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Treatment of Impaired Perfusion in Septic Shock
ADRENAL AND RENAL PHYSIOLOGY, AND MEDICAL RENAL DISEASE
had a duration of response of 7 years. This interesting article would suggest that there is a limited role for chemotherapy in selected patients with malignant transformation. Jerome P. Richie, M.D.
Long-Term Survival After High-Dose Salvage Chemotherapy for Germ Cell Malignancies With Adverse Prognostic Variables D. A. VAENA, R. ABONOUR AND L. H. EINHORN, Division of Hematology-Oncology, Indiana University School of Medicine and Walther Cancer Institute, Indianapolis, Indiana J Clin Oncol, 21: 4100 – 4104, 2003 Purpose: Independent prognostic variables for patients undergoing high-dose chemotherapy (HDCT) as salvage modality for germ cell tumors (GCT) were previously described, and a score was created. Patients with more than 2 points had a poor prognosis. However, these data were from patients treated from 1984 to 1993, and most received a single HDCT course. In this study, we evaluated outcomes at Indiana University and determined the applicability of the Beyer score to contemporary poor-risk patients. Patients and Methods: We performed a retrospective analysis of patients who received salvage HDCT between 1988 and 2001 and had at least one of the following characteristics: platinum-refractory or absolutely platinum-refractory GCT, primary mediastinal nonseminomatous GCT (PMNSGCT), human chorionic gonadotropin (HCG) ⱖ 1,000 mU/mL or alpha-fetoprotein (AFP) ⱖ 1,000 ng/mL before HDCT. Primary end points were overall and 2-year failure-free survival (FFS). Results: Eighty patients were identified. Fifty-six were platinum refractory, 23 had a Beyer score greater than 2, and 13 had PMNSGCT. Fifty-six patients received two HDCT courses. HDCT included carboplatin and etoposide. Forty-three patients received HDCT as first salvage modality. Median overall survival was 14.7 months. The 2-year FFS was 32%. No relapses have occurred after 2 years from HDCT. Patients with greater than 2 points in the Beyer score, platinum-refractory patients, and patients with HCG ⱖ 1,000 mU/mL, AFP ⱖ 1,000 ng/mL, and PMNSGCT had 2-year FFS of 30%, 37%, 26%, 18%, and 0%, respectively. Conclusion: Results with PMNSGCT remained poor. However, other patients with poor prognosis should not be denied an attempt at curative salvage HDCT. Editorial Comment: Approximately 70% of cases of metastatic testicular cancer evidence cure with cisplatin based chemotherapy. Options for cases that progress or do not respond include high dose chemotherapy with bone marrow transplant or now peripheral stem cell transplant. The authors reviewed their extensive experience at 1 institution with 80 patients receiving salvage high dose chemotherapy during a 13-year period. Many of the cases were refractory to cisplatin. The majority received high dose chemotherapy with etoposide and carboplatin. The authors report a solid 30% freedom from relapse. As with other series, patients with primary mediastinal nonseminomatous germ cell tumor faired poorly. Jerome P. Richie, M.D.
ADRENAL AND RENAL PHYSIOLOGY, AND MEDICAL RENAL DISEASE Treatment of Impaired Perfusion in Septic Shock E. RUOKONEN, I. PARVIAINEN Kuopio, Finland
AND
A. UNSARA, Department of Intensive Care, Kuopio University Hospital,
Ann Med, 34: 590 –597, 2002 Severe sepsis and septic shock are relatively common problems in intensive care. The mortality in septic shock is still high, and the main causes of death are multiple organ failure and refractory hypotension. Impaired tissue perfusion due to hypovolemia, disturbed vasoregulation and myocardial dysfunction contribute to the multiple organ dysfunction. Treatment of hemodynamics in septic shock consists of appropriate fluid therapy guided by invasive monitoring combined with vasoactive drugs aiming to correct hypotension and inappropriately low cardiac output. The drug of choice for low vascular resistance is norepinephrine, while insufficient myocardial contractility is commonly treated with dobutamine. The use of norepinephrine seems to be associated with better prognosis as compared to results from the use of dopamine or epinephrine. In septic shock, vasopressin levels are low, and therefore vasopressin has been advocated as a vasopressor. Its effectiveness and safety have not yet been documented, and so far it is regarded as an experimental treatment. Recent data support the use of corticosteroid, at least in some of the
1207
1208
ADRENAL AND RENAL PHYSIOLOGY, AND MEDICAL RENAL DISEASE
