Quality of life and symptom burden in patients with breast cancer treated with mastectomy and lumpectomy.

INTRODUCTION: Mastectomy (MAS) and lumpectomy (LUMP) are the two common local surgical treatments for early breast cancer. There has been a debate whether MAS or LUMP results in better quality of life (QOL). The purpose of this study was to examine the symptom burden (SB) and QOL of both MAS and LUMP patients. METHODS: Patients at the Louise Temerty Breast Cancer Centre in Toronto, Canada, were approached to complete two self-administered questionnaires, the Edmonton Symptom Assessment Score (ESAS) and the Functional Assessment of Cancer Therapy-Breast (FACT-B) cancer edition. Additionally, patient demographics were recorded from medical records. Patients were divided into two cohorts depending on their surgical treatment: MAS and LUMP. The QOL and SB, assessed by FACT-B and ESAS, respectively, of MAS and LUMP patients were compared. The analysis was repeated excluding patients with metastases. RESULTS: From January to August 2014, 614 MAS and 801 LUMP patients were accrued. The MAS patients reported a lower QOL in all categories, except social well-being. There was however no statistical difference in ESAS scores for MAS and LUMP patients with non-metastatic breast cancer. CONCLUSION: This study supports existing literature that SB of MAS and LUMP patients without metastases are similar. QOL of MAS patients including those with metastases was lower than that of LUMP patients.

Long-term follow-up of late morbidity, cosmetic outcome and body image after breast conserving therapy. A study from the Danish Breast Cancer Cooperative Group (DBCG).

UNLABELLED: The Danish Breast Cancer Cooperative Group (DBCG) introduced BCT as a standard treatment in Denmark in 1990. The aim of this study was to investigate late morbidity, cosmetic outcome, and body image after BCT and to associate these outcome variables with patient, tumor, and treatment characteristics. MATERIAL AND METHODS: A total of 214 patients treated with BCT from 1989-2002 participated in a long-term follow-up visit comprising an interview, clinical examination, photos of the breast region and completion of a questionnaire on Body Image. RESULTS: Median follow-up time was 12 years (range 7-20). Moderate to severe fibrosis was found in 23% of patients and was associated with chemotherapy [OR 2.6, CI (1.1; 5.9), p = 0.02], large breast size [OR 3.2, CI (1.6; 6.4), p = 0.001], and smoking [OR 2.4, CI (1.1; 4.9), p = 0.02]. Patients with a satisfactory cosmetic outcome, when assessed by a clinician, were characterized by small tumors [OR 3.2, CI (1.5; 6.8), p = 0.003] and small to medium sized breasts [OR 2.0, CI (1.1; 3.5), p = 0.002]. Fifty percent of patients scored good or excellent when assessed by a clinician compared to 88% when reported by the patients themselves. Patients satisfied with their own cosmetic outcome were the younger patients [< 50 years; OR 3.2, CI (1.1; 8.6), p = 0.03] with no postoperative complications [OR 3.3, CI (1.2; 9.2), p = 0.02]. Regarding body image 15% felt less feminine, 25% felt less sexually attractive, and 28% of patients had changed their clothing habits as a result of the disease or treatment. CONCLUSION: The majority of patients were satisfied with their cosmetic outcome after BCT, whereas only half of the patients were found to have a good or excellent cosmetic outcome when assessed by the clinician. Body image was found to be only minimally disturbed in the majority of patients. The level of moderate to severe fibrosis was acceptable compared to both national and international studies with similar patient compositions.

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.

Genetic polymorphisms in DNA repair and damage response genes and late normal tissue complications of radiotherapy for breast cancer.

