bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of isotope‐labeled somatostatin analogs for visualization of islet cell tumors
Authors: van Eyck C. H. J. , Braining H. A. , Reubi J. C. , Bakker W. H. , Oei H. Y. , Krenning E. P. , Lamberts S. W. J.
Published: May 2005

The results of visualization of the islet cell tumors of 25 patients after intravenous administration of two isotope‐labeled somatostatin analogs (123I‐Tyr3‐octreotide and111In‐octreotide) are described. The primary tumors, as well as previously often unrecognized distant metastases were visualized in 20 of the 25 patients (80%). Parallel in vitro detection of somatostatin receptors on those tumors that had also been visualized in vivo indicates that the ligand binding to the tumor in vivo indeed represents binding to specific somatostatin receptors. The detection of somatostatin receptors on these tumors in vivo predicted a good suppressive effect of octreotide on hormonal hypersecretion by these tumors. It is an easy, quick, harmless procedure that is valuable for localization of primary endocrine pancreatic tumors and their often radiologically and clinically not yet recognized metastases.
Surgical treatment of the Zollinger‐Ellison syndrome
Authors: Stadil F. , Bardram L. , Gustafsen J. , Efsen F.
Published: May 2005

A consecutive series of patients with Zollinger‐Ellison syndrome (ZES) is reported. A total of 53 cases were diagnosed, treated, and followed by one department during the period 1971–1990. Curative surgery was considered in all cases after suppression of acid secretion and after localization of the tumors. Exploratory laparotomy was not employed. Of the 53 patients 13 (24%) died from metastatic gastrinoma during the study. Tumors were ultimately located in 31 of the patients, and 21 of these patients were operated. A total of 12 patients (21%) were cured. The best results were obtained after Whipple pancreaticoduodenectomy in patients with small tumors located after percutaneous transhepatic portography with blood sampling for gastrin assay. In this group 9 of 10 operated patients were cured. Multiple endocrine neoplasia type I did not seem to preclude curative resection. The findings support an aggressive attitude toward local diagnosis and surgical treatment in ZES patients, but they also stress the need for improvements in methods for localizing tumors.
Surgical management of malignant islet cell tumors
Authors: Grant Clive S.
Published: May 2005

The surgical management of pancreatic islet cell carcinomas poses a complicated set of questions resulting from their rare occurrence and the difficulty in establishing a diagnosis in early cases or, conversely, the problems inherent in dealing with metastatic disease. However, because their biologic behavior is rather indolent, a real opportunity exists not only for cure but also for meaningful palliation. These goals apply both to the tumor itself and the effects of the hormones they may secrete. The challenge facing the multidisciplinary management team in general, and the surgeon specifically, is to achieve the optimal combination of surgical resection and other treatment options. While the precept of aggressive excision applies to most islet cell carcinomas, it is not universally applicable. In contrast to other islet cell tumors, insulinomas are overwhelmingly benign, and are well treated by enucleation or limited pancreatic resection. Although based on relatively few cases, cytoreductive surgery seems beneficial for malignant insulinomas. Advances that have occurred over the past decade in Zollinger‐Ellison syndrome have markedly altered surgical management. Medication which reliably prevents ulcer formation has permitted the surgical perspective to be redirected from end organ ablation to curative tumor excision. Multicentricity and metastases, however, limit the extent to which cure can actually be achieved. Patients with vasoactive intestinal peptide‐producing tumors and glucagonomas are very rare, and when possible, should undergo tumor resection to correct the severe hormonally caused metabolic derangements. Increasingly recognized are islet cell carcinomas that do not produce clinical syndromes. They may be confused with ductal carcinomas, but when resected, lead to distinctly superior survival rates among patients.
Pulmonary function after cholecystectomy performed through Kocher's incision, a mini‐incision, and laparoscopy
Authors: Coelho Julio C. U. , de Araujo Roberto P. M. , Marchesini Jõao B. , Coelho Izabel C. M. M. , de Araujo Luiz R. R.
Published: May 2005

Comparative pulmonary function after cholecystectomy performed through Kocher's incision, a mini‐incision, and laparoscopy was evaluated. Forty‐five patients were randomly and prospectively divided into three groups of 15 each, depending on the surgical access employed. Forced vital capacity (FVC), forced expiratory volume at 1 second (FEV1), and forced expiratory flow at 25% to 75% (FEF25–75%) were determined 1 to 3 days before and 16 to 24 hours after cholecystectomy. The percent reduction of FVC (p=0.0170), FEV1(p=0.0191), and FEF25–75%(p=0.0045) was smaller after laparoscopic cholecystectomy than after Kocher's incision cholecystectomy. The percent reduction of FVC (p=0.0170) was smaller after mini‐incision cholecystectomy than after Kocher's incision cholecystectomy. There was no difference in the FEV1(p=0.0971) or FEF25–75%(p=0.2058) between these two groups. FEF25–75%was significantly less impaired in the laparoscopic group than in the mini‐incision group (p=0.0327). No difference between these two groups was found in FVC (p=0.5755) or FEV1(p=0.3952). It is concluded that postoperative pulmonary function is less impaired after laparoscopic cholecystectomy than after either mini‐incision or Kocher's incision cholecystectomy.
Bile duct injury during laparoscopic cholecystectomy: Mechanism of injury, prevention, and management
Authors: Asbun Horacio J. , Rossi Ricardo L. , Lowell Jeffrey A. , Munson J. Lawrence
Published: May 2005

