PubMed Health⌕ Search

Biomedical subjects

M R Weiser

Publications and source records attributed to M R Weiser.

15 recordsLinked to original sources
PubMed2001

Lymphovascular invasion enhances the prediction of non-sentinel node metastases in breast cancer patients with positive sentinel nodes.

BACKGROUND: Fifty percent of patients with sentinel lymph node (SLN) metastases have no metastatic disease in non-SLNs on axillary lymph node dissection (ALND). The goal of this study is to determine which patients have metastatic disease limited to the SLN, and, therefore, may not require completion ALND. METHODS: Of the first 1000 patients undergoing SLN biopsy at Memorial Sloan-Kettering Cancer Center, using a combined blue dye and isotope technique, 231 (26%) had positive SLN. Of these, 206 underwent completion ALND. They are the study group for this report. RESULTS: The likelihood of non-SLN metastasis was inversely related to three clinicopathologic variables: tumor size < or = 1.0 cm; absence of lymphovascular invasion (LVI); and SLN micrometastases (< or = 2 mm). None of 24 patients with all three predictive factors had non-SLN metastases, whereas 58% of patients with none of the factors had disease in the non-SLN. CONCLUSION: Patients with small breast cancers, no LVI, and SLN micrometastases have a low risk of non-SLN metastases, and may not require completion ALND.

Adult↗
PubMed2001

Laparoscopy predicts metastatic disease and spares laparotomy in selected patients with pancreatic nonfunctioning islet cell tumors.

INTRODUCTION: Our objective was to compare the efficacy of CT alone to CT followed by laparoscopy in determining resectability of pancreatic nonfunctioning islet (NFI) cell tumors. METHODS: A retrospective analysis from 1993 to 1999 revealed 48 patients who underwent surgical evaluation for NFI cell tumors. Of these, 34 (71%) patients underwent laparoscopy and CT for either diagnostic purposes or tumor staging. CT and laparoscopic criteria for curative resectability were defined and the sensitivity, specificity, and predictive value of both modalities in determining resectability were calculated. RESULTS: The most frequent tumor location and presenting symptoms were pancreatic head (n = 27, 56%) and abdominal pain (n = 31, 65%), respectively. Median tumor size was 4.0 cm. In the laparoscopy group, curative resection was performed in 20 cases (59%). CT followed by laparoscopy was more sensitive than CT alone in predicting resectability (93% vs. 50%, P = 0.03) with similar specificity (both 100%). The predictive value for tumor resectability was 74% for CT alone and 95% for CT followed by laparoscopy. Reasons for unresectability identified at laparoscopy but not indicated by CT were liver metastases (n = 6) or nodal disease (n = 1). Four of these patients were spared a laparotomy while the other three patients underwent surgical palliation and all are alive with disease (AWD). In those not undergoing laparoscopy (n = 14), curative resection was performed in 64% (n = 9). Four of these patients underwent resection, despite having metastases, and three are AWD. CONCLUSIONS: NFI cell tumors of the pancreas present as large masses with frequent metastases. Despite metastatic disease, prolonged survival is often achieved with or without open surgical treatment. Laparoscopy can be used in diagnosis and accurately identifies metastases not seen on CT, thus sparing laparotomy in some patients.

Adenoma, Islet Cell↗
PubMed2000

Laparoscopic total mesorectal excision with autonomic nerve preservation.

Laparoscopy has greatly influenced abdominal surgery. We hypothesize that the benefits of minimally invasive surgery are applicable to rectal cancer. A cadaver model of laparoscopic rectal resection with total mesorectal excision (TME) and autonomic nerve preservation was utilized to explore this hypothesis. The principles of TME were followed, including high vascular ligation, sharp mesorectal dissection, and identification and preservation of the autonomic pelvic nerves. After proving feasibility in the cadaver model, a clinical study was performed on patients with mid to low rectal cancers. We observed acceptable morbidity with this minimally invasive technique of rectal resection and TME. We conclude that there is growing evidence that laparoscopic methods can be applied to patients with rectal cancer.

Adenocarcinoma↗
PubMed2000

Is routine intraoperative frozen-section examination of sentinel lymph nodes in breast cancer worthwhile?

