Additive prognostic value of preoperative plasma glucose concentrations in calves undergoing abdominal surgery.

Surgical abdominal emergencies in calves are associated with a guarded prognosis, especially if neonates are affected. Because hypoglycemia has been associated with sepsis and endotoxemia, this study aimed to assess the prognostic relevance of preoperative plasma glucose concentrations (GLUC) in calves requiring surgery for an acute abdominal disorder. For this purpose, data from retrospective and prospective case series were analyzed, consisting of 586 and 83 hospitalized calves, respectively. The outcomes of calves were evaluated until hospital discharge (both study populations) and for 3 mo following discharge by a phone call to the farmer (prospective study population). For the retrospective study population, the overall survival rate was 31.2%. Calves with a negative outcome (NO) had significantly lower median GLUC (4.3 mmol/L) than calves with a positive outcome (PO; 5.0 mmol/L). The survival rates of calves with GLUC <2.4 mmol/L and 2.4 to 3.1 mmol/L were 3.6 and 8.3%, respectively. The inclusion of GLUC improved a previous prognostic model based on plasma l-lactate concentration and age. The resulting analyses indicated that NO was associated with low age (<7 d), hyper-l-lactatemia (>8.84 mmol/L), and GLUC <4.4 mmol/L (age 7-20 d) and <3.3 mmol/L (age ≥21 d), respectively. The area under the receiver operating characteristic curve of this model was 0.79 (95% confidence interval: 0.76-0.83) and the resulting sensitivity and specificity for NO at the optimal probability cut-point of 0.69 were 66.7 and 85.8%, respectively. For the prospective study population, the established model had sensitivity and specificity for predicting NO after 3 mo (proportion 24%) of 61.9 and 85%, respectively. In both study populations, hypoglycemia was significantly associated with intraoperative evidence of a septic process within the abdominal cavity. The present analyses show that hypoglycemia was highly indicative of a poor prognosis and serious intraoperative findings such as peritonitis. Determination of GLUC should therefore be part of the diagnostic work-up in calves suffering from an acute abdominal emergency.

Prognostic utility of pre- and postoperative plasma l-lactate measurements in hospitalized cows with acute abdominal emergencies.

The aim of the present analyses was to compare the prognostic value of pre- and postoperative l-lactate measurements in hospitalized cows requiring surgical intervention for an acute abdominal emergency, such as gastrointestinal ileus or peritonitis. For this purpose, we analyzed data from retro- and prospective case series, consisting of 754 and 98 cows, respectively. Plasma l-lactate concentrations (L-LAC) were determined upon admission to the hospital (both study populations), immediately before initiation of surgical intervention (prospective study population), and 6, 12, 24, 48, and 72 h later (prospective study population). The outcome of cows was evaluated until hospital discharge (both study populations) and 3 mo after discharge by a phone call to the farmer (prospective study population). A negative outcome was defined as death or euthanasia during hospitalization, or if discharged animals had an unsatisfied owner or were culled for medical reasons that were directly related to the initial abdominal emergency. For the retrospective study population, the overall survival rate until hospital discharge was 66%. Cows with a negative outcome (median: 6.81 mmol/L) had significantly higher L-LAC than cows with a positive outcome (3.66 mmol/L) of therapy. At the individual diagnosis level, L-LAC was associated with mortality in cows with a diagnosis of abomasal volvulus, local peritonitis, hemorrhagic bowel syndrome, and jejunal volvulus. Considering the whole study population, the area under the receiver operating characteristic curve was 0.66. For the prospective study population, the proportion of cows with a positive outcome was 65% until hospital discharge and 61% after the 3-mo observation period. At all sampling times, before and during the first 12 h after surgical intervention, cows with a negative outcome had significantly higher L-LAC than cows with a positive outcome. The largest area under the receiver operating characteristic curve for L-LAC was observed at 6 h (0.89). A cut-point of 1.77 mmol/L was identified, which had a sensitivity and specificity for predicting a negative outcome until hospital discharge of 88.9 and 73.4%, respectively. The present analyses confirmed previous findings in calves and show that persistent hyper-l-lactatemia during the early postoperative period is a more reliable indicator for a negative outcome than hyper-l-lactatemia before initiation of surgical intervention.

