bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of octreotide acetate for control of symptoms in patients with islet cell tumors
Authors: Maton Paul N.
Published: May 2005

Gut tumor syndromes are rare, occurring in less than two cases per million population per year: Insulinomas are most common and gastrinomas are less common; all the others are extremely rare. Conventional treatment of the symptoms caused by these tumors has included surgery, hepatic arterial embolization, and chemotherapy; some patients with Zollinger‐Ellison syndrome (ZES) have been treated with specific agents such as gastric antisecretory drugs. The development of octreotide, a synthetic, long‐acting analogue of the natural peptide somatostatin, has offered an alternative to such therapies. Octreotide has a half life of >100 minutes and inhibits both physiological‐ and tumor release of many peptides. It also has direct effects on the gut that modify secretion and motility. Octreotide has been shown to be particularly useful for the symptoms of tumors producing vasoactive intestinal peptide (VIP), and of the carcinoid syndrome. It is also useful in patients with glucagonomas, with growth hormone‐releasing hormone producing tumors, and in some patients with Cushing's syndrome and unresectable insulinomas. Octreotide is effective in patients with ZES, but alternative therapies such as omeprazole are more effective, safer, and more convenient for those patients. Side effects of octreotide have not been troublesome in these patients, but the incidence of long term effects is still not entirely clear. Octreotide has proved to be a significant advance in the treatment of patients with islet cell tumors.
Somatostatin analog Sandostatin and inhibition of tumor growth in patients with metastatic endocrine gastroenteropancreatic tumors
Authors: Arnold Rudolf , Neuhaus Christian , Benning Ralph , Schwerk Wolf B. , Trautmann Michael E. , Joseph Klaus , Bruns Christian
Published: May 2005

A prospective study was performed to determine the efficacy of octreotide (Sandostatin®; SMS 201–995) 200 μg tid in controlling tumor growth. The study included 21 patients with metastasized endocrine GEP tumors: 6 gastrinomas, 8 carcinoid syndromes, 7 nonfunctioning tumors. Treatment was performed for 3 to 59 months (median 15 months). Evaluation of the response to octreotide was facilitated in 12 patients by a pretreatment observation period of 3 to 47 months (median 17 months) during which the natural growth behavior was determined. Based on the presence or absence of a control period prior to treatment, 5 patients were considered to be responders, 7 as questionable responders (no pretreatment phase available), and 9 as nonresponders. None of the 21 patients had documented shrinkage of the tumor mass. The most favorable response was tumor standstill. In all but one responder an escape to an initially favorable response occurred after 6 to 28 months (median 14 months). Proved inhibition of growth was paralleled by a reduction of serum and urine hormone parameters, whereas unaltered progression of tumor growth was observed also in the presence of hormone suppression. Tumor growth and hormone release was inhibited in the absence and presence of somatostatin receptors on the tumor. It is concluded that octreotide exerts a limited effect on metastatic GEP tumor growth. The evaluation of a response to octreotide is facilitated by an observation period prior to the drug that provides information on growth characteristics of the tumor. The presence of octreotide receptors does not predict the success of therapy.
Percutaneous transhepatic portal embolization using newly devised catheters: Preliminary report
Authors: Nagino Masato , Nimura Yuji , Hayakawa Naokazu
Published: May 2005

Two 5.5 French triple‐lumen balloon catheters were devised to improve percutaneous transhepatic portal embolization (PTPE) as preoperative management of patients undergoing extensive liver resection. Using these catheters, an ipsilateral approach for embolization is achieved through a portal branch of the liver using fibrin glue mixed with Lipiodol as the embolic material. This approach proved safer and more reliable than the traditional contralateral approach: (1) The portal branch to be resected is punctured; (2) the left and right anterior portal embolization is conducted simultaneously through a single portal puncture; and (3) the catheter sheath can consequentially be removed soon after PTPE without requiring further treatment.
Experimental study of pylorus and pyloric vagus preserving gastrectomy
Authors: Yunfu Lu , Yiding Hou , Shouren Jia , Cuiying Guo
Published: May 2005

In an attempt to prevent the sequelae of conventional gastrectomy, such as rapid gastric emptying, dumping syndrome, intestinal content reflux, indigestion, and poor absorption, we have devised the pylorus and pyloric vagus preserving gastrectomy (PPVPG). Experimenting on 48 dogs, we found theoretic grounds for using our design and obtained the desired effects‐retaining the merits of conventional subtotal resection of the stomach, with acidity reduction, while avoiding the above‐mentioned complications.
Exogenous growth hormone: Effects on the catabolic response to surgically produced acute stress and on postoperative immune function
Authors: Vara‐Thorbeck R. , Guerrero J. A. , Rosell J. , Ruiz‐Requena E. , Capitán J. M.
Published: May 2005