Breast-conserving surgery followed by radiotherapy is effective in reducing recurrence; however, telangiectasia and fibrosis can occur as late skin side effects. As radiotherapy acts through producing DNA damage, we investigated whether genetic variation in DNA repair and damage response confers increased susceptibility to develop late normal skin complications. Breast cancer patients who received radiotherapy after breast-conserving surgery were examined for late complications of radiotherapy after a median follow-up time of 51 months. Polymorphisms in genes involved in DNA repair (APEX1, XRCC1, XRCC2, XRCC3, XPD) and damage response (TP53, P21) were determined. Associations between telangiectasia and genotypes were assessed among 409 patients, using multivariate logistic regression. A total of 131 patients presented with telangiectasia and 28 patients with fibrosis. Patients with variant TP53 genotypes either for the Arg72Pro or the PIN3 polymorphism were at increased risk of telangiectasia. The odds ratios (OR) were 1.66 (95% confidence interval (CI): 1.02-2.72) for 72Pro carriers and 1.95 (95% CI: 1.13-3.35) for PIN3 A2 allele carriers compared with non-carriers. The TP53 haplotype containing both variant alleles was associated with almost a two-fold increase in risk (OR 1.97, 95% CI: 1.11-3.52) for telangiectasia. Variants in the TP53 gene may therefore modify the risk of late skin toxicity after radiotherapy.

Function of muscles of flexors and extensors of the elbow joint in women after treatment of breast cancer.

BACKGROUND: Limited function of the upper limb is the main problem after radical therapy of breast cancer. The shoulder joint is most commonly affected. However, even the simplest movements involve entire muscle groups. The aim of this study was to assess elbow flexor and extensor function in women following treatment of breast cancer. MATERIAL AND METHODS: 47 women at a mean age of 62 years (range 45 - 77 years) post Patey mastectomy participated in the study. The function of muscles of the elbow joint (peak torque, work, power) was examined by isokinetic testing. RESULTS: Statistically significant differences were revealed in the group of 47 women between the dominant vs. non-dominant side of the body. Weakness of the elbow extensors and flexors on the operated side was revealed in subgroup analysis. Decreased force and velocity parameters of elbow flexors and extensors were noted in women with cancer on the dominant (right) side (subgroup 1) and the differences between body sides were no longer statistically significant. However, in women with cancer on the non-dominant side (subgroup 2), the discrepancy between the limbs increased and was statistically significant. Mean differences were not statistically significant only with respect to peak torque of the elbow extensors. CONCLUSIONS: Treatment of breast cancer causes not only weakness of shoulder muscles but also of elbow-moving muscles. Treatment of cancer of the left breast can lead to false positive (too high), and treatment of cancer of the left breast, false negative (too low) functional impairment of the elbow extensors and flexors.

Decreased muscle strength following management of breast cancer.

PURPOSE: To assess whether muscle strength, power and endurance at the affected shoulder were reduced in women treated for breast cancer. Secondly, we assessed whether muscle performance was explained by management or other symptoms. METHODS: Participants were 40 women (mean +/- SD: 56.7 +/- 11.6 yr) who had completed all treatments for breast cancer at least 6 m previously. We measured dynamic concentric strength at one repetition maximum (1RM), endurance at 90% 1RM, and power through a range of 40-100% 1RM for shoulder protractors, extensors and retractors. Strength and endurance, but not power, were measured for shoulder flexors. Additionally, maximal grip strength, passive shoulder range of motion and arm circumference were measured. Self-reported symptoms were recorded using a questionnaire. RESULTS: Shoulder protractors (p = 0.011), retractors (p = 0.007), and extensors (p = 0.009), but not flexors, were significantly weaker on the affected side compared to the unaffected side. Muscle power and endurance at the shoulder and grip strength were not impaired. Inter-limb differences in muscle strength were not explained by the surgical and medical management of the cancer. Self-reported weakness correlated poorly with our measures of muscle strength. CONCLUSIONS: Long-term weakness occurs about the shoulder secondary to treatment for breast cancer. Strategies to prevent weakness need to be considered.

The Quality of Life and Degree of Depression of Patients Suffering from Breast Cancer.