BACKGROUND: Routine intraoperative frozen section (FS) of sentinel lymph nodes (SLN) can detect metastatic disease, allowing immediate axillary dissection and avoiding the need for reoperation. Routine FS is also costly, increases operative time, and is subject to false-negative results. We examined the benefit of routine intraoperative FS among the first 1000 patients at Memorial Sloan Kettering Cancer Center who had SLN biopsy for breast cancer. METHODS: We performed SLN biopsy with intraoperative FS in 890 consecutive breast cancer patients, none of whom had a back-up axillary dissection planned in advance. Serial sections and immunohistochemical staining for cytokeratins were performed on all SLN that proved negative on FS. The sensitivity of FS was determined as a function of (1) tumor size and (2) volume of metastatic disease in the SLN, and the benefit of FS was defined as the avoidance of a reoperative axillary dissection. RESULTS: The sensitivity of FS ranged from 40% for patients with Tla to 76% for patients with T2 cancers. The volume of SLN metastasis was highly correlated with tumor size, and FS was far more effective in detecting macrometastatic disease (sensitivity 92%) than micrometastases (sensitivity 17%). The benefit of FS in avoiding reoperative axillary dissection ranged from 4% for Tla (6 of 143) to 38% for T2 (45 of 119) cancers. CONCLUSIONS: In breast cancer patients having SLN biopsy, the failure of routine intraoperative FS is largely the failure to detect micrometastatic disease. The benefit of routine intraoperative FS increases with tumor size. Routine FS may not be indicated in patients with the smallest invasive cancers.

Adult↗
PubMed2000

Repeat resection of pulmonary metastases in patients with soft-tissue sarcoma.

BACKGROUND: Even after an apparent complete resection of sarcomatous pulmonary metastases, 40% to 80% of patients will re-recur in the lung. The benefit of subsequent re-resection is poorly defined. This study examines patient survival after repeat pulmonary exploration for re-recurrent metastatic sarcoma at a single institution. STUDY DESIGN: Between July 1982 and December 1997, data on 3,149 adult in-patients with soft tissue sarcoma were prospectively gathered. Of these, pulmonary metastases were present or developed in 719 patients and 248 underwent at least one resection. Of the patients relapsing in the lung after an apparently complete resection, 86 underwent reexploration. Disease-specific survival (DSS) after re-resection was the end point of the study. Time to death was modeled using the method of Kaplan and Meier. The association of factors to time-to-event end points was analyzed using the log-rank test for univariate analysis and the Cox proportional hazards model for multivariate analysis. Clinicopathologic factors were analyzed with the Pearson chi-square or Fisher's exact test when appropriate. RESULTS: The median DSS after re-resection for all patients undergoing at least two pulmonary resections was 42.8 months with an estimated 5-year survival of 36%. The median DSS in patients with complete reresection was 51 months (n = 68) compared with 6 months in patients with an incomplete re-resection (n = 16, p<0.0001). Patients with one or two nodules at re-resection (n = 39) had a median DSS of 51 months compared with 20 months in patients with three or more nodules (n = 40, p = 0.003). Patients in whom the largest metastasis re-resected was less than or equal to 2 cm (n = 33) had a median DSS of 44 months compared with 20 months in patients with metastasis greater than 2 cm (n = 43, p = 0.033). Patients with primary tumor high-grade histology (n = 75) had a median DSS of 32 months and patients with low-grade histology (n = 11) had a median DSS that was not reached (p = 0.041). Three independent prognostic factors associated with poor outcomes may be determined preoperatively: > or =3 nodules, largest metastases > 2 cm, and high-grade primary tumor histology. Patients with either zero or one poor prognostic factor had a median DSS > 65 months and patients with three poor prognostic factors had a median DSS of 10 months. CONCLUSIONS: Reexploration for recurrent sarcomatous pulmonary metastases appears beneficial for patients who can be completely re-resected. Outcomes are described by factors that may be determined preoperatively, including metastasis size, metastasis number, and primary tumor histologic grade. Patients who cannot be completely re-resected or those with numerous, large metastasis and high-grade primary tumor pathology have poor outcomes and should be considered for investigational therapy.

Adolescent↗
PubMed1999

Intestinal reperfusion injury is mediated by IgM and complement.

Intestinal ischemia-reperfusion injury is dependent on complement. This study examines the role of the alternative and classic pathways of complement and IgM in a murine model of intestinal ischemia-reperfusion. Wild-type animals, mice deficient in complement factor 4 (C4), C3, or Ig, or wild-type mice treated with soluble complement receptor 1 were subjected to 40 min of jejunal ischemia and 3 h of reperfusion. Compared with wild types, knockout and treated mice had significantly reduced intestinal injury, indicated by lowered permeability to radiolabeled albumin. When animals deficient in Ig were reconstituted with IgM, the degree of injury was restored to wild-type levels. Immunohistological staining of intestine for C3 and IgM showed colocalization in the mucosa of wild-type controls and minimal staining for both in the intestine of Ig-deficient and C4-deficient mice. We conclude that intestinal ischemia-reperfusion injury is dependent on the classic complement pathway and IgM.

