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Debulking nephrectomy in metastatic renal cancer.

Up to one third of patients with renal cell carcinoma will present with metastatic disease, and 20 to 40% of those with clinically localized disease will eventually be found to have metastatic involvement. Prognosis continues to be guarded for this population, with a 2-year survival of only 10 to 30%. Although advances are being made in the medical management of renal cell carcinoma, the role of surgery in the treatment algorithm is also being additionally refined. Palliative surgery either via nephrectomy or metastasectomy has a role in certain well-selected patients. There are also data to support total metastasectomy at the time of either nephrectomy or recurrence in a small subset of patients with minimal, resectable metastases. More controversial is the idea of cytoreductive nephrectomy as an adjunct to immunotherapy. Recent phase III trials indicate that nephrectomy may play an important role in management of metastatic renal cell carcinoma in conjunction with cytokine-based immunotherapy. Nephrectomy is also an essential component of tumor-based vaccine and adoptive immunotherapy protocols and may play a role in other novel therapies.

Carcinoma, Renal Cell↗

Mortality and morbidity after nephrectomy for renal cell carcinoma using a transperitoneal anterior subcostal incision.

OBJECTIVES: We have reviewed our surgical experience to document intra- and postoperative mortality and morbidity in 656 patients with renal cell carcinoma who underwent nephrectomy through a transperitoneal anterior subcostal incision (TASI). MATERIALS AND METHODS: From 1986 to 1997 we performed 656 nephrectomies for renal cell carcinoma using a TASI. Details of the surgical procedure are presented together with a retrospective analysis of the postoperative data concerning both the patient and the complications related to this approach. RESULTS: The mean time of operation was 130 min and the mean discharge from hospital 11 days. An additional surgical procedure in relation with the cancer facilitated by this approach was necessary in 2.1% of cases. The rates of intra- and postoperative complications were respectively 6.4 and 29.7%. The rate of intestinal complications was 1.8% and a splenic injury occurred in 8% of left nephrectomy. The mortality rate was 0.6%. CONCLUSIONS: The TASI is a large convenient incision which allows safe control of the renal pedicle in a very large number of renal tumors, even those located in the upper pole of the kidney. The rate of gut complications is very acceptable. Splenic injury is the major problem during left nephrectomy but careful dissection and surgical experience could decrease this complication, especially in case of upper pole renal tumor. We consider the TASI to be the main radical nephrectomy incision for renal cell carcinoma.

Adolescent↗

Nephrectomy - indications, complications and postoperative mortality in 646 consecutive patients.

OBJECTIVE: To gain information about the indications for and complications of conventional nephrectomy, also to create standards for future evaluation of nephrectomies performed by minimal invasive techniques. METHODS: We present a historical 20 years' series of 646 consecutive nephrectomies performed in the period of 1978-1997. Malignant disease led to the operation in 437 cases, of which 98 were urothelial tumors in the renal pelvis or ureter. 209 kidneys were removed due to benign conditions. The incidence of nephrectomy for benign conditions has declined from 75 in the first 5-year period to 32 in the last. RESULTS AND DISCUSSION: Postoperative complications occurred in 100 patients (15.5%). Nephrectomy for malignant disease had a significantly higher rate of complications than operations for benign conditions (p<0.001), especially hemorrhagic complications and pneumonias were more frequent. There were no differences as a result of the operative approach. Reoperation was carried out in 3.0% of the cases. Overall mortality rate (<30 days) was 3.1%.

Aged↗

Biochemical, histological and behavioral consequences of nephrectomy in young and aged mice.

BACKGROUND: This study investigates the effect of nephrectomy in young and aged mice on some biochemical, histological and behavioural aspects. METHODS: Each age group, 2- and 12-months-old, comprised a sham-operated group, a unilaterally nephrectomized group and a subtotally nephrectomized group. Consequences of nephrectomy were examined 10 days postsurgery on urea and guanidino compound levels in body fluids and brain; the remaining kidney by light-microscopic examination; and learning and memory abilities using the Morris water maze task. RESULTS: Effect of nephrectomy on urea and guanidino compound levels in plasma, urine and brain was significantly more pronounced in the young age group. Some guanidino compounds show a tendency to decrease with aging in the sham-operated group and the two nephrectomized groups. Higher compensatory kidney hypertrophy was found in younger nephrectomized mice whereas in older mice glomerular mesangial expansion was a common feature. Finally, young mice with subtotal nephrectomy displayed a slight but significant impairment in memory and learning; whilst old nephrectomized mice manifested no impairment. CONCLUSIONS: Nephrectomy induces more changes in younger mice than in older mice as observed in higher variation of urea and guanidino compound levels, glomerular volume and kidney hypertrophy and decline in spatial learning and memory.

