ESO-ESMO fifth international consensus guidelines for breast cancer in young women (BCY5).

We dedicate this manuscript in memory of a dear friend and colleague Bella Kaufman. The fifth International Consensus Symposium for Breast Cancer in Young Women (BCY5) took place virtually in October 2020, organized by the European School of Oncology (ESO) and the European Society of Medical Oncology (ESMO). Consensus recommendations for the management of breast cancer in young women were updated from BCY4 with incorporation of new evidence to inform the guidelines. Areas of research priorities as well as specificities in different geographic and minority populations were identified. This manuscript summarizes the ESO-ESMO international consensus recommendations, which are also endorsed by the European Society of Breast Specialists (EUSOMA).

Axillary staging for breast cancer during pregnancy: feasibility and safety of sentinel lymph node biopsy.

BACKGROUND: Safety of sentinel lymph node (SLN) biopsy for breast cancer during pregnancy is insufficiently explored. We investigated efficacy and local recurrence rate in a large series of pregnant patients. PATIENTS AND METHODS: Women diagnosed with breast cancer who underwent SLN biopsy during pregnancy were identified from the International Network on Cancer, Infertility and Pregnancy, the German Breast Group, and the Cancer and Pregnancy Registry. Chart review was performed to record technique and outcome of SLN biopsy, locoregional and distant recurrence, and survival. RESULTS: We identified 145 women with clinically N0 disease who underwent SLN during pregnancy. The SLN detection techniques were as follows: 99mTc-labeled albumin nanocolloid only (n = 96; 66.2%), blue dye only (n = 14; 9.7%), combined technique (n = 15; 10.3%), or unknown (n = 20; 13.8%). Mapping was unsuccessful in one patient (0.7%) and she underwent an axillary lymph node dissection (ALND). Mean number of SLNs was 3.2 (interquartile range 1-3; missing n = 15). Positive SLNs were found in 43 (29.7%) patients and 34 subsequently underwent ALND. After a median follow-up of 48 months (range 1-177), 123 (84.8%) patients were alive and free of disease. Eleven patients experienced a locoregional relapse, including 1 isolated ipsilateral axillary recurrence (0.7%). Eleven (7.6%) patients developed distant metastases, of whom 9 (6.2%) died of breast cancer. No neonatal adverse events related to SLN procedure during pregnancy were reported. CONCLUSIONS: SLN biopsy during pregnancy has a comparably low axillary recurrence rate as in nonpregnant women. Therefore, this method can be considered during pregnancy instead of standard ALND for early-stage, clinically node-negative breast cancer.

Improved prognosis of young patients with breast cancer undergoing breast-conserving surgery.

BACKGROUND: The aim of the present study was to evaluate how breast cancer prognosis has evolved over time in young women treated with breast-conserving surgery (BCS). METHODS: Data from patients younger than 40 years who had BCS and whole-breast radiotherapy in a single cancer centre between 1997 and 2010 were analysed. The patients were followed until 2016. Endpoints were local recurrence, any breast cancer-related event and death from any cause. RESULTS: A total of 1331 patients were included in the study. After a median follow-up of 9·3 years, 114 local recurrences, 289 breast cancer-related events and 138 deaths had occurred. Women were divided into three groups of similar size based on tertiles of the date of diagnosis: 1997-2002 (524 patients), 2003-2005 (350) and 2006-2010 (457). The risk of local recurrence was 1·42 per 100 person-years in women diagnosed in the first interval, 0·85 per 100 person-years in the second and 0·48 per 100 person-years in the third (P for trend = 0·028). The respective values were 3·01, 2·52 and 2·07 per 100 person-years for any breast cancer-related event (P = 0·004), and 1·59, 1·22 and 0·64 per 100 person-years for death (P = 0·003). Each passing year was associated with a decreasing risk of local recurrence (hazard ratio (HR) 0·93, 95 per cent c.i. 0·87 to 1·00), any breast cancer-related event (HR 0·94, 0·91 to 0·98) and death (HR 0·89, 0·83 to 0·94). A major improvement in prognosis was observed after 2005, when the classification of breast cancer molecular subtypes and use of trastuzumab were implemented in routine clinical practice. CONCLUSION: In the past two decades, both local control and overall prognosis have improved significantly in young women (aged less than 40 years) with breast cancer who undergo BCS.