INTRODUCTION: Breast cancer and its treatment change the perception of mastectomized women of their physical appearance, which leads to depression and has a negative effect on the overall quality of life of those woman. AIM: We wanted to assess the quality of life and the degree of depression of patients suffering from breast cancer, on the basis of a standardised questionnaire to assess the patients' quality of life (QLQ-C-30 BR-23), and the degree of depression using Beck's Depression Inventory (BDI, II). MATERIALS AND METHODS: The research was conducted on a sample of 160 patients, who were surveyed before and after the surgical procedure. The inclusion criteria for the research were: patients suffering from breast cancer aged between 18 and 70 years, cancer diagnosed by FNB or CORE biopsy. The patients were divided into two groups: patients having breast-conserving surgery and patients having radical surgical treatment. RESULTS: There were 47 or 39.37% patients who underwent breast-conserving surgery and 113 or 70.62% patients who underwent radical surgery. The results of the survey conducted show that there was no difference in the quality of life of patients before and after surgery, regardless of the type of surgical procedure undertaken. However, there was a significant different in the degree of depression between patients subjected to different surgical procedures, where the patients surveyed post-surgery after radical mastectomy showed a higher degree of depression than the patients surveyed after breast-conserving surgery. CONCLUSION: There is no difference in the quality of life before and after surgery, regardless of the type of operation. However, there is a significant difference in the degree of depression in patients after radical mastectomy, who showed a higher degree of depression than the surveyed patients who underwent breast-conserving surgery.

Quality of life among breast cancer patients undergoing autologous breast reconstruction versus breast conserving therapy.

PURPOSE: Besides the quality of the aesthetic results, the quality of life after surgery is one of the most important criteria when reviewing different operation methods, especially in oncologic diseases. This study was performed to evaluate the difference in the health-related quality of life following breast conserving surgery and autologous breast reconstruction after mastectomy. PATIENTS AND METHODS: Hundred and forty-four breast cancer patients were included in this study. Sixty seven patients underwent breast conserving surgery followed by radiotherapy. In 77 patients a mastectomy was performed with immediate or late reconstruction. To evaluate the health-related quality of life we used the SF-36 self-administered questionnaire. RESULTS: A significant difference was found in quality of life in the subscale "physical functioning" showing better results in the breast reconstruction group (P = 0.01). No significant difference was found in the other subscales, but there was a tendency to a better "emotional role" among the breast reconstruction patients. CONCLUSION: Our study demonstrated that autologous tissue breast reconstruction in breast cancer patients did not affect adversely the health-related quality of life compared to breast conserving therapy when the quality of life is assessed by the standardized questionnaire SF-36. In particular, the physical function is not reported to be significantly influenced negatively by the more extensive surgical therapy.

Does hospital discharge policy influence sick-leave patterns in the case of female breast cancer?

The objective was to investigate how differences among hospitals in the shift from in-patient care to day surgery and a reduced hospital length of stay affect the sick-leave period for female patients surgically treated for breast cancer. All women aged 18-64 who were diagnosed with breast cancer in 2000 were selected from the National Cancer Register and combined with data from the sick-leave database of the National Social Insurance Board and the National Hospital Discharge Register (N = 1834). A multi-factorial model was fitted to the data to investigate how differences in hospital care practice affected the length of sick-leave. The main output measure was the number of sick-leave days after discharge during the year following surgery. The confounders used included age, type of primary surgical treatment, whether or not lymph node dissection was performed, labour-market status, county, and readmission. Women treated with breast-conserving surgery had a 54.7-day (-71.9 < or = CI(95%) < or = -37.5) shorter sick-leave period than those with more invasive surgery. The day-surgery cases had 24.3 (-47.5 < or = CI(95%) < or = -1.1) days shorter sick-leave than those who received overnight care. The effect of the hospital median length of stay (LOS) was U-shaped, suggesting that hospitals with a median LOS that is either short or long are associated with longer sick-leave. In the intermediate range, women treated in hospitals with a median LOS of 2 days had 22 days longer sick-leave than those treated in hospitals with a mean LOS of 3 days. This is possibly a sign of sub-optimising.

Achievements of physical therapy in patients after modified radical mastectomy compared with quadrantectomy, axillary dissection, and radiation for carcinoma of the breast.

