Treatment of postoperative peritonitis of small-bowel origin with continuous enteral nutrition and succus entericus reinfusion.

HYPOTHESIS: Proximal intestinal stomas established by the exteriorization of leaking anastomosis in the presence of peritonitis can be used to reinfuse succus entericus and provide adequate enteral nutrition. DESIGN: Retrospective analysis of prospectively gathered data from a cohort of consecutive patients admitted between January 1993 and December 1999 for postoperative peritonitis requiring laparotomy and the construction of one or more small-bowel stomas. SETTING: Tertiary referral center with a surgical intensive care unit experienced in the treatment of intra-abdominal sepsis and succus entericus reinfusion. PATIENTS: Twenty-one consecutive patients with postoperative peritonitis originating from a jejunal or ileal leak. We excluded patients with established enterocutaneous fistulae, abscesses amenable to percutaneous drainage or other conservative treatments, and postoperative peritonitis caused by ileocolic or ileorectal anastomosis. INTERVENTIONS: Early laparotomy with exteriorization of small-bowel leak(s), and continuous enteral nutrition (CEN) and succus entericus reinfusion (SER) via the distal portion of the stoma until gastrointestinal continuity was restored. MAIN OUTCOME MEASURES: Feasibility of CEN and SER with temporary, diverting small-bowel stomas and their associated postoperative morbidity and mortality rates. RESULTS: One patient died, and 14 experienced complications. For technical reasons, CEN and SER were discontinued early on in 7 patients. The mean duration of CEN and SER was 58 days and 61 days, respectively. Enteral feedings allowed the suppression of central venous access after a median of 28 days, with 82 days as a median time to restoration of intestinal continuity. CONCLUSIONS: Although the exteriorization of small-bowel leaks with CEN and SER is generally feasible and effective in the treatment of critically ill patients with peritonitis secondary to small-bowel leaks, it is associated with significant morbidity and mortality, in part relating to patients' underlying diseases.

[Intensive care after digestive surgery: the outcome in elderly patients]. / Réanimation en chirurgie digestive: devenir des patients âgés.

STUDY AIM: In surgical intensive care, the results must be analyzed both in terms of mortality and quality of life; this is particularly important in elderly patients for whom recovery remains uncertain. The aim of this prospective study was to assess the early and late prognosis in elderly patients (aged over 75 years) admitted to a digestive surgical intensive care unit (DSICU) for mortality, quality of life, patient autonomy, and also the predictive factors involved. PATIENTS AND METHODS: Over a one-year period, 182 patients were admitted to a tertiary referral DSICU; 30 of these subjects were over 75 years old, and formed the basis of this study. The following data were analyzed: hospital mortality rate; mortality rate at six months, and quality of life at six months (Kamofsky scale). These factors were correlated with the severity of the patient's state at admission and also with the causal disease, circumstances connected with admission, and duration of stay in the DSICU. RESULTS: The hospital mortality rate of patients was 23% (7/30 patients), and the overall mortality rate at six months was 40% (12/30 patients). Of the 12 patients who stayed in the DSICU for more than ten days with a simplified acute physiology score (APS) = 10, not one was alive at six months post-DSICU admission. The 18 remaining patients were still alive at six months, and 72% of them (13/18 patients) had regained their previous post-operative autonomy. CONCLUSION: These results provide reference data for this patient category. The results concerning long-term survival and the good functional outcome are encouraging. If the prognostic criteria defined in this investigation are confirmed by further studies, they may help in making the sometimes difficult decisions regarding elderly patients hospitalized in a DSICU.

Localized squamous-cell cancer of the esophagus: retrospective analysis of three treatment schedules.