Age Factors↗

Laparoscopic radical nephrectomy.

Laparoscopic radical nephrectomy has gained in popularity as an accepted treatment modality for localized renal cell carcinoma at many centers worldwide. Laparoscopic radical nephrectomy may be performed via a transperitoneal or retroperitoneal approach. Mostly, the transperitoneal approach is used. Current indications for laparoscopic radical nephrectomy include patients with T(1)-T(3a)N(0)M(0) renal tumors. Herein, transperitoneal as well as retroperitoneal laparoscopic approaches are described. Surgical outcomes and complications from published series are reviewed with comparison to open surgery. Special related concerns as oncologic principles, organ retrieval, lymphadenectomy, and concomitant adrenalectomy are addressed. In conclusion, laparoscopic radical nephrectomy is now established with considerable advantages; decreased postoperative morbidity, decreased analgesic requirements, improved cosmesis, shorter hospital stay and convalescence. Although no long-term follow-up is available, short and intermediate follow-up results confirm the effectiveness of laparoscopic radical nephrectomy.

Carcinoma, Renal Cell↗

Retroperitoneal laparoscopic living-donor nephrectomy. Preliminary results.

PURPOSE: Living-donor nephrectomy is performed via a standard flank approach during open surgery in contrast to laparoscopy where kidneys are procured transperitoneally. Being more familiar with retroperitoneal laparoscopy for the surgery of the upper urinary tract, we investigated the feasibility of live donor nephrectomy by this approach. MATERIAL AND METHODS: We performed laparoscopic retroperitoneal left-sided nephrectomy in 3 living donors. The patients were placed in lumbotomy position. The retroperitoneal space was developed with blunt finger dissection, through a 2-cm mini-lumbotomy under the 12th rib in the posterior axillary line. 5 trocars were inserted. After primary access to the renal artery and vein, these were dissected to their junctions with the aorta and inferior vena cava, respectively, before freeing the kidney of its perinephric attachments. The kidney was delivered manually, through the slightly enlarged initial subcostal incision. RESULTS: The average duration of surgery was 83 min; warm ischemia time less than 5 min. Average blood loss was 120 cm(3). Donors did not present any postoperative morbidity and were discharged after an average of 2.3 days. Mean analgesic requirement was 5 mg morphine sulphate equivalent (0-15). Average convalescence was 13.3 days (10-18). All 3 kidneys harvested laparoscopically had immediate function with urine production after graft revascularization; serum creatinine levels returned to normal within 1 week. The first patient presented ureteral stenosis 2 months after surgery. He underwent ureteropyeloplasty using his native ureter. CONCLUSIONS: Laparoscopic living-related-donor nephrectomy become a new standard for organ harvesting. Our data suggest that retroperitoneal laparoscopic donor nephrectomy may represent a reasonable option in centers in which more extensive experience has been accumulated with retroperitoneal than with transperitoneal laparoscopy for the surgery of the upper urinary tract.

Female↗

Application of the microwave tissue coagulator: is it beneficial to partial nephrectomy?

