Association between changes in quality of life scores and survival in non-small cell lung cancer patients.

In patients with advanced cancer, quality of life is as meaningful to patients as the actual length of life. We investigated whether changes in quality of life could predict survival in non-small cell lung cancer. Quality of life was evaluated using EORTC QLQ-C30 (European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire). Cox regression evaluated the prognostic significance of baseline, 3-month and changes in quality of life scores after adjusting for age, gender, treatment history and stage. Two hundred and seventeen patients were men and 213 women. One hundred and fifty-nine patients had stage III while 271 had stage IV disease. Baseline quality of life scales predictive of survival upon multivariate analysis were physical (hazard ratio, 0.90; 95% confidence interval, 0.81-0.98; P= 0.02) and global (hazard ratio, 0.92; 95% confidence interval, 0.87-0.96; P < 0.001). On multivariate analysis, no change variables were significantly predictive of survival. However, in stage IV patients, change in physical function over a period of 3 months showed marginal significance such that every 10-point increase in physical function change score was associated with an 8% decreased risk of death. These findings should be used in clinical practice to systematically address quality of life-related problems of lung cancer patients throughout their treatment course.

Surgical educator preferences regarding key objective structured clinical examination topics.

BACKGROUND: Numerous methods are used for assessing the performance of surgical residents and students. Unfortunately, these same methods are often unsatisfactory. One technique that is gaining increased favor is the Objective Structured Clinical Examination (OSCE). It is unclear what areas of evaluation might best be included in such an examination so as to optimize its value. Therefore, this study evaluated the opinions of an international body of surgical educators. METHODS: A survey was distributed to 674 attending surgical educators; it asked respondents to select and rank the five most important topics from four areas. These areas included 84 topics from History Taking, Physical Examination, Data Interpretation, and Surgical Technique. A weighted score was calculated for each topic by assigning points according to a Likert scale ranking. RESULTS: Among 674 surveys distributed, 243 responses (36.1%) were received; 25 of the 243 responses were excluded, for a usable response rate of 218/674 (32.3%). The five highest ranked topics were (History Taking) "abdominal pain" 29.2%, "breast mass" 10.8%, "gastrointestinal bleeding" 8.5%, "bowel obstruction" 8.5%, "trauma" 7.2%; (Physical Examination) "acute abdomen" 28.9%, "trauma survey" 18.2%, "breast examination" 15.8%, "peripheral vascular" 8.9%, "cardiopulmonary" 7.5%; (Data Interpretation) "chest X ray" 21%, "abdominal series" 20.2%, "CT scan" 19.6%, "mammogram" 10.1%, "cervical spine films" 5.2%; and (Surgical Technique) "central line" 16.1%, "basic suture skills" 14.2%, "bowel anastomosis" 8.0%, "informed consent" 7.9%, "intubation" 6.4%. CONCLUSION: This survey offers useful data regarding those skills viewed as most important by experienced surgical educators, and offers guidelines for composition of surgical OSCEs.

Mechanisms of taxotere-related drug resistance in pancreatic carcinoma.

BACKGROUND: Pancreatic adenocarcinoma (PAC) is generally refractory to most chemotherapeutic agents, including docetaxel (Taxotere; TXT). Specific mechanisms for TXT-related drug resistance in PAC have not been defined. The hypothesis of this study was that PAC resistance to TXT is primarily related to P-glycoprotein (P-gp), the expression product of multiple drug resistance (MDR)-1, as opposed to lung resistance protein (LRP) or multidrug resistance protein (MRP). MATERIALS AND METHODS: The sensitivity of the PAC cell line SUIT-2 and its sublines to TXT, doxorubicin (DOX) and 5-fluorouracil (5-FU) was evaluated with a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay. MDR1 (P-gp), MRP, LRP, and beta-tubulin isotype gene expressions were detected at the messenger RNA level by reverse transcription-polymerase chain reaction (RT-PCR). Verapamil and indomethacin (IMC) were used to test the functionality of P-gp and MRP, respectively. RESULTS: The SUIT-2 subline S-020 and the TXT-selected SUIT-2 cell line S2/TXT were significantly resistant to TXT. Both showed cross-resistance to DOX but no resistance to 5-FU. RT-PCR demonstrated strong expression of P-gp in S-020 and S2/TXT and weaker or no expression in other cells lines. MRP and LRP expression was found in most of these cell lines but had no relationship to the TXT resistance. TXT resistance in S2-020 and S2/TXT could be reversed by verapamil but not by IMC. Levels of beta-tubulin isotype II and III were increased in S2/TXT compared with S-020 and SUIT-2. CONCLUSIONS: Intrinsic and acquired TXT resistance is primarily mediated by P-gp, but not by MRP or LRP, and is markedly reversed by the P-gp modulator verapamil. Hence future related studies should focus on the use of agents that block the transporter action of P-gp.

