Ultrasound predictors of thyroid cancer.

OBJECTIVE: To identify ultrasound (US) features associated with cancer in thyroid nodules. MATERIAL AND METHOD: During a two and a half-year period, medical charts, US images, and pathological findings in 629 consecutive patients with thyroid nodules who underwent US examination as well as fine needle aspiration biopsy (FNAB) or surgical excision or both were retrospectively reviewed. Clinical and US findings associated with thyroid cancer were identified using statistical models. RESULTS: Unequivocal cytological or pathological findings were available for 578 patients. Forty-eight patients (8%) had thyroid cancer. Independent clinical and US features associated with thyroid cancer included younger age, symptoms other than palpable mass, solid nodules, fewer number of nodules, presence of calcifications, and enlarged cervical lymph nodes. The combination of all these features was most specific for the diagnosis of thyroid cancer. The absence of all these features could rule out all thyroid cancers. CONCLUSION: The risk of the thyroid cancer in patients with thyroid nodules could be estimated by using relevant clinical and US features.

New inflammatory indicators for cell-based liquid biopsy: association of the circulating CD44+/CD24- non-hematopoietic rare cell phenotype with breast cancer residual disease.

BACKGROUND: Breast cancer residual disease assessment in early-stage patients has been challenging and lacks routine identification of adjuvant therapy benefit and objective measure of therapy success. Liquid biopsy assays targeting tumor-derived entities are investigated for minimal residual disease detection, yet perform low in clinical sensitivity. We propose the detection of CD44-related systemic inflammation for the assessment of residual cancer. METHODS: Circulating CD44+/CD45- rare cells from healthy, noncancer- and cancer-afflicted donors were enriched by CD45 depletion and analyzed by immuno-fluorescence microscopy. CD44+ rare cell subtyping was based on cytological feature analysis and referred to as morphological index. AUC analysis was employed for identification of the most cancer-specific CD44+ subtype. RESULTS: The EpCam-/CD44+/CD24-/CD71-/CD45-/DNA+ phenotype alludes to a distinct cell type and was found frequently at concentrations below 5 cells per 5 mL in healthy donors. Marker elevation by at least 5 × on average was observed in all afflicted cohorts. The positive predicted value for the prediction of malignancy-associated systemic inflammation of a CD44+ rare cell subtype with a higher morphological index was 87%. An outlook for the frequency of sustained inflammation in residual cancer may be given to measure 78%. CONCLUSION: The CD44+ rare cell and subtype denotes improvement in detection of residual cancer disease and may provide an objective and alternative measure of disease burden in early-stage breast cancer.

The relative false negative rate of isosulfan blue in detecting sentinel lymph nodes in early breast cancer.

OBJECTIVE: To determine the false negative rate of the isosulfan blue injection method of SLN detection in early breast cancer, relative to that of the combined blue dye and radiocolloid injection method. MATERIAL AND METHOD: Seventy women with early breast cancer underwent the combined method of SLN detection during the period between September 2007 and December 2008. Standard criteria for each method were used to identify SLNs. Each SLN was labeled as identified by the blue dye, the radiocolloid and as being positive or negative for cancer cells. RESULTS: Subjects were 50 years old with tumors of size 2.3 cm on the average. The average number of SLNs harvested was 2.5 nodes per subject. The detection rate for the isosulfan blue method was 91% (64/70). The relative false negative rate of the blue dye was zero (0/64). CONCLUSION: Experienced surgeons who use the isosulfan blue method of SLN detection in early breast cancer can be reasonably confident that the false negative rate of the isosulfan blue method was similar to that of the combined method.

Breast cancer cells in the afferent lymphatic tracts of sentinel lymph nodes.