BACKGROUND AND PURPOSE: A retrospective study comparing chemotherapy and radiation, esophagectomy alone versus preoperative radiochemotherapy and surgery in localized squamous-cell esophageal carcinoma. MATERIALS AND METHODS: Between 1989 and 1995, 139 patients (40 stage I, 77 stage IIA and 22 stage IIB according to the UICC 78 TNM classification) were treated in two different institutions. They were divided into three groups according to the treatment proposed: E group (treatment by esophagectomy; n = 30), RCT+E group (treatment by preoperative radiochemotherapy and esophagectomy; n = 46), RCT group (treatment by radiochemotherapy; n = 63). Factors like age, tumor localization and stage were similar in all groups. An intention to treat analysis was made. RESULTS: The E group showed no postoperative mortality, while in the RCT+E group, the surgery mortality was 12.8%. The mortality after RCT was 1.7%. After preoperative radiochemotherapy, a pathological complete response was observed in 25% of cases and the curative resection rate was higher (82% after RCT + E versus 60% after E). The 5-year survival difference between the three groups was not relevant (E group, 12.6%; RCT group, 25.8%; RCT + E group, 38.7%). The median survival was 29, 24 and 28.5 months, respectively. The event-free survival was identical for the E group and the RCT group. For patients treated by radiochemotherapy, local and/or distant relapses were significantly reduced by esophagectomy (relapses occurred in 51% of patients in the RCT + E group versus 75% in the RCT group, P = 0.017). Palliative care (dilatations, prosthesis, gastrostomy or jejunostomy) to improve dysphagia was necessary for 38% of patients treated by exclusive radiochemotherapy versus 11% of patients treated by surgery (P = 0.001). CONCLUSIONS: Treatments by esophagectomy or radiochemotherapy were not significantly different. Preoperative radiochemotherapy and surgery lead to a higher survival rate than exclusive radiochemotherapy, however, with a high postoperative mortality rate. This study suggests the relevance of a prospective randomized trial to compare RCT+E and RCT alone.

Delayed adjuvant tamoxifen: ten-year results of a collaborative randomized controlled trial in early breast cancer (TAM-02 trial)

AIM: Immediate adjuvant tamoxifen reduces disease recurrence and improves survival in patients with early breast cancer. However, is it too late to administer tamoxifen to patients who have already undergone treatment, but were unable to benefit from this adjuvant therapy? The French National Cancer Centers (FNCLCC) have investigated the efficacy of delayed tamoxifen administration in a randomized controlled trial. PATIENTS AND METHODS: From September 1986 to October 1989, women with primary breast cancer, who had undergone surgery, radiotherapy, and/or received adjuvant chemotherapy but not hormone therapy more than two years earlier, were randomized to receive either 30 mg/day tamoxifen or no treatment. The 10-year disease-free and overall survival rates of the two groups of patients and of various subgroups were determined according to the Kaplan-Meyer method and compared by the log-rank test. RESULTS: This intention-to-treat analysis comprised 250 Introduction women in the tamoxifen group and 244 in the control group. Patient characteristics (age, T stage, number of positive nodes, receptor status, and interval since tumor treatment) were comparable in both groups. Delayed adjuvant tamoxifen significantly improved overall survival only in node-positive patients and in patients with estrogen receptor-positive (ER+) or progesterone receptor-positive (PR+) tumors. Disease-free survival, however, was significantly improved in the global population and in several patient subgroups (node-positive, ER+, PR+). Patients in whom the interval between primary treatment and delayed adjuvant tamoxifen was greater than five years also had significantly improved disease-free survival. CONCLUSIONS: Overall and disease-free survival results indicate that delayed adjuvant tamoxifen administration (30 mg/day) is justified in women with early breast cancer, even if this treatment is initiated two or more years after primary treatment.

Management of postoperative peritonitis after anterior resection: experience from a referral intensive care unit.

PURPOSE: Anastomotic leakage is the main cause of death after anterior resection. If it causes a single abscess, it may be successfully cured by percutaneous drainage, but in case of extensive peritoneal infection (multiple abscesses and generalized peritonitis), it is associated with a 40 to 60 percent mortality. This study aimed at evaluating aggressive, one-stage surgical management in such cases. METHODS: All patients referred to our surgical intensive care unit during the past ten years with generalized, multilocular, intra-abdominal sepsis after anterior resection were reviewed. There were 32 patients, with a mean age of 65 years, among which 15 (47 percent) were referred from other institutions. The mean Acute Physiology and Chronic Health Evaluation II score on admission was 18. All patients underwent a laparotomy with complete peritoneal exploration, intraoperative lavage, fecal diversion, capillary drainage of the pelvis excluding the rectal stump or the leaking anastomosis from the peritoneal cavity, and primary closure of the abdomen. A Hartmann's operation was done in 22 cases, and conservation of the anastomosis with proximal colostomy was done in 10 cases. The choice was based on the size of the leak, the viability of the colon, and the site of the anastomosis. RESULTS: Four patients died (12 percent), and five patients (16 percent) had recurrent sepsis. When the anastomosis had been conserved, restoration of continuity was achieved in all cases. After Hartmann's operation 8 patients of 19 survivors kept a permanent stoma; 7 had undergone a low anterior resection. CONCLUSIONS: Extensive intra-abdominal infection after anterior resection may be efficiently controlled by a surgical approach combining peritoneal debridement, fecal diversion, and capillary drainage of the pelvis. Intestinal continuity may be restored after diversion stoma or Hartmann's procedure after high anterior resection. This is not the case after a Hartmann's operation after a low colorectal anastomosis, and this procedure should be avoided whenever possible.