The first purpose of the present prospective randomized study was to determine if the protein catabolic response after operation could be restrained by administration of hypocaloric parenteral nutrition (HPN) plus human growth hormone (hGH). Our second aim was to determine if the administration of hGH could improve the systemic host defenses, thereby reducing the risk of infection. We performed a placebo‐controlled randomized double‐blind trial in 180 patients after elective cholecystectomy with or without choledochoduodenostomy (placebo=control group,n=93; hGH‐treated group,n=87). The results obtained in this study show that positive nitrogen balance can be achieved during the postoperative period from the first 24 hours onward, with a combination of HPN support (1.0–1.5 g protein/kg/day and 900 kcal/day) together with the administration of small doses (8 IU) of hGH. The potassium balance tended to follow the same positive balance as the nitrogen balance. Our study shows that in the control group, treated only with HPN, a significant decrease in serum levels of some acute‐phase proteins (retinol‐binding protein, transferrin, prealbumin), albumin, total proteins, and immunoglobulins occurs by the 5th postoperative day. In the GH group the values of all the above‐mentioned proteins do not change or tend to rise if compared to preoperative levels. In the GH‐treated group liver function appeared to improve at the start of the study. GH and somatomedin C levels were similar in the two groups and had not changed significantly in the control group by the 5th postoperative day. In the GH‐treated group a significant increase in serum levels of GH and somatomedin C on postoperative day 5 was observed. Glucose levels in the control group were unaltered, but in the GH‐treated group a clear increase in glucose concentration was observed. On the other hand, insulin values on postoperative day 5 in the GH group rose to almost twice those of the control group. After operation the number of normoergic patients in the control group fell from 56 to 40; in the GH‐treated group the opposite was the case: the number of normoergic patients increased from 59 to 81. The number of anergic patients remained constant (n=11) in the control group and disappeared in the GH‐treated group. Wound infection was found in 16 patients (17.2%) of the control group but in only 3 (3.4%) of the GH‐treated group. Hospitalization averaged 12.5 ±7.1 days in the control group versus 9.6 ±3.6 days in the GH‐treated group (p < 0.05). With moderate surgical injury (cholecystectomy with or without choledochoduodenostomy) hGH can optimize utilization of adjuvant HPN and overcome the protein catabolic effects of the trauma response. As a result, body cell mass is preserved, wound healing is promoted, and immunologic function is enhanced.
Laparoscopic cholecystectomy: A minor abdominal trauma?
Authors: Schippers Ekkehard , Öttinger Alexander P. , Anurov Michael , Polivoda Michael , Schumpelick Volker
Published: May 2005

Clinical observations following laparoscopic surgery indicate a shorter period of postoperative ileus than after conventional surgery. The aim of our study was to verify disorders of postoperative motility of the small intestine by means of implanted electrodes after laparoscopic and conventional cholecystectomy (CHE) in an animal model. Four weeks after implantation of three electrodes on the jejunum, CHE was performed laparoscopically in 5 dogs and in an additional 5 dogs by laparotomy. Independent of the type of operation, normal motility (especially the migrating motility complex) was abolished during the early postoperative period. Electrical activity was characterized by the basic electrical rhythm. Time to the occurrence of the first postoperative activity front, indicating restoration of motility, varied significantly depending on the type of operation: It was 5.5 ±1.0 hours after laparoscopic CHE and 46 ±5 hours after conventional CHE. These results support the hypothesis that small peritoneal incisions and less manipulation of the intestine during laparoscopic surgery result in reduced abdominal trauma.
Management of bile duct injuries and strictures following cholecystectomy
Authors: Raute M. , Podlech P. , Jaschke W. , Manegold B. C. , Trede M. , Chir B.
Published: May 2005

During 7057 conventional cholecystectomies (1972–1991), 16 bile duct injuries occurred, amounting to a risk of 0.22%. A total of 1022 laparoscopic cholecystectomies were performed without such a complication since April 1990. In a retrospective study, 64 patients (16 of our patients and 48 referrals) with an injury or stricture due to conventional cholecystectomy were investigated. In 14 of our 16 patients the injury was recognized and immediately repaired with a good long‐term result of 93%, including one successful repair of a subsequent stricture. Two cases of unrecognized injury were managed by nonoperative means. The group of 48 referred patients comprised 10 early postoperative complications (21%) and 38 strictures after an “uneventful” cholecystectomy. Of the 64 total patients, 10 (16%) underwent nonoperative treatment, and 54 required surgery. The mean follow‐up period after surgery was 7.4 ±4.9 years. Most cases (93%) were repaired by bilioenteric anastomosis (i.e., foremost hepaticojejunostomy) with an 18% restricture rate. Including second and third repairs for restricture, a total of 60 operations (14 primary and 46 secondary reconstructions) were performed without hospital mortality. A good long‐term result after stricture repair was achieved in 75% of the patients, whereas 17% had a poor outcome owing to restricture or death (10% had related mortality within 10 years). The other 8% had a moderate result due to recurrent cholangitis. Thus immediate repair of a bile duct injury offers the better chance of a favorable prognosis compared to secondary stricture repair.
Historical review of pancreatic islet transplantation
Authors: Downing Richard
Published: May 2005

This historical perspective attempts to document the origin and early work of islet tissue transplantation. In the final analysis, most of these early experiments were failures. However, the ideas were clearly appropriate and in place at a very early phase. The first islet tissue transplantation was done in 1893; that is 29 years prior to the Banting's and Best's discovery of insulin therapy. Most of our current active approaches have been tried in the past. As is the case in many areas in science, the problems were defined with ideas and solutions outlined long ago. Yet, the problems were not solvable because of inadequate technology. The insight behind these early experiments must be admired, knowing the limited knowledge that was available. Keeping this historical perspective in mind as we work through our technologic opportunities may be of assistance as we approach our goal of clinical islet transplantation.
Fetal pancreas as a donor organ
Authors: Brown Josiah , Danilovs John A. , Clark William R. , Mullen Yoko S.
Published: May 2005