Although several studies have shown a low incidence of bile duct injuries during laparoscopic cholecystectomy, concerns remain because of the sustained increase in the number of referrals for biliary reconstruction after the procedure. Twenty‐one patients have been referred to our institution because of major bile duct injuries after laparoscopic cholecystectomy. The injury was recognized during the laparoscopic procedure in only 6 of the 21 (29%). Nineteen patients underwent hepaticojejunostomy at least once, one patient required hepaticojejunostomy and repair of a choledochoduodenal fistula, and one patient needed repair of a biliary colonic fistula. Hepaticojejunostomy above the bifurcation was required in 10 patients (50%), at the bifurcation in 3, and below the bifurcation in 7. Nine of the eleven patients in whom the initial repair was performed at the local hospital presented with early stricture (median 7 months). The common denominator of the development of bile duct injuries during laparoscopic cholecystectomy is the failure to identify the structures of the triangle of Calot. Specific steps during laparoscopic cholecystectomy to avoid bile duct injuries are described. Expertise in hepatobiliary surgery appears to optimize results of biliary reconstruction.
Isolation and transplantation of islet tissue
Authors: Scharp David W.
Published: May 2005

Recently, there have been remarkable advances in the area of islet tissue isolation and immuno‐alteration that place islet tissue transplantation on the verge of clinical trials. This paper reviews the islet isolation advances by focusing on 5 approaches: altering the pancreas in vivo, distending and/or perfusing the pancreas in vitro, chopping the pan‐creas, isolating either intact islets or islet cells, and purifying the islet tissue. This review also focuses on 3 areas of islet tissue transplantation: islet tissue preparation, transplantation sites, and the prevention of rejection. Advances in these areas should solve the remaining technical problems currently preventing clinical trials.
The effect of islet transplantation on complications in experimental diabetes of the rat
Authors: Federlin Konrad F. , Bretzel Reinhard G.
Published: May 2005

Experimental diabetes in the rat induces secondary complications of kidney, eye, and nervous system similar to the changes observed in humans. Transplantation of a sufficient number of isolated islets from isogeneic donors inhibits or reverses those lesions. Detailed studies have been made in order to examine renal glomerular and tubular lesions in diabetic rats prior to and following transplantation. Streptozotocin‐treated rats after 2 to 3 months begin to develop renal lesions with severe morphological changes, such as enlargement of the mesangial space, thickening of the capillary wall, deposition of IgG and C3, vacuolization of the tubular epithelial cells, and protein casts. Functional disturbances including increased glomular filtration rate, proteinuria, accumulation of basement membrane products (glucosyltransferase in the kidney, laminin P2, 7‐S collagen in serum), and increased excretion of brush border enzymes in the urine also developed. Intraportal islet transplantation leading to normalization of fasting blood glucose and insulin and of body weight either prevented these lesions or reversed early changes. Advanced renal changes are not reversible; however, further progression is halted. The experimental data support the view that rigid control in human diabetics may help to prolong the phase without secondary complications and that islet transplantation in the future may be a useful therapy.
Cryopreservation of insulin‐producing tissue in rats and dogs
Authors: Rajotte Ray V. , Warnock Garth L. , Kneteman Norman N.
Published: May 2005

Transplantation of frozen‐thawed islets of Langerhans normalized urine volume, urine glucose, plasma glucose, and weight gain in diabetic rats. However, these animals had abnormal intravenous glucose tolerance tests (ivGTT) at 3 mo post‐transplant. Modified cryopreservation protocols were extended to canine islet‐containing tissue: a higher temperature was used during equilibration in the 2 M dimethyl sulfoxide. Recipients of frozen‐thawed isografts had prolonged normoglycemia with plasma glucose <105 mg/100 ml for up to 18 mo. During ivGTT at 6 mo post‐transplant, K values (decline in glucose concentration, %/min) were similar in dogs autotransplanted with fresh (K=1.22±0.37) or cryopreserved tissue (K=1.8±0.4). Because of the similar compactness of the pancreas in humans and dogs, this canine model should be useful for formulating an optimal cryopreservation technique for human islets.
Experimental immuno‐alteration
Authors: Lacy Paul E.
Published: May 2005

In the past few years, remarkable advances have been made in preventing rejection of islet allografts and xenografts (rat to mouse) by 6 procedures which do not involve continuous immunosuppressive therapy of recipient rodents. Four methods alter or destroy passenger lymphoid cells in the islets prior to transplantation. These include in vitro culture of donor rat islets at low temperature and a single injection of anti‐lymphocyte serum in the recipients, culture of rat or mouse islet aggregates in 95% O2, and pretreatment of mouse islets with Ia antibody and complement or with a monoclonal antidendritic cell antibody and complement. Two methods induce partial tolerance in recipients by preimmunization with donor blood treated either with Ia antibody and complement or ultraviolet irradiation. These preimmunization procedures permit the use of untreated donor islets.

