Biomedical subjects
R E Schwarz
Publications and source records attributed to R E Schwarz.
Acute postoperative dermatosis at the site of the electrocautery pad: sweet diagnosis of a burning issue.
Acute febrile neutrophilic dermatosis or Sweet's syndrome is a well-described acute condition with possible paraneoplastic and inflammatory associations. A case of a 49-year-old man with a prior history of Hodgkin's disease is described, who underwent a laparotomy for operative treatment of a small intestinal stricture and therapy-refractory gastroesophageal reflux. Incidentally, mild mesenteric lymphadenopathy was encountered, and a biopsy confirmed the presence of a new, unrelated low-grade follicular lymphoma. Two weeks postoperatively, the patient developed a tender erythematous plaque at the site of the Bovie electrocautery pad on the proximal thigh. Over the following week, the affected area extended in size, and became markedly edematous and infiltrated, with hemorrhagic surface studding. Multiple small plaques, some with annular arrays of pustules, were found on the opposite lower extremity, the lower back, and the arms. A skin biopsy suggested the presence of Sweet's syndrome, and corticosteroid treatment was initiated. All cutaneous manifestations disappeared within 48 h except for the presence of postinflammatory erythema. Acute neutrophilic dermatoses have not been previously described in this postoperative presentation. The differential diagnostic importance of this emergent entity and the potential for it being caused by surgical trauma are discussed.
Transcutaneously tunneled central venous lines in cancer patients: an analysis of device-related morbidity factors based on prospective data collection.
BACKGROUND: Long-term transcutaneous tunneled central venous catheters are frequently placed in cancer patients, accounting for significant costs and morbidity. Factors influencing outcome, though, are poorly studied. METHODS: Between June 1991 and June 1993, 923 central venous tunneled catheters were placed in 791 patients at Memorial Sloan-Kettering Cancer Center. Placement-, device-, and patient-related parameters were charted prospectively (median follow-up: 120 days) and correlated to device-specific outcome events. RESULTS: Median patient age was 28.5 years (range: 0.025 - 84.5). Disease distribution included hematologic malignancies (64.7%), solid tumors (30.4%), and others (4.9%). Primary indications for line access included chemotherapy (72.8%), bone marrow transplantation (18.7%), total parenteral nutrition (6.4%), and drug administration (2.1%). There were 11 insertion complications (1.2%), including insertion failure (n = 6), hemorrhage (n = 4), and malposition (n = 1). Subsequent to placement, a proven or suspected device-specific complication occurred in 540 lines (58.5%). Per 10,000 catheter days, there were 17.6 infection episodes, 8.1 thrombotic complications, 6.9 instances of catheter breakage, 3.5 accidental or inadvertent cases of displacement, and 0.6 device leaks. Reasons for line removal or other termination of follow-up were patient's death (32.1%), treatment end (28%), infection (19.6%), suspected infection (6.3%), displacement (6.8%), thrombosis (3.1%), leak (1%), and others (3.1%). Median device-specific duration was 365 days, compared with a median complication-free device-specific duration of 167 days (P < 0.0001), reflecting a highly significant device salvage rate after complications. Catheter tip position emerged as the dominant independent prognostic factor for reduced device-specific duration or complication-free device-specific duration. CONCLUSIONS: Transcutaneous tunneled central venous lines can be placed safely, with a considerable incidence of subsequent device-specific complications, but a high salvage rate. Factors determining outcome are related to device placement, as well as the patient's disease status. In this study, patients alive 90 days after catheter placement had a 37% chance for a device complication, with a 20% chance for device loss. Future analyses of intermediate-term intravenous access should employ the measurement of device-specific outcome as a reference parameter to assess clinical results.
Esthetic reconstruction after mastectomy for inflammatory breast cancer: is it worthwhile?