Second Axillary Sentinel Lymph Node Biopsy for Breast Tumor Recurrence: Experience of the European Institute of Oncology.

PURPOSE: This retrospective study aimed to determine the feasibility, accuracy, and recurrence rates of lymphoscintigraphy and the new sentinel lymph node biopsy (SLNB) for patients with ipsilateral breast tumor recurrences who were treated previously with conservative surgery and had negative SLNB results. METHODS: The study was conducted at the European Institute of Oncology in Milan and included 212 patients with the diagnosis of operable local breast cancer recurrence. They had been treated previously with conservative surgery and showed negative SLNB results. They subsequently underwent additional breast surgery and a second SLNB between May 2001 and December 2011. RESULTS: Preoperative lymphoscintigraphy demonstrated at least one new axillary sentinel lymph node (SLN) in 207 patients (97.7 %), whereas no drainage was observed in five patients (2.3 %). One or more SLNs were surgically removed from 196 of the 207 patients. Isolation of SLNs from the remaining 11 patients could not be accomplished. The success rate for the SLNB was 92.5 %. Extra-axillary drainage pathways were visualized in 17 patients (8 %). The annual axillary recurrence rate after a median follow-up period of 48 months was 0.8 %, and the cumulative incidence of axillary recurrence at 5 years was 3.9 %. CONCLUSIONS: A second SLNB should be considered for patients with operable local breast tumor recurrence who underwent conservative surgery and had negative SLNB results. The procedure is technically feasible and accurate for selected patients.

The effect of metformin on apoptosis in a breast cancer presurgical trial.

BACKGROUND: Metformin has been associated with antitumour activity in breast cancer (BC) but its mechanism remains unclear. We determined whether metformin induced a modulation of apoptosis by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) overall and by insulin resistance status in a presurgical trial. METHODS: Apoptosis was analysed in core biopsies and in surgical samples from 100 non-diabetic BC patients participating in a randomised trial of metformin vs placebo given for 4 weeks before surgery. RESULTS: Eighty-seven subjects (45 on metformin and 42 on placebo) were assessable for TUNEL measurement at both time points. TUNEL levels at surgery were higher than that at baseline core biopsy (P<0.0001), although no difference between arms was noted (metformin arm: median difference surgery-biopsy levels +4%, interquartile range (IQR): 2-12; placebo arm: +2%, IQR: 0-8, P=0.2). Ki67 labelling index and TUNEL levels were directly correlated both at baseline and surgery (Spearman's r=0.51, P<0.0001). In the 59 women without insulin resistance (HOMA index<2.8) ,there was a higher level of TUNEL at surgery on metformin vs placebo (median difference on metformin +4%, IQR: 2-14 vs +2%, IQR: 0-7 on placebo), whereas an opposite trend was found in the 28 women with insulin resistance (median difference on metformin +2%, IQR: 0-6, vs +5%, IQR: 0-15 on placebo, P-interaction=0.1). CONCLUSION: Overall, we found no significant modulation of apoptosis by metformin, although there was a trend to a different effect according to insulin resistance status, with a pattern resembling Ki67 changes. Apoptosis was significantly higher in the surgical specimens compared with baseline biopsy and was directly correlated with Ki67. Our findings provide additional evidence for a dual effect of metformin on BC growth according to insulin resistance status.

Mastectomy without radiotherapy: outcome analysis after 10 years of follow-up in a single institution.