The use of the fetal pancreas as a donor organ for the treatment of diabetes has been explored in the rat and currently is being tried in minipigs. Growth and development of a fetal pancreas under the kidney capsule of a diabetic rat is sufficient to completely reverse streptozotocin diabetes; the organ contains 20–25% of the insulin content of a normal adult pancreas. The fetal pancreas grows and develops most fully in normoglycemic environment. Cryopreservation results in nearly complete survival of the pancreas and provides time for tissue and blood typing and testing for compatibility of donor and recipient lymphocytes using the Mixed Leucocyte Reaction. These methods have been developed in human systems. Removal of the pancreas from the fetus and transplantation prior to a critical period of exocrine development (18 days in the rat, 55 in the pig) are followed by atrophy of exocrine elements and a pure endocrine organ results. This obviates the problem of exocrine enzymes. Venous drainage of insulin from the transplanted pancreas into the liver provides the most effective response when the supply of insulin is limited. Metabolic studies in successfully‐transplanted rats indicate complete reversal of the diabetic state to normal. These include blood glucose and insulin levels and responses to stimuli, the activity levels of 6 enzymes in the liver, glucagon levels, and the response to arginine stimulation and glucose metabolism during and after pregnancy.

Methods that have been used to prevent rejection, all of which have been partially effective, include donor liver pretreatment and short‐term immunosuppression, total lymphoid irradiation combined with donor bone marrow, and treatment of the donor organ to eliminate immune cells by digestion and culture. Additional research will be required to develop an effective and safe method for prevention of allograft rejection in the minipig prior to application to diabetic humans.
Transplantation of organ‐cultured fetal pancreas: Experimental studies and potential clinical application in diabetes mellitus
Authors: Mandel T. E.
Published: May 2005

Transplantation of organ‐cultured fetal islets of Langer‐hans may be one way of overcoming the dual difficulties of finding a suitable source of tissue and controlling graft rejection. Experiments in mice have clearly shown that fetal pancreas is an excellent source of islets. Tissue from one donor can be used to treat one or more recipients and provides excellent control of drug‐induced diabetes, including prevention of diabetic renal microangiopathy. The fetal islets display selective survival in vitro and organ culture can be used to obtain large amounts of tissue for transplantation. In addition, growth in “normoglycemic” media results in functional maturation of the fetal tissue.

Culture conditions can be modified to eliminate from the putative graft immunogenic “passenger leukocytes,” the cells responsible for initiating graft rejection. Such immunogenic cell—depleted grafts can be transplanted across histocompatibility barriers without the need for recipient immunosuppression.

Fetal human pancreas shares many properties in common with fetal mouse pancreas. Continuing growth and differentiation occur in vitro and following xenotransplantation into athymic mice. However, fetal human pancreas is frequently damaged by ischemia before it can be used, and also appears to be more susceptible to oxygen toxicity than is fetal mouse pancreas. Nevertheless, when fresh human tissue is available, it may be a suitable source of islets for transplantation in type I diabetics.
Theory and practice of immunoregulation by tissue treatment prior to transplantation
Authors: Lafferty Kevin J. , Prowse Stephen J.
Published: May 2005

According to the classical view of allograft rejection, the transplanted tissue is the source of antigen that stimulates a T‐cell response, which in turn sets up the rejection process. Research now indicates that two signals are required for lymphocyte activation. The first signal is provided by antigen binding by the T‐cell receptor. A stimulator cell provides an inductive molecule, costimulator activity, which is the second signal. The stimulator cell model of lymphocyte activation has resulted in a new passenger leukocyte concept, in which these passenger cells are seen to play a central role in graft rejection. Appropriate treatment of a tissue prior to transplantation can afford a marked reduction in its immunogenicity for the host. It is now possible to eliminate or at least reduce tissue immuno‐genicity by removal of leukocytes from the transplant prior to grafting. This phenomenon has been demonstrated to be effective with both endocrine tissue and larger organs, such as the kidney. There is some variation in the effectiveness of the technique with different tissues which can be related to the degree of leukocyte contamination. Allografts of pretreated tissue can induce a state of specific unresponsiveness in the adult recipient. Although the mechanism of this tolerance is not fully understood, the existence of the phenomenon is one of the most encouraging recent developments in transplantation biology.
Immunogenetic considerations in islet transplantation: The role of Ia antigens in graft rejection
Authors: Bach Fritz H. , Morrow Charles E. , Sutherland David E. R.
Published: May 2005

As demonstrated by Faustman et al., islets that are pretreated with Ia antibodies and complement show markedly prolonged survival as compared with islets, with the same immunogenetic disparity, without antibody pretreatment. In order to test whether it is simply the absence of an allo‐Ia disparity that accounts for this finding, we have transplanted islets across class I disparities alone; in certain cases, such islets are rapidly rejected. Yet, even though there is no allo‐Ia difference on such islets, pretreatment of the islets with anti‐Ia monoclonal antibody also results in markedly prolonged survival. We suggest that the presence of Ia antigens may serve as a differentiation marker for cells that can present class I antigens in an immunogenic manner; further, allo‐Ia antigens can lead to a stronger anti‐class I rejection response.
Immunologic factors in pathogenesis and treatment of human and animal diabetes
Authors: Naji Ali , Silvers Willys K. , Bartlett Stephen T. , Francfort John , Barker Clyde F.
Published: May 2005