Invasiveness and MMP expression in pancreatic carcinoma.

BACKGROUND: Previous investigations have suggested that expression of matrix metalloproteinases (MMPs) may be related to increased invasiveness of various tumors. This study evaluated a possible relation between pancreatic tumor cell invasiveness and MMPs. METHODS: A Matrigel invasion assay was performed with pancreatic tumor cell line SUIT-2 and its sublines S2-007, S2-013, S2-020, and S2-028. The degree of invasiveness of stimulated and unstimulated cell lines was correlated with MMP gene expression measured by RT-PCR and MMP protein product measured by gelatin zymography. Cell lines were stimulated by 12-O-tetradecanoylphorbol-13-acetate (TPA), concanavalin (Con-A), and polymerized collagen type I gel (Vitrogen). RESULTS: For SUIT-2, S2-007, S2-013, S2-020, and S2-028, 3.2, 1.0, 4.1, 6.4, and 0.4%, respectively, of the cells invaded the Matrigel membrane. TPA, Con-A, and Vitrogen resulted in the up-regulation of MMP-2 in S2-020. TPA and Vitrogen resulted in up-regulation of MMP-9 in each of the cell lines, while Con-A could up-regulate MMP-9 expression only in SUIT-2. There was no constitutive expression of either MMP-2 or MMP-9 in SUIT-2 or its sublines. There was a positive relationship between Matrigel invasiveness and up-regulation of MMP-2 and MMP-9 expression. CONCLUSION: These data suggest that, while MMP-2 and MMP-9 are not constitutively expressed in pancreatic carcinoma cell lines, they may be up-regulated by TPA, Con-A, and Vitrogen. Since MMP-2 and MMP-9 expression correlated with degree of tumor cell invasiveness, the ability to up-regulate MMP-2 and MMP-9 expression may play a role in facilitating pancreatic tumor cell invasion.

Objective Structured Clinical Examination technical skill stations correlate more closely with postgraduate year level than do clinical skill stations.

Validity of an examination format is supported by its ability to distinguish levels of training among examinees. The Objective Structured Clinical Examination (OSCE) is a developing format generally composed of various types of task-oriented stations used to evaluate clinical skills of students and residents. The ideal composition of OSCE stations to maximize validity has not been determined. We examined the relative correlation between selected types of stations and level of resident postgraduate year (PGY). A 12-station OSCE was administered to surgical residents of all PGY levels at a university program. Individual station scores were correlated with PGY level. The overall correlation of the total examination score with PGY level was good (R = 0.681). Technical skill stations exhibited a significantly greater correlation with PGY level (0.679 vs 0.203) as compared with clinical skill stations (P < 0.05). These data suggest that technical skill evaluation is more sensitive in distinguishing level of training of surgical residents than is clinical skill evaluation.

Diagnostic and interventional ultrasound for breast disease.

The availability of reliable, portable computer-enhanced ultrasonography with high-frequency transducers has improved breast ultrasonography such that its role has increased dramatically. Diagnostic characteristics of breast lesions may be used to categorize these lesions according to their relative risk for malignancy. Furthermore, breast ultrasonography may be used to guide needle aspiration and biopsy of lesions so indicated by diagnostic evaluation. Results of ultrasound-guided aspiration and core biopsy accurately diagnose specific histopathology thereby avoiding unnecessary open biopsy for benign lesions and facilitating therapeutic planning for malignant lesions.

Cytokine biosynthesis by tumor-infiltrating T lymphocytes from human non-small-cell lung carcinoma.

