带蒂穿支皮瓣在乳房再造术中的应用

与游离穿支皮瓣相比,带蒂穿支皮瓣分离技术更加简单,安全系数更高,而且供区畸形更小。近年来,应用带蒂穿支皮瓣技术已经成为乳房再造手术一种新的选择, 甚至是一些患者的首选方案。常用的带蒂穿支皮瓣有胸背动脉穿支皮瓣、肋间动脉穿支皮瓣(外侧肋间动脉穿支皮瓣、前侧肋间动脉穿支皮瓣)等,其他可用的选择包括前锯肌动脉穿支皮瓣,腹壁上动脉穿支皮瓣,胸外侧动脉穿支皮瓣等。为了提高手术设计的精确性,术前需要评估穿支血管的质量,并对其定位穿支。皮瓣的设计相比游离皮瓣手术而言,显得更加重要。虽然带蒂穿支皮瓣在乳房再造领域的作用尚不能取代游离皮瓣的金标准地位,但随着“损伤最小化”重建概念的日渐推广,带蒂穿支皮瓣将会成为乳房再造领域里的一种新的趋势。     

Breast reconstruction using perforator flaps

BACKGROUND: Perforator flaps allow the transfer of the patient's own skin and fat in a reliable manner with minimal donor-site morbidity. The deep inferior epigastric artery (DIEP) and superficial inferior epigastric artery (SIEA) flaps transfer the same tissue from the abdomen to the chest for breast reconstruction as the TRAM flap without sacrificing the rectus muscle or fascia. Gluteal artery perforator (GAP) flaps allow transfer of tissue from the buttock, also with minimal donor-site morbidity. INDICATIONS: Most women requiring tissue transfer to the chest for breast reconstruction or other reasons are candidates for perforator flaps. Absolute contraindications to perforator flap breast reconstruction include history of previous liposuction of the donor site or active smoking (within 1 month prior to surgery). ANATOMY AND TECHNIQUE: The DIEP flap is supplied by intramuscular perforators from the deep inferior epigastric artery and vein. The SIEA flap is based on the SIEA and vein, which arise from the common femoral artery and saphenous bulb. GAP flaps are based on perforators from either the superior or inferior gluteal artery. During flap harvest, these perforators are meticulously dissected free from the surrounding muscle which is spread in the direction of the muscle fibers and preserved intact. The pedicle is anastomosed to recipient vessels in the chest and the donor site is closed without the use of mesh or other materials. CONCLUSIONS: Perforator flaps allow the safe and reliable transfer of abdominal tissue for breast reconstruction.     

Microvascular reconstruction of the breast

The growth of microsurgical procedures has led to significant technological, scientific, and clinical advances that have made these procedures safe, reliable, reproducible, and routine in most major medical centers. In many instances, free flap reconstruction has become the primary reconstructive method for many major defects, including breast reconstruction. The advantages of free flap breast reconstruction include better flap vascularity, broader patient selection, easier insetting of the flap, and decreased donor site morbidity. Free flap breast reconstruction can occur either at the time that the mastectomy is performed or as a delayed reconstruction following a previous mastectomy. Immediate reconstructions have the advantage of avoiding scar contracture and fibrosis within the mastectomy flaps and at the recipient vessel site. The most common recipient vessel sites are the thoracodorsal vessels and the internal mammary vessels. The thoracodorsal vessels are most frequently used in immediate reconstruction because they are partially exposed during the mastectomy procedure. The internal mammary vessels are used more frequently in delayed reconstructions, to avoid repeat surgery in the axilla. This recipient site also allows more medial placement of the reconstruction. Flap selections for free autogenous breast reconstruction include the transverse rectus abdominis myocutaneous (TRAM) flap, the superior gluteal myocutaneous flap, the inferior gluteal myocutaneous flap, the lateral thigh flap, and the deep circumflex iliac soft tissue flap (Rubens). The TRAM flap is most commonly used in free flap breast reconstruction. For patients with inadequate abdominal tissue or prior abdominal surgery, the superior gluteal flap is typically used. Both the TRAM flap and the superior gluteal flap can be designed as perforator flaps, preserving all of the involved muscle and, in the TRAM perforator, all the rectus fascia. These flaps are more technically demanding, with minimal impact on donor site function. The other flaps are less frequently used and limited to special patient circumstances. Free flap autogenous breast reconstruction provides a natural, long-lasting result with a high degree of patient satisfaction. Semin. Surg. Oncol. 19:264-271, 2000.     