BACKGROUND/AIM: The indications of partial nephrectomy have expanded after the introduction of new techniques for preventing excessive blood loss and avoiding deterioration of the renal function after clamping the renal pedicle. We present our clinical experience of partial nephrectomy for renal tumors using a microwave tissue coagulator. PATIENTS AND METHODS: Between April 1996 and January 2000, 34 patients underwent open partial nephrectomies in the Kobe City General Hospital. The microwave tissue coagulator was used for resection of the renal parenchyma, but in deeper lesions a sharp dissection was performed. Twenty-two patients (groups 1 and 2) underwent partial nephrectomy without vascular control (14 renal pedicles were not disturbed in group 1 patients, and 8 renal pedicles were dissected but not clamped in group 2 patients). Another 12 patients (group 3) underwent vascular control with ligation of the tumor-feeding segmental arteries before parenchymal resection. The patients of group 1 underwent wedge resections, while those of groups 2 and 3 underwent segmental or transverse partial nephrectomies. RESULTS: Complete tumor resection was done in all 34 patients. In group 1, the microwave tissue coagulator was very effective to control the blood loss (mean 330 ml). In larger resections, this method only was inadequate to control the blood loss (mean 489 ml in group 2), so that we needed vascular control. However, despite vascular control, mean blood losses of about 943 ml because of deeper venous bleeding occurred in group 3, and, moreover, postoperative renal infarctions occurred in 2 patients. Other complications were urinary fistula formation in 16 patients (47%) and renal pelvic stenoses in 2 patients (5.8%). All of the urinary fistulas were easily repaired by simple suturing intraoperatively. CONCLUSIONS: Especially in wedge resection, the microwave tissue coagulator achieved safe resection without vascular control which differs from other new techniques. However, in larger resections, a combination with other techniques may be necessary to decrease blood loss and the rate of complications.

Adult↗

Does radical nephrectomy with immunochemotherapy have any superiority over embolization alone in metastatic renal cell carcinoma? A preliminary report.

INTRODUCTION: We evaluated the results and effects of radical nephrectomy followed by immunochemotherapy and embolization alone on the survival of patients with metastatic renal cell carcinoma. PATIENTS AND METHODS: The study included 20 patients with histologically confirmed renal cell carcinoma. Ten patients were in the combined therapy group and the other 10 patients who were unable to undergo nephrectomy because of poor performance status or unresectable tumor were in the embolization group. Radical nephrectomy was performed on patients with good performance status (WHO criteria 0-1). Immunochemotherapy (interferon alpha 2a and 5-fluorouracil) was started within 1 month after surgery. A dose of 9 x 10(6) U/day interferon alpha 2a was subcutaneously administered 3 times a week. A dose of 750 mg/m2 5-fluorouracil was administered intravenously during 4 h in the first 5 days of treatment. 5-Fluorouracil therapy was converted to weekly intervals after the first 12 days. Combined therapy was continued for 3 months. Ethanol was used for transarterial embolization. The main renal arteries and parasitic arteries of the tumor were embolized. RESULTS: There were no significant differences in age distribution, sex, affected side, tumor size and T stage between the groups. After completion of the combined therapy, 6 patients showed progression at the first control. Only 1 patient (10 %) had stable disease throughout the 10 months after combined therapy. One patient died of myocardial infarction on the 4th day in the embolization group. While progressive disease within the first 3 months was detected in 6 patients, the other 3 patients (30%) had stable disease for 14, 17 and 55 months, respectively. There was no complete response in any group and no patient was alive (died of renal cell carcinoma) at the time of the analysis of the study data. Whereas the median survival time was 11 months (1-80) (mean +/- SE: 22.2 +/- 9.1) in the combined group, this time was a median of 1 month (1-74) (mean +/- SE: 17.5 +/- 8.6) in the embolization group. There was no statistically significant difference in survival time between the groups (p > 0.05). CONCLUSION: In this preliminary report, the clinical findings in embolization-group patients were definitively worse than the nephrectomy plus immunochemotherapy-group patients. In spite of these differences, combination therapy using radical nephrectomy and immunochemotherapy could not show superiority to embolization alone, especially in terms of survival time.

Adult↗

Urinary enzyme excretion after donor nephrectomy.

A number of recent studies of long-term kidney donors have reviewed glomerular function and blood pressure. Little attention has been paid to the potentially damaging effects of compensatory hyperfiltration on renal tubular cells after donor nephrectomy. The urinary excretion of high-molecular-weight enzymes is a sensitive indicator of renal tubular cell damage. This study compares the urinary excretion of four enzymes (alanine aminopeptidase, alkaline phosphatase, N-acetyl-beta-D-glucosaminidase, and lactate dehydrogenase) in a group of 77 subjects who had undergone unilateral nephrectomy up to 21 years previously with 52 healthy non-nephrectomized controls. The urinary excretion for all four enzymes by the remaining kidney after contralateral nephrectomy in the kidney donors was significantly greater than the enzyme excretion per single kidney in the control group (p less than 0.001). No correlation was found between the degree of enzymuria and either glomerular filtration rate or time since nephrectomy. The elevated activity of urinary enzymes in kidney donors may be related to increased metabolism by the renal tubular cells after contralateral nephrectomy. This study suggests that long-term compensatory hyperfiltration does not damage tubular cells, at least over this time scale.