Recent evidence suggests that the pathogenesis of insulindependent (type I, juvenile onset) diabetes mellitus may have an important autoimmune component, possibly triggered by a viral infection. This evidence includes mononuclear infiltration of the endocrine pancreas, circulating islet cell antibodies, and a strong association with certain HLA alleles (DR3 and DR4). The biologic response (apart from allograft rejection) of diabetic hosts to transplanted islets has been examined in an animal model of spontaneous diabetes which closely resembles the human condition (the BB rat). In this syndrome, MHC‐compatible islet allografts suffered autoimmune destruction even when rejection was excluded by experimental design. Implications of this finding with respect to human islet and/or pancreas transplantation are discussed.
Cyclosporine and pancreas transplantation
Authors: Gray D. W. R. , Morris P. J.
Published: May 2005

A variety of experiments have thus far shown cyclosporine to be not nearly as successful in preventing rejection of pancreas allografts (islets, fetal, vascularized segmental) in experimental animals as it is with other tissues. Clinical experience has also been relatively disappointing, although surgeons at most centers have the impression that it is marginally better than azathioprine and steroids. The role of cyclosporine in pancreas transplantation, and indeed the place of pancreas transplantation, remains uncertain at this time.
Experimental vascularized segmentai pancreatic and islet transplantation in the baboon
Authors: du Toit Don F. , Heydenrych Jacobus J. , Smit Ben , Louw Gabriel , Zuurmond Theuns , Laker Lida , Els Daniel , Weideman André , Wolfe‐Coote Sonja , van der Merwe Emanuel A. , Groenewald Wilhelm A.
Published: May 2005

The present study was undertaken to evaluate the effectiveness of cyclosporine (CYA) and total body irradiation (TBI) or total lymphoid irradiation (TLI) in suppressing segmental pancreatic allograft rejection in totally pancreatectomized outbred Chacma baboons. In addition, the study includes our preliminary results with subcapsular renal autotransplantation of dispersed autologous pancreas in the primate.

CYA in doses of 25–50 mg/kg per day produced a slight but significant prolongation of graft survival. There was a wide variation of daily CYA serum trough levels exhibited between primates on the same daily oral dose, and there was no clear correlation between absolute CYA serum trough levels and rejection. Although heterotopic auto‐ or allotransplantation of the tail of the pancreas in the baboon was capable of maintaining normoglycemia in pancreatectomized baboons until rejection of the graft, glucose intolerance, reduced K‐values, and hypoinsulinemia were consistent findings during glucose tolerance tests, suggesting transplantation of an insufficient islet cell mass.

Animals that received 76 rad (TBI) remained normoglycemic between 14 and 36 days with a median of 22 days, which indicated a modest but significant prolongation of graft survival. Animals treated with TLI (600 rad) sustained graft function between 7 and 31 days with a median of 17 days. The optimal regimen of irradiation in terms of cumulative dose, dose per fraction, number of fractions, and frequency of irradiation still requires refinement in this model.

Primates receiving subcapsular autologous dispersed pancreas failed to become normoglycemic and plasma glucose levels never dropped below 12 mmol/L. Postmortem examination revealed diffuse chemical peritonitis associated with surrounding fat necrosis and autodigestion of the retroperitoneal tissues, suggesting that this technique has no clinical application at present.
Experience in human segmental pancreas transplantation
Authors: McMaster P. , Michael J. , Adu D. , Gibby O. M. , Vlassis T.
Published: May 2005

Pancreas transplantation in the United Kingdom was initiated just over a decade ago and interest further developed with the introduction of ductal injection techniques and cyclosporin. However, graft losses associated with technical problems remain a significant problem, and experiences over the last year with other units initiating programs suggest progress continues to be slow.
The revolution in breast cancer surgery: Science or anecdotalism?
Authors: Fisher Bernard
Published: May 2005

During the past 15 to 20 years, there have resulted revolutionary changes in the local/regional management of primary breast cancer. Why have those changes come about? Has science played a role or have they been entirely related to the experiences of a few who have “tampered with tradition” for some nebulous reason? This report traces the pathway of change from Halsted's time to the present and attempts to point out wherever possible the relation of these changes to science and/or to “anecdotalism.” It traces the origins of the Halstedian hypothesis of cancer management, the reasons for its perpetuation, and the clinical challenges to it which were really not challenges at all. A description of laboratory and clinical research in the 1960's which led to an alternative hypothesis is presented, as is a description of how clinical trials tested the alternative hypothesis. The results of those trials, recently reported, lend support to a concept of surgery for cancer which embodies biological principles rather than the mechanistic and anatomical principles of the past. A brief discussion is provided relative to how cancer surgery interrelates with other modalities and the article concludes with the author's concept of a surgical oncologist.
Adjuvant chemotherapy in stage II breast cancer: A brief overview of the NSABP clinical trials
Authors: Wolmark Norman , Fisher Bernard
Published: May 2005