PURPOSE: The purpose of this work was to assess the capacity of tumor-infiltrating leukocytes (TIL) from human non-small-cell lung carcinoma (NSCLC) specimens to synthesize type-1 and type-2 cytokines. METHODS: TIL were isolated from tumors following digestion with collagenase/DNase and further enriched by ficoll-hypaque gradient centrifugation. Membrane phenotypes and intracellular cytokine protein expression of TIL were assessed by flow cytometry. RESULTS: The majority of TIL expressed the CD3 antigen with a CD4:CD8 ratio of approximately 2:1. Other leukocytes such as macrophages (CD14), B lymphocytes (CD20), and natural killer (NK) cells (CD56) were also found to infiltrate the tumors, but in significantly lower numbers. Owing to the limited recovery of non-CD3(+) leukocytes, our analysis of cytokine biosynthesis has focused on T lymphocytes. In the absence of activation, a small percentage of CD3(+) TIL synthesized cytokines ( <4%). Following activation with anti-CD3+interleukin-2 (IL-2), CD3(+) TIL synthesized predominantly a type-1 cytokine profile; however, the type-2 cytokines, IL-6 and IL-10, were also detected in a small percentage of infiltrating cells. Following activation with phorbol 12-myristate 13-acetate + ionomycin, CD3(+) TIL also expressed more type-1 than type-2 cytokines and in significantly greater numbers of cells. The CD3(+)CD8(+) component of the TIL synthesized only type-1 cytokines, whereas the CD3(+)CD4(+) component synthesized both type-1 and type-2 cytokines. CONCLUSION: These results show that the majority of the TIL isolated from NSCLC specimens are T lymphocytes with the capacity to synthesize type-1 cytokines.

Ultrasound-guided needle biopsy of the breast.

BACKGROUND: To determine the role of office-based ultrasound in the early clinical evaluation of breast masses, a consecutive series of diagnostic and interventional breast ultrasounds performed in the surgeon's office were prospectively studied. METHODS: A series of 1028 diagnostic ultrasounds were performed in 662 patients over 2 years. The clinical-pathologic data from those patients undergoing ultrasound-guided fine-needle aspiration biopsy (FNAB; n = 267 patients) and/or core needle biopsy (CNB; n = 210 patients) were reviewed. RESULTS: Of the 267 patients undergoing initial FNAB, 179 cysts were identified; 25 patients underwent no additional intervention, and 63 patients with apparently solid lesions underwent subsequent CNB. Core needle biopsy was the initial interventional approach in 147 cases. Of the 210 total patients in whom a CNB was performed, needle biopsy pathologic findings included:fibroadenoma, 57 patients; fibrocystic breast change, 82 patients; carcinoma, 53 patients; abscess/cyst, 12 patients; and other, 6 patients. Operative excision was performed in 106 of these 210 patients. There was a significantly higher false-negative rate among those patients who underwent an initial FNAB (20%; 2/10 patients) as compared with those patients undergoing CNB (3.6%; 2/55 patients; P < . 05). No cancers have been identified in those patients undergoing a benign CNB and followed for 6 to 30 months (median, 18 months). CONCLUSION: Office-based diagnostic ultrasound and interventional ultrasound that uses core needle biopsy is an effective adjunct to the early clinical evaluation of breast masses.

Use of ultrasound-guided fine needle aspiration biopsy in the management of thyroid disease.

Fine-needle aspiration biopsy (FNAB) of thyroid nodules has resulted in fewer patients needing thyroidectomy. Nondiagnostic FNAB specimens may require surgery for diagnosis. Ultrasound can help decrease nondiagnostic biopsies by visualizing lesions and guiding biopsy needles. Between 1996 and 1997, 76 patients had ultrasound-guided needle biopsies of thyroid nodules. Sixteen patients had clearly palpable nodules, whereas 19 were described as difficult to palpate. There were 32 patients who presented with either prominent thyroids or enlarged lobes. Six patients presented only with nonspecific symptoms, and 3 had nodules discovered incidentally on imaging studies. Biopsies were diagnostic in 73 of 76 (96%) patients. This varied with the size of the nodule, with the rate of nondiagnostic biopsies being 13 per cent in lesions <1.0 cm and 3 per cent in lesions >2.0 cm. Fifteen patients had surgery based on the FNAB, with a surgical yield of malignancy of 47 per cent. Ultrasound-guided FNAB is extremely useful in evaluating thyroid lesions that are difficult to palpate or nonpalpable, as well as the remainder of the gland and surrounding structures. The use of ultrasound guidance in performing FNAB results in a low rate of nondiagnostic biopsies, which may decrease the number of unnecessary thyroidectomies performed to rule out malignancy.

Functional analysis of tumor-infiltrating leukocytes in breast cancer patients.