Acetylglucosaminidase↗

Effect of unilateral nephrectomy on gene expression of metalloproteinases and their inhibitors.

Levels of mRNA encoding for metalloproteinase (MMP) 1, 2, 3 and 9 and tissue inhibitor of metalloproteinase (TIMP) 1 were measured in both the renal cortex and glomeruli following unilateral nephrectomy or a sham operation. The expression of MMP-1 and MMP-3 increased 3-fold (p < 0.001) within the renal cortex 24 h following nephrectomy, and then gradually decreased to the control level after 7 days. In contrast, expression of MMP-2 and MMP-9 remained unchanged following nephrectomy. TIMP-1 mRNA levels also significantly increased 4-fold (p < 0.001) within the renal cortex 12 h following nephrectomy, followed by a decrease to the control level after 3 days. In contrast, the glomerular expression of MMP-1, -2, -3 and TIMP-1 remained stable while minimal MMP-9 mRNA was detectable. MMPs and TIMP-1 may be associated with the early stages of renal hypertrophy following unilateral nephrectomy.

Animals↗

Transplantation in autosomal dominant polycystic kidney disease without nephrectomy.

Some transplantation centers still suggest nephrectomy in patients with autosomal dominant polycystic kidney disease (ADPKD) before kidney transplantation at least in selected cases. We wanted to learn whether prior nephrectomy is beneficial. The outcome of kidney transplantation in 47 consecutive ADPKD patients without prior nephrectomy was compared with that in matched controls with respect to complications of ADPKD. Although ADPKD patients were older than controls (mean, 50.1 vs. 40.3 years), there was no statistically significant difference in 1- and 5-year allograft survival between ADPKD patients and controls: 76.6 and 68.0%, respectively, in ADPKD patients, and 83.9 and 56.3% in controls. After a mean follow-up of 66.5 months 3 patients with ADPKD had cyst infections and were managed with antibiotics. Two patients had episodes of hematuria; neither required invasive therapy. There was no renal malignancy and clinical sign of urolithiasis in any patient. No posttransplantation nephrectomy was required. With only few indications remaining, there is no rationale for routine pretransplantation nephrectomy in patients with ADPKD.

Adult↗

Retroperitoneal laparoscopic nephrectomy in children. Preliminary report of 18 cases.

Laparoscopic nephrectomy is a new procedure which remains to be evaluated in adults and children. This technique enables the reduction of parietal complications and sequelae. The majority of indications, e.g. renal dysplasia, destroyed kidneys due to obstructive or refluxing uropathy, are suitable for laparoscopic nephrectomy. Contraindications are Wilm's tumor and trauma which represent only 20% of nephrectomies in our experience. As in open surgery, a retroperitoneal approach seems more logical and better adapted than a transperitoneal approach to perform nephroureterectomy for benign disease. From August 1993 to December 1995, we attempted 18 retroperitoneal laparoscopic nephrectomies in children aged from 3 months to 14 years. The patient is placed in a lateral position, and after creation of a retropneumoperitoneum under direct vision control without balloon dissection, three or four ports are needed, renal vessels are dissected, then clipped or coagulated if small. Destroyed kidneys are generally of small size, so they can be extracted via a 10- or 12-mm cannula site without morcellation. Operative time is 35-210 min (median 106 min). There were no major complications and only one conversion. In conclusion, retroperitoneal laparoscopic nephrectomy in children is a feasible and safe procedure in well-trained hands.

Adolescent↗

A gamma-melanocyte stimulating hormone-like peptide causes reflex natriuresis after acute unilateral nephrectomy.

