Management of variceal hemorrhage.
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Adult↗
Biomedical subjects
Emmanuel E Zervos
Publications and source records attributed to Emmanuel E Zervos.
Post-shunt resource consumption favors small-diameter prosthetic H-graft portacaval shunt over TIPS for patients with poor hepatic reserve.
OBJECTIVE: To define the role of surgical shunting for patients with poor hepatic reserve (Child's class C) in the era of TIPS. SUMMARY BACKGROUND DATA: Most physicians prefer TIPS to surgical shunting for patients with poor hepatic reserve because of anticipated poor long-term survival. METHODS: Sixty-two patients of Child's class C with bleeding varices not amenable to endoscopic sclerotherapy or banding were prospectively randomized to undergo TIPS or 8-mm prosthetic H-graft portacaval shunt (HGPCS) from 1993 to 1999. Resource consumption and survival after shunting were determined. RESULTS: Twenty-nine patients underwent TIPS and 33 underwent HGPCS. After HGPCS, survival at 3 years was favorable but not statistically superior. TIPS was more often associated with shunt stenoses/occlusions, recurrent hemorrhage, shunt revisions, and shunt failure. Long-term follow-up documented that after HGPCS, patients required fewer hospital and ICU days and fewer units of RBCs transfused. After HGPCS, cost of care was less, as was the median cost of care per day of survival. CONCLUSIONS: For Child's class C patients undergoing HGPCS or TIPS, long-term survival is similar, though favoring HGPCS. Similarly, measures of resource consumption and cost of care following hospital discharge favor HGPCS. HGPCS should be preferentially applied for acceptable patients without access to convenient capable post-shunt care or without definitive plans for imminent transplantation.
Adult↗
Patterns of recurrence after sentinel lymph node biopsy for breast cancer.
BACKGROUND: Sentinel lymph node biopsy (SLNB) is gaining acceptance as an alternative to axillary lymph node dissection. The purpose of this study was to determine the frequency and pattern of disease recurrence after SLNB. METHODS: Two-hundred twenty-two consecutive patients undergoing SLNB from April 6, 1998, to October 27, 1999, and who were >or=24 months out from their procedure were identified from a prospectively maintained database. Retrospective chart review and data analysis were performed to identify variables predictive of recurrence. RESULTS: The median patient follow-up was 32 months (range, 24-43 months). A total of 159 patients (72%) were sentinel lymph node (SLN) negative and had no further axillary treatment. Five of these patients (3.1%) developed a recurrence (one local and four distant), with no isolated regional (axillary) recurrences. Sixty-three patients (28%) were SLN positive and underwent a subsequent axillary lymph node dissection. Six of these patients (9.5%) developed a recurrence (three local, one regional, and two distant). Pathologic tumor size (P <.001), lymphovascular invasion (P =.018), and a positive SLN (P =.048) were all statistically significantly associated with disease recurrence. CONCLUSIONS: With a minimum follow-up of 24 months, patients with a negative SLN and no subsequent axillary treatment demonstrate a low frequency of disease recurrence. This supports the use of SLNB as the sole axillary staging procedure in SLN-negative patients.
Adult↗
MMP-2 and TIMP-1 are derived from, not in response to, pancreatic cancer.
INTRODUCTION: Genetic therapy aimed at disturbing the balance between matrix metalloproteinases (MMP) and their natural tissue inhibitors (TIMP) in treatment of pancreatic cancer requires an understanding of whether MMP and TIMP are tumor- or host-derived. This study was undertaken to determine whether production of MMP-2 and TIMP-1 is by, or in response to, pancreatic cancer. METHODS: PANC-1 (poorly differentiated human pancreatic cancer) or CD-1 (PANC cells transfected to overproduce TIMP-1) cells were implanted into the pancreata of 20 nude mice. After sacrifice, tumors and peritumoral stroma underwent immunohistochemical staining for human and murine MMP-2 and TIMP-1. Normal murine pancreas served as control. All stains were reviewed in a "blinded" manner by a pathologist and graded relative to normal control pancreata. RESULTS: Control pancreata displayed faint murine MMP-2 and TIMP-1 staining and no human MMP-2 or TIMP-1. MMP-2 was most prominent in peritumoral stroma, while TIMP-1 was most prominent in tumors. CD-1 tumors contained very high levels of TIMP-1 compared to PANC-1 tumors and control pancreata. Tumoral and peritumoral MMP-2 were overwhelmingly human. As well, tumoral TIMP-1 was predominantly human. CONCLUSIONS: In a murine model for human pancreatic cancer, nearly all TIMP-1 and MMP-2 expression is tumor-derived (i.e., human). Pharmacologic and gene therapy aimed at disturbing the MMP/TIMP balance in pancreatic cancer should be targeted toward tumor-specific mechanisms and warrants continued investigation.
Animals↗
TIMP-1 overexpression in pancreatic cancer attenuates tumor growth, decreases implantation and metastasis, and inhibits angiogenesis.