Prognostic relevance of pre- and postoperative plasma l-lactate measurements in calves with acute abdominal emergencies.

In both human and veterinary medicine, l-lactate is a well-established prognostic biomarker of disease severity and mortality and has also attracted increasing attention in bovine medicine due to the availability and validation of cheap and portable l-lactate analyzers. The aim of the present study was to evaluate the prognostic accuracy of plasma L-lactate measurements in calves with acute abdominal emergencies before and during the initial therapeutic period after surgical intervention. A prospective observational study was carried out involving 83 hospitalized calves up to an age of 7 mo, which required surgical intervention for reasons of an acute abdominal emergency such as gastrointestinal ileus or peritonitis. Plasma l-lactate (L-LAC) concentrations were determined immediately before initiation of surgery and 6, 12, 24, 48, and 72 h later. The outcome of calves was evaluated 3 mo after discharge by a phone call to the farmer, and a positive outcome was defined if the calf was still alive and the owner was satisfied with the animal's postsurgical progress. A total of 29% of calves were discharged from the hospital and the proportion of calves with a positive outcome after the 3-mo period was 24%. At all sampling times during the first 48 h after initiation of surgical intervention, calves with a negative outcome had significantly higher L-LAC than calves with a positive outcome. A binary logistic regression analysis indicated that the odds for a negative outcome during the 3-mo observation period increased by a factor of 1.23 [95% confidence interval (CI): 1.04-1.44] for every mmol/L increase of L-LAC before initiation of surgical intervention, but by a factor of 5.29 (95% CI: 1.69-16.6) and 5.92 (95% CI: 1.29-27.3) at 12 and 24 h, respectively. The largest area under the receiver operating characteristic curve for L-LAC was observed at 12 h (0.91; 95% CI: 0.83-0.99), and a cut-point of 2.75 mmol/L was identified that had a sensitivity and specificity for predicting a negative outcome of 68 and 100%, respectively. In conclusion, persistent hyper-l-lactatemia during the early postoperative period is a more reliable indicator for a negative outcome in calves with acute surgical abdominal emergencies than hyper-l-lactatemia before initiation of surgical intervention. Postoperative measurements of L-LAC are therefore a clinically useful tool to identify patients with an increased risk for a negative outcome at an early stage after surgical intervention was carried out.

Prognostic value of preoperative plasma l-lactate concentrations in calves with acute abdominal emergencies.

Acute abdominal emergencies in calves due to abomasal disorders, gastrointestinal ileus, or peritonitis are characterized by a rapid disease progression and usually require immediate surgical intervention. Those conditions are associated with a guarded prognosis, and the aim of the present study was to assess the prognostic relevance of preoperatively measured plasma l-lactate concentrations (l-LAC) in a large study population of calves with a broad spectrum of acute abdominal emergencies. For the purpose of this study, the medical records of 587 calves admitted to a veterinary teaching hospital over a 10-yr period were analyzed retrospectively. Plasma l-LAC was measured as part of a routinely performed biochemistry panel before initiation of surgical intervention. Hyper-l-lactatemia (plasma l-LAC >2.2 mmol/L) was evident in 75% of calves, and the overall survival rate until hospital discharge was 31%. Calves with a negative outcome were younger (median: 3.4 vs. 6 wk) and had higher plasma l-LAC (median: 4.96 vs. 3.09 mmol/L) than calves with a positive outcome. At the individual diagnosis level, l-LAC was associated with mortality in calves with a diagnosis of mesenteric torsion, right-sided dilated abomasum, small intestinal volvulus, or paralytic ileus, but not in calves suffering from peritonitis, malformations, abomasal volvulus, bloat, or small intestinal intussusceptions. Considering the whole study population, the area under the receiver operating characteristic (ROC) curve for plasma l-LAC was 0.66 [95% confidence interval (CI): 0.61-0.70]. A classification tree analysis indicated that l-LAC >8.84 mmol/L and age categories of <3 wk and <1 wk were independent predictors of mortality. The area under the ROC curve of this model was 0.75 (95% CI: 0.71-0.79) and the resulting sensitivity and specificity for the prediction of nonsurvival at the optimal probability cut-point of 0.62 were 67.7 and 76.6%, respectively. In conclusion, hyper-l-lactatemia is common in calves suffering from acute abdominal emergencies. Markedly increased plasma l-LAC is associated with an increased mortality risk, but it is not possible to reliably predict the outcome of affected calves based on a single, preoperative measurement. However, a clinically important finding of this study was that the ability to predict a negative outcome is improved when the age of the calf is considered in addition to plasma l-LAC.