Since 1972 the National Surgical Adjuvant Breast and Bowel Project (NSABP) has completed 5 adjuvant chemotherapy protocols into which over 3,500 histologically nodepositive patients have been entered; data for this review are derived predominantly from the first 3 studies. Each study was performed sequentially with the intent of identifying patient subsets responding to 1, 2, or 3 chemotherapeutic agents. Comparison of disease‐free survival in patients receiving l‐phenylalanine mustard (L‐PAM) or placebo after 10 years of follow‐up disclosed that L‐PAM was beneficial in patients up to 49 years of age, but not in women ⩾50 years. Further analysis indicated that the subset of patients ⩽49 years with 1–3 positive nodes sustained the greatest increment in disease‐free survival with single‐agent L‐PAM. The addition of 5‐fluorouracil (5‐FU) to L‐PAM was superior to L‐PAM alone in patients ⩾50 years of age, particularly those with ⩾4 positive nodes. This effect became attenuated after 6 years of follow‐up. The 3‐drug regimen of L‐PAM, 5‐FU, and methotrexate failed to provide a benefit over and above that achieved by the L‐PAM‐5‐FU combination in all subsets examined. Two further NSABP protocols are described in which the addition of Adriamycin® to L‐PAM and 5‐FU is addressed. The rationale for the current generation of NSABP adjuvant chemotherapy trials using short intensive Adriamycin® and cyclophosphamide regimens is discussed. The results continue to underscore the heterogeneous response to chemotherapy demonstrated by patient subsets characterized on the basis of age and nodal status.
Adjuvant CMF chemotherapy in operable breast cancer: Ten years later
Authors: Bonadonna Gianni , Rossi Anna , Valagussa Pinuccia
Published: May 2005

This article reports the 10‐year results of a trial testing radical mastectomy with or without adjuvant cyclophosphamide, methotrexate, and fluorouracil (CMF) in 386 women with breast cancer and positive axillary lymph nodes. The long‐term analysis confirmed that adjuvant chemotherapy was able to produce a significant relapse‐free survival improvement (43.4%) versus control (31.4%,p<0.001) and a trend in total survival (55.2% versus 47.3%,p=0.10). Both relapse‐free survival and total survival benefit were significant in premenopausal women. Relapsefree survival was not influenced by drug‐induced amenorrhea. In both treatment groups, the results were inversely related to the number of histologically involved axillary nodes. On relapse, salvage treatment applied in the control group failed to produce superior results compared to those achieved in the CMF group and yielded a similar median survival from first relapse between control (37 months) and CMF (32 months) patients. The incidence of severe myelosuppression and hair loss was low (less than 10%) and reversible. Prolonged chemotherapy was not associated with an increased incidence of second neoplasms. We conclude that CMF, as given in this study, was able to improve the course of premenopausal women with high‐risk breast cancer during the first decade following radical mastectomy.
A randomized trial of CMF versus CMFVP as adjuvant chemotherapy in women with node‐positive stage II breast cancer: A CALGB study
Authors: Wood William C. , Weiss Raymond B. , Tormey Douglass C. , Holland James F. , Henry Patrick H. , Leone Louis A. , Rafla Sameer , Silver Richard T. , Carey Robert W. , Lesnick Gerson J. , Weinberg Vivian E. , Korzun Ann H. ,   Cancer and Leukemia Group B
Published: May 2005

Women treated by mastectomy for node‐positive breast carcinoma were randomly assigned to receive an induction course and 2 years of maintenance chemotherapy with cyclophosphamide, methotrexate, and 5‐fluorouracil (CMF) or CMF plus vincristine and prednisone (CMFVP). Five‐hundred twenty‐five evaluable patients were entered between 1975 and 1980. CMVFP was superior to CMF for patients with more than 3 positive nodes(p=0.01) with disease‐free survival of 50% at 5 years with CMFVP compared with 36% with CMF. The advantage of CMFVP was not seen in patients with 1–3 positive nodes and was most marked in patients with 10 or more nodes. This suggests benefit from increased treatment with increasing disease burden. The superiority of CMFVP was more marked in postmenopausal patients(p=0.04) than in premenopausal(p=0.12). The advantage of CMFVP in disease‐free survival is not yet apparent in overall survival.
Adjuvant therapy for breast cancer with positive axillary nodes designed according to estrogen receptor status
Authors: Rivkin Saul E. , Knight William A. , McDivitt Robert , Cruz Tony , Foulkes Mary , Osborne C. Kent , Fabian Carol J. , Costanzi John J.
Published: May 2005

This is a preliminary report of the Southwest Oncology Group in which therapy is randomized by estrogen receptor (ER) data. Estrogen receptor‐negative patients receive either 1 or 2 years of cyclophosphamide, methotrexate, 5‐fluorouracil, vincristine, and prednisone (CMFVP). The ER‐positive group receive CMFVP for 1 year and/or hormonal therapy. The findings to date include: (a) Estrogen receptor‐positive patients have a significantly longer disease‐free interval compared to ER‐negative patients (p =0.004); (b) there is no significant difference in diseasefree interval for ER‐negative patients who receive either 1 or 2 years of CMFVP; (c) the data for ER‐positive patients is too preliminary to report for disease‐free or total survival; and (d) toxicity is acceptable because of frequent monitoring and examinations which result in the low percentage of life‐threatening toxicity.
Adjuvant chemotherapy in postmenopausal women: Results of sequential noncross‐resistant regimens
Authors: Brambilla Cristina , Rossi Anna , Valagussa Pinuccia , Bonadonna Gianni
Published: May 2005