Postoperative peritonitis originating from the duodenum: operative management by intubation and continuous intraluminal irrigation.

BACKGROUND: The mortality rate associated with postoperative peritonitis remains high, especially when the source of infection cannot be eradicated. Such is the case with peritonitis arising from the duodenum, as primary closure is futile and intubation alone may be followed by local complications. METHODS: Forty-nine consecutive patients with postoperative peritonitis originating from a duodenal leak and a mean Acute Physiology And Chronic Health Evaluation II score of 17.7 were treated according to the following procedure: a three-channelled spiral drain was inserted through the leak and extraluminal drains were placed near the duodenal defect. Intraluminal irrigation was undertaken immediately through the infusion channel of the spiral drain. RESULTS: Eleven patients died and 26 suffered complications. The mean duration of intubation was 21 days. CONCLUSION: Intubation with intraluminal irrigation has proved effective in a homogeneous group of patients with peritonitis due to duodenal leakage.

Reoperation for severe pancreatitis: a 10-year experience in a tertiary care center.

OBJECTIVES: To analyze the specific problems encountered in treating patients previously operated on for necrotizing pancreatitis and to determine the benefit of such a complex and demanding procedure. DESIGN AND SETTING: Review of a case series in an academic tertiary care referral center. PATIENTS: Forty-four consecutive patients referred and reoperated on in 10 years. INTERVENTIONS: Reiterative laparotomy with complete debridement of all necrotic sites, followed by Mikulicz packing. Mikulicz packs were replaced by removable drains allowing both local prolonged lavage and open drainage of large solid necrotic debris. Enteral nutrition was performed through a feeding jejunostomy. Associated gastrointestinal tract lesions were simultaneously treated. MAIN OUTCOME MEASURES: Operative findings, bacteriological status of necrosis, in-hospital mortality, length of hospitalization, and surgical complications and their management. RESULTS: Necrosis was infected in 36 (82%) of the 44 cases and associated gastrointestinal tract lesions were found in 20 (45%) of these patients. Mortality was 23%, and was significantly (P = .03) related to the preoperative clinical status. Surgical complications occurred in 31 (70%) of the 44 patients necessitating surgical treatment in 18 (41%) of these patients. Mean (+/- SD) stay in the intensive care unit was 66+/-8 days for survivors. CONCLUSION: This complex and demanding surgical procedure is worthwhile, yielding mortality rates comparable to those observed in de novo severe necrotizing pancreatitis.

[Tamoxifen adjuvant delays early breast cancer. Results of a cooperative randomized trial]. / Tamoxifène adjuvant retardé dans le cancer du sein curable. Résultats d'un essai coopératif randomisé.

Adjuvant tamoxifen (TAM) has been proved to reduce recurrence and mortality in early breast cancer, nevertheless many patients did not receive TAM as adjuvant therapy after local treatment. In order to study the efficacy of delayed TAM therapy in patients who were not given immediate adjuvant hormonal treatment, a multicenter randomized trial has been conducted by the French National Cancer Centers (FNCLCC). According to eligibility criterias all women with breast cancer who received curative local treatment at least 2 years before (surgery +/- radiotherapy) with or without adjuvant chemotherapy but no hormonal treatment could have been included. Between September 1986 and October 1989, 494 women were randomized to receive either TAM 30 mg/day for 5 years or no treatment. Patients' characteristics such as age, tumoral stage, number of positive nodes, receptors status and time from local treatment were equally distributed in the 2 groups. An improvement in the disease free survival in the TAM treated patients can be observed with a significative difference (p = 0.05), nevertheless the overall survival is not improved in the TAM group. In the same way, in nodes positive patients although no significative improvement in the overall survival can be observed, a significative improvement in the disease free survival (p = 0.05) can be noted. In estradiol receptors positive patients tamoxifen gives a significative reduction in the odds of death (p = 0.04) and recurrence (p = 0.03). The disease free improvement seems to be limited to 50 and more years old patients. The first results of this trial lead to prescribe tamoxifen to all postmenopausal women previously treated for an early breast cancer without adjuvant tamoxifen treatment.