BACKGROUND: Matrix metalloproteinases (MMPs) are involved in pancreatic cancer progression. This study was undertaken to determine the effects of overexpression of a natural tissue inhibitor of MMP (TIMP-1) on pancreatic cancer cell growth, metastasis, and angiogenesis. METHODS: A poorly differentiated human pancreatic cancer cell line (PANC-1) underwent gene transfection to overexpress TIMP-1 (CD-1 cells). One million PANC-1 or CD-1 cells were injected into 40 nude mice subcutaneously (N = 20) or orthotopically (N = 20). Mice were sacrificed at 120 days. TIMP-1 overexpression by CD-1 cells was confirmed prior to injection and after necropsy. Immunohistochemical staining was undertaken after necropsy to evaluate tumors for TIMP-1, MMP-2, apoptosis (TUNEL), and angiogenesis (CD-31). RESULTS: Tumors of CD-1 cells were less likely to implant (35% vs 70%, P = 0.05) and grew to smaller size (0.5 g +/- 0.03 vs 1.5 g +/- 0.20, P < 0.001) than tumors of PANC-1 cells. As well, subcutaneous CD-1 tumors appeared later than PANC-1 tumors (45 days +/- 2.0 vs 27 days +/- 2.2, P < 0.001). Orthotopic CD-1 tumors metastasized less often than PANC-1 tumors (20% vs 60%, P < 0.05). MMP-2 expression was similar in PANC-1 and CD-1 tumors, while CD-1 tumors showed increased TIMP-1 expression, increased apoptosis, and decreased angiogenesis relative to PANC-1 tumors. CONCLUSIONS: TIMP-1 overexpression reduces pancreatic cancer cell implantation, growth, metastasis, and angiogenesis, while increasing tumor apoptosis, all without altering MMP-2 production. This study demonstrates the potential role of TIMP-1 as a target in gene therapy for pancreatic cancer.
Animals↗
Matrix metalloproteinases and their role in pancreatic cancer: a review of preclinical studies and clinical trials.
Matrix metalloproteinases (MMPs) have received much attention in recent years for their role in a variety of malignancies. Pancreatic cancer is no exception; MMP-2 and MMP-9 show high levels of expression in clinical and experimental models. Inhibition of MMPs has shown great promise with synthetic inhibitors, such as BB-94, as tumorostatic agents in preclinical models, particularly when these are combined with gemcitabine. These findings have led to several clinical trials using the MMP inhibitors Marimastat and BAY12-9566. Herein, we discuss the roles of MMPs and their inhibition in pancreatic cancer.
Animals↗
Sentinel lymph node biopsy results in less postoperative morbidity compared with axillary lymph node dissection for breast cancer.
BACKGROUND: This study was designed to compare the postoperative morbidity and socioeconomic impact of sentinel lymph node biopsy (SLNB) with axillary lymph node dissection (ALND) in patients with early stage breast cancer. METHODS: A prospective, nonrandomized, controlled study was designed to include patients who underwent breast conservation surgery and SLNB +/- ALND. Group A consisted of patients who had a negative SLNB and did not go on to completion ALND. Group B consisted of patients who underwent a SLNB followed by a completion ALND because either (1) their sentinel node contained cancer or (2) they were within the validation phase of our institution's sentinel lymph node protocol. Patients were evaluated with a questionnaire and underwent a standardized physical examination to determine arm circumference. RESULTS: Data were obtained from 96 patients with a mean follow-up period of 15 months (range 8 to 29). Significant differences were seen in subjective measurements of arm complaints and arm numbness (P <0.001), with fewer complaints reported in group A. The difference in mid-bicep and antecubital fossa circumferences was significant when comparing the ratio of the procedure arm with the nonprocedure arm and when subtracting the nonprocedure arm from the procedure arm (P <0.003 and P <0.016, respectively) in favor of group A. Axillary surgery was performed as an outpatient procedure in 88% of group A patients, compared with 15% in group B (P <0.001). Furthermore, 71% of group A patients returned to "normal activity" in less than 4 days, in comparison with 7% of group B (P <0.001). CONCLUSIONS: SLNB results in less postoperative morbidity in terms of subjective arm complaints and mid-arm swelling. Expeditious return to work or normal activity after SLNB has potentially significant socioeconomic consequences.
Aged↗
Lymphatic mapping in solid neoplasms: state of the art.
BACKGROUND: Lymphatic mapping and sentinel lymph node biopsy is an established technique for the staging and treatment of melanoma. The success of lymphatic mapping in this realm has broadened its application to other solid neoplasms. This update reviews the status of sentinel lymph node biopsy in its most widely cited applications. METHODS: Seminal manuscripts on lymphatic mapping in melanoma, breast, colon, vulvar, cervical, lung, gastric, and head and neck cancers are reviewed. RESULTS: Studies suggest that the application of lymphatic mapping as a staging tool in breast cancer and melanoma is justified when applied by trained surgeons. Additional validation is necessary before sentinel node biopsy is advocated in gynecologic, colon, lung, and head and neck cancer. CONCLUSIONS: As in breast cancer and melanoma, validation of the sentinel node concept in other solid tumors must occur in institutions other than those in which the technique is being developed before it is generally applied to other neoplasms.
Breast Neoplasms↗
Surgical management of early-stage pancreatic cancer.
BACKGROUND: Pancreatic cancer remains a difficult disease to treat. Diagnosis at an early stage may allow curative treatment with resection. In the past, the mortality associated with surgical treatment of pancreatic carcinoma was prohibitive but mortality associated with resection is now commensurate with all other major oncologic resections. Thus, the focus of surgical management has shifted to address several issues: the diagnosis and evaluation of patients with suspected pancreatic cancer, the role of preoperative endobiliary stenting, the role of laparoscopy, the extent of resection, the role of adjuvant and neoadjuvant treatment, and the role of specialized centers in treating the disease. METHODS: The current literature is reviewed to address these issues and help guide physicians who first encounter patients with suspected pancreatic cancer as well as surgeons who ultimately resect them. Practical evidence-based information to guide the decision-making process is provided. RESULTS: Surgical morbidity and mortality have achieved parity with other types of major oncologic resection, and a distinct survival advantage is possible when such therapy is applied early in the disease stage. Issues regarding the use of stents, extent of resection, and pre- vs post-operative chemoradiation therapy are becoming clearer as our collective experience broadens. CONCLUSIONS: Surgical treatment of pancreatic cancer should be aggressively pursued given the clearly established survival advantage and relief of symptoms achieved when it is applied appropriately.
Antineoplastic Agents↗