Previous studies have shown that acute unilateral nephrectomy stimulates sodium (UNaV) and potassium (UKV) excretion by the remaining kidney through reflex pathways requiring an intact pituitary gland, and the natriuresis is accompanied by an increase in the plasma concentration of a peptide or peptides derived from the adrenocorticotropic hormone-beta-endorphin precursor molecule pro-opiomelanocortin. We tested the hypothesis that gamma-melanocyte stimulating hormone (gamma-MSH) was such a peptide involved in the postnephrectomy natriuresis. In six rats undergoing sham nephrectomy, no change in UNaV or UKV occurred and plasma immunoreactive gamma-MSH-like material was 40 +/- 18 (SD) fmol/ml 2 hours after the sham procedure. In 10 rats undergoing acute unilateral nephrectomy, UNaV and UKV from the remaining kidney increased significantly, and immunoreactive gamma-MSH was 81 +/- 36 fmol/ml (p less than 0.02). In individual studies, the increase in UNaV after nephrectomy correlated with the postnephrectomy concentration of immunoreactive gamma-MSH (r = 0.75, p less than 0.001). In 17 rats injected with serum or globulin from control rabbits, unilateral nephrectomy led to the expected increases in UNaV and UKV. In 23 rats injected with serum or globulin from rabbits immunized against gamma-MSH, no postnephrectomy natriuresis occurred and the kaliuresis was blunted. In hydropenic, mineralocorticoid-treated rats, intravenous infusion of synthetic gamma-MSH led to natriuresis and kaliuresis with no change in inulin clearance; pretreatment with rabbit anti-gamma-MSH antiserum blocked this effect of peptide infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of changes in sodium or potassium balance, and nephrectomy, on adrenal renin and aldosterone concentrations.

An active form of renin was confirmed in the adrenal gland of rats. It had a molecular weight of 40,000, generated angiotensin I (AI) from natural renin substrate at pH 7.4, and was found at concentrations 30 to 60 times higher than plasma renin in rats on a normal diet. Changes in sodium diet induced changes in adrenal capsular renin concentration (high Na 2.21 +/- 0.34, normal Na 4.34 +/- 0.53, low Na 13.19 +/- 1.67 ng AI/mg protein/hr). A high potassium diet also increased adrenal capsular renin from 5.27 +/- 0.53 to 39.78 +/- 5.68 ng AI/mg protein/hr, while plasma renin concentration decreased from 7.28 +/- 0.63 in the normal diet to 5.05 +/- 0.60 on the high potassium diet. Neither diet altered the concentration of renin in the fasciculata-medullary portion of the adrenal gland. Nephrectomy markedly increased the renin concentration in the adrenal capsules without any effect on the decapsular cells (20 hours after nephrectomy, 71.5 +/- 10.6 ng AI/mg protein/hr). Sodium loading or dexamethasone treatment prior to nephrectomy blunted the rise in adrenal renin (nephrectomy + dexamethasone = 27.64 +/- 4.33 ng AI/mg protein/hr; nephrectomy + NaCl = 38.70 +/- 5.82 ng AI/mg protein/hr). In all experiments, there was a positive correlation between adrenal renin and adrenal aldosterone concentrations, but the experiments did not rule out the possibility that this positive correlation was due to two independent variables changing in the same direction and not causally related. In conclusion, adrenal renin may be a local hormone, involved in the regulation of aldosterone production.

Adrenal Glands↗

Nephron-sparing surgery--strategies for partial nephrectomy in renal cell carcinoma.

The use of partial nephrectomy for renal cell carcinoma has continuously changed in the clinical practice. Previously it was mostly used in imperative cases, in patients with a solitary kidney or in patients with a risk of renal failure. An increased number of incidentally detected renal cell carcinomas are diagnosed due to the advances of the radiological methods. These tumours tend to be smaller and generally with a lower stage. The reported excellent results of partial nephrectomy have promoted the use of nephron-sparing surgery also in patients with a normal contralateral kidney and tumours smaller than 4-5 cm. The technical outcome is excellent with a low operative morbidity and a good oncologic control. Therefore partial nephrectomy has become a standard technique in the treatment of properly selected patients. Laparoscopy with its reduced postoperative pain and shorter rehabilitation time, has encouraged the interest in minimally invasive nephron sparing surgical techniques. Although low, the risk of local tumour recurrence and surgical complications are higher after nephron-sparing surgery compared with radical nephrectomy. Furthermore, long-term renal function remains adequate in most patients with a normally functioning contralateral kidney also after radical nephrectomy. Albeit these facts, there is convincing evidence justifying nephron-sparing surgery to be used routinely for patients with a small renal cell carcinoma and a normal functioning contralateral kidney.