Decreased transmission of Enterobacteriaceae with extended-spectrum beta-lactamases in an intensive care unit by nursing reorganization.

In our gastrointestinal surgical intensive care unit (SICU), the large number of patients with multiple enterostomies enhances the risk of nosocomial transmission of gut extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBLE) by health care workers. A control study performed in our SICU from June-August 1992 showed an ESBLE gut colonization rate of 70%. To reduce this rate, nursing procedures were intensified or modified, particularly handwashing, single-use equipment and waste control. To test the efficiency of these procedures, 64 patients hospitalized for more than two days from September 1992-March 1993 were screened for gut acquisition of ESBLE. Rectal samples were taken within 48 h after admission and then weekly. After nursing reorganization, the ESBLE colonization rate dropped significantly to 40% (P < 0.001). Twenty patients (31.7%) acquired a gut ESBLE, after a mean of 24.3 +/- 13.7 days. Each patient was colonized with one, two or three ESBLE (Klebsiella pneumoniae, Escherichia coli and Enterobacter aerogenes). Baseline characteristics of the 20 colonized and 39 non-colonized patients showed no significant difference (Student's t-test, P > 0.05). The nursing workload, estimated as a omega index, was greater in the colonized group (P < 0.001). These findings show that strict observance of nursing procedures can significantly reduce ESBLE acquisition in a high-risk surgical unit.

[Surgery of acute necrotizing pancreatitis. Active prolonged drainage in 157 consecutive patients]. / Chirurgie des pancréatites aiguës nécrosantes. Drainage actif prolongé chez 157 patients consécutifs.

OBJECTIVES: Conventional surgery and non-surgical methods have given unsatisfactory results for the treatment of acute necrotic pancreatitis. We therefore adoptive active prolonged drainage with the aim of controlling both acute enzyme toxicity and secondary necrosis. METHODS: One hundred fifty-seven patients with necrotic pancreatitis defined as the presence of extensive pancreatic or peripancreatic necrosis at laparotomy were divided into three groups according to previous care: group 1 no prior medical or surgical treatment (n = 46, 29%), group 2 prior medical but no surgical treatment (n = 48, 31%) and group 3 prior medical and surgical treatment (n = 63, 40%). Spiral drains were placed in the drainage grooves after necrosectomy and post-operative drainage with Mikulicz bags. Continuous lavage-drainage was then maintained for 45 days. Enteral nutrition was initiated on day 7 (mean) and increased progressively to 75 kcal/kg/day so parenteral nutrition could be interrupted 8 days later. RESULTS: There were 28 deaths (18%) including 6 in group 1, 10 in group 2 and 12 in group 3 (13, 21 and 19% respectively). Deaths were due to early multiple organ failure (n = 16), progressive degradation of the clinical situation (n = 8) and sudden death despite improvement (n = 4). Complications requiring re-operation occurred in 44 patients (28%). Among the 129 survivors, mean duration of hospitalization was 70 days including 60 days in the intensive care unit. CONCLUSIONS: Compared with results from former series, active prolonged drainage appears to be more adapted to the natural history and anatomic presentation of acute necrotic pancreatitis.

Hepatic arterial infusion of floxuridine in patients with liver metastases from colorectal carcinoma: long-term results of a prospective randomized trial.