This article reports the 6‐year results of a controlled adjuvant trial carried out in 140 postmenopausal women aged 65 years or less having resectable breast cancer and positive axillary nodes. Within 4 weeks after surgery, patients were started on cyclophosphamide, methotrexate, and fluorouracil and prednisone (CMFP) for 6 cycles followed by Adriamycin® plus vincristine (AV) for 4 cycles. Chemotherapy was delivered with minimal dose reduction schedule. Patients were randomized to receive standard dose regimen for both combinations (treatment A) or progressive dose intensification (treatment B). There was no significant difference in the relapse‐free (RFS) and overall survival (OS) rates between the 2 treatment groups. Treatment results were inversely related to the number of involved axillary nodes. In the subset with 1 to 3 positive nodes, present findings are superior (RFS 75.2%, OS 84.2%) when retrospectively compared to the 6‐year results achieved with adjuvant CMF in the same postmenopausal subset (12 cycles: RFS 55.4%, OS 67.3%; 6 cycles: RFS 47.5%, OS 65.5%). Acute toxicity was moderate and reversible, and no patient showed signs of cardiomyopathy. The results of this trial indicate that sequential noncross‐resistant combinations administered with minimal dose reductions can favorably affect the postoperative course of postmenopausal women with limited nodal involvement. The study design does not allow for quantitating the relative contribution of CMFP versus AV chemotherapy.
Six‐year results of a controlled trial of tamoxifen as single adjuvant agent in management of early breast cancer
Authors: Wilson A. J. , Baum M. , Brinkley D. M. , Dossett J. A. , McPherson K. , Patterson J. S. , Rubens R. D. , Smiddy F. G. , Stoll B. A. , Richards D. , Ellis S. H.
Published: May 2005

A randomized controlled trial of tamoxifen as a single adjuvant agent after mastectomy for early breast cancer, reported on at an average follow‐up of almost 2 years in 1983, has now been followed up to a maximum of 6 years. One thousand two hundred eighty five patients aged 75 or less were entered into the trial. Premenopausal women with positive axillary nodes and postmenopausal women with both positive and negative axillary nodes were randomized to receive either tamoxifen 10 mg twice daily for 2 years or to the untreated control group with systemic therapy reserved until the time of relapse. Forty‐six percent of the trial population had primary tumor specimens assayed for estrogen receptor (ER) content. There has been a highly significant reduction in death rate, with 45 (34%) fewer deaths observed in the treated group than in the control group. This benefit appeared to be independent of menopausal, nodal, or ER status.
Synchronous multiple early gastric carcinoma: A study of 178 cases
Authors: Noguchi Yoshikazu , Ohta Hirotoshi , Takagi Kunio , Ike Hideyuki , Takahashi Tomoyuki , Ohashi Ichiro , Kuno Keijiro , Kajitani Tamaki , Kato Yo
Published: May 2005

Over the past 3 decades, ending in 1979, resection has been performed in 7,220 patients with gastric carcinoma. Synchronous multiple gastric carcinoma, according to the diagnostic criteria of Moertel, was found in 468, of which 178 (38%) were “early.” There were 135 double, 33 triple, and 10 quadruple early carcinomas. Fewer than one‐third of the smaller tumors were diagnosed preoperatively, and 61.5% of the smaller lesions were less than 10 mm in diameter. In 53% of the patients, the smaller lesions were in the lower one‐third of the stomach with the main lesion in the upper one‐third, whereas in 13% the smaller neoplasms were located in the upper one‐third of the stomach with the main lesion in the lower one‐third. The clinical significance of the smaller lesions was their location relative to the resection line. When planning treatment of gastric carcinoma, it is important to evaluate the whole stomach before and during the operation and after examining the resected specimen. The 5‐year survival rate for patients with multiple early gastric carcinoma was 85.8%.
A comparison of the prophylactic value of cefotetan and metronidazole in appendectomy
Authors: Buckels John A. C. , Brookstein Roger , Bonser Robert , Bullen Barry , Alexander‐Williams John
Published: May 2005

In a prospective randomized trial of 97 patients undergoing appendectomy, the prophylactic value of cefotetan, a new semi‐synthetic cephamycin with activity against a wide range of aerobic and anaerobic bacteria, has been compared with that of metronidazole. A significantly lower wound sepsis rate was found with cefotetan (4.2%) than with metronidazole (19.1%). The superior results of cefotetan appear to be due to its anti‐aerobic as well as anti‐anaerobic activity.
Lasers in gynecology
Authors: Bellina Joseph H.
Published: May 2005

The CO2 laser is widely used in gynecology. It has been most effective in the treatment of intraepithelial cervical neoplasia. Tissue healing is superior to that observed with other destructive modalities. The laser is also useful in the treatment of vaginal lesions because relatively inaccessible sites can be treated by allowing reflection of the beam through the use of mirrors. The laser has also been used intra‐abdominally primarily for adhesiolysis, fimbrioplasty, tubal reanastomosis and cornual reimplantation. The laser has also been useful for the treatment of ovarian endometriosis. The scarring resulting from laser destruction is minimal and patients generally have a much shorter course of convalescence than when the scalpel or electrocoagulation techniques are used.
Phototherapy of tumors
Authors: Bown S. G.
Published: May 2005

Lasers provide a means of delivering high intensity light to small well‐defined areas under precise control. The biological response depends on the light wavelength and intensity and the absorption characteristics of the target organ. The most important effects are thermal and include tissue vaporization, necrosis with later sloughing, and necrosis stimulating an inflammatory response which may lead to local fibrosis. The Carbon Dioxide Laser can cut or vaporize neoplastic tissue in areas accessible to rigid endoscopy, but the more penetrating Nd YAG and Argon laser beams can be transmitted via flexible fibers and have greater potential for destroying larger tumors without unacceptable damage to surrounding areas. More selective tumor phototherapy is possible in some organs by sensitization with HpD (hematoporphyrin derivative) and subsequent treatment with a dye laser. This effect is non‐thermal and depends on the production of singlet oxygen by activated HpD. The precision possible for local treatment of solid tumors with lasers is greater than for almost any other techniques, but careful quantitative studies are needed to establish the appropriate treatment parameters in any particular situation.
The role of lasers in otolaryngology
Authors: Carruth J. A. S.
Published: May 2005