BACKGROUND: The immune system is capable of responding to cancer as evidenced by systemic, regional, and intratumoral leukocyte activation. For individual patients there is no predictable relationship between leukocyte composition, or function, and the prognosis of the disease. MATERIALS AND METHODS: Leukocytes from tumor tissues (TIL, n = 17), axillary lymph nodes (LNL, n = 26), and peripheral blood (PBL, n = 25) of human breast cancer patients were evaluated for the ability to synthesize type 1 cytokines (TNF alpha, IFN gamma, and IL-2) and type 2 cytokines (IL-4, IL-6, and IL-10) by flow cytometry. The capacity of these cells to mediate in vitro cytotoxicity against the ZR 75-1 breast cancer cell line was simultaneously evaluated. RESULTS: To cells (CD3+) were the major leukocyte population detected in each tissue with CD4+ cells being predominant in TIL, LNL, and PBL. Type 1 cytokines were the predominant type produced by stimulated T cells for each population with a statistically greater proportion of IFN gamma + T cells in TIL as compared with LNL and PBL (P = 0.013 and 0.04, respectively). However, LNL and PBL had a significantly greater proportion of IL2+ T cells as compared with TIL from the same patient (P = 0.02 and 0.01, respectively). The tumoricidal function could be stimulated with recombinant human IL-2 in each leukocyte population with substantially higher levels of activity being produced in TIL from node-positive as compared with node-negative patients. CONCLUSIONS: This study demonstrates that there are differences in the capacity of leukocytes from different anatomical sites of breast cancer patients to synthesize immunostimulatory cytokines and mediate tumor cell cytotoxicity. Such differences may reflect prognostically distinct subgroups of patients and might also provide a rationale for the development of biological approaches to therapy in selected patients.

Thyroid reoperations: indications and risks.

Thyroid reoperations can be technically difficult and associated with an increased risk of complications. To determine the indications for reoperations and the risk of postoperative complications with these procedures, records of 362 patients undergoing thyroidectomy by a single surgeon (R.A.P.) were reviewed. Thirty-two patients had a reoperation. The group consists of 21 women and 11 men with an average age of 55 years (range, 31-79). Twenty-four patients had 1 prior operation, and 8 patients had 2 or more. We performed 4 of the initial operations, and 28 were done by surgeons at other centers. Fourteen reoperations were done for symptomatic multinodular goiter (MNG), and 5 because of a change in the histologic diagnosis from benign to cancerous. The remainder were for further treatment of malignancy. The most common operation was completion thyroidectomy (31). In 3 patients, either unilateral or bilateral modified radical neck exploration was performed. One patient required median sternotomy. One subtotal thyroidectomy was also performed. Recurrent laryngeal nerve injury occurred in 2 patients. It resolved in 1 patient but was permanent in another, who had 3 operations for MNG. One of the 2 patients with preoperative unilateral vocal cord paralysis had return of function after removal of a substernal goiter. The other had a permanent nerve injury from the original surgery. Three patients had postoperative hypocalcemia (calcium <8.0 mg/dL). This resolved in all patients within 1 to 6 months. One patient who had a third operation for MNG had postoperative hemorrhage necessitating tracheostomy for airway control. Another patient developed a seroma that resolved within 2 months. We conclude that reoperations are indicated for both benign and malignant thyroid disease. Because they carry a higher risk of complications, every effort should be made to avoid them by performing definitive initial treatment.

Breast ultrasound.

Ultrasound of the breast has been demonstrated to be an extremely effective tool in the evaluation of mammographically detected breast lesions. The technique is relatively straightforward and may be learned in a relatively short time by experienced breast clinicians. It is likely that the future care of patients with diseases of the breast will continue to be increasingly dependent on image-guided breast biopsy techniques. Therefore, surgeons would do well to familiarize themselves with this modality. This is likely to streamline patient care, improve cost efficiency, and facilitate therapeutic planning. Finally, the current health care climate is likely to encourage the use of ultrasound of the breast by surgeons.

Myoepithelial hamartoma of the duodenal wall.