Animals↗
PubMed1997

alpha 1-Acid glycoprotein reduces local and remote injuries after intestinal ischemia in the rat.

The aim of this study was to look at the role of alpha 1-acid glycoprotein as a natural anti-inflammatory agent with particular respect to its antineutrophil and anticomplement activity. A recombinantly engineered form of sialyl Lewisx (sLe(x))-bearing alpha 1-acid glycoprotein (sAGP) was administered intravenously to pentobarbital-anesthetized rats after 50 min of intestinal ischemia just before 4 h of reperfusion. A non-sLe(x)-bearing form of AGP (nsAGP) was used as control. sAGP-treated animals had a 62% reduction (P < 0.05) in remote lung injury, assessed by 125I-albumin permeability, compared with those treated with nsAGP (permeability index of 3.61 +/- 0.15 x 10(-3) and 5.18 +/- 0.67 x 10(-3), respectively). There was a reduction in pulmonary myeloperoxidase levels in sAGP-treated rats compared with nsAGP-treated rats. Complement-dependent intestinal injury, assessed by 125I-albumin permeability was reduced by 28% (P < 0.05) in animals treated with sAGP (7.58 +/- 0.63) compared with those treated with nsAGP (10.4 +/- 0.54). We conclude that sAGP ameliorates both complement- and neutrophil-mediated injuries.

Animals↗
PubMed1997

Experimental murine acid aspiration injury is mediated by neutrophils and the alternative complement pathway.

Acid aspiration may result in the development of the acute respiratory distress syndrome, an event associated with significant morbidity and mortality. Although once attributed to direct distal airway injury, the pulmonary failure after acid aspiration is more complex and involves an inflammatory injury mediated by complement (C) and polymorphonuclear leukocytes. This study examines the injurious inflammatory cascades that are activated after acid aspiration. The role of neutrophils was defined by immunodepletion before aspiration, which reduced injury by 59%. The injury was not modified in either P- or E-selectin-knockout mice, indicating that these adhesion molecules were not operative. C activation after aspiration was documented with immunochemistry by C3 deposition on injured alveolar pneumocytes. Animals in which C activation was inhibited with soluble C receptor type 1 (sCR1) had a 54% reduction in injury, similar to the level of protection seen in C3-knockout mice (58%). However C4-knockout mice were not protected from injury, indicating that C activation is mediated by the alternative pathway. Finally, an additive effect of neutrophils and C was demonstrated whereby neutropenic animals that were treated with sCR1 showed an 85% reduction in injury. Thus acid aspiration injury is mediated by neutrophils and the alternative C pathway.

Animals↗
PubMed1996

Reperfusion injury of ischemic skeletal muscle is mediated by natural antibody and complement.

Reperfusion of ischemic tissue induces an acute inflammatory response that can result in necrosis and irreversible cell injury to both local vascular endothelium and parenchyma. To examine the pathogenesis of ischemia/reperfusion injury, we have used mice deficient in complement components C3, C4, or serum immunoglobulin in a hindlimb model of ischemia. We found that mice homozygous deficient in C3 or C4 were equally protected against reperfusion injury based on a significant reduction in leakage of radiolabeled albumin out of the vasculature. This demonstrates that classical pathway complement is an important factor in the initiation of inflammation following reperfusion. Furthermore, mice deficient in serum immunoglobulin were equally protected and this protection could be reversed by reconstitution with serum from normal mice. Thus, this report describes a novel mechanism for reperfusion injury that involves antibody deposition and activation of complement leading to inflammation permeability.

Animals↗
PubMed1996

Complement inhibition by soluble complement receptor type 1 fails to moderate cerulein-induced pancreatitis in the rat.