ESMO Consensus Conference on testicular germ cell cancer: diagnosis, treatment and follow-up.

The European Society for Medical Oncology (ESMO) consensus conference on testicular cancer was held on 3-5 November 2016 in Paris, France. The conference included a multidisciplinary panel of 36 leading experts in the diagnosis and treatment of testicular cancer (34 panel members attended the conference; an additional two panel members [CB and K-PD] participated in all preparatory work and subsequent manuscript development). The aim of the conference was to develop detailed recommendations on topics relating to testicular cancer that are not covered in detail in the current ESMO Clinical Practice Guidelines (CPGs) and where the available level of evidence is insufficient. The main topics identified for discussion related to: (1) diagnostic work-up and patient assessment; (2) stage I disease; (3) stage II-III disease; (4) post-chemotherapy surgery, salvage chemotherapy, salvage and desperation surgery and special topics; and (5) survivorship and follow-up schemes. The experts addressed questions relating to one of the five topics within five working groups. Relevant scientific literature was reviewed in advance. Recommendations were developed by the working groups and then presented to the entire panel. A consensus vote was obtained following whole-panel discussions, and the consensus recommendations were then further developed in post-meeting discussions in written form. This manuscript presents the results of the expert panel discussions, including the consensus recommendations and a summary of evidence supporting each recommendation. All participants approved the final manuscript.

Risk factors for the development of hypokalemia in neonatal diarrheic calves.

BACKGROUND: Neonatal diarrheic calves have a clear negative potassium balance because of intestinal losses and decreased milk intake but in the presence of acidemia, they usually show normokalemic or hyperkalemic plasma concentrations. OBJECTIVES: To assess whether marked hypokalemia occurs in response to the correction of acidemia and dehydration and to identify factors that are associated with this condition. ANIMALS: Eighty-three calves with a clinical diagnosis of neonatal diarrhea. METHODS: Prospective cohort study. Calves were treated according to a clinical protocol using an oral electrolyte solution and commercially available packages of 8.4% sodium bicarbonate, 0.9% saline and 40% dextrose infusion solutions. RESULTS: The proportion of hypokalemic calves after 24 hours of treatment (19.3%) was twice as great as it was on admission to the hospital. Plasma K(+) after 24 hours of treatment was not significantly correlated to venous blood pH values at the same time but positively correlated to venous blood pH values on admission (r = 0.51, P < .001). Base excess on admission (Odds ratio [OR] = 0.81, 95% confidence interval [CI] = 0.70-0.94), duration of diarrhea (OR = 1.37, 95% CI = 1.05-1.80), milk intake during hospitalization (OR = 0.54, 95% CI = 0.37-0.79) and plasma sodium concentrations after 24 hours (OR = 1.12, 95% CI = 1.01-1.25) were identified to be independently associated (P < .05) with a hypokalemic state after 24 hours of treatment. CONCLUSIONS AND CLINICAL IMPORTANCE: Findings of this study suggest that marked depletion of body potassium stores is evident in diarrheic calves that suffered from marked metabolic acidosis, have a low milk intake and a long history of diarrhea.

Effects of alkalinization and rehydration on plasma potassium concentrations in neonatal calves with diarrhea.