BACKGROUND: Because inflammatory breast cancer (IBC) has been viewed as a malignancy with a poor likelihood of longterm survival, few women have been offered esthetic reconstruction after mastectomy for IBC. Recent advances in multimodality therapy have improved the outcomes for women with this disease. The purpose of this review was to assess the results of esthetic breast reconstruction in the population with IBC. STUDY DESIGN: Review of medical records at the City of Hope National Medical Center for the 10-year period ending in May 1997, revealed 23 women who underwent elective esthetic breast reconstruction after mastectomy for IBC. The records of these patients were reviewed retrospectively. Patients requiring reconstruction for large surgical chest wall defects were not included in the review. RESULTS: Treatment for IBC included mastectomy in all patients, chemotherapy in 22, and chest wall radiation therapy in 14. Immediate reconstruction was performed at the time of mastectomy (n = 14) or was delayed (n = 9). The types of reconstruction included transverse rectus abdominis musculocutaneous flap (n = 18), latissimus dorsi flap (n = 2), or prosthetic mammary implant reconstruction (n = 3). Seven women chose to undergo additional reconstruction procedures (ie, nipple reconstruction) after their initial reconstruction. With a median followup of 44 months for survivors, 16 patients developed recurrence after reconstruction. Of these, 6 were local recurrences and 10 were distant failures. Seven patients are currently alive with no evidence of disease, 4 are currently alive with disease, and 12 have died as a result of breast cancer. The median disease-free survival after reconstruction was 19 months. The median overall survival after reconstruction for all patients was 22 months. The only negative predictor of survival was a positive surgical margin at mastectomy. CONCLUSIONS: The significant emotional and esthetic benefits of breast reconstruction should be available to women with IBC. In light of the improving prognosis of IBC with current aggressive multimodality treatment, reconstructive procedures should be offered as part of comprehensive therapy.
A carcinoembryonic antigen-secreting adenocarcinoma arising within a retrorectal tailgut cyst: clinicopathological considerations.
Retrorectal tailgut cysts (TGC) develop from postanal fetal gut remnants. They have specific radiological and histopathological features that distinguish them from dermoid cysts, enteric duplication cysts, and teratomas. We report a patient with a carcinoembryonic antigen-producing adenocarcinoma arising within a TGC who underwent resection through a combined anterior laparotomy/posterior pelvic approach. Despite complete resection and delayed but complete functional recovery, diffusely metastatic disease was encountered 6 months after resection. Diagnostic, therapeutic, histopathological, and oncological implications of this illustrative case are discussed. It seems possible to use carcinoembryonic antigen measurements for treatment planning and for assessing treatment response for this rare disease. The described outcome also suggests that TGC can develop malignant degeneration and should be resected at the time of diagnosis.
Endothelial-monocyte activating polypeptide II, a novel antitumor cytokine that suppresses primary and metastatic tumor growth and induces apoptosis in growing endothelial cells.
Neovascularization is essential for growth and spread of primary and metastatic tumors. We have identified a novel cytokine, endothelial-monocyte activating polypeptide (EMAP) II, that potently inhibits tumor growth, and appears to have antiangiogenic activity. Mice implanted with Matrigel showed an intense local angiogenic response, which EMAP II blocked by 76% (P < 0.001). Neovascularization of the mouse cornea was similarly prevented by EMAP II (P < 0.003). Intraperitoneally administered EMAP II suppressed the growth of primary Lewis lung carcinomas, with a reduction in tumor volume of 65% versus controls (P < 0.003). Tumors from human breast carcinoma-derived MDA-MB 468 cells were suppressed by >80% in EMAP II-treated animals (P < 0.005). In a lung metastasis model, EMAP II blocked outgrowth of Lewis lung carcinoma macrometastases; total surface metastases were diminished by 65%, and of the 35% metastases present, approximately 80% were inhibited with maximum diameter <2 mm (P < 0.002 vs. controls). In growing capillary endothelial cultures, EMAP II induced apoptosis in a time- and dose-dependent manner, whereas other cell types were unaffected. These data suggest that EMAP II is a tumor-suppressive mediator with antiangiogenic properties allowing it to target growing endothelium and limit establishment of neovasculature.
Platelet counts and prognosis of pancreatic cancer.
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Influence of hospital volume on mortality following major cancer surgery.
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Use of the sentinel lymph node to determine metastases of gastrointestinal malignancies: a word of caution.
Identifying the sentinel lymph node has been shown to carry prognostic and therapeutic implications in the surgical treatment of solid tumors. Recently, sentinel lymphadenectomy has been described for gastrointestinal malignancies, but its clinical value remains uncertain. We describe the case of a patient with appendiceal carcinoid who underwent a right hemicolectomy 4 months after appendectomy, out of concern over residual local or regional disease. One sentinel lymph node was identified in the colonic mesentery using the blue dye technique. This sentinel node and 35 others were negative for metastases, but one lymph node not identified through blue dye carried evidence for micrometastatic disease on hematoxylin and eosin (H&E) and immunohistochemical chromogranin stains. The case raises some issues about the value and limitations of sentinel lymph node biopsies in gastrointestinal cancer. Aspects related to technique, learning curve, gastrointestinal lymphatic drainage patterns, the impact of prior operations, and the limited therapeutic implications compared to cutaneous or subcutaneous solid malignancies are discussed. We conclude that at this point in time, the information obtained from biopsies of sentinel lymph nodes during the surgical treatment of gastrointestinal cancer should be utilized with due caution.