Post-Mastectomy Breast Reconstruction: A History in Evolution

Although the need for mastectomy has been evident for many years, postmastectomy reconstruction has been recognized as an achievable outcome for only a little over a century. A review of the evolution of both autologous and prosthetic options for reconstruction was undertaken. The earliest attempts at reconstruction used autologous techniques that were either unsuccessful, not reproducible, or were associated with significant morbidity. Prosthetic techniques became sought after, with silicone prostheses widely used until concerns about potential adverse effects led to the investigation of alternate options. With these concerns shown to be unfounded, silicone and saline prostheses evolved with successive generations of implants. Concurrent advances in reconstructive surgery led to a revival in autologous techniques for breast reconstruction, with microsurgical free-tissue transfer potentiating a new range of potential donor sites. The abdominal wall became the donor site of choice, and with the advent of perforator flaps, morbidity associated with flap harvest was minimized. In cases where the abdominal wall is unsuitable, flaps such as the superior and inferior gluteal artery perforator flaps, the musculocutaneous gracilis flap, and the “stacked” deep inferior epigastric artery perforator flap are frequently used options. The development of minimally invasive techniques for implant placement and flap harvest, such as endoscopy, continue to evolve, and research in tissue engineering offers a vision for a future without the need for a donor site.     

Choice of flaps for breast reconstruction

The optimal method for breast reconstruction should be safe, reliable, and accessible for every patient, and it should display little or no donor-site morbidity. After comparing mammary implants it has been found that autogenous breast reconstruction can create a ptotic, soft, symmetrical breast mound. The transverse rectus abdominis musculocutaneous flap (TRAM) remains the most popular method for autogenous reconstruction. Modern trends in breast reconstruction using the TRAM flap have promoted adequate blood supply to the flap while minimizing donor-site defects in the anterior abdominal wall. The pedicled TRAM flap remains one of the most frequently used flaps, but the indirect blood supply in this flap has required many modifications and refinements. Such modifications have included the bipedicled TRAM flap, the free TRAM flap, and the supercharged TRAM flap. To avoid donor-site morbidities, the muscle-sparing free TRAM, deep inferior epigastric perforator flap (DIEP), and superficial inferior epigastric artery (SIEA) flap were introduced. The DIEP perforator flap requires meticulous technique but offers proven reliability and a low rate of complications. As surgeons become more comfortable with harvesting DIEP flaps, the frequency of usage seems likely to increase. The latissimus dorsi musculocutaneous flap, gluteus maximus musculocutaneous flap, and others may be selected when these modifications of free TRAM flap are unavailable or unusable.     

Surgical techniques for personalized oncoplastic surgery in breast cancer patients with small- to moderate-sized breasts (part 2): volume replacement

Oncoplastic breast surgery has become a popular choice of treatment for breast reconstruction after mastectomy. There are two different techniques in oncoplastic surgery depending on the volume of the excised breast tissue. One is the volume displacement procedure, which combines resection with a variety of different breast-reshaping and breast-reduction techniques; the other is the volume replacement procedure in which the volume of excised breast tissue is replaced with autologous tissue. In this study, current authors performed various volume replacement techniques based on the weight of the excised tumor and its margin of resection. We used a latissimus dorsi myocutaneous flap for cases in which the resection mass was greater than 150 g, and for cases in which the resection mass was less than 150 g, we used a regional flap, such as a lateral thoracodorsal flap, a thoracoepigastric flap, or perforator flaps, such as an intercostal artery perforator flap or a thoracodorsal artery perforator flap. In the patients with small to moderate-sized breasts, when a postoperative deformity is expected due to a large-volume tumor resection, the replacement of non-breast tissue is required. Many of whom have small breasts, oncoplastic volume replacement techniques in breast-conserving surgery allow an extensive tumor excision without concern of compromising the cosmetic outcome and can be reliable and useful techniques with satisfactory aesthetic results.     

