There have been several new developments in breast cancer research. Investigators are closer to identifying the breast cancer gene, which may aid in the diagnosis and treatment of the disease. The more established routine of screening mammography has been questioned by the results of the Canadian National Breast Screening Study. Many authors challenge this study's validity. Largely because of screening mammography, noninvasive breast cancer is one of the most frequently diagnosed types of breast cancer. The treatment options for noninvasive breast cancers are discussed along with recent publications. The option of breast-conserving therapy for early stage cancers is also reviewed. Recent investigators have sought to identify the most appropriate patients for breast conservation. This overview also discusses treatment options for advanced cancers and the use of hormonal therapy for all patients with breast cancer.
Pancreatic endocrine tumors are rare, yet can cause significant morbidity due to excessive secretion of hormones. Octreotide is effective in reducing the plasma concentrations of many of these hormones. The availability of potent H2-receptor antagonists and omeprazole has altered the emphasis in patients with Zollinger-Ellison syndrome away from total gastrectomy and towards resection of the gastrinoma for potential cure. Fifty percent of insulinomas and gastrinomas are not evident on preoperative imaging studies, despite their sophistication. Calcium angiography, endoscopic ultrasonography, isotope-labeled octreotide scanning, and injection of methylene blue during secretin angiography are recent imaging modalities that have shown promise in the localization of these tumors. Intraoperative ultrasound has emerged as the best method for operative detection of insulinomas. Duodenotomy and intraoperative endoscopic transillumination are especially important in the surgical management of Zollinger-Ellison syndrome because 30% to 40% of gastrinomas are located in the duodenum. The management of patients with multiple endocrine neoplasia type 1 and Zollinger-Ellison syndrome continues to be controversial. Some advocate an aggressive surgical approach, whereas others have had little success in rendering patients eugastrinemic.
The standard treatment of peripheral arterial occlusion has been operative, employing embolectomy, thrombectomy, or bypass grafting to restore blood flow to the compromised extremity. Intra-arterial thrombolysis has been advocated as an initial intervention designed to unmask the anatomic lesion responsible for the occlusive event, with a directed or endovascular modality thereafter. Four thrombolytic agents are in clinical use: streptokinase, urokinase, recombinant tissue plasminogen activator, and acylated plasminogen streptokinase activator complex. The agents differ with respect to efficacy of thrombolysis, fibrin specificity, and cost. At present, urokinase is the most widely used. Recent randomized clinical trials suggest a benefit of thrombolytic therapy in the initial management of acute peripheral arterial occlusion, with improved patient survival and similar amputation rates compared with immediate open intervention. Each modality has its place in specific patient subcategories; the determination of which patients are best served by a specific modality awaits the results of large clinical trials.
The goals of pancreatic transplantation are to improve the quality of life for the diabetic patient, reverse the metabolic abnormalities of diabetes, and prevent the dreaded secondary complications. Although transplantation of the whole pancreas is the only therapy that reliably achieves euglycemia, the complications associated with this procedure and the need for immunosuppression make it undesirable except to a select subpopulation of type I diabetic patients. Islet cell transplantation is the exciting alternative; however, insulin independence has been achieved in only 10% to 20% of patients. Although advances in technology could make islet transplantation the treatment of choice for type I diabetic patients, islet transplantation currently remains an experimental procedure. Diabetes is not commonly considered a surgical disease, but surgeons have made major contributions to its treatment and must remain active in the development of new treatment modalities for this debilitating disease.
Traditional open hernia repairs are usually performed as outpatient procedures under local anesthesia, with minimal morbidity and low recurrence rates. To be widely accepted, any new procedure must at least match current standards of performance. This review summarizes the most widely used techniques for laparoscopic inguinal herniorrhaphy. Early results of over 1700 cases using these techniques are reported. Recurrence was lowest using the total extraperitoneal repair. In selected patients, laparoscopic inguinal herniorrhaphy is a safe and comparable alternative to standard open repairs.
The rapid evolution and acceptance of laparoscopic cholecystectomy for the management of symptomatic cholelithiasis and acute and chronic cholecystitis are unprecedented in modern surgical practice. With rapid advances in laparoscopic and endoscopic instrumentation and surgical skills, many surgeons are developing minimally invasive techniques and strategies for treating the patient with known, suspected, or unsuspected choledocholithiasis. Recent articles describing the current status, complications, results, and future directions of laparoscopic and endoscopic management of common bile duct stones are reviewed. The role of endoscopic retrograde cholangiopancreatography and sphincterotomy, laparoscopic exploration of the common bile duct, choledochoscopy, and percutaneous transhepatic extraction techniques are discussed.
