Regulation of prostaglandin availability in human fetal lung by differential localisation of prostaglandin H synthase-1 and prostaglandin dehydrogenase.

Specialisation of the respiratory portion of human fetal lung commences around 20-24 weeks gestation. In contrast, human fetal lung in vitro has the capacity to self-differentiate from 12 weeks gestation when grown in media devoid of growth factors or hormones, suggesting activation of autocrine or paracrine factors in vitro, or removal of the fetus from in utero inhibitory mechanisms. Prostaglandins play a key role during in vitro human fetal lung development and are synthesised by prostaglandin H synthase-1 (PGHS-1) and inactivated by 15-hydroxyprostaglandin dehydrogenase (PGDH) with formation of inactive 13,14-dihydro-15-keto-prostaglandins. We have used quantitative immunohistochemistry to determine expression and localisation of PGHS-1, PGDH, PGE2 and 13,14-dihydro-15-keto-PGE2 (PGEM) in human fetal lung with in situ hybridisation to localise PGHS-1 and PGDH mRNA. For the catabolic enzyme PGDH, amounts of mRNA, protein and enzyme product PGEM are increased within epithelium of distal as compared to more proximal airways. For PGHS-1, comparable amounts of mRNA, protein and enzyme product PGE2 are found in proximal and distal lung epithelium. Catabolism by PGDH is a sensitive mechanism for regulating bioavailability of prostaglandins and we propose that active catabolism of prostaglandins within human fetal lung epithelium is an inhibitory mechanism retarding epithelial differentiation in utero.

Tumorigenic potential of extracellular matrix metalloproteinase inducer.

Extracellular matrix metalloproteinase inducer (EMMPRIN), a glycoprotein present on the cancer cell plasma membrane, enhances fibroblast synthesis of matrix metalloproteinases (MMPs). The demonstration that peritumoral fibroblasts synthesize most of the MMPs in human tumors rather than the cancer cells themselves has ignited interest in the role of EMMPRIN in tumor dissemination. In this report we have demonstrated a role for EMMPRIN in cancer progression. Human MDA-MB-436 breast cancer cells, which are tumorigenic but slow growing in vivo, were transfected with EMMPRIN cDNA and injected orthotopically into mammary tissue of female NCr nu/nu mice. Green fluorescent protein was used to visualize metastases. In three experiments, breast cancer cell clones transfected with EMMPRIN cDNA were considerably more tumorigenic and invasive than plasmid-transfected cancer cells. Increased gelatinase A and gelatinase B expression (demonstrated by in situ hybridization and gelatin substrate zymography) was demonstrated in EMMPRIN-enhanced tumors. In contrast to de novo breast cancers in humans, human tumors transplanted into mice elicited minimal stromal or inflammatory cell reactions. Based on these experimental studies and our previous demonstration that EMMPRIN is prominently displayed in human cancer tissue, we propose that EMMPRIN plays an important role in cancer progression by increasing synthesis of MMPs.

National Cancer Data Base survey of breast cancer management for patients from low income zip codes.

BACKGROUND: The National Cancer Data Base (NCDB), a joint project of the American College of Surgeons Commission on Cancer and the American Cancer Society, is a cancer management and outcomes data base for health care organizations. It provides a comparative summary of patient care that is used by participating hospitals and communities for self-assessment. The most current (1995-1996) breast cancer data on patients from low income zip codes are described here. METHODS: Since 1989, eight Calls for Data have been issued, yielding a total of 191,714 reports of non-Hispanic white patients with breast cancer for the years analyzed, 1995-1996. A total of 1961 hospital cancer registries have participated in at least one of the Calls for Data. RESULTS: A diverse range of breast cancer cases was reported from a variety of geographic locations and medical care environments. There were general similarities in the treatment of patients from the different income groups; however, some differences were reported. Among patients from lower income zip codes, 60.7% were age 60 years or older, compared with 55.1% from other income zip code groups. The AJCC stage distribution was reported as less favorable for patients from low income zip codes than for other patients. The percentage of patients from low income zip codes diagnosed as Stage 0 or I was 51.2%, compared with 55.9% of patients from the other income zip codes. Of patients from lower income zip codes, 12.1% were reported to have Stage III or IV disease, compared with 10.0% of patients from other income zip codes. Patients from low income zip codes received less tissue-sparing surgery. Of patients from low income zip codes, 14.9% received partial mastectomy with or without radiation or systemic therapy, compared with 18.3% of patients from other income zip codes. The percentage of patients from low income zip codes who received a partial mastectomy with axillary lymph node dissection was 23.3% for patients from other income zip codes, the percentage was 30.5%. Conversely, 49.8% of patients from lower income zip codes received a modified radical mastectomy, compared with 40.5% of patients from other income zip codes. CONCLUSIONS: Further improvements in the early diagnosis and surgical treatment of low income patients can probably be achieved. Programmatic activities that further explain or reduce the apparent nonpreferred treatment of some low income patients should be encouraged.