The impact of splenectomy on outcomes after resection of pancreatic adenocarcinoma.
BACKGROUND: Splenectomy at the time of resection of esophageal, gastric, or colon cancer has been correlated with inferior longterm survival. No such effect has yet been demonstrated for pancreatic cancer. STUDY DESIGN: Patients undergoing resection of pancreatic adenocarcinoma with curative intent at Memorial Sloan-Kettering Cancer Center between October 1983 and October 1995 were identified from a prospective clinical database. The impact of splenectomy on hospital stay and survival was calculated with univariate and multivariate nonparametric methods. RESULTS: Of 332 patients undergoing pancreatectomy, 326 with confirmed local or regional disease only formed the study cohort. Of these, 37 underwent concomitant splenectomy (11.4%). Splenectomy was significantly correlated with distal or total pancreatectomy, primary location in tail or body, portal vein invasion or resection, a larger maximal tumor diameter, and an operative blood loss of greater than 2,000 mL. Death or need for reoperation was not affected by splenectomy. Patients undergoing splenectomy had a higher median transfusion requirement (3 versus 1; p = 0.002). The median postoperative length of stay was 15 days regardless of splenectomy. At a median followup of 16.3 months (36.4 months for surviving patients), the median actuarial survival was 12.2 months with splenectomy versus 17.8 months without splenectomy (p<0.005). On multivariate analysis, splenectomy emerged as an independent factor predictive of decreased postoperative survival (p = 0.02), in addition to pathologic lymph node status (p = 0.0002), tumor diameter (p = 0.0004), and tumor differentiation (p = 0.007). Tumor location within the pancreas and the type of pancreatectomy were not independent prognostic factors influencing survival. CONCLUSIONS: After pancreatectomy for pancreatic cancer, splenectomy has no significant measurable impact on postoperative recovery, but has a negative influence on longterm survival independent of disease-related factors. Unless required because of tumor proximity or invasion, splenectomy should be avoided in the operative treatment of exocrine pancreatic cancer at any location.
Wheatgerm agglutinin-mediated toxicity in pancreatic cancer cells.
Lectin binding specificities for carbohydrate allow phenotypic and functional characterization of membrane-associated glycoproteins expressed on cancer cells. This analysis examined wheatgerm agglutinin binding to pancreatic cancer cells in vitro and the resulting toxicity. Membrane preparations of nine human pancreatic carcinoma cell lines were studied for lectin binding using wheatgerm agglutinin (WGA), concanavalin A (ConA) and phytohaemagglutinin-L (PHA-L) in a lectin blot analysis. Cell proliferation in vitro was measured by thymidine incorporation in the absence or presence of lectins at various concentrations. Sialic acid binding lectins or succinyl-WGA (succWGA) served as controls. WGA toxicity was tested after swainsonine or neuraminidase pretreatment. Binding and uptake of fluorescein-labelled lectins was studied under fluorescence microscopy. All pancreatic cell lines displayed high WGA membrane binding, primarily to sialic acid residues. Other lectins were bound with weak to moderate intensity only. Lectin toxicity corresponded to membrane binding intensity, and was profound in case of WGA (ID50 at 2.5-5 microg ml(-1)). WGA exposure induced chromatin condensation, nuclear fragmentation and DNA release consistent with apoptosis. Important steps for WGA toxicity included binding to sialic acid on swainsonine-sensitive carbohydrate and lectin internalization. There was rapid cellular uptake and subsequent nuclear relocalization of WGA. In contradistinction to the other lectins studied, WGA proved highly toxic to human pancreatic carcinoma cells in vitro. WGA binding to sialic acid residues of N-linked carbohydrate, cellular uptake and subsequent affinity to N-acetyl glucosamine appear to be necessary steps. Further analysis of this mechanism of profound toxicity may provide insight relevant to the treatment of pancreatic cancer.
Soft tissue masses of the chest wall and axilla: has metastatic melanoma been considered?
