Biomedical subjects
Publications and source records attributed to A T Lefor.
We have created a technique of laparoscopic wedge biopsy of the liver that uses the Endo-GIA instrument. Two staple lines are placed at right angles on the edge of the liver to release a wedge of hepatic parenchyma. We have used this technique as part of a laparoscopic staging procedure for Hodgkin's lymphoma and found it to be simple and rapidly performed.
Interleukin-2 and hyperthermia have been used individually to treat a variety of tumors in both experimental and human trials. Combined adoptive immunotherapy and hyperthermia is an exciting new line of investigation. Previous work in our laboratory has shown that combined local hyperthermia and rIL-2 therapy can significantly decrease the rate of tumor growth. In this study, we investigated the effect of combined whole-body hyperthermia (WBHT) and rIL-2 on the growth of subcutaneous MCA-105 murine tumors in C57BL/6 mice. Treatment of both microscopic (day 3) and macroscopic (day 10) tumors was evaluated. In the treatment of microscopic tumors, animals received either no treatment; rIL-2 (3 x 10(5) IU ip tid) on days 3-7; plus WBHT (41 degrees C for 30 min) on days 3, 5, and 7; or WBHT only days 3, 5, and 7. In treating macroscopic tumors, animals received either no treatment; rIL-2 on days 10-14; plus WBHT on days 10, 12, and 14; or WBHT only on days 10, 12, and 14. While combined treatment and WBHT alone had no significant effect on the growth of microscopic tumors, combined IL-2 and WBHT significantly reduced the rate of tumor growth of macroscopic tumors. These results suggest that the tumor microenvironment plays a critical role in combined WBHT and rIL-2 therapy, and may be due to effects of WBHT on the tumor vasculature.
A case of multiple bilateral synchronous Warthin's tumors of the parotid glands with a simultaneous pleomorphic salivary adenoma in one patient is presented. This case appears to be unique. Only three previous cases of multiple synchronous bilateral Warthin's tumors have been reported. The occurrence of salivary tumors of different histologic types in the same patient is also rare. Twenty cases of Warthin's tumor that occurred with pleomorphic salivary adenoma were found in our review of the literature. However, none of these represented synchronous bilateral multiple Warthin's tumors.
The role of operative staging of patients with Hodgkin's disease continues to evolve. First described in 1969, the indications for this procedure continue to be redefined. Recent advances in surgical instrumentation have allowed procedures such as cholecystectomy, colon resection, nephrectomy, and splenectomy to be performed laparoscopically. We report a case of a complete staging procedure for Hodgkin's disease including splenectomy, performed laparoscopically. The patient had an uneventful recovery and returned to work 11 days postoperatively. While performing this operation laparoscopically does not alter the indications for the procedure, laparoscopic staging of Hodgkin's disease may result in shorter hospitalization and recovery time while providing complete pathologic staging of subdiaphragmatic disease.
Although cutaneous melanoma is rare in African-Americans, it continues to have a poor prognosis. We reviewed our experience with 13 African-American patients who had cutaneous melanoma diagnosed between 1969 and 1990. Eight of these 13 lesions were on the foot. These lesions were seen at a late stage, and 50% of them were more than 3 mm in thickness. Nine of these 13 patients had recurrent disease. This series of patients had a 92% 1-year and a 61% actuarial 5-year survival, with a median follow-up of 45 months. This study emphasizes the need for awareness of the occurrence of this disease in the African-American population in an effort to reduce the mortality from cutaneous melanoma.
The role of splenectomy in the management of immune thrombocytopenia purpura is well known. Recent improvements in laparoscopic technology have significantly expanded the variety of general surgical procedures amenable to a minimally invasive approach. An initial experience of four cases of immune thrombocytopenic purpura managed by laparoscopic splenectomy is presented. The entire procedure was completed under laparoscopic guidance in three of four cases, and a counterincision was required to control bleeding in one patient. The procedure is performed with five operating ports including a camera port, two retraction ports, and two dissection ports. Dissection begins at the lower pole of the spleen and progresses cephalad to the hilum where major vessels are individually ligated and divided. The short gastric vessels are divided with a linear laparoscopic stapler. The lateral peritoneal attachments are divided, and the spleen is removed intact through a 6 cm fascial incision at the umbilicus. Laparoscopic splenectomy appears to be a safe and efficacious procedure that is useful in the management of certain hematologic diseases and may ultimately be performed for a variety of pathologic conditions involving the spleen.