Flexion of the shoulder, abduction, and external rotation in 90 degrees abduction are impaired after operations for breast cancer. We compared postoperative range of motion in 27 patients who underwent modified radical mastectomy and 21 patients who underwent quadrantectomy with axillary dissection and radiation therapy. The patients in the quadrantectomy group demonstrated a significantly higher range of flexion on postoperative day 1 and the day of suture removal. After 3 months, all patients had regained their preoperative range of flexion, with no difference between the groups. The better compliance of the quadrantectomy group to physical therapy may indicate that they suffer less pain and require a briefer or less intensive course of physical therapy.

Breast reconstruction with myocutaneous flaps in previously irradiated patients.

Breast reconstructions performed with latissimus dorsi and transverse rectus abdominis myocutaneous (TRAM) flaps in 82 patients with a history of previous chest-wall irradiation were compared with similar reconstructions in 202 nonirradiated patients to determine whether prior irradiation was associated with more frequent complications and to determine the success rate of breast reconstruction using distant flaps in irradiated patients. The mean dose of radiation administered was 5637 cGy. Complications in the reconstructed breast were more frequent in the irradiated patients (39 percent) than in the nonirradiated patients (25 percent; p = 0.03). In the irradiated group, breast complications were more common in reconstructions performed with the latissimus dorsi flap (63 percent) than in those performed with the TRAM flap (33 percent; p = 0.063). Aesthetic outcomes also were slightly poorer in the irradiated patients. Although complications were more common and aesthetic outcomes not as good in previously irradiated patients, we do not consider such irradiation to be a contraindication to breast reconstruction.

Immediate free TRAM reconstruction in lumpectomy and radiation failure patients.

Local recurrence after lumpectomy and radiation therapy indicates failed breast conservation surgery. These patients often proceed to mastectomy and are candidates for autogenous breast reconstruction. Free transverse rectus abdominus muscle (TRAM) reconstruction in these patients is complicated by repeated axillary dissection and the use of irradiated tissue. Complication rates for pedicled TRAMs have been reported at 33 percent when used in irradiated tissue beds. We report our results using the free TRAM for breast reconstruction after lumpectomy and radiation failure. All patients within this study developed a local recurrence after lumpectomy and radiation therapy. All patients had undergone axillary dissection for staging at the time of their lumpectomy. Patient records were reviewed for patient age, total radiation dose, associated risk factors for TRAM failure, operative time, donor vessels used for anastomosis, status of the native thoracodorsal vessels at the time of surgery, and postoperative complications. Over a 7-year period, 16 TRAM patients had undergone previous breast conservation surgery. Of these 16 patients, 14 underwent reconstruction with a planned free TRAM after simple mastectomy. Average operating room time was 7 hours. There were no partial or total flap losses. Complications were seen in 14 percent of the overall group. Overall, we found that the free TRAM provided an excellent aesthetic result with a lower complication rate than previously reported for pedicled TRAM flaps in irradiated beds. The thoracodorsal vessels provided an adequate donor vessel in 93 percent of the cases. The free TRAM provides a superior alternative in immediate reconstruction in patients who have failed breast conservative surgery.

Strengths of early physical rehabilitation programs in surgical breast cancer patients: results of a randomized controlled study.

BACKGROUND: In the immediate postoperative period surgical breast cancer patients can face many problems including functional limitation of the shoulder, edema, pain and depression. Although those symptoms can alleviate during the stages of the therapeutic route, most of the time concur significantly to the everyday life discomforts decreasing sharply the quality of life. Therefore, is essential to pay attention to the functional problems of breast cancer patients in order to ensure a quick and complete physical and psychosocial recovery. AIM: Aim of this study, comparing 2 groups of patients, one that underwent to early physical rehabilitation program (EPRP) and one as a control group, is to evaluate: functional improvements of the glenohumeral joint mobility, antalgic effect of EPRP, improvements and/or worsening of quality of life. DESIGN: Randomized controlled study. SETTING: Inpatient and outpatient clinic, Breast Unit, "San Giuseppe Moscati" Hospital, Avellino, Italy. POPULATION: Seventy women planned for Madden's modified radical mastectomy or for segmental mastectomy with axillary dissection in the period from March 2010 to February 2011. METHODS: Patients were randomly assigned to treated and control group. All participants were evaluated before surgery and postoperatively at fifth day, first, sixth and twelfth month. Patients of the treated group, underwent first, to assisted cautious mobilization of hand, wrist and elbow and after drainage removal, to twenty physiotherapy sessions under the guide of a physiotherapist. RESULTS: Within group statistical analysis evidenced that TG regained normal function at 1 year after surgery while CG was unable to do so for flexion, abduction and internal rotation movements. TG manifested general and statistically significative improvements in QoL. Improvements in the grade of pain perceived were observed starting from the first postoperative month. CONCLUSION: Postoperative early physical rehabilitation programme in surgical breast cancer patients surgically treated significantly improves glenohumeral joint mobility, reduces pain and widely improves the quality of life. CLINICAL REHABILITATION IMPACT: Early rehabilitation plays a key role in the physical and psycho-social recovery for breast cancer patients surgically treated with axillary dissection.