Isolated axillary and chest wall soft tissue masses are an uncommon presentation of metastatic cancer. The authors present three patients in whom malignant melanomas metastatic to these sites had been misdiagnosed, leading to inappropriate oncologic treatment planning in all three cases. The presumed diagnoses, even after fine-needle aspiration or trucut biopsies, were soft-tissue sarcoma (n = 2) and undifferentiated breast cancer (n = 1). The combination of taking a thorough history and performing proper immunohistochemical analysis of the biopsy material would have suggested the presence of malignant melanoma in all cases. As the disease appeared locoregionally limited in all patients, radical surgical resection with extended lymphadenectomy was performed without significant dysfunction of the upper extremity. One patient agreed to postoperative immunotherapy with interferon-alpha. Two patients are currently alive 17 and 14 months after operation. One patient was found to have systemic recurrence at 5 months, one experienced two isolated local recurrences in a prior operative site that were amenable to reresection and presently has no evidence of disease 12 months after resection, and one patient remains free of disease at 14 months. Clinical presentation, suggested diagnostic workup, and therapeutic implications are discussed to avoid misdiagnoses in this setting of possible clinical presentations of metastatic melanoma.
Extranodal follicular dendritic cell tumor of the abdominal wall.
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Lymphoepithelial cyst of the pancreas. No evidence for Epstein-Barr virus-related pathogenesis.
Compared to pseudocyst formation after prior pancreatitis, true cysts of the pancreas are rare. Pancreatic cysts with irregular wall components or a mucinous content raise the suspicion for the presence of a cystic neoplasm, and surgical resection is recommended. A case of a patient with a history of prostate cancer is described in whom a cyst of the pancreatic tail was discovered incidentally. Based on the radiographic features, which did not support the presence of a serous cystadenoma, a spleen-preserving distal pancreatectomy was performed. Histologic features were characteristic for a lymphoepithelial cyst (LEC) of the pancreas, lined with thinned squamous epithelium surrounded by benign lymphoid tissue. Since LECs of the parotid gland, which are associated with acquired human immunodeficiency, are frequently related to Epstein-Barr virus (EBV) infection, EBV in situ hybridization was performed and did not reveal evidence for EBV. Twenty-eight instances of pancreatic LECs have been reported, primarily affecting adult males, without evidence of increased numbers of EBV-positive cells. The pathogenesis, differential diagnosis, and clinical implications of lymphoepithelial pancreatic cysts are discussed.
An orthotopic in vivo model of human pancreatic cancer.
BACKGROUND: Pancreatic cancer is a highly lethal disease that frequently presents in advanced stages. For most patients, treatment with great clinical efficacy does not exist. Relevant in vivo models to test novel therapies are highly desirable. METHODS: The human pancreatic ductal adenocarcinoma cell line Panc-1 was injected intraperitoneally into SCID mice. The pattern of the resulting peripancreatic as well as metastatic disease was examined. Survival experiments after chemotherapy with gemcitabine or doxorubicin, and after immunotherapy with p53-specific cytotoxic T lymphocytes were performed. RESULTS: All animals developed isolated pancreatic tumor implants within 48 hours after injection. After the formation of invasive pancreatic tumor nodules, peripancreatic and portal adenopathy developed, causing biliary obstruction. All tumor-bearing animals died of disease within 5 to 12 weeks. Survival after gemcitabine treatment and after p53-CTL injection was significantly prolonged, with some animals remaining tumor-free. Doxorubicin treatment did not yield extended survival, but led to significant toxicity. CONCLUSION: Intraperitoneal injection of Panc-1 cells into SCID mice produces a quasi-orthotopic tumor development model that shares many characteristics with human pancreatic cancer. The ease of cell injection, avoidance of cumbersome surgical intervention with its resulting mortality, and the reliable development of obstructive jaundice as a dependent comorbid factor render this a useful model for in vivo testing of novel therapeutic approaches to pancreatic cancer. Our initial therapeutic studies demonstrate that in vitro antitumor efficacy against Panc-1 cancer cells does not necessarily predict the in vivo response, highlighting the preclinical experimental value of this model.
A mortality-free decade of pancreatoduodenectomy: is quality independent of quantity?