BACKGROUND: Increased plasma potassium concentrations (K(+)) in neonatal calves with diarrhea are associated with acidemia and severe clinical dehydration and are therefore usually corrected by intravenous administration of fluids containing sodium bicarbonate. OBJECTIVES: To identify clinical and laboratory variables that are associated with changes of plasma K(+) during the course of treatment and to document the plasma potassium-lowering effect of hypertonic (8.4%) sodium bicarbonate solutions. ANIMALS: Seventy-one neonatal diarrheic calves. METHODS: Prospective cohort study. Calves were treated according to a clinical protocol using an oral electrolyte solution and commercially available packages of 8.4% sodium bicarbonate (250-750 mmol), 0.9% saline (5-10 L), and 40% dextrose (0.5 L) infusion solutions. RESULTS: Infusions with 8.4% sodium bicarbonate solutions in an amount of 250-750 mmol had an immediate and sustained plasma potassium-lowering effect. One hour after the end of such infusions or the start of a sodium bicarbonate containing constant drip infusion, changes of plasma K(+) were most closely correlated to changes of venous blood pH, plasma sodium concentrations and plasma volume (r = -0.73, -0.57, -0.53; P < .001). Changes of plasma K(+) during the subsequent 23 hours were associated with changes of venous blood pH, clinical hydration status (enophthalmos) and serum creatinine concentrations (r = -0.71, 0.63, 0.62; P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: This study emphasizes the importance of alkalinization and the correction of dehydration in the treatment of hyperkalemia in neonatal calves with diarrhea.

Personalizing, not patronizing: the case for patient autonomy by unbiased presentation of management options in stage I testicular cancer.

Testicular cancer (TC) is the most common neoplasm in males aged 15-40 years. The majority of patients have no evidence of metastases at diagnosis and thus have clinical stage I (CSI) disease [Oldenburg J, Fossa SD, Nuver J et al. Testicular seminoma and non-seminoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2013; 24(Suppl 6): vi125-vi132; de Wit R, Fizazi K. Controversies in the management of clinical stage I testis cancer. J Clin Oncol 2006; 24: 5482-5492.]. Management of CSI TC is controversial and options include surveillance and active treatment. Different forms of adjuvant therapy exist, including either one or two cycles of carboplatin chemotherapy or radiotherapy for seminoma and either one or two cycles of cisplatin-based chemotherapy or retroperitoneal lymph node dissection for non-seminoma. Long-term disease-specific survival is ∼99% with any of these approaches, including surveillance. While surveillance allows most patients to avoid additional treatment, adjuvant therapy markedly lowers the relapse rate. Weighing the net benefits of surveillance against those of adjuvant treatment depends on prioritizing competing aims such as avoiding unnecessary treatment, avoiding more burdensome treatment with salvage chemotherapy and minimizing the anxiety, stress and life disruption associated with relapse. Unbiased information about the advantages and disadvantages of surveillance and adjuvant treatment is a prerequisite for informed consent by the patient. In a clinical scenario like CSI TC, where different disease-management options produce indistinguishable long-term survival rates, patient values, priorities and preferences should be taken into account. In this review, we provide an overview about risk factors for relapse, potential benefits and harms of adjuvant chemotherapy and active surveillance and a rationale for involving patients in individualized decision making about their treatment rather than adopting a uniform recommendation for all.

[Update on first-line and relapse chemotherapy for testicular cancer]. / Update Erstlinien- und Rezidivchemotherapie beim Hodentumor.

Germ-cell cancer (GCC) is still the most common cancer diagnosis in men between the ages of 20 and 45 years with an increasing incidence. Due to effective and standardized algorithms that have been developed to stratify patients into different risk groups, remarkable progress has been made in the medical treatment of testicular cancer with an overall cure rate of 88%. The application of surgery, radiotherapy and chemotherapy, the choice of chemotherapy agents as well as treatment duration is defined in international consensus guidelines. The guidelines are based on histology, tumor stages and presence or absence of already known and well-established risk factors. These stringent parameters guarantee the optimal curative treatment options for each GCC patient and can avoid overtreatment as well as undertreatment. For patients with early stage disease, careful consideration between possible side effects due to an adjuvant therapy and the expected relapse rate must be made, whereas in advanced tumor stages the optimal sequence of chemotherapy, surgery and radiotherapy is the focus. In patients who progress or relapse after first-line therapy, the issue of optimal treatment represents a particular challenge and is far more complex. It needs to take into account the analysis of special prognostic variables for a further risk-tailored therapy. A careful weighting between the chosen regimen and the often higher rate of treatment failure in contrast to increased toxic side-effects is mandatory.The disregard of accurate risk stratification and application of accepted treatment standards for patients with GCC at the time of initial diagnosis or at relapse is associated with developing more extensive disease and more intensive treatment. It also results in lower cure rates with the need for further therapy or leads to death of the patient without ever having had a chance for cure.