Early rehabilitation reduces the onset of complications in the upper limb following breast cancer surgery.

BACKGROUND: Breast cancer (BC) is currently the most frequent tumor in women. Through the years, BC management has evolved towards conservative surgery. However, even minimally invasive surgery can cause neuromotor and/or articular impairments which can lead to permanent damage, if not adequately treated. AIM: To clinically evaluate upper ipsilateral limb function and the impact of certain post-surgical consequences arising after invasive or breast-conserving surgery for early BC, by intervening, or not intervening, with an early rehabilitation program. To investigate physical morbidity after sentinel (SLND) or axillary lymph node dissection (ALND) and after reconstructive surgery in the treatment of early BC. DESIGN: Observational prospective trial. SETTING: Inpatient and outpatient treatment. POPULATION: Eighty-three females participated in the study: 25 patients did not begin physiotherapy during hospitalization (Group A), 58 patients received early rehabilitation treatment (Group B). METHODS: The patients of Groups A and B were compared with respect to the following criteria: shoulder-arm mobility, upper limb function, and presence of lymphedema. All patients were assessed at 15-30, 60 and 180 days after surgery. RESULTS: Statistically significant differences, in favor of Group B, were encountered at the 180-day follow-up visit, especially with respect to articular and functional limitation of the upper limb. CONCLUSION AND CLINICAL REHABILITATION IMPACT: The results of the present study show that early assisted mobilization (beginning on the first postoperative day) and home rehabilitation, in conjunction with written information on precautionary hygienic measures to observe, play a crucial role in reducing the occurrence of postoperative side-effects of the upper limb.

Sarcoma of the breast: outcome and reconstructive options.

INTRODUCTION: Surgery is the mainstay of treatment for all breast sarcomas. The role of adjuvant chemotherapy and radiation therapy has not been clearly defined. The aim of this single-center retrospective study was to analyze prognostic factors, outcome, and recent advances. MATERIALS AND METHODS: Data from 203 patients with all breast sarcomas treated in a single center were collected from 1996 to 2010. Phyllodes tumors and metastatic disease at presentation were excluded from the population. Thirty-six women and 1 man were included in the analysis. Local recurrence, metastatic disease, survival, and reconstructive outcome were evaluated. RESULTS: Thirty-four patients out of 37 (91.9%) had an angiosarcoma and 3 had a stromal sarcoma (8.1%). Twenty-one patients (56.8%) had previously undergone breast radiation therapy for breast carcinoma or lymphoma. Twenty-six patients (70.3%) underwent mastectomy, 14 of whom (53.8%) with breast reconstruction. Thirty-six patients (97.3%) had free margins, 1 (2.7%) had a microscopically focally involved margin after surgery. Five patients received adjuvant chemotherapy and 6 received adjuvant radiation therapy. Median follow-up was 58 months (range, 4-146 months). Twelve sarcoma-related deaths were observed with a 5-year cumulative incidence of 43.4%. Twenty-four sarcoma-related events were observed with a 5-year cumulative incidence of 70.8%. The same figure was 49.7% in patients affected by primary sarcoma and 85.7% in patients with secondary sarcoma (P = .06). CONCLUSION: Secondary sarcomas were associated with a higher risk of events. Patients undergoing breast conservative surgery or reconstruction after mastectomy did not show a worse prognosis compared with patients undergoing mastectomy.