patients with septic shock. Also, activated protein C, a drug with anti-inflammatory and antithrombotic properties decreases mortality in patients with septic shock. Editorial Comment: This is a review of the pathophysiology of septic shock. It is of particular interest because of its comments on the use of corticosteroids. Before 1990 a number of randomized controlled studies and several meta-analyses demonstrated that there was no benefit from corticosteroid use in septic shock. However, since the 1990s 2 studies, although somewhat small, have shown evidence of benefit. In both studies there was a decreased need for vasosuppressors and/or decreased time of use, and a lesser degree of organ failure. Thus, we have come full circle in the use of bolus corticosteroids as well as infusion corticosteroids for the treatment of septic shock. At this time it certainly is not wrong to give a patient a bolus of corticosteroids at the initiation of an event of septic shock. W. Scott McDougal, M.D. Computed Tomography-Guided Percutaneous Acetic Acid Injection Therapy for Functioning Adrenocortical Adenoma S. MINOWADA, T. FUJIMURA, N. TAKAHASHI, H. KISHI, K. HASUO AND M. MINAMI, Departments of Urology and Radiology, International Medical Center of Japan and Department of Radiology, Faculty of Medicine, University of Tokyo, Tokyo, Japan J Clin Endocrinol Metab, 88: 5814 –5817, 2003 We reported the outcomes of computed tomography (CT)-guided percutaneous acetic acid injection therapy for functioning adrenocortical adenomas. With the patient in a prone position, the puncture needle was inserted vertically downward into the adenoma with frequent CT scanning. After confirmation by pilot injection with contrast medium, a small aliquot of 40 –50% acetic acid was injected and repeated. Between 1997 and 2002, 18 sessions of CT-guided injection therapy, including one session of ethanol injection, were performed on 10 patients (five patients with primary aldosteronism and five patients with Cushing’s or subclinical Cushing’s syndrome) without any complications except transient upper abdominal pain during the acetic acid injection. The follow-up period ranged from 5– 69 months. The treatment resulted in almost an extirpation of the adrenocortical hyperfunction in seven patients after one or two sessions. CT-guided percutaneous acetic acid injection might be a simple, cost-effective, and far less invasive treatment for small functioning adreno-cortical adenomas. Editorial Comment: The authors report the use of concentrated acetic acid instead of alcohol to treat benign lesions of the adrenal. They suggest that acetic acid is more effective than ethanol in causing dissolution of collagen and tumor necrosis. The authors treated 10 patients, 5 with primary aldosteronism and 5 with Cushing’s disease, all of whom had lesions smaller than 4 cm. Of those patients with primary aldosteronism 4 had a successful outcome, whereas of those with Cushing’s disease only 2 had a therapeutic response. Patients tolerated the procedure reasonably well, although they had some abdominal pain immediately following the injection. The patients were hospitalized following treatment. Clearly, acetic acid may be one modality used. However, with newer tissue ablative techniques using current technology, which delivers energy to the lesion, injection of toxic agents will probably not achieve widespread popularity in the future. W. Scott McDougal, M.D. Surgical Management of Adrenal Cysts T. G. LAL, K. R. KAULBACK, A. BOMBONATI, J. P. PALAZZO, R. B. JEFFREY AND R. J. WEIGEL, Departments of Surgery and Pathology, Thomas Jefferson University, Philadelphia, Pennsylvania, and Department of Radiology, Stanford University, Stanford, California Am Surg, 69: 812– 814, 2003 Adrenal cysts are rare and are often found incidentally during abdominal imaging for another reason. We describe two cases of adrenal cysts, one of which was found to be a cystic pheochromocytoma. Most cystic pheochromocytomas are not diagnosed by urinary screening studies, and the first indication of a pheochromocytoma may be hemodynamic instability during resection. We review the literature on adrenal cysts and make recommendations for the management of cystic adrenal masses. Editorial Comment: This is a report of 2 cases of adrenal cysts—a relatively rare lesion found at 0.07% of autopsies. Pseudocysts are the most common, which generally occur as a result of hemorrhage. However, as this article indicates, occasionally they may be malignant and in particular may contain pheochromocytoma. With respect to the latter these patients are often asymptomatic. On imaging there is usually some enhancement or some solid component. The authors propose that adrenal cysts, which are symptomatic, should be removed laparoscopically. Simple adrenal cysts less than 4 cm may be followed. This is a reasonable review of a rare lesion. W. Scott McDougal, M.D.
had a duration of response of 7 years. This interesting article would suggest that there is a limited role for chemotherapy in selected patients with malignant transformation. Jerome P. Richie, M.D.