BACKGROUND: To identify breast cancer cells in the afferent lymphatic tracts of axillary sentinel lymph nodes (SLNs). MATERIAL AND METHOD: The authors performed a prospective study of 1 00 breast cancer patients who underwent SLN biopsy between June 2009 and January 2010. The afferent lymphatic tracts of SLNs were identified by isosulfan blue or radiocolloid or both and were examined histologically. RESULTS: One hundred three SLNs and afferent lymphatic tracts were examined. The mean age of the patients was 53.2 years (range, 24 to 78 years). The median number of SLNs was 2 (range, 1 to 7). Twenty-four (24%) patients had positive SLNs. Most patients had stage I breast cancer (67%). Three patients with positive SLNs (13%) and stages IIB-IIIC breast cancers had tumor cells in the afferent tract tissue. There were no tumor cells in the afferent tracts of negative SLNs. CONCLUSION: Only a small proportion of operable breast cancer patients have tumor cells in the afferent lymphatic tract tissue of SLNs. There was a probable trend for more advanced stage breast cancer to harbor tumor cells in the afferent lymphatic tract tissue.

Borderline phyllodes tumor arising in accessory breast tissue at the axilla.

Accessory breast tissue is an anatomical variation which occurs during embryogenic development. It appears most frequently at the axilla. Benign and malignant processes in general breast tissue can occur in accessory breast tissue. We report a case of 76-year-old female presented with palpable, huge mass at the right axilla which pathology of the mass was borderline phyllodes tumor. Phyllodes tumors arising in accessory breast tissue is an extremely rare condition. And this case study showed more detail on phyllodes tumor which would encourage the advance in management of the disease.

Large Mammary Paget Disease without Underlying Breast Carcinoma.

Mammary Paget disease is an uncommon type of breast cancer. Redness, scaling, and thickness involving the nipple and areola are common clinical symptoms. Invasive breast cancer was found in nearly 90% of these patients. Only a few cases of mammary Paget disease with no underlying cancer have been described, with a better prognosis. Treatment options include wide excision or mastectomy. However, if the lesion is very extensive, breast reconstruction may be required. We reported a rare case of extensive Paget disease in a 65-year-old woman who had a 7-year history of a 14 × 19 cm progressively enlarging erythematous scaling lesion that covered her entire left breast. No evidence of related malignancy or metastatic lesion was seen. A left mastectomy with sentinel lymph node biopsy and immediate pedicled transverse rectus abdominis myocutaneous flap reconstruction was chosen. There is uncertainty about axillary node metastasis since multiple enlarged and palpable left axillary lymph nodes were seen. She had axillary lymph node dissection instead. A histological examination confirmed the diagnosis of Paget disease of the nipple in the absence of underlying breast cancer and there was no evidence of axillary lymph node metastasis. This article emphasizes the need to pay close attention to diagnosis, progression, and treatment of the disease.

Predictive factors of axillary lymph node metastasis in breast cancer.

OBJECTIVE: To identify clinical, radiologic and pathologic factors significantly related to axillary lymph node (ALN) metastasis in women with operable breast cancer. MATERIAL AND METHOD: Records of women with operable invasive breast cancer treated between July 2002 and May 2006 were reviewed Data on the number of axillary nodes, number of positive nodes, preoperative clinical, mammographic, and pathologic characteristics of each breast cancer were retrieved. Multiple logistic regression analyses were used to identify significant predictors of ALN metastasis. RESULTS: Records of 590 patients were reviewed Positive ALNs were found in 302 patients (51%). Independent and significant predictors of ALN metastasis included younger age, larger tumor size, presence of lymphovascular invasion, category 5 mammograms and low mammographic breast density. The combination of age less than 60 years, low mammographic breast density, category 5 mammogram, tumor larger 1 cm., and presence of lymphovascular invasion, had a specificity for predicting ALN metastasis of over 95%. CONCLUSION: A combination of clinical, radiologic, and pathologic characteristics highly specific for predicting ALN metastasis was found This prediction rule might be useful for selecting breast cancer patients for full ALN dissection without a preliminary SLNB.

Sentinel lymph node biopsy after neoadjuvant treatment of breast cancer using blue dye, radioisotope, and indocyanine green: Prospective cohort study.