Breast reconstruction using free medial circumflex artery perforator flaps: intraoperative anatomic study and clinical results

Background

A free fascioadipocutaneous flap obtained from the medial thigh is suitable for breast reconstruction in Asian women with a small-to-moderate breast size. In this region, both a medial circumflex femoral artery perforator flap (MCFAp flap) and a posterior medial thigh perforator flap (PMTp flap) are options, based on perforators from the deep femoral vessels. Here, we evaluated the anatomic basis of the medial circumflex femoral artery (MCFA) perforators from the medial circumflex femoral vessels.

Methods

Between July 2010 and June 2014, 53 patients (55 flaps) underwent breast reconstruction using a fascioadipocutaneous flap from the medial thigh. MCFA perforators larger than or equal to 0.5 mm in this region were investigated. The following parameters were recorded intraoperatively: number of perforators, perforator locations, distance of the perforating point from the proximal thigh crease and anterior border of the gracilis muscle.

Results

The total number of perforators was 131, with a mean of 2.4. The number of perforators coursing through the gracilis muscle (gracilis perforators) was the largest, followed by septocutaneous perforator coursing between the adductor longus and gracilis muscle. The average perforating point was located 6.5 cm below the proximal thigh crease and 2.2 cm from the anterior border of the gracilis muscle. Of the 102 procedures performed since 2006, 15 flaps were elevated as MCFAp flaps and there was no major complication.

Conclusions

In some cases, MCFA perforators are dominant in this region compared to PMT perforators. A perforator map can be helpful for identifying adequate MCFA perforators intraoperatively.

     

Complications in Post-mastectomy Immediate Breast Reconstruction: A Ten-year Analysis of Outcomes

IntroductionImmediate breast reconstruction offers cosmetic and psychological advantages post-mastectomy. There are various options of reconstruction, and this study aims to evaluate the associated complications.Patients and MethodsThis is a single-center retrospective study analyzing data from January 1, 2008 to December 31, 2017 for immediate breast reconstruction procedures post-mastectomy performed at an academic breast unit. Procedures included expander and implant insertion, latissimus dorsi, pedicle transverse rectus abdominis musculocutaneous (TRAM), free TRAM, and deep inferior epigastric perforator. Complications and reoperative complications (defined as those requiring a reoperation within the first 30-day period), and associated risk factors were investigated using separate logistic regressions, and odds ratios (ORs) were calculated.ResultsA total of 243 post-mastectomy immediate breast reconstruction procedures and complications rates were analyzed. The overall complication rate was 27.6%, comprised mainly of reconstruction-specific complications such as post-TRAM hernia or bulges, fat necrosis, and implant capsular contracture and leakage. The rate of reoperative complications was relatively low at 6.6%. The flap failure rate was similar between expander/implant reconstruction and autologous reconstruction methods at 3.3% and 5.6%, respectively (P = .60). Logistic regression identified significantly higher risks associated with diabetes mellitus (OR, 5.21; P = .022), obesity (OR, 5.80; P = .016), and free pedicle autologous reconstruction (OR, 3.975; P = .046) for reoperative complications.ConclusionDifferent methods of immediate breast reconstruction post-mastectomy are feasible and safe. However, patient variables and procedure choice should be taken into consideration when counseling patients on reconstructive options, as they are strong predictors for postoperative complications.     

游离腹部皮瓣乳房重建的应用及研究进展

乳腺癌发病率居女性新发恶性肿瘤的第一位,外科治疗是重要的治疗手段之一。全乳切除术后乳房重建能在不影响肿瘤学安全性的前提下,提高患者的生存质量,其中,自体组织乳房重建因其特有的优势成为乳房重建的重要方式之一,而游离腹部皮瓣是自体组织乳房重建中最理想的材料。该研究将对游离腹部皮瓣乳房重建手术的临床应用、手术时机及并发症进行综述,旨在探讨游离腹部皮瓣乳房重建的应用及研究进展。     

Donor-Site Morbidity and Quality of Life after Autologous Breast Reconstruction with PAP versus TMG Flap

The transverse myocutaneous gracilis (TMG) and the profunda artery perforator (PAP) flap are both safe choices for autologous breast reconstruction originating from the same donor region in the upper thigh. We aimed to compare the post-operative outcome regarding donor-site morbidity and quality of life. We included 18 patients who had undergone autologous breast reconstruction with a PAP flap (n = 27 flaps). Prospective evaluation of donor-site morbidity was performed by applying the same questionnaire that had already been established in a previous study evaluating TMG flap (n = 25 flaps) outcome, and results were compared. Comparison of the two patient groups showed equivalent results concerning patient-reported visibility of the donor-site scar and thigh symmetry. Still, the TMG group was significantly more satisfied with the scar (p = 0.015) and its position (p = 0.001). No difference was found regarding the ability to sit for prolonged periods. Donor-site wound complications were seen more frequently in the PAP group (29.6%) than in the TMG group (4.0%). Both groups expressed rather high satisfaction with their quality of life. Both flaps show minimal functional donor-site morbidity and high patient satisfaction. To minimize wound healing problems in PAP patients, thorough planning of the skin paddle is necessary.     