An analysis of male and female breast cancer treatment and survival among demographically identical pairs of patients.

BACKGROUND: Male breast cancer is rare, and there are no large comparative studies to guide treatment. We used National Cancer Data Base data on 4755 men and 624,174 women who had breast cancer (1985-1994) to identify equivalent groups of male and female breast cancer patients. METHODS: For each man with breast cancer, the next woman treated at the same hospital was sought who matched the man's age (within 5 years), ethnicity, income category, and stage. We identified 3627 closely matched pairs of male and female patients with breast cancer. RESULTS: Men were more likely to be treated with mastectomy (modified radical, 65% of men versus 55.1% of women; radical, 2.5% of men versus 0.9% of women; simple, 7.6% of men versus 3.4% of women; P <.001), and more likely to receive radiation therapy after mastectomy (men, 29%; women, 11%; P <.001). Men treated with lumpectomy were less likely to receive radiation therapy (men, 54%; women, 68%; P <. 001). Men were also less likely to receive chemotherapy (26.7% of men versus 40.6% of women; P <. 001) after any surgical treatment. CONCLUSIONS: This large comparative study is the first to detail stage-specific differences in contemporary treatment strategies for highly comparable groups of men and women treated for breast cancer. Further studies of male breast cancer should focus on identifying prognostic factors and defining optimal therapy.

Laparoscopic anatomy of the pelvis.

The laparoscopic anatomy of the pelvis is reviewed. Both male and female anatomy are detailed, and special emphasis is placed on avoiding anatomic complications of laparoscopic pelvic surgery.

Axillary dissection in breast-conserving surgery for stage I and II breast cancer: a National Cancer Data Base study of patterns of omission and implications for survival.

BACKGROUND: Breast conservation (partial mastectomy, axillary node dissection or sampling, and radiotherapy) is the current standard of care for eligible patients with Stages I and II breast cancer. Because axillary node dissection (AND) has a low yield, some have argued for its omission. The present study was undertaken to determine factors that correlated with omission of AND, and the impact of the decision to omit AND on 10-year relative survival. STUDY DESIGN: A retrospective review of National Cancer Data Base (NCDB) data for 547,847 women with Stage I and Stage II breast cancer treated in US hospitals from 1985 to 1995 was undertaken. A subset of 47,944 Stage I and 23,283 Stage II women treated with breast-conserving surgery (BCS) was identified. Cross-tab analysis was used to compare patterns of surgical care within this subset. Relative survival was calculated as the ratio of observed survival to the expected survival for women of the same age and racial/ethnic background. RESULTS: The rate of BCS with and without AND increased steadily from 17.6% and 6.4% of patients from 1985-1989, to 36.6% and 10.6% of patients from 1993-1995 respectively. AND was more likely to be omitted in women with Stage I than women with Stage II disease (14.5% versus 5.5%). Similarly, AND was omitted more frequently in women with Grade 1 than women with higher grades (Grade 1, 14.9%; Grade 2, 10.1%; Grade 3, 7.1%; Grade 4, 7%). Although the rate of BCS with AND varied considerably according to location in the breast, the overall rate of BCS without AND appeared independent of site of lesion. Women over the age of 70 years were more than twice as likely to have AND omitted from BCS than their younger counterparts. Women with lower incomes, women treated in the Northeast, or at hospitals with annual caseloads <150 were all less likely to undergo AND than their corresponding counterparts. Ten-year relative survival for Stage I women treated with partial mastectomy and AND was 85% (n = 1242) versus 66% (n = 1684) for comparable women in whom AND was omitted. BCS with AND followed by radiation therapy for Stage I disease resulted in 94% (n = 5469) 10-year relative survival, compared with 85% (n = 1284) without AND. Addition of both radiation and chemotherapy to BCS with AND for Stage I disease resulted in 86% (n = 2800) versus 58% (n = 512) without AND. In contrast, Stage II women treated with BCS with AND followed by radiation and chemotherapy experienced a 72% 10-year relative survival. CONCLUSIONS: A significant number of women with Stage I breast cancer do not undergo AND as part of BCS. The trend is most pronounced for the elderly, but significant fractions of women of all ages are also being undertreated by current standards. Ten-year survival is significantly worse when AND is omitted. This adverse survival effect is not solely from understaging.