BACKGROUND: The breast cancer treatment paradigm has shifted to neoadjuvant treatment. There are many advantages to neoadjuvant treatment, such as tumor downsizing, in vivo tumor biology testing, treating micrometastasis, and achieving complete pathological response (a surrogate marker for overall survival). However, in the post neoadjuvant settings, sentinel lymph node biopsy can be done using a dual staining technique to decrease the false-negative rate (FNR) and increase the detection rate. However, many hospitals are not equipped to use radioisotopes. Here we investigate the detection rate and accuracy of sentinel lymph node biopsy in post neoadjuvant treatment breast cancer, comparing radioisotope, isosulfan blue, and indocyanine green (ICG) approaches. MATERIAL AND METHODS: This prospective study includes breast cancer patients (T2-4, N1-2) who had received neoadjuvant treatment. Carcinomas were confirmed by tissue pathology. Patients who had previous surgical biopsy or surgery involving the axillary regions, and those with a history of allergy to ICG, isosulfan blue, or radioisotope were excluded from the study. RESULT: The study was done between July 1, 2019 to March 31, 2020. The mean age of participants was 53 years. Fourteen (60.87%) were post-menopause, two (8.7%) were perimenopause, and seven (30.43%) were premenopause. The clinical-stage distribution of the participants was: 2A (8.7%), 2B (34.78%), 3A (43.48%), and 3B (13.04%). The primary tumor size was 4.82 ± 2.73 cm. The lymph node size was 1.8 ± 0.96 cm. The detection rates at the individual level were 95.23% with ICG, 85.71% with isosulfan blue, and 85.71% with a radioisotope. The detection rate increased up to 100% when the ICG and blue dye methods were combined. The FNRs of sentinel lymph node biopsy at the individual level were: 10% using ICG, 30% using isosulfan blue, and 40% using radioisotope. At the lymph node level, the detection rates were 93.22% using ICG, 81.78% using isosulfan blue, and 53.87% using a radioisotope. The FNRs of sentinel lymph node biopsy at the lymph node level were 19.05% with ICG, 21.43% with isosulfan blue, and 18.03% with a radioisotope. However, the FNR was less than 10% when ICG, isosulfan blue, and a radioisotope were combined. CONCLUSION: We can perform sentinel lymph node biopsy by combining blue dye with ICG as an optional modality and achieve a comparable outcome with combine radioisotope in locally advanced breast cancer after neoadjuvant treatment.

Is It Reasonable to Use Indocyanine Green Fluorescence Imaging to Determine the Border of Pedicled TRAM Flap Zone IV?

BACKGROUND: The contralateral lateral section (zone IV) of a pedicled transverse rectus abdominis musculocutaneous (TRAM) flap is generally removed intraoperatively. The border of zone IV is usually identified anatomically using the Hartrampf classification. In this study, we used the indocyanine green (ICG) fluorescence method to determine the border of zone IV and find the correlation with clinical flap outcome. METHODS: The study recruited breast cancer patients who underwent a pedicled TRAM flap reconstruction. The border of zone IV was identified using the intraoperative ICG fluorescence imaging. The medial border of the removed specimen was sent for a pathological examination of vascular density. RESULTS: A total of 29 patients underwent a pedicled TRAM reconstruction. In 16 patients, the border of zone IV identified by ICG fluorescent imaging was identical to the anatomical border. The ICG imaging showed distinct perfusion patterns, which we divided into 4 categories: sequential, simultaneous, low midline scar, and delayed pattern. Overall, there were no patient with total flap loss, 1 patient had a partial flap loss and 4 patients had a fat necrosis. Neither the ICG perfusion time nor the pathological vascular density correlates with the clinical flap outcome. The delayed ICG perfusion pattern (category IV) has the highest fat necrosis rate, although it is not statistically significant. CONCLUSIONS: In this study, more than half of the patients have ICG perfusion corresponding with the Hartrampf zone, which reflected the conventional practice of zone IV pedicled TRAM flap removal. Some ICG perfusion patterns could be helpful, especially in low midline and delayed pattern.

Comparisons of complications between extended latissimus dorsi flap and latissimus dorsi flap in total breast reconstruction: A prospective cohort study.