Long-Term Survival After High-Dose Salvage Chemotherapy for Germ Cell Malignancies With Adverse Prognostic Variables D. A. VAENA, R. ABONOUR AND L. H. EINHORN, Division of Hematology-Oncology, Indiana University School of Medicine and Walther Cancer Institute, Indianapolis, Indiana J Clin Oncol, 21: 4100 – 4104, 2003 Purpose: Independent prognostic variables for patients undergoing high-dose chemotherapy (HDCT) as salvage modality for germ cell tumors (GCT) were previously described, and a score was created. Patients with more than 2 points had a poor prognosis. However, these data were from patients treated from 1984 to 1993, and most received a single HDCT course. In this study, we evaluated outcomes at Indiana University and determined the applicability of the Beyer score to contemporary poor-risk patients. Patients and Methods: We performed a retrospective analysis of patients who received salvage HDCT between 1988 and 2001 and had at least one of the following characteristics: platinum-refractory or absolutely platinum-refractory GCT, primary mediastinal nonseminomatous GCT (PMNSGCT), human chorionic gonadotropin (HCG) ⱖ 1,000 mU/mL or alpha-fetoprotein (AFP) ⱖ 1,000 ng/mL before HDCT. Primary end points were overall and 2-year failure-free survival (FFS). Results: Eighty patients were identified. Fifty-six were platinum refractory, 23 had a Beyer score greater than 2, and 13 had PMNSGCT. Fifty-six patients received two HDCT courses. HDCT included carboplatin and etoposide. Forty-three patients received HDCT as first salvage modality. Median overall survival was 14.7 months. The 2-year FFS was 32%. No relapses have occurred after 2 years from HDCT. Patients with greater than 2 points in the Beyer score, platinum-refractory patients, and patients with HCG ⱖ 1,000 mU/mL, AFP ⱖ 1,000 ng/mL, and PMNSGCT had 2-year FFS of 30%, 37%, 26%, 18%, and 0%, respectively. Conclusion: Results with PMNSGCT remained poor. However, other patients with poor prognosis should not be denied an attempt at curative salvage HDCT. Editorial Comment: Approximately 70% of cases of metastatic testicular cancer evidence cure with cisplatin based chemotherapy. Options for cases that progress or do not respond include high dose chemotherapy with bone marrow transplant or now peripheral stem cell transplant. The authors reviewed their extensive experience at 1 institution with 80 patients receiving salvage high dose chemotherapy during a 13-year period. Many of the cases were refractory to cisplatin. The majority received high dose chemotherapy with etoposide and carboplatin. The authors report a solid 30% freedom from relapse. As with other series, patients with primary mediastinal nonseminomatous germ cell tumor faired poorly. Jerome P. Richie, M.D.
ADRENAL AND RENAL PHYSIOLOGY, AND MEDICAL RENAL DISEASE Treatment of Impaired Perfusion in Septic Shock E. RUOKONEN, I. PARVIAINEN Kuopio, Finland
AND
A. UNSARA, Department of Intensive Care, Kuopio University Hospital,
Ann Med, 34: 590 –597, 2002 Severe sepsis and septic shock are relatively common problems in intensive care. The mortality in septic shock is still high, and the main causes of death are multiple organ failure and refractory hypotension. Impaired tissue perfusion due to hypovolemia, disturbed vasoregulation and myocardial dysfunction contribute to the multiple organ dysfunction. Treatment of hemodynamics in septic shock consists of appropriate fluid therapy guided by invasive monitoring combined with vasoactive drugs aiming to correct hypotension and inappropriately low cardiac output. The drug of choice for low vascular resistance is norepinephrine, while insufficient myocardial contractility is commonly treated with dobutamine. The use of norepinephrine seems to be associated with better prognosis as compared to results from the use of dopamine or epinephrine. In septic shock, vasopressin levels are low, and therefore vasopressin has been advocated as a vasopressor. Its effectiveness and safety have not yet been documented, and so far it is regarded as an experimental treatment. Recent data support the use of corticosteroid, at least in some of the
1207
1208
ADRENAL AND RENAL PHYSIOLOGY, AND MEDICAL RENAL DISEASE