Recent developments in the understanding of antigen processing and presentation and T-cell receptor recognition of antigens have immediate applications to the cellular immunotherapy of cancer. The specific antigens and processed peptide sequences responsible for T-cell recognition of some human melanomas have recently been identified. T cells with antitumor activity are undergoing genetic modification to improve their function and clinical efficacy. In addition, novel T-cell constructs are being created with chimeric T-cell receptors that confer new tumor reactivities to these lymphocytes. Current understanding of the basic processes involved in the immune recognition and destruction of tumors is allowing the manipulation of these processes to enhance experimental clinical therapies.
esplraton failure implies that the respirator) R ,em i; unable to maintain a11 alwolar ventilation which is capable of coping with the amount of carbon dioside being produced by the body (ie alveolar hypoventilation). Thus the amount of osygen added to the arterial blood and carbon dioxide eliminated is reduced \vith resultant arterial hyoxia and hypercapnia. As is seen in Table 1, alveolar ventilation may develop in the three groups of conditions: pulmonary disease. estrapulmonan disease, and central respiratory depression. Respirator) failure develops most commonly in patients sutTering from chronic ainvay obstruction, such as chronic bronchitis and/or emphysema, and in patients suffering from neuromuscular diseases, severe obesity and disorders of the chest cage such as kyphoscoliosls. or in severe chest injunes. Alveolar h>yoventilation also results \\.hen the central control of respiration by the medullaq respiratory centers is depressed by drugs such as barbiturates, narcotics and tranquilizers, or anesthesia. In addition, the medullary respiratory center may become relatively insensitive to increases in arterial pCO, in patients who are suffering from chronic hypoxia and h)percapnia. In diseases involving the pulmonary parench>ma, the pulmonary vasculature, or pleura. hyposia frequently develops because there is a mismatching of the distribution of blood and gas. but the alveolar ventilation is usually adequate to ehminate carbon dioside. On the other hand. when there is superimposed bronchial obstruction, infection or pulmonan congestion, the alveolar ventilation may be inadequate relative to the carbon dioside production. so that severe h>posia and carbon dioxide retention may develop. -'Professor of Medicine, University of Manitoba; Sledical Director, D. .4. Stewart Cenbe for the Study and Treatment of Resprrator). Disease; Director, Respirator! Div~sion, Cllnrcal Invertieahon L'nit, \\'lnn#peg General Hospital. \Vmnipeg. XIan~toha IVIlen hypouia and h>percapnia develop acutely. it is a true emergency w~hich requires immediate therapy. The most Important factor in establishing the diagnosis of respirator) failure is a high index of ~ u ~ p i c i o n . This is particularly true if an acute infection, thromboembolism or other catastrophy, such as spontaneous pneumothorax. develops in any of the above underlying conditions, and if oxygen or 'I depressant medication has been administered. The clinical manifestations of respiratory failure depend upon the underlying disease process. the precipitating factors and the severity of the hyporia and h!percapnia. The clinical findings due to h>poxia and hypercapnia are predominantly neurologic, F U , disturbances of consciousness. headache, and muscular movements, and cardiovascular, eg, tachycardia. a bounding pulse, and usually an elevated blood pressure. However, in severe cases, the blood pressure often falls and is associated with generalized vasodilatation and profuse s\veating. Physical examination is of little benefit in establishing the diagnosis of inadequate alveolar ventilation unless the condition is extremely obvious. The definitive assessment of the adequacy of the alveolar ventilation can only be obtained by measurement of the arterial blood gas tensions and pH. Table 2 indicates the arterial blood findings in acute and chronic respirator). failure. In both situations. analysis of the arterial blood reveals hyposia (unless the patient is receiving 0, ) , and an elevated carhon dioxide tension. In acute respirator) failure, the carbon dioside content is normal and the pH lo\\.; n.hile in chronic respirator). failure, because hicarbonate has been retained to compensate for the elevated p C 0 2 , the carbon dioxide content is elevated and serum chloride low. Cnder normal circumstances, the compensator). retention of bicarbonate is sufficient to bring the pH to a Ion. normal value. On the other hand. a metabolic alkalosis is occasionally present because of potassium depletion.
Over the past 30 years, numerous major centers have published analyses of potential factors influencing survival following resection of gastric cancer. The independent significance of depth of tumor penetration and lymph node status has been consistently documented. With proper staging, we know which patients are most likely to die of their disease. Unfortunately, adjuvant treatment in surgical resection has not altered patient outcome. Emphasis should now be on selecting the patients who should receive radical surgery for cure, adjuvant therapy with a hope for cure, or palliation. This brief review concentrates on recent developments in our ability to stage patients preoperatively, developments that may change the way we approach the patient with stomach cancer in the future.