Carcinoma, Renal Cell↗

The timing of immunotherapy and nephrectomy in multimodality treatment of metastatic renal cell carcinoma.

Multimodality treatment of metastatic renal cell carcinoma with immunotherapy and cytoreductive surgery is controversial. Especially the benefit of removing asymptomatic primary tumors in synchronous metastatic renal cell cancer has been debated since several non-randomized, retrospective studies revealed an improved response to immunotherapy and prolonged survival following initial nephrectomy. Two recent randomized prospective trials both demonstrated a prolonged survival in those who were randomly assigned to undergo nephrectomy of the primary tumor prior to treatment with interferon alfa-2b than in those who were assigned to undergo treatment with interferon alfa-2b alone. In these trials the survival benefit was limited and strongly influenced by overall performance score. The timing of immunotherapy, either as neoadjuvant (prior to nephrectomy) or adjuvant treatment (following nephrectomy) in the multimodality approach of synchronous metastatic renal cell carcinoma remains controversial. Selection of patients, the possible mechanisms underlying the survival advantage of the combination of nephrectomy and immunotherapy, and the timing of the treatment modalities are discussed herein.

Carcinoma, Renal Cell↗

Clipless management of the renal vein during hand-assist laparoscopic donor nephrectomy.

BACKGROUND: Laparoscopic live donor nephrectomy has become the preferred method of donor nephrectomy at many transplant centers. The laparoscopic stapling device is commonly used for division of the renal vessels. Malfunction of the stapling device can occur, and is often due to interference from previously placed clips. We report our experience with a clipless technique in which no vascular clips are placed on tributaries of the renal vein at or near the renal hilum in order to avoid laparoscopic stapling device misfires. METHODS: From December 20, 2002 to April 12, 2005, 50 patients underwent hand-assisted laparoscopic left donor nephrectomy (LDN) at our institution. Clipless management of the renal vein tributaries was used in all patients, and these vessels were divided using either a laparoscopic stapling device or the LigaSureTM device (Valleylab, Boulder, CO). The medical and operative records of the donors and recipients were reviewed to evaluate patient outcomes. RESULTS: The mean follow-up time was 14 months. Of the 50 LDN procedures, there were no laparoscopic stapling device malfunctions and no vascular complications. All renal allografts were functioning at the time of follow-up. CONCLUSION: Laparoscopic stapling device failure due to deployment across previously placed surgical clips during laparoscopic live donor nephrectomy can be prevented by not placing clips on the tributaries of the renal vein. In our series, there were no vascular complications and no device misfires. We believe this clipless technique improves the safety of laparoscopic donor nephrectomy.

Female↗

Treatment with nephrectomy only for small, stage I/favorable histology Wilms' tumor: a report from the National Wilms' Tumor Study Group.

PURPOSE: Children younger than 24 months with small (< 550 g), favorable histology (FH) Wilms tumors (WTs) were shown in a pilot study to have an excellent prognosis when treated with nephrectomy only. PATIENTS AND METHODS: A study of nephrectomy only for the treatment of selected children with FH WT was undertaken. Stringent stopping rules were designed to insure closure of the study if the true 2-year relapse-free survival rate was 90% or lower. RESULTS: Seventy-five previously untreated children younger than 24 months with stage I/FH WTs for which the surgical specimen weighed less than 550 g were treated with nephrectomy only. Three patients developed metachronous, contralateral WT 1.1, 1.4, and 2.3 years after nephrectomy, and eight patients relapsed 0.3 to 1.05 years after diagnosis (median, 0.4 years; mean, 0.51 years). The sites of relapse were lung (n = 5) and operative bed (n = 3). The 2-year disease-free (relapse and metachronous contralateral WT) survival rate was 86.5%. The 2-year survival rate is 100% with a median follow-up of 2.84 years. The 2-year disease-free survival rate (excluding metachronous contralateral WT) was 89.2%, and the 2-year cumulative risk of metachronous contralateral WT was 3.1%. CONCLUSION: Children younger than 24 months treated with nephrectomy only for a stage I/FH WT that weighed less than 550 g had a risk of relapse, including the development of metachronous contralateral WT, of 13.5% 2 years after diagnosis. All patients who experienced relapse on this trial are alive at this time. This approach will be re-evaluated in a clinical trial using a less conservative stopping rule.

Disease-Free Survival↗