The aim of this study was to identify the prognostic factors associated with the risk of loco-regional recurrence (LRR) of women undergoing mastectomy and complete axillary dissection without radiotherapy. We analyzed data from 650 women operated between 1997 and 2001 in a single institution. Median follow-up was 10 years. Overall survival was 89.8 % at 5 years and 76.6 % at 10 years. The 10-year cumulative incidence of LRRs was 10.0 % (5.0, 10.5, 15.8, and 18.5 % in patients with 0, 1-3, 4-9, and ≥10 positive lymph nodes (LNs), respectively). Sixty-two (9.5 %) LRRs were observed, 5 (0.8 %) of which occurred in the axillary LNs. Supraclavicular LNs recurrences (n = 16, 2.5 %) occurred more frequently in patients with four or more positive LNs, Ki-67 ≥ 20 % or extensive peritumoral vascular invasion (PVI). At multivariable analysis, nodal status was the only prognostic factor for local events, while nodal status, Ki-67 and PVI were significant prognostic factors for recurrences in the regional LNs. Moreover, within each category of positive LNs, high values of Ki-67 and extensive PVI were associated with the highest risk of LRR while low values of Ki-67 and absence of extensive PVI were associated with the lowest risk of LRR. Women with node-negative tumors have the lowest risk of LRR and represent the group of patients that might benefit the least from radiotherapy. PVI and Ki-67 might help tailoring PMRT indications among patients with positive LNs. Finally, the very low incidence of recurrences in the axillary LNs raises questions about the inclusion of the axilla in the radiation field.

Prognosis in women with small (T1mic,T1a,T1b) node-negative operable breast cancer by immunohistochemically selected subtypes.

Knowledge is limited about prognostic significance of breast cancer subtypes among women with small invasive node-negative breast tumours. We explored patterns of recurrence in 1691 women with pT1mic/T1a/T1b, pN0 and M0 breast cancer according to four immunohistochemically defined tumour subtypes: (i) Luminal A (ER-positive, PgR-positive, HER2-negative and Ki-67 < 14%); (ii) Luminal B (ER-positive and/or PgR-positive, HER2-positive and/or Ki-67 ≥ 14%); (iii) HER2-positive, both endocrine receptors absent; and (iv) Triple Negative. At multivariate analysis, women with the Triple Negative breast cancer subtype had an increased risk of loco-regional relapse (LRR) (Hazards Ratio (HR) 3.58; 95%CI: 1.40-9.13) and breast cancer related events (HR 2.18; 95%CI: 1.04-4.57). Overall, Luminal B subtype was not associated with a statistically significant increased risk of recurrence compared with Luminal A, while patients with Luminal B subtype tumours overexpressing HER2 had a 2 fold risk of reduced breast cancer related survival (BCS), but not an increased risk of LRR and distant metastases. Women with HER2 breast cancer subtype had a statistically significant increased risk of LRR (HR 4.53; 95%CI: 1.56-13.1), distant metastases and reduced BCS (HR 3.22; 95%CI: 1.44-7.18) and overall survival (HR 2.87; 95%CI: 1.05-7.89) when compared with the Luminal A subtype, at multivariate analysis. In conclusion, women with small size, node-negative, breast cancer are at higher risk of relapse if with HER2-positive endocrine receptor absent or Triple Negative disease.

Analysis of local and regional recurrences in breast cancer after conservative surgery.

BACKGROUND: A minority of patients treated conservatively for breast cancer will develop local or regional recurrences. Our aim was to determine how their occurrence may be linked to the evolution of the disease. PATIENTS AND METHODS: We analyzed 2784 women treated for early-stage breast cancer by quadrantectomy and whole-breast irradiation in a single institution. We evaluated the prognostic factors associated with local, regional and distant recurrences and the prognostic value of local and regional recurrences on systemic progression. RESULTS: After a median follow-up of 72 months, we observed 33 local events, 35 regional events and 222 metastases or deaths as first events (5-year cumulative incidence 1.1%, 1.2% and 7.6%, respectively). Size, estrogen receptor status, Her2/Neu and Ki-67 were associated with all three types of events, while axillary status and vascular invasion were associated only with the occurrence of metastases or death. Young age increased the risk of local recurrence. Local and regional recurrences were associated with an increased risk of systemic progression: hazard ratios 2.5 [95% confidence interval (CI) 1.1-5.8] and 5.3 (95% CI 3.0-9.5), respectively. CONCLUSIONS: Local and regional recurrences after breast-conserving surgery are rare events. They are markers of tumor aggressiveness and indicators of an increased likelihood of distant metastases.

Prognosis and adjuvant treatment effects in selected breast cancer subtypes of very young women (<35 years) with operable breast cancer.