Laparoscopic biliary bypass for inoperable pancreatic cancer.

Laparoscopic biliary bypass provides an attractive alternative to endoscopic stenting for nonresectable pancreatic carcinoma. Laparoscopic gastroenterostomy may be added if duodenal obstruction is present. These simple palliative procedures achieve long-term relief of jaundice and duodenal obstruction. The laparoscopic approach allows early discharge from the hospital with minimal incisional pain, both of which are highly beneficial to patients with limited lifespan.

The National Cancer Data Base 10-year survey of breast carcinoma treatment at hospitals in the United States.

BACKGROUND: The National Cancer Data Base (NCDB), a joint project of the American College of Surgeons Commission on Cancer and the American Cancer Society, is a cancer management and outcome data base for health care organizations. It provides a comparative summary of patient care that is used by participating hospitals and communities for self-assessment. The most current (1995) data are described herein. METHODS: Since 1989, seven calls for data have been issued, yielding reports on a total of 240,031 breast carcinoma patients for the years included in this analysis. A total of 1849 hospital cancer registries responded to at least 1 of the calls for data. RESULTS: A continuous improvement in care was reported. By 1995, 45.8% (nearly one-half) of breast carcinoma patients were diagnosed early as Stage 0 or I, and early stage patients (Stage 0 or I) were most often treated with partial mastectomy (in 58% of cases). Favorable 10-year relative survival rates for Stage 0 (95%) and Stage I (88%) breast carcinoma patients were reported. Patients who were presumed to be Stage I and were not selected for axillary dissection had poorer survival. Survival differences were reported for different treatment groups within individual stage strata. Over the 10-year observation period, fewer patients from lower-income neighborhoods were diagnosed with early stage breast carcinoma. In general, the annual relative survival rate remained constant over the 10-year observation period (with no plateau after 5 years) within each stage and for all stages combined. CONCLUSIONS: Improvements in diagnosis and treatment during the period 1985-1995 were demonstrated by these data. The NCDB breast carcinoma data are appropriate norms for formal quality assurance purposes, such as those specified by the Standards of the Commission on Cancer published by the American College of Surgeons Commission on Cancer. Cancer committees and other clinicians working within the hospital setting should assess and compare stage distribution, stage specific treatment patterns, and the correlations between the outcomes of patients and both disease stage and treatment.

Breast disease complicating pregnancy.

Cancer complicating pregnancy is uncommon, with an incidence of approximately 1 in 1000 pregnancies. The obstetrician attending 250 deliveries per year would need to accumulate 40 years of clinical experience to encounter two to three cases of PABC. The increases in the size, weight, vascularity, and density of the breasts associated with pregnancy make the detection of mass lesions difficult both clinically and mammographically. Most of the benign lesions seen in pregnancy are the same ones seen in the nongravid state. Most cases of PABC present as painless masses, and as many as 90% of these masses are detected by breast self-examination. Women with PABC generally have more advanced disease with larger tumors, a higher percentage of inoperable lesions, and a higher percentage of nodal involvement. Because most PABC presents with a palpable mass, the role of imaging modalities in the evaluation of these patients remains limited. Fine-needle aspiration cytology is the initial procedure of choice for evaluating breast masses during pregnancy and lactation. Therapeutic abortion does not improve survival. The general principle is to treat the cancer and to allow the pregnancy to proceed. No studies have shown an adverse effect of a subsequent pregnancy even in patients with positive axillary nodes and patients in whom pregnancy occurs earlier than 2 years after treatment.