Hyperkalemia in neonatal diarrheic calves depends on the degree of dehydration and the cause of the metabolic acidosis but does not require the presence of acidemia.

Hyperkalemia is a clinically important electrolyte imbalance in neonatal diarrheic calves that has previously been associated with skeletal muscle weakness and life-threatening cardiac arrhythmias. The aim of the present retrospective analysis was to identify risk factors for hyperkalemia in a convenience sample of 832 calves (≤ 21 d of age) with a clinical diagnosis of diarrhea admitted to a veterinary teaching hospital. Plasma potassium concentrations were most closely associated with parameters of dehydration and renal function such as serum creatinine [Spearman correlation (rs) = 0.61], urea (rs = 0.51), and inorganic phosphorus concentrations (rs = 0.64). Plasma potassium concentrations were weakly associated with venous blood pH (rs = -0.21). Although venous blood pH was not predictive in a multivariate linear regression analysis, the odds of having hyperkalemia (>5.8 mmol/L) in acidemic calves was found to be 8.6 times as high as in nonacidemic calves [95% confidence interval (CI): 4.8-15.4]. However, the presence of hyperkalemia depended on the nature of an existing acidosis, and the odds for the presence of hyperkalemia in acidemic calves with hyper-D-lactatemia (>3.96 mmol/L) were only 0.15 times as high as in acidemic calves with normal D-lactate concentrations (95% CI, 0.11-0.22). Acidemia in hyperkalemic diarrheic calves was associated with hyponatremia and increased concentrations of inorganic phosphorus, L-lactate, and unidentified strong anions that presumably included uremic anions such as sulfate. We conclude that hyper-D-lactatemia in neonatal diarrheic calves is not usually associated with elevated plasma potassium concentrations. Application of the simplified strong ion acid-base model indicated that dehydration is an important contributor to the pathogenesis of hyperkalemia and acidemia in neonatal calves with diarrhea.

Tumor marker kinetics predict outcome in patients with relapsed disseminated non-seminomatous germ-cell tumors.

BACKGROUND: An early serum tumor marker (TM) decline during chemotherapy was shown to independently predict survival in patients with poor-prognosis disseminated non-seminomatous germ-cell tumors (NSGCTs). The aim of this study was to assess whether a TM decline (TMD) also correlates with the outcome in the salvage setting. PATIENTS AND METHODS: Data regarding 400 patients with progressive or relapsed disseminated NSGCTs after first-line chemotherapy prospectively accrued onto two phase III clinical trials were obtained. Serum alpha-fetoprotein (AFP) and/or human chorionic gonadotropin (hCG) were assessed at baseline and after 6 weeks of chemotherapy. A total of 297 patients, 185 and 112 in the training and validation sets, with initially abnormal TMs for whom a change from baseline could be established were used for this analysis. RESULTS: An unfavorable decline in either AFP or hCG was predictive of progression-free survival (PFS) [hazard ratio, HR = 2.15, (95% CI 1.48-3.11); P < 0.001; 2-year PFS rate: 50% versus 26%] as was the Lorch prognostic score (LPS). In the multivariate analysis, an unfavorable TMD, stratified based on the LPS, was an independent adverse prognostic factor for PFS and OS. CONCLUSION: An unfavorable TMD during the first 6 weeks after chemotherapy is associated with a poorer outcome in patients with relapsed disseminated NSGCTs.

Maintaining success, reducing treatment burden, focusing on survivorship: highlights from the third European consensus conference on diagnosis and treatment of germ-cell cancer.