BACKGROUND: There is limited knowledge about prognosis of selected breast cancer subtypes among very young women. PATIENTS AND METHODS: We explored patterns of recurrence by age according to four immunohistochemically defined tumor subtypes: Luminal A and Luminal B (estrogen receptor positive and/or progesterone receptor positive and either human epidermal growth factor receptor 2 (HER2) positive and/or high Ki-67), HER2-positive (and) endocrine receptor absent and Triple Negative, in 2970 premenopausal patients with pT1-3, pN0-3 and M0 breast cancer. RESULTS: Patients <35 years of age (315, 11%) presented a significantly increased risk of recurrence and death [hazards ratio (HR) = 1.65, 95% confidence interval (CI) 1.30-2.10 and HR = 1.78, 95% CI 1.12-2.85, respectively] when compared with older patients (2655, 89%) with similar characteristics of disease. This was true considering patients with Luminal B [HR = 1.62, 95% CI 1.21-2.18 for disease-free survival (DFS) and HR = 2.09, 95% CI 0.96-4.53 for overall survival (OS)] and with Triple Negative (HR = 2.04, 95% CI 1.11-3.72 for DFS and HR = 2.20, 95% CI 1.10-4.41 for OS) breast cancer, observing the highest risk of recurrence in the younger patients with HER2-positive breast cancer (HR = 2.37, 95% CI 1.12-5.02) when compared with older patients. CONCLUSIONS: Very young patients with Triple Negative, Luminal B or HER2-positive breast cancer have a worse prognosis when compared with older patients with similar characteristics of disease.

Unavoidable mastectomy for ipsilateral breast tumour recurrence after conservative surgery: patient outcome.

BACKGROUND: In the case of ipsilateral breast tumour recurrence (IBTR) after breast-conserving surgery (BCS), a second conservative surgical approach maybe considered in some motivated patients whereas in others mastectomy is unavoidable. PATIENTS AND METHODS: From 1997 to 2004, 282 patients presented at the European Institute of Oncology with an operable invasive IBTR after BCS. One hundred and sixty-one (57%) underwent a second conservative surgery, whereas 121 patients (43%) were given a mastectomy and represent the study population. We investigated the prognosis and determined predictive factors of outcome. RESULTS: Median time from primary breast cancer to IBTR was 41 months (range 5-213). Recurrences were T2-T4 and/or multifocal in 83 cases (68.6%). With a median follow-up of 5 years after mastectomy, 5-year overall survival (OS) and disease-free survival (DFS) were 73.3% [95% confidence interval (CI) 65.0% to 81.6%] and 50.4% (95% CI 40.9% to 59.8%), respectively. At the multivariate analysis, early onset of IBTR, presence of vascular invasion and Ki67 >or=20 of the recurrent tumour were found to significantly affect both DFS and OS. CONCLUSIONS: In women who need mastectomy for IBTR, early onset of the relapse, high proliferation index and presence of vascular invasion represent the worst prognostic factors.

Oncological results of immediate breast reconstruction: long term follow-up of a large series at a single institution.

BACKGROUND: Reconstruction of the breast after mastectomy is an integral part of the complete management of breast cancer. However, a delay in the reconstruction is usually proposed after the mastectomy in case of invasive cancer, while there is a general agreement for immediate breast reconstruction in case of in situ tumors. PATIENTS AND METHODS: Among a total of 677 patients having undergone a mastectomy between 1997 and 2001, 518 (76.5%) underwent an immediate breast reconstruction (IBR). All the patients had a Patey mastectomy for invasive cancer (T1-T3). An adjuvant medical treatment was given according to the biological characteristics of the tumor and lymph node status. No patient received any kind of radiotherapy. The median follow up was 70 months (range 13-114). RESULTS: The local recurrence rate was 5.2% for the group of IBR and 9.4% for the mastectomy group without IBR (NoIBR). The regional metastases rate was 1.4 vs. 1.3%. The rate of distant metastases was 13.9 vs. 16.4%. Contra-lateral breast tumor was observed in 1.5 vs. 1.3%. Death rate was 10.4 vs. 16.4%. No statistical difference was observed between the two groups in terme of overall survival (OS) and disease free survival (DFS) (HR(IBR vs. NoIBR): 1.03 and 0.99 for OS and DFS, respectively). CONCLUSION: At our institution we have compared a large series that have undergone IBR (518) with a control group (159) and followed over a prolonged period of time (70 months). This study provides the best available results to suggest that IBR is a safe and reliable treatment option for the managing invasive breast cancer.