Two methods have been developed for the mass isolation of canine islets. Initial studies indicate that low‐temperature culture of donor canine islets and a single injection of anti‐lymphocyte serum will prevent rejection of canine islet allografts. The technical problems remaining for human islet allografts are selection of the optimum method of preventing islet allograft rejection based on studies in the dog, adaptation of the mass islet isolation techniques to the human pancreas, and selection of a safe and optimum site for transplantation.
Pancreatic islet transplantation: Immuno‐alteration with ultraviolet irradiation
Authors: Hardy Mark A. , Lau Henry T. , Weber Collin , Reemtsma Keith
Published: May 2005

To circumvent rejection of allogeneic pancreatic islet grafts, we have examined the use of ultraviolet (UV) irradiation to inactivate allostimulatory cells in blood prior to their use for the induction of donor‐specific tolerance and to decrease the immunogenicity of pancreatic islets by direct UV irradiation. UVB (280–320 nm) irradiation of blood can effectively abrogate lymphocyte stimulatory capacity in an MLC, while subsequent transfusions of appropriately UV irradiated blood have indefinitely prolonged islet allograft survival in the Lewis to ACI rat strain combination (greater than 250 days), without the use of immunosuppressive agents. This treatment is donor specific in that third‐party W/F islet allograft survival is not prolonged in ACI rats transfused with UV‐treated Lewis blood (MST, 7.5 days). When W/F rats are used as donors of blood, moderate prolongation of W/F islet allograft survival is obtained (MST of 21±12 days). When non‐UV‐treated W/F blood is transfused, rejection of W/F islets is accelerated (MST of 2 days versus no treatment control of 6.5 days) in the ACI recipient.

UV irradiation of rat dendritic cells can completely abrogate their powerful stimulatory activity in an MLC at a dose of 900 J/m2. Rat islets subjected to this same dose of UV irradiation do not exhibit any alteration in their endocrine function when transplanted into syngeneic diabetic animals. UV irradiated (900 J/m2) Lewis islets transplanted into non‐immunosuppressed ACI rats showed marked prolongation of survival (greater than 80 days).

We conclude that UV irradiation is effective in immuno‐alteration of the stimulatory cells in blood and can selectively decrease immunogenicity of pancreatic islets without being deleterious to their endocrine function. Both these methods are readily applicable to islet transplantation in other animals and eventually in humans.
Islet immuno‐isolation: The use of hybrid artificial organs to prevent islet tissue rejection
Authors: Scharp David W. , Mason Norbert S. , Sparks Robert E.
Published: May 2005

Immuno‐isolation protects islet tissue from rejection by enclosing it within semi‐permeable membranes. Four major techniques have been developed to achieve this goal: (1) Extravascular diffusion chambers. These can be implanted in many locations but are limited by host fibroblastic responses which further reduce diffusion capability. (2) Intravascular diffusion chambers. These have improved diffusion characteristics dependent on design but have serious vascular access problems. (3) Intravascular ultrafiltration chambers. These have a more rapid response since they do not rely on diffusion but have an additional problem of protein deposition on their membranes. (4) Microencapsulation. This technique incorporates the islet tissue inside a biochemical membrane making it more efficient. Yet the technique is limited by membrane instability. Immuno‐isolation offers an alternative to immunosuppression, but the biotechnology must be improved to develop suitable materials for effective clinical trials.
Minnesota experience with 85 pancreas transplants between 1978 and 1983
Authors: Sutherland David E. R. , Chinn Patricia L. , Goetz Frederick C. , Elick Barbara A. , Najarian John S.
Published: May 2005

We have performed 85 pancreas transplants in 79 diabetic patients since 1978 in a new clinical trial. Fifty grafts were from cadaver donors (32 segmental, 18 whole organ) and 35 (segmental) were from related donors (4 parent, 17 HLA identical and 7 non‐identical siblings, 6 identical twins, 1 cousin). All the grafts from the living related donors were immediately transplanted, but 48% of the cadaver donor grafts were stored at 4°C in silica gel‐filtered plasma for an average of 11.4 hours. Of the 67 recipients with HLA‐DR typing, 27% were DR3, 30% were DR4, and 39% were DR3,4 (96% for one or both). Fifty‐five percent of the recipients had had functioning renal allografts from 6 to 9 months earlier, while 45% were not renal recipients who had serum creatinine levels < 2.5 mg/100 ml and had not been previously immunosuppressed. Of the 75 patients transplanted, 62 (83%) are alive and 23 (32%) are insulin independent ranging from 1 to 65 months after transplant. The 1‐year actuarial graft survival rate is 25% overall, 36% from related and 16% from cadaver donors. Thirteen (17%) of the 75 have been insulin independent for more than 1 year. Graft failure resulted from technical error in 22 (26%) [10 from vascular problems, 4 (open duct) from severe ascites, 3 from peritonitis, 2 (pancreatico‐jejunostomy) from pancreatic leaks, and 3 from inadequate preservation]. Thirteen patients died (5 with functioning grafts): 6 from infections, 4 from cardiovascular disease, 1 from hyperkalemia, 1 from anaphylaxis to ALG, and 1 from unknown causes as a sudden death at home. One of the unresolved problems is that of the optimal technique to handle exocrine drainage. Of the 3 duct‐ligated grafts, all failed technically, and the 4 prolamine‐injected grafts had no long‐term function. Of the 15 open‐duct grafts, 53% were technical failures with 3 currently functioning. Of the 28 pancreatic‐jejunal grafts, 29% failed technically with 13 functioning from 1 to 28 months. Of the 35 silicone‐injected grafts, 9% technically failed with 7 currently functioning from 3 to 36 months. The 35 living related pancreatic donors have shown 2 (6%) to develop abnormal glucose tolerance tests, 2 (6%) to acquire complications requiring additional surgical correction, and 1 (3%) to show a nonoperative pancreatic complication. We favor cyclosporine A over azathioprine but the results must be individualized. Questions regarding autoimmune recurrence of disease are also raised by our studies in identical twins.
Segmental pancreatic transplantation with enteric exocrine diversion
Authors: Groth Carl‐Gustav , Tydén Gunnar , Lundgren Göran , Wilczek Henryk , Klintmalm Göran , Öst Lennart , Gunnarsson Rolf , Östman Jan
Published: May 2005