BACKGROUND: The latissimus dorsi (LD) flap is one of the most popular techniques in breast reconstruction. Although numerous studies have not shown functional impairment of the shoulder after surgery, other studies have reported significant functional impairment, especially after extended LD flap reconstruction. The present study compared functional deficit and shoulder movement between extended LD and LD flap reconstruction. MATERIALS AND METHODS: Between December 2015 and May 2018, this study enrolled 31 patients undergoing LD flap reconstruction. Data on patient demographics, operative details, morbidities, and degree of shoulder movement were collected. Outcomes were compared between the extended LD and LD flap groups. RESULTS: Twenty-one women and 10 women underwent LD flap and extended LD flap reconstruction, respectively. The median patient age was 43 years. No demographic data differed between groups. Seroma, especially around the back incision, was the most common complication (90.5% in the LD flap and 90% in the extended LD group). Five patients in the LD flap group and one patient in the extended LD flap group showed decreased shoulder range of motion (ROM) at 6 months post-operation. Only one patient in the LD flap group showed impairment based on American Shoulder and Elbow Surgeons Shoulder Score (ASES). The results did not differ significantly between groups; however, the LD flap group showed faster functional recovery. CONCLUSION: LD flap reconstruction can be performed with a very low impact on shoulder function. We observed a slightly decreased ROM for both LD flap techniques, with no impact on functional outcome.

Evaluation the effect of preserving intercostobrachial nerve in axillary dissection for breast cancer patient.

BACKGROUND: The Intercostobrachial nerve (ICBN) is responsible for sensory function in the axillar and upper arm. The majority of surgeons routinely sacrifice the ICBN during axillary lymph node dissection (ALND) because of technical difficulties. Therefore, the aim of this study was to assess the effects of the preservation or division of the ICBN on the incidence of post-operative sensory disturbance, health-related quality of life (HRQOL), and the physical functions of the upper limbs. METHODS: We performed a randomized double-blind trial comparing the incidence of sensory disturbance, HRQOL and physical functions of upper limbs in the preservation and the removal of the ICBN. Clinicians performed sensory evaluation at 2 weeks and 3 months after surgery. The sensory evaluation included questionnaires (subjective evaluation) and physical examination (objective evaluation) to evaluate sensory disturbance of the upper arm. HRQOL and physical function of upper limbs was accessed before surgery and at three months after surgery, using Short Form-36 and QuickDASH questionnaires, both in Thai language versions. RESULTS: At the end of the surgical procedures there were 15 patients in the preserved group (group P) and 28 patients in the non-preserved group (group N). In as-treated analysis, there was no significant difference between the groups in pain, sensory loss, physical examination of touch and pinprick sensation, and areas of sensory dullness. HRQOL found that the reported pain in P group was higher than N group in both intention-to-treat and as-treated analysis. In the QuickDASH scores of physical functions of the upper limbs there was a significant difference, 9.1 in group P and 20.5 in group N (P=0.013). CONCLUSIONS: ICBN preservation provides no benefit to improving sensation, but there are benefits in HRQOL and physical functions of upper limbs at three months after surgery.

Idiopathic granulomatous mastitis: A retrospective cohort study between 44 patients with different treatment modalities.