Second axillary sentinel node biopsy for ipsilateral breast tumour recurrence.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is the standard procedure for axillary staging in patients with primary operable breast cancer and uninvolved axillary nodes. These patients increasingly have breast-conserving surgery (BCS), and 5 to 10 per cent develop ipsilateral breast tumour recurrence during follow-up. If axillary nodes remain clinically uninvolved after a previous negative SLNB the question remains whether second SLNB is a suitable option. METHODS: Between January 2000 and October 2006, 202 patients who had previously had BCS and a negative SLNB developed an ipsilateral breast tumour recurrence. Of these, 65 women with clinically negative axillary nodes were offered a second SLNB; 57 had received adjuvant radiotherapy after BCS. RESULTS: In 63 women, preoperative lymphoscintigraphy showed an axillary sentinel node (identification rate 97 per cent). In five, this was associated with extra-axillary migration. Sentinel node metastases were detected in seven women; in two this was the only metastasis. At a median follow-up of 45.9 months, no axillary recurrence had occurred in the women who had not had axillary dissection. CONCLUSION: Second SLNB after previous BCS and negative SLNB plus adjuvant radiotherapy may be offered to selected women with ipsilateral breast tumour recurrence.

[Conservative approach for breast cancer. The experience of the European Institute of Oncology]. / L'approccio conservativo al carcinoma mammario.L'esperienza dell'Istituto Europeo di Oncologia.

Conservative surgery represents the standard care for patients with early breast cancer. The aim of this review was to discuss the extension of conservative surgery in controversial fields such as after primary chemotherapy for large tumours or the possibility to repeat conservative surgery for a local reappearance. The project of a conservative approach to breast cancers continues with sentinel node biopsy which is worldwide performed more and more frequently. In our institute sentinel node biopsy is the standard procedure in the axillary staging of breast cancer even in those clinical scenarios which were previously considered either controversial or a contraindication such as in multicentric breast cancer, during pregnancy, in intra-ductal neoplasias, after primary chemotherapy, and male breast cancer. This conservative approach is completed by the possibility to deliver a partial breast irradiation and to provide patients with more personalized adjuvant treatments tailored on the biological features of the tumour.

Sentinel lymph node biopsy in multicentric breast cancer. The experience of the European Institute of Oncology.

AIM: To present our experience with sentinel lymph node biopsy (SLNB) performed in patients with multicentric breast cancer. METHODS: Between May 2001 and May 2004, 42 patients with multicentric breast cancer and a clinically negative axilla underwent lymphatic mapping either by a single subareolar (n = 25) or a double peritumoral/subdermal injection (n = 17) of 99Tc-HSA nanocolloids. The sentinel lymph node (SLN) was evaluated by intraoperative frozen section and axillary dissection was performed only in case of positive SLN. RESULTS: Mean age was 49 years (range 25-78). Mean number of SLNs identified by lymphoscintigraphy was 1.36 (range 1-5) and mean number of SLNs removed at surgery was 1.55 (range 1-5), with an identification rate of 100%. The mean number of hot spots identified by lymphoscintigraphy was similar in patients who underwent single or double injections (1.36 and 1.35, respectively). In 21 of 42 patients the SLN was positive, and in seven of these 21 patients the SLN was the only positive node. After a median follow-up of 24 months no overt axillary metastases occurred in patients with negative SLN. CONCLUSIONS: The number of SLNs is not dependent on the number and site of injections. SLNB is our standard procedure for nodal staging in patients with multicentric breast cancer and a clinically negative axilla.

Contralateral risk reducing mastectomy in patients with sporadic breast cancer. Benefits and hazards.