Vascular endothelial growth factor induces tissue factor and matrix metalloproteinase production in endothelial cells: conversion of prothrombin to thrombin results in progelatinase A activation and cell proliferation.

Production of vascular endothelial growth factor (VEGF) by cancer cells at invasive and metastatic sites is an important aspect of tumor angiogenesis. Although known primarily as a mitogen and a vascular permeability factor (VPF) for endothelial cells, VEGF/VPF has been proposed to induce the expression of procoagulant factors in endothelial cells. In this study, we have explored the ramifications of VEGF induction of tissue factor (TF) in human umbilical vein endothelial cells (HUVECs) and subsequent activation of progelatinase A. Within 3 hr of incubation with VEGF/VPF, endothelial cells accelerate TF generation as measured using chromogenic substrate assays for coagulation factors Xa and thrombin. Incubation of VEGF/VPF-pre-treated cells with prothrombin and factors X, Va, and VIIa at 37 degrees C and subsequent generation of thrombin resulted in activation of secreted endothelial progelatinase A as demonstrated by gelatin zymography. Anti-thrombin III or antibodies to TF inhibited thrombin generation and progelatinase A activation. VEGF/VPF also directly increased HUVEC secretion of interstitial collagenase, tissue inhibitor of metalloproteinases (TIMP-1) and, to a lesser extent, gelatinase A. The effect of thrombin on endothelial proliferation in serum-free media was examined. Thrombin was a growth factor for HUVECs at a lower dose than that required for progelatinase A activation. Whereas TIMP-2 abrogated thrombin-induced progelatinase A activation, it had no significant effect on thrombin-induced endothelial cell growth. We propose that an early step in tumor angiogenesis involves VEGF-induced thrombin generation and increased MMP production with subsequent activation of endothelial progelatinase A and degradation of the underlying basement membrane.

Regional diversity and breadth of the National Cancer Data Base.

BACKGROUND: The National Cancer Data Base (NCDB), a joint project of the Commission on Cancer of the American College of Surgeons and the American Cancer Society, is a cancer management and outcomes data base for health care organizations. It provides a comparative summary of patient care that is used by participating hospitals and communities for self-assessment. This article describes the most current (1995) data. METHODS: Since 1989, 7 calls for data have been issued, yielding a total of 5,558,389 cancer patient reports for the years 1985-1995. A total of 1849 hospital cancer registries have participated in at least 1 of the calls for data. RESULTS: One thousand one hundred and fourteen hospitals from 50 states and the District of Columbia reported 655,627 cases for the diagnosis year 1995. The hospitals represented a wide range of sizes (187 [16.8%] with 1000+ cases annually, 405 [36.4%] with 500-999 cases annually, 255 [22.9%] with 300-499 cases annually, 211 [18.9%] with 100-299 cases annually, and 56 [5%] with < 100 cases annually) and types (21 [1.9%] National Cancer Institute [NCI]-recognized cancer centers, 119 [10.7%] government hospitals, 102 [9.2%] teaching hospitals, 256 [23.0%] large community hospitals, 297 [26.7%] medium/small community hospitals, and 257 [23.1%] nongovernmental hospitals without approval status from the Commission on Cancer or NCI recognition). Remarkably similar distributions of cases by primary site and age were reported from each of six U.S. geographic regions. In addition, within each of these six regions, the cases were reported from a wide range of income strata and ethnicities. For several states, relatively few cancer cases were reported. For several examples of relatively rare patient and tumor groups, all reported cases between 1985-1995 included potentially useful quantities of patients in whom further study of such special groups was warranted. CONCLUSIONS: The authors conclude that the reported cases most likely are representative at the regional (but not state) level of cancer patients diagnosed and treated at U.S. hospitals with regard to types of cancer and ages of the patients. They conclude further that cancer reporting may be quite diverse within each region with regard to other known patient and reporting institution characteristics.