PURPOSE: A multicentric randomized study that compared patients who received intrahepatic arterial infusion (HAI) to a group of patients who did not receive HAI (control group) was performed for unresectable hepatic metastases from primary colorectal carcinoma. PATIENTS AND METHODS: One hundred sixty-six patients were assigned randomly to HAI of floxuridine (5 fluoro-2'deoxyuridine [FUDR]) 0.3 mg/kg/d for 14 days every 4 weeks or to the control group; this latter group, depending on the investigator's choice, was either under observation or received systemic fluorouracil (5-FU). The same regimen of systemic 5-FU also was administered to the HAI group in the event of extrahepatic progression. No crossover from the control group to the HAI group was permitted. The mean duration of follow-up was 54 months (range, 31 to 72), and 163 patients were analyzed. RESULTS: A significant improvement was observed in the survival rate for the 81 patients assigned to HAI group (P less than .02) with a 1-year survival rate of 64% versus 44% in the control group (82 patients). The 2-year survival rate was 23% versus 13%. The median survival was 15 months versus 11 months for the HAI group and the control group, respectively. Survival was better for patients with a less than 30% liver involvement, and for those treated in more specialized centers. The hepatotoxic effects of HAI were observed in 47 patients (chemical hepatitis [n = 28], and biliary sclerosis [n = 19]). The 1-year rate of sclerosing cholangitis was equal to 25%. Gastrointestinal toxicity was infrequent and consisted of gastritis or diarrhea. CONCLUSIONS: Therapy with HAI of FUDR improves the survival of patients with liver metastases over colorectal carcinoma. However, the methods that are used to diminish the toxicity of HAI and efficient systemic chemotherapy, such as a combination of 5-FU and leucovorin, are required to prevent extrahepatic metastases.

[Colonic complications of acute necrotizing pancreatitis]. / Complications coliques au cours des pancréatites aiguës nécrosantes.

Among 126 patients operated upon for acute necrotizing pancreatitis in our department over a 10-year period starting in November 1979, 17 had a colonic resection. Colectomy was made mandatory by a necrotic or ischaemic appearance (12 cases, including 3 bowel perforations), an isolated perforation (2 cases) or extensive fat necrosis of the pericolonic atmosphere (3 cases). The hospital mortality was 5 out of the 17 cases. In 6 patients, the pathological results suggested that colonic resection was unnecessary. Since May 1988, a diverting loop ileostomy has been performed whenever colonic viability was found to be dubious at laparotomy. After this policy was introduced no case of secondary colonic complication was encountered. Nevertheless, there still are "abusive" colectomies unjustified by the pathology. Their number should be reduced by a more cautious indication of colonic resection in acute necrotizing pancreatitis.

Efficiency of enteral nitrogen support in surgical patients: small peptides v non-degraded proteins.

In a prospective study, 12 intensive care patients, after abdominal surgery, received three alternate six-day courses of two enteral diets with identical nitrogen (0.3 g N/kg per day) and energy (60 kcal/kg per day) supply. The protein hydrolysate (PH) diet contained enzyme-hydrolysed casein and lactoserum (60% small peptides), while the non-degraded protein (NDP) diet contained a nitrogen source of similar amino acid composition, but in the form of non-degraded proteins. The patients were randomised to receive either PH-NDP-PH or NDP-PH-NDP. Parameters reflecting protein metabolism were assessed in the plasma, urine, and stomal effluent on days 1, 6, 12, and 18, three hours after stopping the nutrition (t0), and one hour after restarting it (t1). Comparisons of t1 and t0 values showed that 13 amino acids (including the eight essential amino acids) increased significantly with the protein hydrolysate diet, but only two increased with the non-degraded protein diet. Similarly, with protein hydrolysate, insulin-aemia at t1 was significantly higher than at t0 and correlated with plasma leucine, phenylalanine, alanine, and lysine concentrations. In addition, significant improvements in plasma albumin, transferrin, and retinol binding protein concentrations were seen with protein hydrolysate, together with a significant decrease in the plasma phenylalanine/tyrosine ratio and urinary 3-methylhistidine excretion. We conclude that in patients in intensive care after abdominal surgery enteral support containing small peptides is more effective than an equivalent diet containing whole proteins in restoring plasma amino acid and protein levels.

High-output external fistulae of the small bowel: management with continuous enteral nutrition.