The role of the carbon dioxide laser in Otolaryngology is becoming clearly defined and its advantages well recognized. It enables the surgeon to remove tissue, by cell vaporization, immediately with high precision, minimal bleeding, and minimal damage to residual normal tissues. Healing is not complicated by edema and is rapid and remarkably pain free. All these advantages make the CO2 laser of the greatest value in surgery to the airway. Benign, premalignant, and malignant lesions in the food and air passages may be treated by the CO2 laser but in the treatment of some malignancies, further controlled series are needed to establish its role.

The Argon laser, coupled to an operating microscope, may be used to perform delicate surgical procedures in the middle ear with no mechanical trauma to the ossicular chain and inner ear. This use of the Argon laser is currently under assessment.

The dye laser may be used to activate a hematoporphyrin derivative, which is selectively retained by malignant tissues. This causes destruction of the malignant cells with no damage to surrounding normal tissues. Some remarkable results have been reported for this new treatment for malignant disease.
Intraperitoneal approach to regional hyperthermia—possible anticancer applications
Authors: Smith George V. , MacMillan Richard , Stribling Joseph
Published: May 2005

Induction of hyperthermia in dogs by irrigation of the peritoneal cavity via a closed circuit system was evaluated for possible use in the management of cancer patients. Dogs were subjected to lavage of the peritoneal cavity with crystalloid solution at 41°–43°C in a closed circuit system. Temperatures of the liver and hollow viscera were maintained at 40°–42°C for 4 hours. The animals tolerated the procedure, and the parietal incisions and intestinal anastomoses healed without difficulty. Evidence of toxicity was minimal. Plans for studies of this modality in patients with cancer are underway.
Upper gastrointestinal bleeding in renal transplant recipients: The role of prophylactic gastric surgery
Authors: Haffner Jon F. W. , Jakobsen Arnt , Flatmark Audun L.
Published: May 2005

A study of 535 recipients of a first renal graft has been done to analyze whether pretransplant proximal gastric vagotomy (PGV) influenced the frequency of upper gastrointestinal bleeding. The 11‐year period of the study (1969–1979) was divided into two periods: from 1969 to mid‐1973, there were 125 patients, and from 1974 through 1979, there were 410 patients to be studied. Pretransplant gastric resection was performed on 39 recipients with known peptic ulcer disease and, during the 1974–1979 period, pretransplant PGV was performed on 38 patients with demonstrated hyperchlorhydria. Gastroduodenal bleeding developed in 8 of 125 patients (6.4%) during the first period and 19 of 410 patients (4.6%) during the second period, but when resected patients are eliminated, the rates are similar for the two periods (5.1% versus 5%). The overall rate of death from gastroduodenal bleeding was reduced from 4% in the first period to 1.7% in the second, due to a reduction of the bleeding mortality rate from 62% in the first period to 37% in the second. In spite of prophylactic gastric surgery in patients with a previous history of peptic ulcer, some 5–15% of non‐ulcer transplant recipients develop gastroduodenal bleeding after transplantation.
Dextran prophylaxis of fatal pulmonary embolism
Authors: Ljungström Karl‐Gösta
Published: May 2005

Thromboembolic prophylaxis with dextran 70 was given routinely to patients undergoing major surgery from 1970 to 1972 and from 1975 to 1977, using slightly different dosages. During 1968 to 1970 and 1972 to 1974, no routine prophylaxis was given. During the 4 respective 2‐year periods studied, the following number of postoperative fatal pulmonary emboli (FPE) were verified at autopsy: 16 (no prophylaxis); 6 (dextran); 19 (no prophylaxis); and 4 (dextran). The incidence of FPE in relation to major operations was 35/5,094 (0.69%) without prophylaxis, and 10/4,881 (0.20%) with prophylaxis,p < 0.001. The autopsy rate was 93.4% in postoperative deaths. Adherence to prophylaxis was 88 ± 5%. Routine prophylaxis with dextran 70 during surgery is, therefore, effective against fatal pulmonary embolism. Furthermore, it is easy to perform, lacking many of the practical disadvantages of oral anticoagulants and heparin.
Open treatment of abdominal septic catastrophies
Authors: Broomé Albert , Hansson Lars , Lundgren Fredrik , Smedberg Sam
Published: May 2005

From 1973 to 1981, a total of 30 patients undergoing reoperative surgery for serious septic complications were treated without closure of the abdominal cavity. The open wound was covered with gauze soaked in saline. Intraabdominal abscesses could then be evacuated directly, if necessary, under slight general anesthesia in the patient's own bed. Reperitonealization and excess growth of granulation tissue was seen within 2 weeks. Sixteen patients survived. In 10 of these, the wound healed secondarily without any other treatment. In the remaining 6, split‐skin grafts or a pedicled flap was necessary. In 4 patients the abdominal wall almost reestablished itself. The remaining 12 patients showed larger or smaller defects with negligible problems. Patients with severe abdominal sepsis, associated with necrotic wound edges, multiple laparotomies, and multiple organ failures should have the abdominal cavity left completely open.
Colohepatic fistula due to hydatid disease
Authors: Morris D. L. , Smith W. D. F. , Alexander‐Williams J.
Published: May 2005