Fourteen combined cadaveric renal and segmentai pancreatic transplantations with both of the organs provided by the same donor were performed, and exocrine diversion was to the recipient's bowel. Nine of the grafts have failed because of technical surgical complications, and 2 grafts failed because of rejection. Three patients are carrying well‐functioning grafts 6, 19, and 24 months, respectively, after transplantation. Ten of the kidneys are functioning; thus, the use of combined transplantation has not jeopardized the results of renal grafting. Patients who had functioning pancreatic grafts had normal or near‐normal fasting blood glucose levels; studies of intravenous glucose tolerance test revealed k‐values around or just over 1.0 and glycosylated hemoglobin levels were normal. When azathioprine was replaced with cyclosporine, 4 of 6 patients showed a significant decline in k‐value. This deterioration in blood glucose control was reversible by dosage adjustment.
Transplantation for the treatment of insulin‐dependent diabetes: Clinical experience with polymer‐obstructed pancreatic grafts using neoprene
Authors: Dubernard Jean‐Michel , Traeger Jules , Bosi Emanuele , Gelet Albert , El Yafi Seoud , Devonec Marion , Piatti Pier Marco , Chiesa Roberto , Martin Xavier , Mongin‐Long Denise , Touraine Jean‐Louis , Pozza Guido
Published: May 2005

We performed 45 pancreatic transplants in 43 insulin‐dependent diabetics through October, 1983. In 11 cases the pancreas was transplanted alone; in 2 cases it preceded and in 1 case it followed a kidney transplant; and in 31 cases pancreas and kidney were transplanted simultaneously. Forty‐ four transplants were segmental, while in 1 case the pancreas was transplanted whole. The handling of the exocrine secretion was obtained through the duct occlusion technique by neoprene injection. The overall patient survival rate was 84.8%, 73.9%, 64.5%, 50.3%, and 35.0% at 3, 6, 12, 24, and 36 months, respectively. The overall pancreatic graft survival rate was 49.0%, 38.9%, 22.1%, 14.7%, and 7.4% at 3, 6, 12, 24, and 36 months, respectively. The survival rate for the pancreas transplanted simultaneously with kidney was 63.7%, 52.0%, 35.7%, and 23.8% at 3, 6, 12, and 24 months, respectively. Thirty‐four pancreatic grafts (76%) failed due to: rejection (31%), death of the patient (27%), vascular thrombosis (16%), and local infection (2%), while 11 pancreatic grafts (24%) are currently functioning up to 31 months.
Simultaneous renal and intraperitoneal segmental pancreatic transplantation: The Zürich experience
Authors: Baumgartner Dieter , Largiadèr Felix
Published: May 2005

Simultaneous renal and interperitoneal segmental pancreas transplantation with a prolamine‐occluded duct was performed in 15 type I diabetics with end‐stage renal failure. Four pancreas grafts are currently functioning at 2 days, 2 weeks, 30, and 39 months. In 3 patients, both organs were rejected within 6 months; 2 patients died with functioning grafts at 36 hr and 2 months. In 6 patients pancreatic failure for nonimmunological reasons did not jeopardize the simultaneous kidney graft. No adverse effects of duct occlusion with prolamine could be demonstrated. It is concluded that simultaneous renal and pancreatic transplantation is the method of choice in most patients with complicated type I diabetes and end‐stage renal failure.
Pancreas and islet transplant registry data
Authors: Sutherland David E. R.
Published: May 2005

From December 16, 1966, to June 30, 1983, some 337 pancreas transplants in 316 diabetic patients from 305 cadaveric and 32 living related donors were performed at 46 institutions throughout the world. A total of 60 pancreas transplants in 56 patients were performed prior to July 1, 1977, with only 2 functioning for more than 1 year. Therefore, the present era includes 277 pancreas trans‐plants performed in 262 patients at 39 institutions. Seventy‐four of these were done in 1982, while 72 were performed in the first 6 months of 1983 with 11 new institutions reporting. Of the 262 patients in the present era, 74 (28%) have died with 48 (18%) of these dying within the first 3 months of transplantation. Of the 190 pancreas transplants performed up to December, 1982, and available for evaluation of 1‐year graft function, 31 (16%) are currently functioning; another 8 (4%) functioned for 1 year but then failed (7) or the recipient died (1). Of the 72 transplants done in the first 6 months of 1983, there are 26 (37%) still functioning. Results are expressed according to technique of handling the ductal drainage, association with kidney transplantation, and association with the type of immunosuppression. Seventeen non‐diabetic patients (13 with chronic pancreatitis, 4 with adenocarcinoma) had autotransplantation of a segment of the pancreas after pancreatectomy. Thirteen were said to function but follow‐up data are incomplete. There were 73 islet tissue allografts reported as of June 30, 1980, but none of the patients achieved insulin independence. Since then an additional 86 islet tissue allografts have been reported without any insulin independence achieved to make a total of 159 performed without normoglycemia. A total of 79 pancreatectomized patients have received islet tissue autografts with 50% being reported as insulin independent, but the results are difficult to interpret.
The role of radiotherapy following total mastectomy for patients with early breast cancer
Authors: Berstock D. A. , Houghton J. , Haybittle J. , Baum M.
Published: May 2005