BACKGROUND: Idiopathic granulomatous mastitis (IGM) is an uncommon benign chronic inflammatory disease which can clinically and radiographically mimic abscess or breast cancer. Definitive diagnosis was made by histopathology and exclusion of an identifying etiology. Optimal treatment has not been yet established. The aim of this study was to report and describe the clinical signs, radiological findings, managements, clinical course, and clinical outcomes after treatment of IGM. METHOD: We retrospectively studied IGM medical records of 44 patients in our institute collected from March 1990 to October 2016. The patient characteristics, clinical presentations, radiological findings, microbiological workups, tissue pathology, treatment modalities, outcomes, and follow-up data were reviewed and analyzed. The success rate, recurrence rate and time-to-healing were compared focusing on the treatment modalities to find the proper treatments for IGM patient. RESULTS: Forty-four patients were diagnosed as IGM. The median follow-up time was 20.73 months ranging from 1.26 to 118.8 months while the median time of the diagnosis was 21 days ranging from 2 to 246 days. Due to the follow-up period, only thirty-nine patient data were used for the analysis. In the first setting, 30 patients were treated by surgery, 6 patients were treated by using steroid while other 3 patients were treated by other different treatments. Only 25 from 39 patients (64.10%) were cured by the first modality. The overall median time-to-healing was 84 days while the medians of time-to-healing treated by surgery, steroid and the rest were 75, 114.5, and 238 days respectively. The surgical treatment had the shortest time-to-healing but not statistically significant (p = 0.23). Thirteen patients out of twenty-five (52%) had wound complications after performing an excision. Lastly, five patients out of thirty-nine (12.82%) had recurrence. CONCLUSION: IGM is an uncommon benign disease which is hardly distinguished from malignancy. There is not a significant difference among treatment modalities in term of time-to-healing and recurrence of disease. The result shows that surgery is outperformed by the shortest healing time. However, the surgical treatment must be chosen with careful due to high rate of wound complications. Multimodality treatment is recommended as the proper treatments for IGM patient.

Malignant transformation of phyllodes tumor: a case report and review of literature.

Malignant phyllodes may transform from benign phyllodes; low-aggressive malignant phyllodes tumor is manageable by locally wide excision.

Nipple-Areola Complex Sensation after Nipple-sparing Mastectomy.

BACKGROUND: Nipple-sparing mastectomy (NSM) has been proven to be oncologically safe for treating breast cancer. This procedure had been developed to optimize the esthetic outcome and reduce feeling mutilation after mastectomy. Risks of necrotic complications and diminishing nipple-areola complex (NAC) sensation are common complications affecting the patient's satisfaction after the surgery. The evaluation of NAC sensation should be also investigated. METHODS: We prospectively analyzed 55 NSMs that were performed on 52 patients for both therapeutic and prophylactic indications in Ramathibodi Hospital from May 2007 to September 2015. Patients' demographics, operative details, oncologic outcome, and postoperative complications, focusing on NAC sensation and necrotic complications, were analyzed. RESULTS: Forty-seven NSMs (87%) were performed for therapeutic indications, and another 7 NSMs (13%) were risk-reducing operations. Of the 43 patients performing NSM for breast cancer treatment, 33 patients (77%) had invasive cancer and 11 patients (23%) had ductal carcinoma in situ. One subareola base tissue was found an occult cancer, and the NAC was then removed. There were 3 locoregional recurrences after a median follow-up time of 24 months (range, 2-104 months). The NAC sensation was evaluated in a total of 35 patients. Twenty-five patients (46%) underwent serial evaluation after 6 months of operation, and 10 patients were evaluated at more than 1 year after operation. In the first 6 months, 11 patients (44%) showed partial sensation recovery, and 3 more patients had partial recovery after 1-year follow-up. Only 1 patient (2%) had complete sensation recovery in all area of the NAC. In late evaluation group, 7 out of 10 patients had partial recovery. Most pain sensation remained in the lower aspect of the areola away from surgical incision. CONCLUSIONS: NSM is technically feasible in selected patients with low rates of NAC removal. Some patients can preserve the NAC sensation. Long-term outcome should receive follow-up.

Bisphosphonate-related osteonecrosis of jaws in advanced stage breast cancer was detected from bone scan: a case report.

Bisphosphonates (BPs) are indicated to treat skeletal-related events (SREs) for cancer patients with bone metastasis. We report a 79-year-old woman with advanced stage breast cancer with bone metastasis who was prescribed BPs (zoledronate), then developed osteonecrosis of jaw. We provide a brief review of the pathogenesis, diagnosis and treatment of this complication.

Breast reconstruction in pregnancy: a case report of multidisciplinary team approach in immediate autologous flap reconstruction for pregnancy-associated breast cancer.