Pancreatoduodenectomy (PD) for periampullary cancer is a procedure of high morbidity and poor long-term survival. Superior clinical outcome has been described in high-volume institutions or for surgeons with a high case load. All patients undergoing pancreatectomy at the City of Hope National Medical Center (Duarte, CA) between 1987 and 1998 were analyzed retrospectively for postoperative outcome, and correlating or predictive clinicopathological factors were identified. Fifty-four patients underwent pancreatectomy [PD, n = 43; pylorus-preserving PD, n = 8; total pancreatectomy, n = 3]. There were 26 males and 28 females, with a median age of 63 years (range, 19-86). Fifty patients had a malignant diagnosis, and four patients had a benign diagnosis. Nine surgical oncologists performed an average of six pancreatectomies (range, 2-8). There was no perioperative death. Postoperative complications occurred in 30 patients, and infections predominated (n = 17). The median hospital stay was 16.5 days. The median postoperative actuarial survival by cancer site was 56 months (ampullary/ bile duct), 32.5 months (duodenal), 22.5 months (pancreatic), and 23.2 months (others). In this 11-year single institutional experience, PD and total pancreatectomy have been performed without lethal complication. In the setting of an exclusive oncology practice, operative mortality rates and survival outcome can be generated that compare favorably to large center experiences. Quality of outcome after pancreatectomy can be independent of quantity.
Thoracoscopic techniques for the management of intrathoracic metastases. Results.
BACKGROUND: The authors reviewed a series of 74 patients with cancer metastatic to the chest cavity undergoing thoracoscopic procedures. Indications, feasibility, and outcome of thoracoscopy were analyzed. METHODS: Perioperative and survival data on patients undergoing 89 operative thoracoscopic procedures between January 1991 and August 1993 were retrieved from a prospective database. These procedures included pulmonary wedge resection (n = 61), lobectomy (n = 2), pleurodesis (n = 11), pleural biopsy (n = 7), decortication (n = 1), and mediastinal mass resection (n = 2). In 13 cases, combined procedures were performed. Five thoracoscopies were converted to open thoracotomies to facilitate resection. RESULTS: Thoracoscopic pulmonary resections were performed for either diagnostic (n = 45) or curative (n = 18) intent. Diagnostic thoracoscopies were done for lesions in which less invasive biopsy attempts had failed to provide tissue, or that were considered too small for successful percutaneous biopsy. Thoracoscopic diagnostic accuracy was 100%. For the 18 patients undergoing potentially curative resection, mean follow-up is 15.4 months. Sixteen of these patients are currently alive, and eight are free of disease. Five complications related to the procedure included persistent air leak (n = 2), atrial fibrillation (n = 2), and urinary retention (n = 1). Overall hospital stay for thoracoscopic lung resection was 4.6 +/- 2.2 days, for converted open thoracotomy 6.8 +/- 1.9 days, and for patients undergoing pleurodesis 8.9 +/- 5.3 days. Mean chest tube duration after thoracoscopic resection was 2.6 +/- 1.6 days. CONCLUSIONS: Thoracoscopic procedures are safe, well tolerated, and useful for diagnosis and treatment of selected patients with suitable intrathoracic metastatic disease.
Metastatic breast cancer masquerading as gastrointestinal primary.
Seven patients with metastatic breast cancer presenting as gastrointestinal primary are described. These included six gastric and one colonic lesions. None of the patients had known systemic metastases at the time of diagnosis. The mean age at presentation was 66.7 yr (range 55-78). Median interval between breast cancer and gastrointestinal metastasis diagnosis was 6 yr (range 0.25-12.5). Original breast cancer histology included infiltrating lobular cancer (n = 4), infiltrating ductal cancer (n = 1), and a mixed type (n = 2). All patients with gastric involvement presented with epigastric pain and early satiety; the patient with colonic involvement had heme-positive stool. In three cases of gastric tumor and the one case of colonic tumor presentation, a definitive diagnosis of metastatic breast cancer was only confirmed after surgical resection of a presumed primary gastric or colonic malignancy. In the other three cases, pathological diagnostic confirmation was obtained through endoscopic biopsies and comparison to breast biopsy material, and operative treatment was avoided in favor of systemic cytotoxic therapy. The diagnosis was confirmed through similarities between mammary and gastric histopathology with regard to growth pattern, hormone receptor status, or gross cystic disease fluid protein. A high level of suspicion for metastatic breast cancer and a detailed pathological analysis will help avoid unnecessary surgical treatment in patients with a history of mammary carcinoma presenting with a newly diagnosed gastrointestinal neoplasm.