular thyroid disease Data Sources: Relevant articles published in major Engli

Fine-Needle Aspiration Biopsy of the Thyroid: An Appraisal

Objective: To determine the feasibility and efficacy of cryosurgery of breast cancer. Design: In phase 1, carcinogen-induced mammary adenocarcinomas in 13 Sprague-Dawley rats were treated by cryosurgery and were then examined for histopathologic change. In phase 2, transplantable mammary adenocarcinomas in 50 DBA/IJ mice were treated by cryosurgery to determine the effect of varying tumor temperatures, and duration and number of freeze-thaw cycles on tumor viability. In phase 3, 2- to 3-cm ultrasound-monitored cryolesions were formed in the breasts of 4 dogs and 4 sheep. These animals were followed up for procedure-related complications; the histopathologic necrosis of the cryolesions were correlated with the ultrasound images. Based on the results of these experiments, ultrasound-guided cryosurgery of breast cancer was initiated in a human clinical trial. Results: In phase 1, a single, short-term ( Conclusions: In situ breast cryosurgery has been proved to be feasible and efficacious in small and large animal studies and has been successfully performed in 1 patient with breast cancer. The results of this study suggest that ultrasound-guided cryosurgery of breast cancer warrants further investigation. Arch Surg. 1997;132:28-33

https://jamanetwork.com/HttpHandlers/ArticlePdfHandler.ashx?journal=SURG&articleId=596712&pdfFileName=archsurg_132_1_005.pdf

Cryosurgery of Breast Cancer

One-hundred thirty-one primary hepatic resection for colorectal secondary tumors were performed at Rush-Presbyterian-St. Luke's Medical Center between 1975 and 1993. Perioperative mortality occurred in five patients (3.8%). Twenty-three patients had minor morbidities (18%); major morbidity occurred only in the five patients who died. Curative resections were performed in 107 patients. Overall actuarial survival at 2, 3, and 5 years was 62, 42, and 25 per cent, respectively. Patients with extrahepatic disease (5-year survival, 0% vs 27%; P = 0.049) and positive resection margins (0% vs 30%; P < 0.001) had significantly poorer survival. Among the curative resections, patients who had metachronous hepatic resections did significantly better than those who underwent synchronous colon and hepatic resections (35% vs 13%; P = 0.002). This survival benefit persisted when comparison was restricted to patients with synchronous metastases. Age, sex, race, number of lesions, site of colon primary resection, blood transfusion, disease-free interval, and extent of resection had no effect on survival. All patients who are acceptable surgical risks with potentially resectable metastatic colorectal cancer confined to the liver should undergo exploration. Assessment of resectability should include intraoperative ultrasound in all patients to maximize the probability of tumor clearance.

Edgar D. Staren

Papers

Cryosurgery of Breast Cancer

Hepatic resection for metastatic colorectal cancer

Continuous thoracic epidural analgesia for postoperative pain relief following thoracotomy: a randomized prospective study.

Continuous epidural infusion for analgesia after major abdominal operations: a randomized, prospective, double-blind study.

Neuroendocrine carcinomas of the colon and rectum: a clinicopathologic evaluation.