各种皮瓣在足底负重区恶性黑色素瘤术后缺损修复中的应用

目的：探讨足底内侧皮瓣、局部逆行岛状皮辫、外踝上穿支皮瓣、内踝上穿支皮瓣和游离股前外侧皮瓣修复足底负重区恶性黑色素瘤广泛切除术后缺损的优缺点。方法：浙江省肿瘤医院骨和软组织肿瘤外科2010-01-13-2013-12～25收治的23例足底负重区皮肤恶性黑色素瘤患者,进行原发灶广泛切除后分别采用足底内侧皮瓣、局部逆行岛状皮瓣、外踝上穿支皮瓣、内踝上穿支皮瓣及游离股前外侧皮瓣进行修复,对其临床资料和随访结果进行分析。结果：术后缺损面积为4cm×4cm～11cm×9cm,切取皮瓣面积5cmX5cm～12cm×10cm。14倒足底内侧皮瓣全部成活,其中皮瓣最大切取面积为7cm×7cm。1例局部逆行岛状皮瓣出现小部分坏死,二期愈合,4例外踝上及内踝上穿支皮瓣全部成活,其中皮瓣最大切取面积为12cm×10cm。4例游离股前外侧皮瓣中,3例成活,1例皮瓣出现远端部分浅表性坏死,经换药后愈合。所有患者无继发性渍疡出现,患足均可无痛行走。2例行足底内侧皮瓣修复术后出现局部复发。结论：各种皮瓣修复足底黑色素瘤术后缺损均可获得较好疗效,对较小足根部的缺损（直径〈8cm）首选足底内侧皮瓣,较大的缺损可采用内外踝上穿支皮瓣,有显微外科条件的可考虑游离股前外侧皮瓣修复局部皮瓣不能覆盖的缺损。     

Single perforator based anterolateral thigh flap for reconstruction of large composite defects of oral cavity

Composite defects of oral cavity are a reconstructive challenge. Anterolateral thigh flap provides large and pliable tissue for reconstruction of these defects. However, wide variations in the vascular anatomy, variable perforator number and location are reported. The aim of this study was to evaluate the reliability of single perforator based large anterolateral thigh for reconstruction of complex oral cavity defects following ablative surgery. We report a series of 25 consecutive patients who underwent reconstruction of oral cavity defects with anterolateral thigh flap based on single perforator between August 2009 and August 2010. The mean flap dimension was 261cm(2) (range 80-540cm(2)). In 21 patients the flap was bi-paddled and used for inner and outer lining for cheek. None of the flaps developed perforator insufficiency. Two flaps were lost due to delayed neck wound sepsis after 7th post operative day. This study establishes safety and reliability of using a large and/or bi-paddled anterolateral thigh flap based on single perforator for reconstruction of complex oral cavity defects.     

Deep inferior epigastric artery perforator free flaps in head and neck reconstruction

The advantage of free perforator flaps versus free musculocutaneous flaps is the reduced morbidity of the donor site with preservation of nerves, muscles and deep fascia. In this study, we evaluated the reconstruction results of deep inferior epigastric artery perforator (DIEAP) free flaps in the head and neck. A retrospective review was performed of 12 patients with head and neck tumor ablation defects that were reconstructed with the deep inferior epigastric artery perforator (DIEAP) free flaps between January 2004 and December 2006. Reconstruction outcomes and complications were measured. Recipient sites were subdivided into defects of total or subtotal glossectomy (N=6), three-dimensional defects of midface (N=3), through and through defects of the cheek (N=2), and anterior skull base resection with an external skin component defect (N=1).The overall free flap success rate was 92% (11/12). One DIEAP free flap was lost because the draining jugular vein thrombosed. No complications were observed in the donor site, including abdominal bulge or hernia. Due to the advantage of minimum donor site morbidity, the DIEAP free flap is a new and reliable reconstruction choice for head and neck surgical defects.     