During the last years an improving outcome of breast conserving surgery was observed along with the availability of diagnostic procedures allowing early diagnosis. Nevertheless, women with breast cancer are more frequently requesting a radical approach comprising contralateral mastectomy even if they do not have a demonstrated increased genetic risk. In this paper we reviewed the main reasons patients ask for aggressive preventive surgery, the perceived and the real risks of developing contralateral breast cancer, and the potential, if any, survival benefits along with the hazards associated to contralateral risk reducing mastectomy. A respectful management should be given to these women within a multi-disciplinary team. Psychological support is highly encouraged cope fears and uncertainties but treating physicians should provide patients with comprehensive and unbiased data to take the best decision for the single person. Physicians should also give clear information on the benefits of adjuvant therapies which are reducing the incidence of contralateral breast cancer and also of the possible influences of healthy lifestyle (weight control, physical activity, diet) as effective preventive methods.

Physical function of the upper limb after breast cancer surgery. Results from the SOUND (Sentinel node vs. Observation after axillary Ultra-souND) trial.

BACKGROUND: The SOUND (Sentinel node vs. Observation after axillary Ultra-souND) trial is an ongoing prospective randomized study comparing sentinel node biopsy vs. no axillary surgical staging in patients with small breast cancer and negative pre-operative ultra-sound of the axilla. PATIENTS AND METHODS: The first 180 recruited patients were administered the QuickDASH (Disability Arm and Shoulder) questionnaire at different time points (before surgery, 1 week, 6 months and 1 year after surgery) to evaluate the physical function of the ipsilateral upper limb, The QuickDASH score ranges from 0 (no disability) to 100 (complete disability). RESULTS: 176 patients were available for analysis (94 in SNB arm and 82 in observation arm). The two groups were comparable with respect to age, tumor characteristics and treatments. Pre-surgery score values were 3.0% and 2.7% in the SNB arm and observation arm, respectively (P = 0.730). One week after surgery, the score increased to 24.0% in the SNB arm and 10.6% in the observation arm (P < 0.001). After 6 and 12 months, the score decreased in both arms to values similar to baseline values. The overall trend in time of the score was significantly different between the two arms (P < 0.001), even after the exclusion of five patients who received AD in the SNB arm (P < 0.001). CONCLUSIONS: Patients who underwent SNB had a significantly higher rate of disability in the early post-operative period compared to patients who did not. The avoidance of SNB might translate into a considerable reduction of physical and emotional distress.

Breast cancer diagnosed during pregnancy and lactation: biological features and treatment options.

AIM OF THE STUDY: Assessment of biological features and treatment of patients with breast cancer presenting during pregnancy or lactation. PATIENTS AND METHODS: Immunohistochemical analysis of estrogen receptor (ER) and progesterone receptor (PgR), Ki-67, HER2/neu, prognostic markers, treatment and follow-up of 21 patients with breast cancer during pregnancy (BCdP) and 17 with breast cancer during lactation (BCdL) are presented. RESULTS: Median age was 36 and 33 years, median tumour size was 2.4 and 2.5 cm, axillary lymph nodes were positive in 10 of 21 pregnant patients and 11 of 17 lactating patients, respectively. Both ER and PgR were not expressed in six of 21 pregnant women and nine of 17 lactating patients. All the six women who had concurrent diagnosis of breast cancer and pregnancy (first trimester) preferred termination of pregnancy although an alternative option was discussed. Five patients received anthracycline containing chemotherapy during the second and third trimester with no complications for patient and child. Conservative surgery was performed in 15 of 21 patients during pregnancy with no local reappearance after a median follow-up of 24 months. Three pregnant women underwent lymphoscintigraphy and sentinel lymph node biopsy. CONCLUSIONS: Patients who had concurrent diagnosis of breast cancer and pregnancy (early first trimester) preferred termination of pregnancy to allow easier completion of treatment. Conservative surgery was safe also in women with BCdP. Sentinel node biopsy might be considered for pregnant patients with a clinically negative axilla.

Increased interleukin-10 serum levels in patients with solid tumours.