Analysis from a multicenter trial of the management of operable breast cancer now in its fifteenth year has confirmed earlier published results that there are no significant differences in survival and distant recurrence between the two treatment groups (“watch policy” and radiotherapy). However, patients receiving prophylactic radiotherapy at the time of mastectomy continue to have a reduced risk of developing local recurrence as the first sign of treatment failure (p<0.001). This increased risk is related to various known prognostic indicators such as tumor size and histological grade. Detailed analysis of local recurrence data has shown protection for the radiotherapy patients against recurrence in the chest wall and axilla but not in the supraclavicular area. The question of uncontrolled local disease persisting to death has also been addressed.
Mastectomy versus radiotherapy as treatment for stage I‐II breast cancer: A prospective randomized trial at the National Cancer Institute
Authors: Findlay P. A. , Lippman M. E. , Danforth D. , McDonald H. , d'Angelo T. , Gorrell C. R. , Gerber N. L. , Schain W. , Lichter A. S.
Published: May 2005

In 1979, the National Cancer Institute in Bethesda, Maryland initiated a randomized, prospective trial to compare surgery versus radiation therapy in the treatment of stages I and II breast cancer. Surgical treatment consists of total mastectomy with axillary lymph node dissection (modified radical mastectomy) and breast reconstruction; radiation treatment consists of gross tumor excision, axillary lymph node dissection, and comprehensive irradiation including a boost dose to the tumor bed. All patients with pathologically positive axillary nodes receive 11 cycles of adjuvant Adriamycin®/Cytoxan® chemotherapy. As of December 1984, there have been 175 patients entered in the study. Twenty‐three patients have developed disease recurrence (12 mastectomy, 11 radiation), but it is too early to obtain definitive treatment‐related results.
Conservative treatment of breast cancer with the QU.A.RT. technique
Authors: Veronesi Umberto , Zucali Roberto , Del Vecchio Marcella
Published: May 2005

Data are presented from a randomized, prospective clinical trial comparing the Halsted radical mastectomy with quadrantectomy, axillary node dissection, and breast radiotherapy (QU.A.RT.). From 1973 to 1980, a total of 701 patients with tumors <2 cm and clinically negative axillary nodes were accessed; the mean time on study is 8 years. No significant differences were apparent in local/regional recurrence, relapse‐free survival, or survival. Two percent of the patients in either group developed a local recurrence, and an additional 2% demonstrated a regional treatment failure. Relapse‐free survival at 8 years was 79% in the mastectomy group and 80% in patients treated with the quadrantectomy regimen; the proportion of patients surviving was 82.5% and 85%, respectively. In histologically node‐positive patients, there appeared to be prolonged survival for women treated with quadrantectomy (82% versus 70%), although this difference was not statistically significant. It is concluded that for patients meeting the eligibility criteria of this study, there is no demonstrable disadvantage for the use of quadrantectomy, axillary node dissection, and radiotherapy to the ipsilateral breast.
Limited surgical management for primary breast cancer: A commentary on the NSABP reports
Authors: Fisher Bernard , Wolmark Norman
Published: May 2005

This report presents an overview of findings from 2 interrelated studies carried out during the past 15 years by the National Surgical Adjuvant Breast and Bowel Project to determine the efficacy of alternative local and regional treatments of primary breast cancer. Findings from the first clinical trial, begun in 1971 involving 1,665 women, indicate that after 10 years of follow‐up there are no significant differences in disease‐free survival, distant disease‐free survival, or survival among patients treated by radical mastectomy or total mastectomy with and without radiation. The findings also indicate that radiation of internal mammary nodes in patients with inner quadrant lesions does not improve survival and that results obtained at 5 years accurately predict the outcome through 10 years. The second clinical trial, implemented in 1976 and accruing 1,843 women, demonstrates that after 5 years, treatment by segmental mastectomy (lumpectomy) with or without radiation results in disease‐free, distant disease‐free, and overall survival at least equivalent to, and in certain aspects better than, that achieved after total breast removal. Whereas 92% of those treated with radiation remained free of breast tumor at 5 years, when breast radiation was not employed, 72% (p<0.001) were without tumor reoccurrence. In positive‐node patients, 98% of those radiated remained tumor free, whereas only 64% of those receiving no radiation were free of tumor although both groups received chemotherapy.