A rare case of myoepithelial hamartoma of the duodenal wall is presented, and previous case reports found in the literature are reviewed. Myoepithelial hamartomas are thought to arise from displaced pancreatic anlage present along the gastrointestinal tract during embryogenesis, which can differentiate into various pancreatic elements; the most highly differentiated form is heterotopic pancreas. An alternative theory is pancreatic metaplasia of endodermal tissues. We describe a 41-year-old man who presented with abdominal pain and vomiting. CT scanning revealed a mass at the head of the pancreas. A pancreaticoduodenectomy was performed for presumed cystadenoma. Histology of the mass revealed a disorderly arrangement of smooth muscle, dilated and nondilated ducts, pancreatic acinar tissue and mucus glands. The relationship of myoepithelial hamartomas involving the small bowel to similar lesions in the stomach, bile ducts and gallbladder is discussed.

Breast carcinoma metastases.

With careful selection of patients, complete resection of pulmonary metastases from breast carcinoma may be a useful therapeutic option. Such a treatment appears to offer a significant survival benefit when compared with medical treatment alone, or with incomplete resection.

Intraoperative ultrasound in the management of liver neoplasms.

The purpose of this study was to determine the impact of intraoperative ultrasound (IOUS) on the management of patients with neoplasms of the liver. Fifty-nine patients with liver neoplasms (primary, 6; metastatic, 53) and without pre- or intraoperative evidence of extrahepatic disease underwent laparotomy for possible liver resection. Preoperative imaging studies included external ultrasound (n = 12), magnetic resonance imaging (n = 11), and/or computed tomography (n = 57). Intraoperative evaluation on all patients included inspection, bimanual palpation, and ultrasonography. External ultrasound, magnetic resonance imaging, and computed tomography identified all intraoperatively confirmed liver neoplasms in 33, 45, and 67 per cent of cases, respectively. Unsuspected neoplasms were identified in 12 patients (20%) by inspection/palpation and in 19 patients (32%) by IOUS. In eight patients (14%), the occult neoplasms were identified only IOUS, and in one patient the neoplasms were identified only by inspection/palpation. Occult neoplasms identified by IOUS were characterized by small size (less than 2 cm). Findings from the intraoperative evaluation, such as unsuspected neoplasms and vascular proximity or invasion, altered the preoperative plan in 20 (34%) patients. Inspection, and particularly palpation, identifies a number of preoperatively unsuspected liver neoplasms. Intraoperative ultrasound, however, is the most sensitive method for detection of liver neoplasms and influences the operative management in a substantial number of patients.

Hepatic resection for metastatic colorectal 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.

Effectiveness of the thyroid scan in evaluation of the solitary thyroid nodule.

Solitary, palpable thyroid nodules are common, but only a small percentage are malignant. It is important to evaluate these nodules in a cost-efficient manner that avoids missing a cancer. Historically, radioisotope imaging has played a major role in the workup of thyroid nodules; however, with the advent of fine needle aspiration biopsy (FNAB), this role has become less clear. From 1974 to 1994, 770 patients with a solitary nodule underwent thyroidectomy. Preoperatively, 471 had thyroid scans, and 149 had FNAB. The incidence of carcinoma in nodules excised on the basis of thyroid scan was 23 per cent, whereas the incidence of carcinoma was 37 per cent when FNAB was used (P = 0.003). Fine needle aspiration was a significantly better predictor of malignancy than thyroid scan and resulted in a smaller proportion of excisions for benign nodules. Thyroid scan provided little additional information in those patients who underwent FNAB. Because thyroid scans add little in determining which nodules require surgical excision, they should no longer be a routine part of the evaluation of a solitary thyroid nodule.

Invasive therapy of metastatic colorectal cancer to the liver.

Resection, when possible, is still the best hope for cure of colorectal metastasis to the liver. Poor prognostic indicators for survival include heavy tumor burden, the presence of extrahepatic disease, synchronous metastasis, and the inability to perform resection with a 1-cm margin. Questionable poor prognostic indicators include multiple metastases (more than three), bilobar disease, and the need to transfuse patients during resection. Preoperatively, a patient must be evaluated for the extent of liver disease and the presence of extrahepatic disease with a CT of the abdomen and routine studies of the chest. Intraoperatively, a surgeon should be able to perform or obtain ultrasonography of the liver to detect occult metastases and delineate anatomy. The surgeon should be experienced in wedge, segmental, and lobar resection. Equipment for cryotherapy and arterial infusion devices should be available, and staff experienced in these modalities should be present. If all of these factors are present, the options for the invasive treatment of colorectal metastasis to the liver can be carried out in a manner that should provide the most benefit at a low morbidity to this population of patients.