The extent of surgical resection required in the optimal management of differentiated (papillary and follicular) thyroid carcinoma remains controversial. Arguments in favor of total thyroidectomy include the adequate treatment of tumor multifocality, reduction in local recurrence rates and anaplastic transformation, and creating a suitable environment for radioactive iodine scanning and treatment of metastases. The benefits of this procedure have to be weighed against the potential but minimal morbidity.
The survival of infants with biliary atresia has improved significantly during the past two decades as a result of modification of the Kasai hepatoportoenterostomy procedure complemented by advances in liver transplantation. Recent reports suggest that the long-term success rate of the Kasai procedure is 40%. Failures are salvaged by liver transplantation. Advances in organ preservation, the use of reduced-sized grafts, and newer immunosuppressive agents (cyclosporine, FK 506) have strongly influenced these improved results. Unfortunately, liver transplantation is associated with a high complication rate, the risk of opportunistic infection, and an increased rate of malignancy due to immunosuppression. Until immunotolerance can be achieved, the Kasai procedure remains the procedure of choice for infants with biliary atresia. Liver transplantation is a life-saving complementary procedure for patients who fail to drain bile following the Kasai procedure, who are older than 3 to 4 months of age at diagnosis, or who have advanced cirrhosis. In the current era, the overall survival should exceed 80%.
The diagnosis of primary sclerosing cholangitis is made radiologically in patients with extrahepatic obstructive jaundice. This condition lacks a known cause and another method of diagnosis, and its treatment is palliative-mechanical, with bypasses, dilation, or orthotopic liver transplantation. Recent progress has been seen in stratifying patients with respect to prognosis. Stratification is important for conducting clinical trials and for predicting which patients should receive a transplant at an earlier, less risky stage in the course of the disease. Expandable metal stents are on trial in patients with benign or malignant strictures. These newer stents seem to be better than polyethylene stents, although their use has not been reported in sclerosing cholangitis. With survival data used as a measuring point, relief of jaundice does not appear to correlate with increased survival. Of concern has been the association of cholangiocarcinoma with sclerosing cholangitis. Cholangiocarcinoma is difficult to recognize clinically and has a negative impact on the results of transplantation.
The survival rate of patients with carcinoma of the esophagus is dismal. Improvement could be achieved only by earlier diagnosis and radical resection techniques to remove the esophagus and its draining lymphatic bed. En bloc esophagectomy and esophagectomy with three-field lymph node dissection are practiced in some centers in North America, Europe, and Japan. Survival rates with these techniques are better than those obtained with standard resection techniques.
Duodenal gastrinomas are now more frequently recognized as the source of hypergastrinemia in patients with Zollinger-Ellison syndrome. The cell lineage of duodenal gastrinomas may differ from that of pancreatic gastrinomas, which accounts for variations in their clinical behavior. Attempts to localize the submucosal tumors are difficult and are limited by their small size. Intraoperative endoscopic transillumination, selective intra-arterial secretin injection, and duodenotomy with mucosal eversion are currently the most sensitive and reliable methods of localization. Endoscopic ultrasonography and somatostatin scintigraphy further enhance the accuracy of preoperative localization of these tumors. Current information based on cure rates and survival data mandates a primary surgical approach in patients with either the sporadic or the multiple endocrine neoplasia type 1-associated form of the disease. Thus, wide local resection of duodenal gastrinomas with removal of all tumor-bearing lymphatic tissue and acid inhibitory pharmacotherapy (proton pump inhibition) may yield 5-year survival rates of 80% to 90%. Similarly, in patients with pancreatic and duodenal gastrinomas as a manifestation of multiple endocrine neoplasia type 1, the additional enucleation of pancreatic lesions with or without distal pancreatectomy has resulted in cure rates of 67% to 100%.
Klatskin tumors, or hilar cholangiocarcinomas, are an uncommon cause of obstructive jaundice. With the advent of sophisticated imaging studies and cholangiography, these tumors can be preoperatively identified in most patients, and a treatment plan can be outlined before operative exploration. Surgical resection of the hepatic bifurcation with the addition of a hepatic lobectomy as indicated by tumor extension is the treatment of choice. Although complete surgical resection improves survival over that achieved with palliative procedures, the 5-year survival rate remains less than 20%. Postoperative radiation therapy may increase long-term survival.
Effective therapy for soft tissue sarcoma of the extremities continues in its lengthy evolution from mandatory amputation or radical compartment resection to multimodality limb salvage procedures. This current approach typically includes preoperative neoadjuvant systemic chemotherapy, followed by negative margin surgical resection in conjunction with radiotherapy. The scope and functional outcome of these resections has been markedly enhanced by the application of microvascular-dependent free tissue transfer techniques. Because of the rarity of this tumor system, problems in soft tissue sarcoma receive proportionally less attention. Nonetheless, the past year has witnessed several important advances in this field, as is discussed.