Impact of insurance payer and socioeconomic status on type of autologous breast reconstruction

IntroductionAutologous breast reconstruction has evolved from more morbid procedures that sacrificed the abdominal muscle (the TRAM or transverse rectus abdominus muscle flap) to “perforator” flaps. Commercial insurers recognized the higher technical demand of perforator flaps by creating procedural codes with higher professional fees. This study examined whether procedure code discrepancies between insurance payers disproportionally incentivize perforator flaps among the commercially insured.MethodsAutologous breast reconstructions identified from the National Inpatient Sample (NIS) were subdivided into microvascular perforator (85.74, 85.75, 85.76), microvascular TRAM (85.73), and pedicled TRAM flaps (85.72). Demographics, comorbidities and access to care were compared. A logistic regression comparing microvascular reconstructions only was used to identify predictors for perforator flap reconstruction.ResultsA total of 66,968 cases of autologous breast reconstruction were identified. Perforator flaps were more likely among the commercially insured (p < 0.001) and higher insurance quartiles (p < 0.001).When comparing microvascular reconstruction, perforator flaps were 1.72 (p < 0.001) times more likely among the commercially insured. As compared to the lowest income quartile, the fourth quartile had an odds ratio of 1.36 (p < 0.001) for perforator flap reconstruction.ConclusionThe presence of a separate perforator flap billing code among the commercially insured may be exacerbating existing socioeconomic disparities in breast cancer reconstruction.     

乳腺癌术后即时扩展型背阔肌肌皮瓣乳房重建27例分析

目的探讨乳腺癌改良根治术后应用扩展型背阔肌肌皮瓣即时乳房重建的疗效。方法对27例乳腺癌患者施行乳腺癌改良根治术（其中6例行保留皮肤的乳腺癌改良根治术,21例行保留乳头、乳晕的乳腺癌改良根治术）,术后即时切取包括背阔肌及其表面的脂肪和岛状皮肤、髂嵴上方脂肪、背阔肌前沿侧胸部脂肪和肩胛区脂肪构成扩展型背阔肌肌皮瓣,转移至胸壁重建乳房。结果27例即时乳房重建全部获得成功。切除乳房的组织量为180-330ml（平均215ml）,移植重建乳房的扩展型背阔肌肌皮瓣组织量为210-380ml（平均245ml）。24例术后辅助化疗,5例辅助放射治疗。随访6～24个月（中位随访12个月）,所有患者均生存,术后无一例局部复发、转移。美容效果：优17例,良6例,一般3例,差1例。结论乳腺癌患者行保留皮肤或乳头乳晕改良根治术后应用扩展型背阔肌肌皮瓣即时乳房重建形态良好,不影响术后辅助治疗和远期疗效,作为目前乳腺肿瘤治疗的一种有效补充手段,值得临床推广。     

Definition of Tumor Bed Boost in Oncoplastic Breast Surgery: An Understanding and Approach

IntroductionDefinition of the tumor bed (TB) is currently guided by intraoperatively placed metal clips. However, this traditional planning method may not be sufficient for tumor cavity defect refilled with modern oncoplastic breast surgery. We explored the impact of a close cooperation between surgeon and oncologist on the accuracy of TB contouring after partial breast reconstruction with chest wall perforator flaps (CWPF).Patients and MethodsA retrospective review of patients who received radiotherapy after CWPF was performed. TB and boost volume were defined by the surgeon, considering clips and the typical radiologic appearance of the flap, and by a radiation oncologist, and results were compared with the surgical specimen volume (SPV). The boost volume was marked as 5 mm penumbral ring thickness of native breast tissue wall around the replaced flap (nonbreast tissue).ResultsThere were no significant differences between SPV and surgeon-defined TB values. Conversely, the radiation oncologist–defined values were significantly smaller than the actual SPV. If a ring-shaped TB boost was delivered, this would have allowed a potential reduction of irradiated tissue of 127.6%.ConclusionTB definition solely by surgical clips may be prone to inaccuracy in case of volume replacement oncoplastic breast surgery. Our approach of combining the clips with the redefinition of the flap on computed tomographic scan may provide more accurate TB definition. Although an ideal ring-shaped boost might be difficult to reproduce in practice, it introduces a new paradigm: a lower radiation dose inside TB is tolerable, if not desirable, at least in CWPF.     