The growth and maturation of the National Cancer Data Base.

BACKGROUND: The National Cancer Data Base (NCDB), a joint project of the Commission on Cancer of the American College of Surgeons and the American Cancer Society, is a cancer management and outcomes data base for health care organizations. It provides a comparative summary of patient care that is used by communities and participating hospitals for self-assessment. The most current (1994) data are described here. METHODS: Six calls for data have yielded a total of 4,580,000 cases for the years 1985-1994. A total of 1735 hospital cancer registries have each participated in at least one of the calls for data. RESULTS: Summing the last year's report from each of the 1227 hospitals that participated in 1994, the cases represent the equivalent of 57% of the estimated 1994 U.S. cancer cases. These data were received from all six regions of the country, including all 50 states. Ninety-seven percent of patients received all or part of their treatment at the reporting hospital. The four most common cancers are carcinomas of the breast (15.7%), lung (14.3%), prostate (13.1%), and colon (7.7%), and collectively they comprise a majority of new cases. CONCLUSIONS: The NCDB is a cancer management and outcomes data base for health care organizations that currently provides data on 57% of the estimated new cases in the U.S. Past data have been used extensively to assess patterns of care and outcomes.

Breast and cervical carcinoma screening services: physicians' perceptions of need.

The Mississippi Breast and Cervical Cancer Control Coalition conducted a survey of health care professionals to assess current practices in the areas of breast and cervical cancer screening. A 22% response rate was obtained, with family practitioners having the highest response rate. Cost was cited as a major barrier to access to screening mammography. Some discrepancies between provider perceptions and currently accepted guidelines were identified.

Gastrointestinal problems in the immunocompromised host. A review for surgeons.

As the immunocompromised patient population grows, the gastrointestinal surgeon is increasingly called upon to make complex diagnostic and therapeutic decisions. The surgeon should first identify the patient as immunocompromised and then categorize the probable degree of immunocompromise as mild, moderate, or severe. Mildly immunocompromised patients tend to present late and with minimal symptoms, but the disease entities are the same ones seen in the general population. Moderately and severely immunocompromised patients may also develop the usual surgical problems, but the differential diagnosis is expanded to include complications of the immunocompromised state or complications of the underlying problem which caused the immune compromise. The expanded differential diagnosis includes infections with atypical organisms, opportunistic neoplasms, neutropenic enterocolitis, complications of medications, and forms of biliary tract disease not seen in the general population. Advances in oncology, transplantation, and the treatment of AIDS, have extended the life expectancy of these patients and increased the immunocompromised population. Prompt appropriate operative therapy may be lifesaving when surgical complications develop.

Project management techniques applicable within the Department of Surgery.

The finite time span and the nonrepetitive nature of the project distinguish it from the routine activities characteristic of the management of a surgical department or division. Defined goals, specific (finite) resource allocation, and identifiable sequential phases also characterize the project. This paper reviews project management techniques that may be useful in the Department of Surgery.

Laparoscopic appendectomy and the management of gynecologic pathologic conditions found at laparoscopy for presumed appendicitis.

A laparoscopic approach to patients with possible appendicitis has increased in popularity. In this article it is compared to the traditional open appendectomy, and the management of frequently found gynecologic pathology masquerading as appendicitis is described.

Laparoscopy for staging and palliation of gastrointestinal malignancy.

The use of laparoscopy in the treatment of malignant diseases is one of the great advances of surgery in the last few decades. Its roles as a diagnostic modality, a staging tool, and a therapeutic avenue for the various malignancies of the abdominal cavity continue to expand. The benefits to cancer patients with regard to reduced morbidity and shorter hospitalizations are well established. As video, optical, insufflation, and instrumentation technologies advance further, laparoscopic techniques for the treatment of cancer can only multiply in depth and breadth.