Pancreatic complications following cardiopulmonary bypass are infrequent but are associated with high mortality. All cases of pancreatic complications following cardiopulmonary bypass from 1972 to 1987 at a single institution were retrospectively reviewed. Of 5621 patients who underwent cardiopulmonary bypass, 25 (0.44%) sustained pancreatic complications. There were 15 cases of acute pancreatitis and 10 cases of pancreatic necrosis, with 11 deaths in the group reviewed, a mortality rate of 44%. Factors that were correlated with mortality associated with pancreatic complications in this study include preoperative hypotension, preoperative use of inotropic agents, and renal failure (preoperative and postoperative). Factors that have been previously associated with mortality from pancreatic complications in other studies, such as fluid sequestration, respiratory failure, sepsis, tachycardia, hypocalcemia, age greater than 55 years, and abnormal laboratory findings, were not found to be significantly associated with mortality in this study. Of the five patients for whom complete data were available, not one patient received greater than 800 mg of calcium per square meter of body surface area in the perioperative period. While the exact mechanism of pancreatic injury remains unclear, based on experimental studies and clinical correlation, it is likely that pancreatic ischemia remains a significant contributing factor. We conclude that no factor specifically associated with cardiopulmonary bypass was correlated significantly with mortality.
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Internal mandibular fixation after resection of advanced oral cavity carcinoma with mandibulectomy has a significant complication rate. We placed the Joe Hall Morris (JHM) external mandibular appliance in 29 patients undergoing mandibulectomy for advanced oral cavity carcinoma. Fourteen patients received postoperative radiation therapy (RT). Three of 29 patients (10%) had complications associated with the JHM appliance: one patient had a broken connecting bar, a second had loosening of a single pin, and a third had loss of fixation requiring complete replacement of the appliance. Complications not associated with the appliance occurred in 8 patients (28%) including mandibular exposure (1), orocutaneous fistula (2), partial flap dehiscence (4), and flap necrosis (1). Oral continence was maintained in 26 patients, and occlusion was normal in 27. The appliance was removed in 12 weeks to 6 months in all patients. The JHM appliance allows for a reliable and rapid immediate fixation of the mandible with acceptable functional and aesthetic results, and no delay or interference with postoperative radiotherapy. Since the life expectancy of these patients is short, most do not require subsequent permanent fixation after removal of the appliance.
We have previously shown that the combination of immunotherapy with interleukin 2 (IL-2) and local hyperthermia (LHT) abrogates the growth of murine subcutaneous tumors significantly more than either modality alone. This study was undertaken to investigate whether the beneficial effect of combined modality therapy could be attributed to increased trafficking of effector cells to the tumor. After inducing MCA-105 sarcomas in the hindlimbs of C57BL/6 mice, animals were given no therapy, LHT, IL-2, or IL-2 + LHT followed by an iv injection of 51Cr-labeled syngeneic splenocytes or LAK cells. Select organs and the tumor-bearing extremity were counted in a gamma counter. IL-2 or LHT alone did not affect lymphocyte migration, while IL-2 + LHT significantly decreased trafficking (P less than 0.001) to the tumor. LAK cells showed increased migration to the tumor site compared to splenocytes in all treatment groups (P less than 0.02). IL-2 caused increased migration of LAK cells but not splenocytes to the lung; this was not affected by LHT. LAK cell trafficking to the spleen was decreased by IL-2 and IL-2 + LHT, while splenocyte migration was decreased in the LHT and combined treatment groups. LHT and IL-2 had no effect on trafficking of either effector cell type to liver or kidney. These results show that the beneficial effect of combined modality therapy may not be due to increased trafficking of lymphocytes to the tumor area. In addition, LAK cells traffic more to subcutaneous tumors than splenocytes, and this cannot be explained by the differential trafficking to other organs. The results of this study will be important in the planning of future experiments with combined adoptive immunotherapy and hyperthermia.
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A variety of malignancies, including hematologic malignancies, Kaposi's sarcoma, as well as adenocarcinomas and squamous cell carcinoma have been reported in association with acquired immune deficiency syndrome. Tumors of the umbilical area are unusual and can represent lesions of urachal origin. These may require extensive resection and are associated with a poor prognosis. We describe here a case of a young woman with AIDS who developed a squamous cell carcinoma of the umbilicus which suggests more than a casual relationship between these two conditions.
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We have previously reported that murine splenocytes incubated in the lymphokine interleukin-2 acquire the ability to mediate the lysis of a variety of fresh tumor cells in short-term chromium-51 release assays. This study was designed to evaluate the effect of lymphokine-activated killer (LAK) cells on fresh normal murine tissues. The susceptibility to lysis by LAK cells of single cell suspensions from a variety of murine tissues including lung, kidney, bone marrow, peripheral blood mononuclear cells, intestinal mucosa, liver, and fetus was studied. While kidney, intestinal mucosa, and peripheral blood mononuclear cells were clearly not lysed, there was a very low level of lysis of lung, bone marrow, liver, and fetus in repeated experiments. Separation of the cell suspensions of lung and bone marrow demonstrated much higher lysis of the adherent cell population, corresponding to an increased number of macrophages in the target cell suspension. Macrophages represent a population of cells particularly sensitive to lysis by LAK cells. All of the normal tissues were highly lysable by LAK cells in antibody-dependent cellular cytotoxicity assays in the presence of the appropriate anti-H-2 antibody. In a series of cold target inhibition studies, fresh normal murine kidney, lung, and bone marrow did not inhibit the lysis of the LAK-sensitive tumor target MCA-102, further demonstrating that fresh normal tissues share little if any of the determinant recognized by LAK cells on tumor targets. However, the MCA-105 and MCA-106 tumors, and the YAC cell line, all of which are sensitive to LAK cell lysis, did inhibit the lysis of MCA-102 tumor. These studies suggest that a common determinant is present on LAK-sensitive tissues that is absent or present in very low amounts on fresh normal tissues.