In November 2011, the Third European Consensus Conference on Diagnosis and Treatment of Germ-Cell Cancer (GCC) was held in Berlin, Germany. This third conference followed similar meetings in 2003 (Essen, Germany) and 2006 (Amsterdam, The Netherlands) [Schmoll H-J, Souchon R, Krege S et al. European consensus on diagnosis and treatment of germ-cell cancer: a report of the European Germ-Cell Cancer Consensus Group (EGCCCG). Ann Oncol 2004; 15: 1377-1399; Krege S, Beyer J, Souchon R et al. European consensus conference on diagnosis and treatment of germ-cell cancer: a report of the second meeting of the European Germ-Cell Cancer Consensus group (EGCCCG): part I. Eur Urol 2008; 53: 478-496; Krege S, Beyer J, Souchon R et al. European consensus conference on diagnosis and treatment of germ-cell cancer: a report of the second meeting of the European Germ-Cell Cancer Consensus group (EGCCCG): part II. Eur Urol 2008; 53: 497-513]. A panel of 56 of 60 invited GCC experts from all across Europe discussed all aspects on diagnosis and treatment of GCC, with a particular focus on acute and late toxic effects as well as on survivorship issues. The panel consisted of oncologists, urologic surgeons, radiooncologists, pathologists and basic scientists, who are all actively involved in care of GCC patients. Panelists were chosen based on the publication activity in recent years. Before the meeting, panelists were asked to review the literature published since 2006 in 20 major areas concerning all aspects of diagnosis, treatment and follow-up of GCC patients, and to prepare an updated version of the previous recommendations to be discussed at the conference. In addition, ∼50 E-vote questions were drafted and presented at the conference to address the most controversial areas for a poll of expert opinions. Here, we present the main recommendations and controversies of this meeting. The votes of the panelists are added as online supplements.

[Chemotherapy for urothelial cancer of the bladder--update 2012]. / Chemotherapie des Urothelkarzinoms der Harnblase--Update 2012.

Despite adequate surgical treatment by radical cystectomy and pelvic lymphadenectomy, about half of patients suffering from muscle-invasive urothelial bladder cancer will die. Both overall and cancer-specific survival has been improved by neoadjuvant chemotherapy. However, it is still not possible to predict who is likely to benefit from neoadjuvant treatment and who will not. In contrast to neoadjuvant chemotherapy, the efficacy of adjuvant chemotherapy has not definitely been proven. In metastatic urothelial cancer chemotherapy is usually a palliative treatment option. However, in a significant proportion of patients, disease stabilisation and even long-term response can be achieved. Important advances to tailor first- and second-line chemotherapy have recently been reported for clinical prognostic parameters. This review discusses the current standards and developments in the chemotherapeutic treatment of urothelial bladder cancer. Furthermore, it should provide a framework for reasonable treatment choices in daily clinical practice.

Metabolic acidosis in neonatal calf diarrhea-clinical findings and theoretical assessment of a simple treatment protocol.

BACKGROUND: Clinical assessment of metabolic acidosis in calves with neonatal diarrhea can be difficult because increased blood concentrations of d-lactate and not acidemia per se are responsible for most of the clinical signs exhibited by these animals. OBJECTIVES: To describe the correlation between clinical and laboratory findings and d-lactate concentrations. Furthermore, the theoretical outcome of a simplified treatment protocol based on posture/ability to stand and degree of dehydration was evaluated. ANIMALS: A total of 121 calves with diagnosis of neonatal diarrhea admitted to a veterinary teaching hospital during an 8-month study period. METHODS: Prospective blinded cohort study. Physical examinations were carried out following a standardized protocol. Theoretical outcome of treatment was calculated. RESULTS: Type and degree of metabolic acidosis were age dependent. The clinical parameters posture, behavior, and palpebral reflex were closely correlated to base excess (r = 0.74, 0.78, 0.68; P < .001) and d-lactate concentrations (r = 0.59, 0.59, 0.71; P < .001), respectively. Thus, determining the degree of loss of the palpebral reflex was identified as the best clinical tool for diagnosing increase in serum d-lactate concentrations. Theoretical outcome of treatment revealed that the tested dosages of sodium bicarbonate are more likely to overdose than to underdose calves with diarrhea and metabolic acidosis. CONCLUSIONS AND CLINICAL IMPORTANCE: The degree of metabolic acidosis in diarrheic calves can be predicted based on clinical findings. The assessed protocol provides a useful tool to determine bicarbonate requirements, but a revision is necessary for calves with ability to stand and marked metabolic acidosis.