While the clinical significance of these findings is obvious, their biological importance has received less attention. When considered in conjunction with other laboratory and clinical investigations, they lend no support for the anatomic and mechanistic precepts that have dictated thinking relative to metastasis production and have influenced surgical thinking. Clinical issues have arisen as a consequence of the 2 studies, particularly the second. Should a mastectomy be performed when lumpectomy specimen margins are involved with tumor? How should tumor reoccurrence in the ipsilateral breast following lumpectomy be managed? Can lumpectomy be employed for subareolar tumors or for tumors ≥4 cm? How extensive need radiation therapy be following lumpectomy? We have commented on all of these issues and have presented our current thinking regarding the management of patients in whom they arise.
Lumpectomy and axillary dissection for breast cancer: Surgical, pathological, and radiation considerations
Authors: Fisher Bernard , Wolmark Norman , Fisher Edwin R. , Deutsch Melvin
Published: May 2005

Recently, the first results were disclosed from a trial carried out by the National Surgical Adjuvant Breast and Bowel Project (NSABP) to evaluate the efficacy of breast conservation. These observations indicate that lumpectomy and axillary dissection plus radiation can be employed instead of total mastectomy for the treatment of a large proportion of women with primary breast cancer. The present report describes the technique of operation (lumpectomy), how the pathological examination of the resected specimen is carried out, and the manner in which radiation therapy is administered to the operated breast. The methodologies are those utilized in more than 1,200 women who for almost a decade have been participants in the NSABP study. It is emphasized that the outcome of patients exposed to breast preservation relates to the expertise of the surgeon, pathologist, and radiation and medical oncologists. The orchestration of care that will result in a satisfactory cosmesis and control of disease in the breast is more complex than is necessary for carrying out a mastectomy. Above all it is emphasized that, although the Halstedian concept for cancer surgery has been displaced, that change does not provide the imprimatur for haphazard surgery.
Adjuvant chemotherapy for operable breast cancer with positive axillary nodes: A comparison of CMFVP versus L‐PAM
Authors: Rivkin Saul E. , Glucksberg Harold , Foulkes Mary , Osborne C. Kent , Tranum William , Gad‐el‐Mawla Nazli , Constanzi John
Published: May 2005

This 5‐year update of a study by the Southwest Oncology Group continues to show that combination chemotherapy utilizing cyclophosphamide, methotrexate, 5‐fluorouracil, vincristine, and prednisone (CMFVP) is superior to melphalan (L‐PAM) used alone. Adjuvant chemotherapy for patients with operable breast cancer and positive axillary nodes treated with continuous CMFVP confers a significantly longer disease‐free and total survival compared to those treated with intermittent L‐PAM. This significant decrease in recurrence and prolongation of survival are demonstrated for the entire CMFVP group and in the following subgroups: premenopausal, postmenopausal, and women with 4 or more axillary nodes. Women with 1 to 3 axillary nodes have a significantly longer disease‐free interval, but a total survival advantage is not statistically significant.
Eight‐year follow‐up of adjuvant therapy for stage II breast cancer
Authors: Hubay Charles A. , Gordon Nahida H. , Pearson Olof H. , Marshall James S. , McGuire William L. ,   Participating Investigators
Published: May 2005

The 8‐year results of a prospective, randomized, clinical trial of 3 treatment regimens in 311 women with stage II breast cancer are reported. Cyclophosphamide, methotrexate, and 5‐fluorouracil (C) were compared with C plus the anti‐estrogen drug tamoxifen citrate (Nolvadex®) (CT) and CT plus Bacillus Calmette‐Guérin vaccinations (CTBCG) as adjuvant therapy postmastectomy. Estrogen receptors (ER) were measured in all primary tumors. The addition of Nolvadex® to chemotherapy significantly decreased the number of recurrences at 8 years. This decrease in recurrence was more pronounced in estrogen receptor‐positive patients as follows: (a) those with ≥ 4 positive lymph nodes; (b) those with tumor diameters ≥ 3 cm; and (c) postmenopausal women.

Addition of Nolvadex® to C had no effect on disease‐free survival in patients with ER‐negative tumors. Immunotherapy with BCG vaccinations had no discernible effect on disease‐free survival. Estrogen receptor measurements in the primary tumor provide important prognostic information regardless of treatment. Estrogen receptor‐positive patients have a lower recurrence rate and lower mortality after 8 years. Both estrogen and progesterone receptor measurements have predictive value for response to endocrine therapy and should be determined in all patients with breast cancer.
Adjuvant tamoxifen and chemotherapy in stage II breast cancer: Interim findings from NSABP protocol B‐09
Authors: Wolmark Norman , Fisher Bernard
Published: May 2005

Data are presented from a prospective clinical trial in which 1,891 patients with histologically confirmed stage II breast cancer were randomized to receive adjuvant therapy consisting of 1‐phenylalanine mustard and 5‐fluorouracil (PF) with and without tamoxifen (T). The findings indicate that the benefit previously noted for the addition of tamoxifen at 2 and 3 years' mean follow‐up is still apparent at 4 years. Although the tamoxifen‐containing regimen prolongs disease‐free survival and survival, this effect is not uniform and is dependent on patient age and tumor receptor content. Only those patients ⩾ 50 years of age demonstrated a benefit from the addition of tamoxifen to chemotherapy. The benefit was influenced by the degree of quantitative tumor receptor content. Patients ⩽ 49 years of age failed to demonstrate a prolongation in disease‐free survival with tamoxifen even when the tumor estrogen receptor content was ⩾100 fmol. Not only was there no benefit attributable to tamoxifen in patients ⩽49 years, if the tumor progesterone receptors were <10 fmol there was a significant diminution in disease‐free survival and survival. The results continue to indicate that the response to PFT therapy is heterogeneous in that only specific patient subsets demonstrate a salutary effect. Whether this phenomenon of heterogeneity is unique to the PFT combination or is an intrinsic biological property of stage II breast cancer remains to be ascertained.
Anti‐estrogen treatment of postmenopausal breast cancer patients with high risk of recurrence: 72 months of life‐table analysis and steroid hormone receptor status
Authors: Rose Carsten , Mouridsen Henning T. , Thorpe Susan M. , Andersen Johan , Blichert‐Toft Mogens , Andersen Knud W. ,   Danish Breast Cancer Cooperative Group
Published: May 2005