Lymphokine activated killer (LAK) cells selectively recognize and lyse a wide variety of tumor cells, including syngeneic, allogeneic, and xenogeneic cells, by a mechanism which remains unknown. It has been shown that trinitrophenyl modification of human peripheral blood lymphocytes (PBLs) and murine blasts induces sensitivity to lysis by LAK cells. We undertook these studies to examine the effects of trinitrophenyl (TNP) on murine normal cells and tumors. Fresh murine PBLs are resistant to LAK mediated lysis and TNP modification of the cell surface has no effect, in direct contrast to results with human cells. However, the addition of anti-TNP antibody demonstrated lysis of the TNP modified cells by an antibody dependent cellular toxicity mechanism showing that these cells can be lysed by LAK cells. Furthermore, TNP did not induce sensitivity to LAK cell mediated lysis on other normal murine tissues including kidney and bone marrow. The lysis of YAC tumor cells is not inhibited by the addition of TNP modified PBLs. A single cell assay demonstrated no conjugation of LAK effector cells and TNP modified PBLs. LAK cells derived from murine PBLs, as is done in the human, were unable to lyse the TNP modified PBLs, ruling out the origin of the LAK cells as the reason for the different results in humans and mice. These observations represent a difference in the spectrum of target cells lysed by human and murine LAK cells, and also demonstrate a response to TNP modification by fresh murine normal tissues and tumors that differs from that observed with murine blasts.(ABSTRACT TRUNCATED AT 250 WORDS)
Pulmonary embolism remains a problem in the United States in terms of both morbidity and mortality. New diagnostic modalities to make rapid diagnosis are now available, and allow for bedside diagnosis of pulmonary embolism without the use of pulmonary angiography. As a reference, a case involving a postpartum patient is reviewed. Use of echocardiography, a device readily available even in small institutions, allowed for early diagnosis and institution of therapy in this particular case and in others. Diagnostic features of pulmonary embolism are discussed and the literature is reviewed.
The use of preoperative computed tomographic (CT) scans of the chest in carcinoma of the esophagus to associate preoperative staging with postoperative survival is controversial. Thirty-two patients who underwent esophagectomy and reconstruction were examined with respect to a variety of variables available on preoperative evaluation, including lesion width on CT scan, lesion length on CT scan, and barium esophagogram. Each variable was evaluated for its ability to predict the presence of extraesophageal spread of tumor, as determined pathologically by logistic regression analysis. Lesions greater than 3.0 cm in width by CT scan were associated with a significantly higher incidence of extraesophageal spread. Tumor location, gender, histologic grade, presence of in situ lesions, vascular invasion, eosinophilia, nodal metastases, and preoperative chemotherapy had no predictive value for survival. Duration of survival was affected by the presence of esophageal spread of disease and lesion width. These results indicate that preoperative CT scanning can predict extraesophageal spread of tumor, and this is associated with overall survival.
The resection of hepatic metastases in patients with extrahepatic disease is of no proven benefit. Preoperative identification of extrahepatic disease may prevent unnecessary laparotomy. Preoperative evaluation including physical examination, computed tomography of the abdomen, full lung tomography or chest-computed tomography, and radionuclide bone scanning identified extrahepatic metastases, most commonly in the lung, in 25 of 132 patients with purported isolated liver metastases. Of 107 patients with negative staging evaluations, intra-abdominal extrahepatic metastases were found in 26 percent (28 of 107) at laparotomy, most commonly in portal and celiac lymph nodes. The presence of extrahepatic disease correlated with greater than 25 percent hepatic replacement by tumor, presence of symptoms, and Dukes' C primary lesions; however, none was predictive. We were unable to develop a model to preoperatively predict the presence of intra-abdominal extrahepatic disease. The authors recommend a preoperative evaluation including physical examination, and computed tomographic scans of the abdomen and chest. A bone scan is required only in patients with symptoms referable to bone. Despite a negative preoperative evaluation, however, a considerable proportion of patients with colorectal hepatic metastases will have extrahepatic disease at the time of abdominal exploration.