乳腺肿瘤整形与乳房重建专家共识(2022年版)

随着乳腺肿瘤整形与乳房重建在国内新的临床应用趋势,更鉴于新的循证医学数据不断累积,中国抗癌协会乳腺癌专业委员会召集外科、整形、放疗、内科、病理等多学科专家,在《乳腺肿瘤整形与乳房重建专家共识(2018年版)》的基础上共同商讨制定了《乳腺肿瘤整形与乳房重建专家共识(2022年版)》,2022年版新增了腔镜乳房重建、胸肌前乳房重建及乳房重建的个案管理等内容,并将初版的保留乳头乳晕的全乳切除章节更名为保守性全乳切除,并做了大量内容补充及更新。共识也对胸肌前乳房重建、游离腹壁下动脉穿支皮瓣(deep inferior epigastric artery perforator flap,DIEP)手术等临床热点进行了详尽的阐述。相信本次更新会给各层级医院提高乳腺肿瘤整形及乳房重建临床水平,提升治疗规范化,优化治疗结局助力,最终提高患者满意度。     

Association of the breast reconstruction modality with the development of postmastectomy lymphedema: A long-term follow-up study

BackgroundWhether the breast reconstruction modality could influence the long-term development of post-mastectomy lymphedema has been little investigated. The present study aimed to evaluate the potential association of the breast reconstruction method with the incidence of lymphedema over an extended follow-up period.MethodsPatients with breast cancer who underwent immediate reconstruction from 2008 to 2014 were reviewed. They were categorized into three groups according to the reconstruction method: tissue expander/implant, abdominal flaps, and latissimus dorsi (LD) muscle flaps. Differences in the cumulative incidence of lymphedema by the reconstruction method were analyzed, as well as their independent influence on the outcome. Further analyses were conducted with propensity-score matching for baseline characteristics.ResultsIn total, 664 cases were analyzed with a median follow-up of 83 months (402 prostheses, 180 abdominal flaps, and 82 LD flaps). The rate of axillary lymph node dissection was significantly higher in the LD flap group than in the other two groups. The 5-year cumulative incidences of lymphedema in the LD flap, abdominal flap, and prosthesis groups were 3.7%, 10.6%, and 10.9%, respectively. In multivariable analyses, compared to the use of the LD flap, that of tissue expander/implant and that of abdominal flaps were associated with increased risks of lymphedema. A similar association was observed in the propensity-score matching analysis. The use of abdominal flaps or prostheses was not associated with the outcomes.ConclusionsOur results suggest that the method of immediate breast reconstruction might be associated with the development of postmastectomy lymphedema.     

CT血管造影在延期DIEP皮瓣乳房重建术中的应用研究

背景与目的:乳房切除术后自体组织重建中,腹壁下动脉穿支(deep inferior epigastric perforator,DIEP)皮瓣越来越受到外科医师的关注,如何安全、有效地进行穿支血管定位、抉择、解剖是制备DIEP皮瓣最大的难点.探讨CT血管造影(computed tomographic angiograp...     

Microsurgical breast reconstruction

Breast cancer, the most common cancer diagnosed in American women, often necessitates mastectomy. Many studies have demonstrated improved quality of life and well-being after breast reconstruction. Numerous techniques are available for breast reconstruction including tissue expander implants and autologous tissues. Microsurgical tissue transfer involves the use of excess skin and fat (flaps) from a remote location to reconstruct the breast. Most often, tissues are transferred from the abdomen and buttocks. Less commonly, thigh flaps are used. These operations can provide durable, esthetic reconstructions. In addition, advances in microsurgical techniques have improved operative success rates to the range of 99%. The selection of an appropriate flap for microsurgical breast reconstruction is multifactorial and is based on patient and oncologic factors. These factors include patient comorbidities, body habitus/availability of donor tissues, cancer stage, and the need for postoperative adjuvant radiation therapy, as well as the risk of cancer in the contralateral breast. Appropriate choice of flap and surgical technique can minimize the risk of operative complications. Additionally, several large series have established that microsurgical breast reconstruction has no impact on survival, or locoregional/distant recurrence rates.