The role of anti‐estrogen treatment of postmenopausal breast cancer patients with high risk of recurrent disease is evaluated in a nationwide, prospective, randomized trial conducted by the Danish Breast Cancer Group. After total mastectomy and postoperative radiotherapy, 829 patients were randomized to treatment with tamoxifen (RT + TAM) for 1 year and 821 were randomized to no further therapy (RT). The recurrence‐free survival (RFS) after 72 months of life‐table analysis is 44% in the RT + TAM treated group, and 40% in the RT group(p=0.0003). Survival is 51% in both treatment groups(p=0.53). The data have been further analyzed with respect to prognostic factors such as age, degree of anaplasia, tumor size, and positive nodes. The RFS is lower in all subsets of patients treated with RT + TAM, but is only significant in patients 50–59 years of age, with tumors of anaplasia grade I, with tumors less than 5 cm, or with 4 or more positive lymph nodes.

Estrogen receptor concentrations were measured in a subset of 291 of these patients. A cut‐off limit of 10 fmol/mg cytosol protein and the use of a Cox proportional hazards model distinguished between patients with long RFS and those with early recurrent disease. Patients with an estrogen receptor content below 100 fmol/mg did not benefit from the endocrine therapy, while those with concentrations above 100 fmol/mg had a significantly longer RFS. Progesterone receptor determinations were performed in 12% of the patients. Progesterone receptor‐positive patients had a lower rate of recurrence when treated with RT + TAM compared to the receptor‐positive patients in the RT group(p=0.017).
The management of nonmetastatic locally advanced breast cancer using primary induction chemotherapy with hormonal synchronization followed by radiation therapy with or without debulking surgery
Authors: Sorace Richard A. , Bagley Caroline S. , Lichter Allen S. , Danforth David N. , Wesley Margaret W. , Young Robert C. , Lippman Marc E.
Published: May 2005

Forty‐three patients with locally advanced breast cancer, 15 with stage IIIA and 28 with stage IIIB, received primary induction chemotherapy, including hormonal synchronization in 38 patients, to a maximum objective clinical response before proceeding to local therapy. Patients achieving a pathological complete response received radiation therapy, while patients with residual disease, partial response (PR), or no change (NC) status received debulking surgery prior to radiation therapy; in all patients, 6 additional months of chemotherapy were administered. Chemotherapy consisted of cyclophosphamide 500 mg/m2 and doxorubicin 30 mg/m2 intravenously day 1; tamoxifen 40 mg/m2 orally days 2–6; premarin 0.625 mg orally every 12 hours 3 times beginning on day 7; methotrexate (mtx) 300 mg/m2 intravenously followed in 1 hour by 5‐fluorouracil 500 mg/m2 intravenously day 8, and leucovorin 10 mg/m2 orally every 6 hours 6 times beginning 24 hours after mtx. Forty‐two patients are evaluable with respect to response, time to progression, and survival. Objective response rate to chemotherapy was 90% with 50% CR, 40% PR, and 10% NC. Median number of cycles of chemotherapy to achieve a CR, PR, or NC was 5, 4, and 4 respectively. Eighteen patients with a CR to chemotherapy were assessed by multiple biopsies (16 patients) or mastectomy (2 patients). Fourteen patients (70%) were proven to be pathological complete responders. Thirty patients have completed combined therapy thus far and all have been rendered disease free. Seven stage IIIB patients have relapsed, 6 of them having inflammatory histological findings. No stage IIIA patients have relapsed. Median survival and time to progression have not been reached for either stage.
Seat belt‐induced trauma to the small bowel
Authors: Christophi C. , McDermott F. T. , McVey I. , Hughes E. S. R.
Published: May 2005

Thirty‐two patients with seat belt‐induced injuries to the jejunum and ileum are reviewed. These patients are classified into 3 groups according to the nature and mechanism of injury. Group I consists of 4 patients with complete transection of the proximal jejunum caused by deceleration forces. Injuries commonly associated include spleen rupture and perforation of the transverse colon and splenic flexure. Group II consists of 6 patients with infarcted ileum caused by crushing forces. Associated injuries include tears to the cecum, aorta, and inferior vena cava. Group III consists of 22 patients with “blowout” perforations of the jejunum and ileum. These injuries are caused by transmitted forces. There are no associated specific injuries related to this group.
Two techniques of measurement of the delayed hypersensitivity skin test response for the assessment of bacterial host resistance
Authors: Christou Nicolas V. , Boisvert Ginette , Broadhead Mary , Meakins Jonathan L.
Published: May 2005