CONCLUSION: Cerulein-induced pancreatitis in rats associated with remote liver and lung dysfunction. Soluble complement receptor 1 (sCR1) does not reduce the local or remote injury. Thus complement activation does not moderate cerulein-induced pancreatitis or the associated liver and injury. BACKGROUND: The local and remote injury of pancreatitis resembles other inflammatory events that are mediated by complement. This study examines the effect of complement inhibition with sCR1 in cerulein-induced pancreatitis in rats. METHODS: Thirteen Sprague-Dawley rats received five hourly subcutaneous doses of cerulein (100 micrograms initially, then 50 micrograms/kg). Six of these animals received hourly i.v. sCR1 (15 mg/kg, a proven complement-inhibiting dose in rats) and the other seven received i.v. saline. In parallel, 12 additional rats received hourly s.c. and i.v. saline. RESULTS: Compared to saline controls, rats receiving cerulein showed increased pancreatic wet-to-dry ratio (3.25:8.52), hematocrit (40 to 47%), ascites volume (2.1 to 6.1 mL), serum amylase (1680 to 10,700 U/L), and ascites amylase (32,200 to 167,000 U/L) (all p < 0.05). None of these parameters were modified by treatment with sCR1. Serum SGPT, which increased from 33.4 to 46.6 U/L in cerulein-infused rats, showed a trend toward reduction to 38.8 U/L in rats treated with sCR1. Cerulein-treated rats also had increased lung myeloperoxidase (0.069 to 0.097 U/g) and lung permeability, as assessed by a alveolar lavage to serum ratio of labeled albumen (0.041:0.121) both p < 0.05). Neither were changed by sCR1 treatment.

Acute Disease↗
PubMed1996

P-selectin mediates intestinal ischemic injury by enhancing complement deposition.

BACKGROUND: Ischemia and reperfusion injury of rodent intestine is complement mediated. P-selectin antagonism reduces local injury, yet neutrophil depletion does not. This study tests the thesis that the protective mechanism of P-selectin antagonists involves complement inhibition. METHODS: We subjected rats (n = 86) to 50 minutes of complete mesenteric ischemia and 4 hours of reperfusion. Treatment with a monoclonal antibody (PB1.3) against P-selectin reduced intestinal injury as judged by 125I-albumin permeability index (7.33 +/- 0.40) compared with saline solution treatment (11.4 +/- 0.49) (p < 0.05). RESULTS: However, intestinal neutrophil sequestration assessed by myeloperoxidase assay was unchanged. Immunohistochemistry revealed that mucosal C5b-9 was deposited in animals treated with saline solution and was absent in the sham group. PB1.3 treatment reduced C5b-9 deposition in the intestinal mucosa compared with that in animals treated with saline solution (p < 0.05). Neutrophil-dependent remote lung injury assessed by 125I-albumin permeability and pulmonary myeloperoxidase assay were not significantly reduced by PB1.3. Treatment with a soluble form of P-selectin ligand, sialyl Lewisx (sLex), reduced intestinal myeloperoxidase (0.065 +/- 0.006) compared with saline solution treatment (0.136 +/- 0.02) (p < 0.05), but it did not reduce permeability. Remote lung permeability was reduced (4.52 +/- 0.65 x 10(-3)) by sLex compared with saline solution treatment (6.11 +/- 0.41 x 10(-3)) (p < 0.05). CONCLUSIONS: Antagonizing the lectin domain of P-selectin and thereby neutrophil adhesion was without local benefit in this model. In contrast, PB1.3 exerted a novel antagonism of P-selectin and reduced complement deposition.

Animals↗
PubMed1996

Anti-selectin therapy modifies skeletal muscle ischemia and reperfusion injury.

Restoration of blood flow to ischemic skeletal muscle results in a reperfusion injury characterized by permeability edema in part mediated by neutrophils that adhere via the selectin family of adhesion molecules. Rats underwent 4 h of hindlimb tourniquet ischemia followed by 4 h reperfusion. The role of neutrophils was determined by rendering one group of animals neutropenic before ischemia. In additional experimental groups, selectins were blocked with either a soluble form of the selectin counter-receptor, sialyl-Lewis X (SLX) or a monoclonal antibody directed against P-selectin (PB1.3). Neutrophil depletion resulted in a 36.1% reduction in hindlimb permeability (p < .05). SLX reduced hindlimb permeability index (PI) 23.9% at 1 mg/kg and 36.1% at 10 mg/kg compared to a nonfucosylated oligosaccharide, sialyl-N-acetylactosamine (p < .05). SLX also reduced neutrophil sequestration by 48.6% (p < .05). PB1.3 reduced hindlimb injury by 26.5% (p < .05) but did not reduce leukosequestration. We interpret these data to indicate that ischemia and reperfusion lead to selectin-mediated neutrophil sequestration. The oligosaccharide SLX, while moderately effective in limiting neutrophil sequestration was as effective as neutrophil depletion in reducing hindlimb permeability. The lack of concordance between the ability of SLX and PB1.3 in limiting neutrophil sequestration and permeability indicate mechanisms of action of these two agents that are in addition to the blocking of adhesion.

Animals↗