Interval between breast-conserving surgery and start of radiation therapy in early-stage breast cancer is not predictive of local recurrence: a single-institution experience.

BACKGROUND: The aim of this study was to evaluate if the interval between breast-conserving surgery and the start of radiotherapy has an effect on local relapse risk. MATERIALS AND METHODS: Between January 2000 and December 2006 a total of 387 patients with T1-2N0+ breast cancer were treated with breast-conserving surgery and radiotherapy, with and without hormone therapy and chemotherapy. Adjuvant radiotherapy was administered to a total dose of 60 to 66 Gy in 30 to 33 fractions. The time intervals between breast-conserving surgery and the start of radiotherapy were < 60, 61 to 120, 121 to 180 and > 180 days. The Kaplan-Meier method was used to calculate local relapse-free survival rates, and the Cox regression method was used to identify predictive factors of local relapse. Evaluated variables were age, tumor location, tumor histologic type, tumor size, surgical margin status, axillary node status, estrogen receptors, tumor grading, adjuvant therapy, adjuvant chemotherapy, radiation therapy, boost dose, and interval between breast-preserving surgery and start of radiation therapy. RESULTS: Five-year local relapse-free survival rates were 97.3% ± 1.5% for patients who did not receive chemotherapy and 94.5% ± 1.9% for patients who received chemotherapy (P = .71). There was no significant difference in local relapse among the 4 interval groups (P = .9). Multivariate Cox regression analysis showed that intervals between breast-conserving surgery and radiotherapy were not associated with higher local relapse risk. CONCLUSION: In our study a delay in administering radiotherapy after breast-conserving surgery was not associated with an increased risk of local relapse. Taking into account contrasting results of many published studies, a larger evaluation of this issue is warranted.

Interstitial high-dose-rate brachytherapy after breast conserving surgery.

We evaluated local recurrence, toxicity rate and cosmetic outcome in 72 patients treated with high-dose-rate (HDR) brachytherapy after breast conserving surgery. HDR brachytherapy was administered: i) as partial breast irradiation (PBI) in 64 patients with low-risk early stage breast cancer, enrolled in a phase II prospective study; ii) as PBI after a second conservative surgery as treatment of local relapse in 3 patients; iii) for delivering a boost after whole breast external beam radiotherapy in 5 patients. Implantation was done during surgery (breast conserving or re-excision to achieve adequate surgical margins), with the wound open, or postoperatively. The implant was well tolerated in all patients, so no premature catheter removal was required. At a median follow-up of 32 months (range 5-52) no local recurrence has been observed. Toxicity was very low. Cosmetic outcome was excellent/good in a high percentage of patients. Our results suggest that PBI administered with HDR brachytherapy is feasible in selected patients with low risk early stage breast carcinoma. PBI seems feasible to repeat radiotherapy after a salvage breast conserving surgery for local relapse in a second attempt to preserve the breast.

Barriers to rehabilitation following surgery for primary breast cancer.

Surgery is a mainstay of primary breast cancer therapy. Alterations in surgical technique have reduced normal tissue injury, yet pain and functional compromise continue to occur following treatment. A tenuous evidence base bolstered by considerable expert opinion suggests that early intervention with conventional rehabilitative modalities can reduce surgery-associated pain and dysfunction. Barriers to the timely rehabilitation of functionally morbid sequelae are discussed at length in this article. Barriers arise from a wide range of academic, human, logistic, and financial sources. Despite obstacles, expeditious and effective post-surgical rehabilitation is being regularly delivered to breast cancer patients at many institutions. This experience has given rise to anecdotal information on the management of common sequelae that may undermine function. The epidemiology, pathophysiology, and management of these sequelae are outlined in this article with an emphasis on the caliber of supporting evidence. Myofascial dysfunction, axillary web syndrome, frozen shoulder, lymphostasis, post-mastectomy syndrome, and donor site morbidity following breast reconstruction are addressed. A critical need for more definitive evidence to guide patient management characterizes the current treatment algorithms for surgical sequelae.