Three hundred and thirty-five patients with high-output enterocutaneous fistulae arising from the small intestine are reported. Median fistula output was 1350 ml/24 h. Eighty-two per cent of patients were referred from other institutions. The fistula opening was associated with evisceration in 165 cases (49 per cent). One or more severity factors were present in 75.5 per cent of the patients. Patients were divided into three groups according to their initial therapy: 21 patients (6 per cent) referred in a moribund state were not operated on (non-intervention); 80 patients (24 per cent) were operated on as an emergency, and the fistula was either exteriorized or defunctioned; 234 patients (70 per cent) were initially managed conservatively. Appropriate local care and nutrition were provided in all cases. Enteral nutrition was the exclusive nutritional support in 285 patients (85 per cent). In 92 cases with proximal fistulae, methods limiting the fistula output or allowing reinfusion of chyme were required. The overall mortality rate was 34 per cent: 100 per cent in the non-intervention group, 55 per cent after emergency surgery, and 19 per cent after conservative treatment. In the latter group, spontaneous closure was obtained in 88 patients (38 per cent). Overall mortality rate was reduced to 19 per cent in patients treated since 1980. Enteral nutrition with appropriate local care may be used in the majority of high-output enterocutaneous fistulae, with an acceptable rate of spontaneous closure. Conservative management is the treatment of choice in the initial period. Emergency surgery should be restricted to the treatment of haemorrhage or intra-abdominal abscesses associated with uncontrolled systemic sepsis.

[Adjuvant radiochemotherapy in operable cancers of the thoracic esophagus. Preliminary results of a multicenter study. A study of 119 cases]. / Radio-chimiothérapie adjuvante dans les cancers opérables de l'oesophage thoracique. Résultats préliminaires d'une étude multicentrique. Etude portant sur 119 cas.

119 operable patients with an oesophageal squamous cell carcinoma were treated preoperatively by a combination of radiotherapy (37 Gy in two courses) and chemotherapy by cisplatin (delivered before each course of radiation). The response was evaluated on the resected specimen. 111 patients underwent operation and 101 tumours were resected. The toxicity was acceptable by reducing the Cisplatin dosage from 100 mg/m2 to 80 mg/m2 for the last 67 patients. A complete response was observed in 24 patients and a partial response in 46. The preliminary results show a 57% eighteen-month survival in the group of resected patients. A controlled study is needed to compare this combined regimen versus surgery alone in curatively resectable patients.

Continuous enteral nutrition during the early adaptive stage of the short bowel syndrome.

Sixty-two patients with the short bowel syndrome (30-150 cm) were managed by continuous enteral nutrition (CEN) in the early adaptive phase. In all, 82 per cent were referrals from other units and 85 per cent of referrals had failure of one or more organ systems on admission. There were intra-abdominal abscesses in 41 per cent of patients and 37 per cent had an enterocutaneous fistula. The diet included polysaccharides, medium chain triglycerides and protein hydrolysates, mixed with a high-viscosity tapioca suspension. An elemental diet was used initially in 15 per cent of patients. Thirty-three patients had an interruption of the gastrointestinal tract by a temporary enterostomy. Chyme was re-infused into the distal intestine in 20 cases. 'Zero-time' was taken as the time of operation or, for referred patients treated conservatively, the date of admission. CEN was commenced at a mean of 14 days from zero-time. Total parenteral nutrition could be discontinued at a mean of 36 days and exclusive oral alimentation was resumed at a mean of 87 days. Patients with small bowel longer than 80 cm attained enteral autonomy earlier than patients with a shorter length. Mean faecal volume did not increase following institution of CEN, suggesting tolerance to the high-viscosity diet. In cases with re-infusion of enteric content, the distal circuit (length of distal small intestine 46 cm) was able to absorb 70 per cent of the volume re-infused (mean volume 2700 ml). Body weight and nutritional markers increased significantly during the course of CEN. This study suggests that enteral autonomy can be attained early in the short bowel syndrome, even under challenging conditions. Elemental formulae do not appear to offer a benefit over polymeric diets.

Adjuvant tamoxifen in postmenopausal breast cancer: preliminary results of a randomized trial.

Between May 1978 and March 1982, 179 postmenopausal women with operable breast cancer were randomized to receive either adjuvant tamoxifen, 40 mg daily for three years (TAM group), or no further treatment (controls). The difference in five-year survival rates (61% in the control group, 72% in the TAM group) was not statistically significant. However, there was a significant improvement in disease-free survival in the TAM group (61%) relative to the controls (44%) (p = 0.008). In estrogen receptor positive patients, tamoxifen improved both the disease-free rate (47% controls, 80% with tamoxifen) and the survival rate (63% to 83%). Similar results were observed in progesterone receptor positive patients. In patients that were estrogen receptor negative, tamoxifen modified neither the survival rate nor the disease-free interval.