patients with septic shock. Also, activated protein C, a drug with anti-inflammatory and antithrombotic properties decreases mortality in patients with septic shock. Editorial Comment: This is a review of the pathophysiology of septic shock. It is of particular interest because of its comments on the use of corticosteroids. Before 1990 a number of randomized controlled studies and several meta-analyses demonstrated that there was no benefit from corticosteroid use in septic shock. However, since the 1990s 2 studies, although somewhat small, have shown evidence of benefit. In both studies there was a decreased need for vasosuppressors and/or decreased time of use, and a lesser degree of organ failure. Thus, we have come full circle in the use of bolus corticosteroids as well as infusion corticosteroids for the treatment of septic shock. At this time it certainly is not wrong to give a patient a bolus of corticosteroids at the initiation of an event of septic shock. W. Scott McDougal, M.D. Computed Tomography-Guided Percutaneous Acetic Acid Injection Therapy for Functioning Adrenocortical Adenoma S. MINOWADA, T. FUJIMURA, N. TAKAHASHI, H. KISHI, K. HASUO AND M. MINAMI, Departments of Urology and Radiology, International Medical Center of Japan and Department of Radiology, Faculty of Medicine, University of Tokyo, Tokyo, Japan J Clin Endocrinol Metab, 88: 5814 –5817, 2003 We reported the outcomes of computed tomography (CT)-guided percutaneous acetic acid injection therapy for functioning adrenocortical adenomas. With the patient in a prone position, the puncture needle was inserted vertically downward into the adenoma with frequent CT scanning. After confirmation by pilot injection with contrast medium, a small aliquot of 40 –50% acetic acid was injected and repeated. Between 1997 and 2002, 18 sessions of CT-guided injection therapy, including one session of ethanol injection, were performed on 10 patients (five patients with primary aldosteronism and five patients with Cushing’s or subclinical Cushing’s syndrome) without any complications except transient upper abdominal pain during the acetic acid injection. The follow-up period ranged from 5– 69 months. The treatment resulted in almost an extirpation of the adrenocortical hyperfunction in seven patients after one or two sessions. CT-guided percutaneous acetic acid injection might be a simple, cost-effective, and far less invasive treatment for small functioning adreno-cortical adenomas. Editorial Comment: The authors report the use of concentrated acetic acid instead of alcohol to treat benign lesions of the adrenal. They suggest that acetic acid is more effective than ethanol in causing dissolution of collagen and tumor necrosis. The authors treated 10 patients, 5 with primary aldosteronism and 5 with Cushing’s disease, all of whom had lesions smaller than 4 cm. Of those patients with primary aldosteronism 4 had a successful outcome, whereas of those with Cushing’s disease only 2 had a therapeutic response. Patients tolerated the procedure reasonably well, although they had some abdominal pain immediately following the injection. The patients were hospitalized following treatment. Clearly, acetic acid may be one modality used. However, with newer tissue ablative techniques using current technology, which delivers energy to the lesion, injection of toxic agents will probably not achieve widespread popularity in the future. W. Scott McDougal, M.D. Surgical Management of Adrenal Cysts T. G. LAL, K. R. KAULBACK, A. BOMBONATI, J. P. PALAZZO, R. B. JEFFREY AND R. J. WEIGEL, Departments of Surgery and Pathology, Thomas Jefferson University, Philadelphia, Pennsylvania, and Department of Radiology, Stanford University, Stanford, California Am Surg, 69: 812– 814, 2003 Adrenal cysts are rare and are often found incidentally during abdominal imaging for another reason. We describe two cases of adrenal cysts, one of which was found to be a cystic pheochromocytoma. Most cystic pheochromocytomas are not diagnosed by urinary screening studies, and the first indication of a pheochromocytoma may be hemodynamic instability during resection. We review the literature on adrenal cysts and make recommendations for the management of cystic adrenal masses. Editorial Comment: This is a report of 2 cases of adrenal cysts—a relatively rare lesion found at 0.07% of autopsies. Pseudocysts are the most common, which generally occur as a result of hemorrhage. However, as this article indicates, occasionally they may be malignant and in particular may contain pheochromocytoma. With respect to the latter these patients are often asymptomatic. On imaging there is usually some enhancement or some solid component. The authors propose that adrenal cysts, which are symptomatic, should be removed laparoscopically. Simple adrenal cysts less than 4 cm may be followed. This is a reasonable review of a rare lesion. W. Scott McDougal, M.D.