We evaluated 2 methods for measuring the delayed hypersensitivity skin test response and related the data to clinical outcome in 586 subjects. Individual intradermal injections of 5 recall antigens and a saline control (Candida, mumps, PPD, trichophytin, and Varidase®) were used in one arm. A specially designed device that applied, simultaneously, 7 antigens and a glycerin control (tetanus, diphtheria, strep antigen, old TB,Candida, Trichophytin, andProteus mirabilis) was used at a separate site. Mean diameters of induration were recorded at 24 and 48 hours. Sepsis was defined as a bacteremia or an abscess identified at surgery or autopsy. Regression analysis of the sums of the mean diameters of induration of the first skin test response obtained by each of the 2 methods showed a positive correlation between the individual antigen technique and the multitest technique (n=1508, X=0.29Y+1.6, r2= 0.633,p<0.0001). Anergy to the individual antigen technique (n=155) was associated with a sepsis rate of 34% and a mortality of 38% compared with 7% sepsis and 3% death rates in reactive patients (n=281,p<0.0001). Similarly, anergy (n=281) to the 7 multitest antigens was associated with a 26% sepsis rate and 23% mortality compared to 5% sepsis and 5% mortality in the reactive subjects (n=242,p<0.0001). Despite the different antigens used in the 2 methods, both gave similar correlations between the delayed hypersensitivity skin test response (DTH) skin test score and sepsis—individual antigen technique: sepsis = 33.1 − 7.9*ln(DTH score) r2= −0.89,p<0.001; multitest technique: sepsis = 27.4 − 7.0*ln(DTH score) r2= −0.79,p<0.001. Patient acceptance of both tests was equal. Both techniques of assessing the DTH response demonstrated a close association with bacterial sepsis, and are useful tools for assessing host resistance in surgical patients.
Median sternotomy in reoperations for primary hyperparathyroidism
Authors: Norton Jeffrey A. , Schneider Philip D. , Brennan Murray F.
Published: May 2005

Thirty‐three patients underwent median sternotomy at reoperation for persistent or recurrent hyperparathyroidism. Radiographic studies correctly localized abnormal tissue to the mediastinum in 21 patients and surgery was successful in 19 of them. In the 12 patients without preoperative localization, surgery was successful in 9. Twenty‐six of 29 patients with a diagnosis of parathyroid adenoma had successful surgery, while only 2 of 4 patients with hyperplasia had successful procedures. In 10 patients the median sternotomy proved unnecessary since the parathyroid abnormality was located at a site reachable through the cervical incision. Abnormal parathyroid glands were found in the thymus (21), posterior to the thymus along the arch (6), within the thyroid (4), and at other ectopic locations. Abnormal parathyroid glands found within the thymus were often smaller than 1 cm in diameter and were detected by the pathologist after dissecting the entire thymus, indicating the need for total thymectomy. The complication rate was 12%, and the mortality rate was 6%.
Lasers in general surgery
Authors: Aronoff B. L.
Published: May 2005

Laser technology has wide application in general surgery. The CO2 laser functions as a scalpel sealing small blood vessels in the process of dividing tissues. The YAG laser has been especially useful in the performance of liver resection and the coagulation of large vascular tumors. The utility of lasers in various types of general surgical procedures is discussed.
Clinical applications of the Argon and carbon dioxide lasers in dermatology and plastic surgery
Authors: Maser Morton R. , Apfelberg David B. , Lash Harvey
Published: May 2005

Since the 1960's, thousands of skin and soft tissue malformations have been treated with the Argon and carbon dioxide lasers. The Argon laser, emitting blue‐green light, is very useful for treating port wine hemangiomas and other cutaneous vascular abnormalities; it has also been applied to a variety of nonvascular skin lesions. Its mechanism of action is essentially heat coagulation.

Carbon dioxide lasers function as hemostatic scalpels by emitting light that is much less selective in its tissue effect. Its role in the resection of hemangiomas and other lesions is discussed.

Histopathologic and tissue culture studies have been undertaken to monitor the effects of laser radiation on tissues. No malignant change has been noted. The Argon and carbon dioxide lasers must be used with great care; safety measures and treatment protocols are outlined.
Laser photocoagulation in alimentary bleeding
Authors: Swain C. P.
Published: May 2005

Laser therapy is theoretically more advantageous than endoscopic techniques such as diathermy in the treatment of alimentary bleeding primarily because the bleeding point is not directly touched or handled during therapy and the amount of energy dissipated in the surrounding tissue is more easily controlled. Only Argon and Neodymium‐Yttrium Aluminum Garnet (Nd Yag) laser beams can be passed down flexible wave guides suitable for endoscopic use in clinical gastroenterology. The Argon laser has been used by several groups for the treatment of patients with upper gastrointestinal bleeding. Success has been achieved in 80 to 95 percent of patients. Randomized trials comparing laser therapy to other modalities or to conservative, nonendoscopic therapy have in general suggested a greater benefit and lower incidence of rebleeding following laser application. Prospects for the utilization of lasers in patients with gastrointestinal bleeding depend crucially on the correct execution of randomized controlled trials currently in progress.
Current use of lasers in pulmonary disease
Authors: Hetzel M. R.
Published: May 2005

The principal role of lasers in pulmonary medicine is, and will probably remain, in the treatment of unresectable tumors. In its most limited capacity, current research has already demonstrated them to be valuable palliation tools in carefully selected cases, where it can improve the last few months of life of patients for whom conventional treatments are ineffective. At best, high power lasers and dye laser HpD systems may eventually offer cures to some patients unsuitable for surgery because of poor respiratory reserve, when the total tumor mass is endoscopically accessible. It is clear, however, that only a minority of lung cancer patients are suitable for laser therapy, and lasers should only be regarded as a promising addition to the current armamentarium against this depressingly lethal disease; rather than a replacement for currently accepted treatments.