[High-dose chemotherapy and residual tumor resection in male germ cell tumors]. / Hochdosischemotherapie und Residualtumorresektion bei Patienten mit Hodentumor.

As a consequence of the unsatisfactory results of conventional dose salvage regimens, in particular for patients with poor prognostic features at the time of relapse or in patients with refractory disease, high-dose chemotherapy (HDCT) was introduced into clinical practice in the late 1980s. The combination of carboplatin and etoposide (CE) still remains the backbone of most high-dose regimens. Multiple modifications with more dose escalations or addition of further drugs have been explored, most often with increased toxicity. With improved expertise in supportive care and the use of peripheral blood stem cells, hematopoetic recovery has been significantly shortened and the initial high treatment-related mortality reduced from more than 10% to about 3%. Since the incorporation of HDCT, even patients with unfavorable prognostic features or patients with second or subsequent relapses can achieve long-term remission. Following HDCT residual tumor resection plays a major role in achieving these long-term results. The proportion of vital residual tumor after HDCT is much higher than in patients after conventional chemotherapy. The role of HDCT remains controversial particularly as a first-line treatment and less so in the first salvage setting. As these patients are rare HDCT and residual tumor resection should only be be provided by high-volume centers with sufficient expertise in performing these complex procedures.

High-dose chemotherapy (HDCT) as second-salvage treatment in patients with multiple relapsed or refractory germ-cell tumors.

BACKGROUND: Survival after high-dose chemotherapy (HDCT) as second-salvage treatment (SST) in multiple relapsed germ-cell tumors (GCTs). PATIENTS AND METHODS: Existing databases in Berlin and Marburg of HDCT trials from 1989 to 2008 were retrospectively screened. Among 534 patients, 71 of 534 (13%) patients were scheduled for HDCT having failed previous conventional-dose first-line and first-salvage chemotherapy regimens; those 49 patients who had received at least cisplatin plus etoposide first-line as well as conventional-dose cisplatin-based first-salvage regimens and were diagnosed after 1 January 1990 were further analyzed. RESULTS: Median age at SST was 32 years (range 19-52 years). Median follow-up for surviving patients was 4 years (range 1.7-8.5 years). Three of 49 (6%) patients either progressed or died before scheduled HDCT; the remaining 46 of 49 (94%) received either single or sequential HDCT. The rate of favorable responses to HDCT was 27 of 49 (55%). Nine patients remain alive and free of progression. One additional patient was lost to follow without progression at 4 years. The projected overall survival rate at 5 years was 17% (95% confidence intervals 7% to 30%). CONCLUSION: HDCT can induce remissions in patients with multiple relapsed GCTs with a long-term survival rate of approximately 17%.

[Salvage treatment in germ cell tumors : high-dose chemotherapy and the impact of prognostic factors]. / Rezidivtherapie von Hodentumoren : Stellenwert der Hochdosistherapie und die Rolle von Prognosefaktoren.

The majority of patients with germ cell tumors who fail first-line treatment will still be cured. Patients without first-line chemotherapy who fail surveillance, radiotherapy, or surgery will be managed according to the treatment algorithms of their primary metastatic disease. These patients usually receive three to four cycles of cisplatin, etoposide, and bleomycin.Salvage treatment of patients who relapse after first-line chemotherapy is more complex and requires an experienced and highly specialized team. Two distinct treatment strategies can be pursued: four cycles of conventional-dose chemotherapy with cisplatin, ifosfamide, and either etoposide, paclitaxel, or vinblastine; or early intensification of first-salvage treatment using sequential high-dose chemotherapy. Salvage surgery is frequently required after completion of salvage chemotherapy to completely resect all radiologic residual manifestations. Patients with brain metastases should receive upfront whole brain radiation concurrent with salvage chemotherapy. Patients with late relapses more than 2 years after first-line treatment should receive immediate salvage surgery whenever this is technically feasible.