In 40 out of 99 patients (40.4%) with solid tumours of different tissue, but the same stage (IV), elevated serum levels of interleukin-10 were observed. The mean levels of the cytokine in patients with malignant melanoma (24.3 ng/ml), pancreatic (6.8 ng/ml) or gastric (6.3 ng/ml) adenocarcinoma were significantly higher than in healthy subjects (3.4 ng/ml) or in patients with uterine fibroma (1.7 ng/ml). Patients with colon (6.8 ng/ml) and renal (5.7 ng/ml) carcinoma had similar values of interleukin-10 but did not significantly differ from controls. Interleukin-10 is known to suppress the functions of both T lymphocytes and macrophages, working as a general dampener of the immune and inflammatory responses. The observation of increased circulating levels of interleukin-10 in cancer patients may have important implications for future investigations, immunological monitoring and therapeutic intervention on neoplastic patients, and suggests a mechanism for tumour cells escaping from immune surveillance.

Perioperative immunonutrition in patients undergoing cancer surgery: results of a randomized double-blind phase 3 trial.

HYPOTHESIS: Perioperative administration of a supplemented enteral formula may reduce the rate of postoperative infections. DESIGN: Prospective, randomized, double-blind clinical trial. SETTING: Department of surgery at a university hospital. PATIENTS: Two hundred six patients with neoplasm of colorectum, stomach, or pancreas. INTERVENTION: Patients were randomized to drink 1 L/d of either a control enteral formula (n = 104) or the same formula enriched with arginine, RNA, and omega3 fatty acids (n = 102) for 7 consecutive days before surgery. The 2 diets were isoenergetic and isonitrogenous. Jejunal infusion with the same formulas was started 6 hours after operation and continued until postoperative day 7. MAIN OUTCOME MEASURES: Rate of postoperative infectious complications and length of hospital stay. RESULTS: Both groups were comparable for age, sex, weight loss, Karnofsky scale score, nutritional status, hemoglobin level, duration of surgery, blood loss, and rate of homologous transfusion. Intent-to-treat analysis showed a 14% (14/102) infectious complication rate in the supplemented group vs 30% (31/104) in the control group (P = .009). In the eligible population, the postoperative infection rate was 11% (9/85) in the supplemented group vs. 24% (21/86) in the control group (P = .02). The mean +/- SD length of postoperative stay was 11.1+/-4.4 days in the supplemented group and 12.9+/-4.6 in the control group (P = .01). CONCLUSION: Perioperative administration of a supplemented enteral formula significantly reduced postoperative infections and length of stay in patients undergoing surgery for cancer.

Artificial nutrition after pancreaticoduodenectomy.

Patients undergoing pancreaticoduodenectomy (PD) often require postoperative artificial nutrition. This trial was undertaken to evaluate whether the route of administration and the composition of the postoperative nutritional support could affect the immunometabolic response and outcome. A prospective, randomized trial was carried out in 212 subjects who underwent PD. Patients were randomized to receive a standard enteral formula (standard group, n = 73) or an enteral formula enriched with arginine, omega-3 fatty acids, and RNA (immunonutrition group, n = 71), or total parenteral nutrition (parenteral group, n = 68). Postoperative feeding started 6 hours after surgery. The three regimens were isocaloric and isonitrogenous. Assessed parameters were phagocytosis ability of polymorphonuclear cells, plasma interleukin-2 receptors, C-reactive protein, retinol binding protein, tolerance of enteral feeding, rate of postoperative complications, and length of hospital stay (LOS). Full nutritional goal (25 kcal/kg) was achieved in 87% of enterally fed patients versus 95% in the parenteral group. Subjects receiving immunonutrition had a significantly better recovery of the immunometabolic parameters on postoperative day 8 compared to the other two groups. The rate of postoperative complications was lower in the immunonutrition group (33.8%) than in either the standard (43.8%) or parenteral group (58.8%) (p = 0.005 immunonutrition vs. parenteral). Also, the mean LOS was shorter in the immunonutrition group than in the standard and parenteral groups (15.1 vs. 17.0 vs. 18.8 days, respectively; p < 0.05). Early postoperative enteral feeding may safely and effectively replace parenteral nutrition in patients undergoing PD. Immunonutrition ameliorates the immunometabolic response and improves outcome compared to parenteral feeding.