Communication of a hepatic hydatid cyst to the colon appears to be extremely rare. We report a 54‐year‐old male who underwent surgery for a huge hydatid cyst. Four days after the cyst was aspirated and many daughter cysts were removed, gross fecal contamination occurred as a result of a 0.5‐cm defect in the right transverse colon. The defect was repaired and the colon temporarily exteriorized. Recovery was uneventful.
The value of the clonidine‐suppression test in the diagnosis of pheochromocytoma
Authors: Karlberg Bengt E. , Hedman Lisbeth , Lennquist Sten , Pollare Thomas
Published: May 2005

We assessed the clinical value of a clonidine‐suppression test in the diagnosis of pheochromocytoma. Three different groups were investigated: group I, 10 patients with operatively verified catecholamine‐secreting tumors (1 extra adrenal paraganglioma); group II, 34 patients with “neurogenic” hypertension; and group III, 14 normotensive, healthy subjects.

Clonidine, 300μg given orally at time zero, significantly reduced mean systolic/diastolic blood pressure (MBP) in all 3 groups: group I, maximum MBP fall ‐19/0 mm Hg; group II, ‐43/21 mm Hg; and group III, ‐25/9 mm Hg, respectively. The maximal MBP fall was seen between 2 and 3 hours after administration of clonidine. Mean plasma concentrations of noradrenaline/norepinephrine (NA) decreased in groups II and III, in group II from 2.6±0.3 to 0.7±0.05 nmol/l (p<0.001), and in group III from 1.3±0.2 to 0.6±0.06 nmol/l, respectively. Plasma concentrations of adrenaline/epinephrine (A) were low < 0.2 nmol/l and remained unchanged during the test. In contrast, in patients with pheochromocytoma (group I), NA and A mean plasma concentrations were high before clonidine, 7.7±2.2 nmol/l for NA and 4.0±1.7 nmol for A, and remained high or somewhat elevated during the 3 hours of observation. No patient showed a decrease in plasma catecholamines during the test.

After successful operation for the catecholamine‐secreting tumors, all 10 patients achieved normal BP (mean 135/83 mm Hg supine) and had normal basal plasma catecholamine concentrations (NA 2.8± 0.5 nmol/l, A<0.2 nmol/l) with normal suppression of NA after clonidine to 1.1± 0.2 nmol/l (p<0.01 compared with basal values). We conclude that the clonidine‐suppression test is a safe and simple diagnostic method for verification or exclusion of pheochromocytomas, especially in patients with normal resting (baseline) catecholamine levels (4 patients in the present study). No significant or clinically relevant side effects were noted during the test apart from some sedation and dry mouth.
Cytostatic drug therapy in anaplastic thyroid carcinoma
Authors: Wenisch Hubertus J. C. , Wagner Roland H. , Schumm‐Draeger Petra ‐Maria , Encke Albrecht
Published: May 2005

Anaplastic thyroid carcinomas are relatively rare and have a poor prognosis. In most cases, radical surgical procedures are impossible. Recently, a combination therapy of surgical resection, percutaneous irradiation, and chemotherapy has been described in the literature. After xenotransplantation in athymic nude mice, anaplastic thyroid carcinomas show the same histological features compared to the donors. By passing the tumor over several generations of nude mice, a constant growth rate has been observed. The model allows testing of therapeutic approaches in thyroid carcinoma tissues under in vivo conditions. In 2 different studies with 2 different anaplastic transplants, a statistically significant growth inhibition could be observed using doxorubicin therapy. In one study, combination therapy was performed. The results show no statistically significant difference in the group treated by doxorubicin alone. Further investigations, under in vivo conditions, will show whether a suitable combination therapy for anaplastic thyroid carcinoma can be developed.
TSH suppression in the management of autonomously functioning thyroid lesions
Authors: Thomas Colin G. , Tawil Mark , Berman Marvin I. , Nayfeh Shihadeh N.
Published: May 2005

Solitary autonomously functioning thyroid lesions (AFTL) are discrete hyperfunctioning nodules whose growth and function do not appear to be dependent on thyroid‐stimulating hormone (TSH). Although they gradually increase in size and function over years, rarely do they progress to produce hyperthyroidism. This article presents the thesis that this “self‐limiting feature” is related to their growth and function being modulated by levels of TSH. Thyroid membranes from autonomously functioning thyroid lesions were examined in 6 patients. A nonlinear Scatchard plot was obtained with the hyperfunctioning thyroid lesion demonstrating high‐affinity, low‐capacity TSH receptor components. These exhibited a binding capacity ranging from 7 to 600 fmol/mg protein in patients with suppressed TSH levels to 1,450 in a euthyroid patient. All lesions exhibited basal adenylate cyclase activity which was stimulated 2–3‐fold by Bovine TSH. A review of the natural history of the lesion demonstrates a decremental increase in size and function with time. In 9 patients receiving thyroid hormone as suppressive therapy observed over a period of 4–14 years, the lesions partially regressed in 4 and did not progress in 5. This concept of growth and function of AFTL being modulated by TSH levels has therapeutic implications when such nodules are identified early in the course of their development. At this time, TSH suppression may be inhibitory to increase in nodule size and secretion of thyroid hormones.