This report presents the results of immediate breast reconstruction with autologous flap in Pregnancy-associated breast cancer (PABC). There was no obstetrics and surgical complications in our report. Immediate breast reconstruction can be performed in PABC after a careful selection. Multidisciplinary team approach is the key in managing these groups of patients.

Donor-Site Complications and Remnant of Rectus Abdominis Muscle Status after Transverse Rectus Abdominis Myocutaneous Flap Reconstruction.

BACKGROUND: Transverse rectus abdominis myocutaneous (TRAM) flap reconstruction after mastectomy in breast cancer patients has become one of the milestones in breast reconstruction. There are several techniques that have been used in an attempt to minimize untoward complications. We present the whole muscle with partial sheath-sparing technique that focuses on the anatomy of arcuate line and the closure of the anterior abdominal wall techniques with mesh and determine factors associated with its complications and outcomes. METHODS: We retrospectively and prospectively review the results of 30 pedicled TRAM flaps that were performed between November 2013 and March 2016, focusing on outcomes and complications. RESULTS: Among the 30 pedicled TRAM flap procedures in 30 patients, there were complications in 5 patients (17%). Most common complications were surgical-site infection (7%). After a median follow-up time of 15 months, no patient developed abdominal wall hernia or bulging in daily activities in our study, but 6 patients (20%) had asymptomatic abdominal wall bulging when exercised. Significant factors related to asymptomatic exercised abdominal wall bulging included having a body mass index of more than 23 kg/m2. CONCLUSION: Pedicled TRAM flap by using the technique of the whole muscle with partial sheath-sparing technique combined with reinforcement above the arcuate line with mesh can reduce the occurrence of abdominal bulging and hernia.

Oncoplastic techniques in breast surgery for special therapeutic problems.

Resection of large tumors can be challenging, from the view point of breast preservation. Oncoplastic techniques are a valuable component of breast surgery in patients with large breast tumors who desire breast preservation. These techniques have been shown to be oncologically safe, while maintaining acceptable breast cosmesis. For locally advanced or recurrent breast cancers, the goals of surgery include local disease control and palliation of clinical symptoms. Oncoplastic surgery is also effective and oncologically safe in these situations. The need to completely remove all foci of cancers with adequate surgical margins often requires the displacement of adjacent or distant skin and soft tissue to cover the resulting soft tissue defect. Sometimes doing so can be cosmetically pleasing as well. In this article we present three special therapeutic problems in three distinct conditions, all resolved with oncoplastic techniques: the benign breast condition, malignant breast condition, and the palliative setting.

Complications and oncologic outcomes of pedicled transverse rectus abdominis myocutaneous flap in breast cancer patients.

BACKGROUND: There are several techniques for harvesting the pedicled transverse rectus abdominis myocutaneous (TRAM) flap after mastectomy in breast cancer patients. We examined the whole muscle with partial sheath sparing technique and determined factors associated with its complications and oncological outcomes. METHODS: We retrospectively reviewed the results of 168 TRAM flaps performed between January 2003 and December 2010, focusing on complications and oncologic outcomes. RESULTS: Among the 168 pedicled TRAM flap procedures in 158 patients, flap complications occurred in 34%. Most of the flap complications included some degree of fat necrosis. There was no total flap loss. Flap complications were associated with elderly patients and the presence of major donor site complications. Abdominal bulging and hernia occurred in 12% of patients. The bi-pedicled TRAM flap and higher body mass index (BMI) were significant factors associated with increased donor site complications. Seven patients (4%) developed loco-regional recurrence. Within a median follow-up of 27 months, distant metastasis and death occurred in 6% and 4% of patients, respectively. CONCLUSIONS: The pedicled TRAM flap using the whole muscle with partial sheath sparing technique in the present study is consistent with the results from previous studies in flap complication rates and oncological outcomes.

Effect of young age, positive margins, and triple negative status on disease recurrence after breast conserving therapy.

BACKGROUND: To determine the risk factors for disease recurrence after breast conserving therapy (BCT) for breast cancer in a group of South-East Asian women. METHODS: Medical and pathological records of women who underwent BCT during the 10-year period from 2001 to 2010 were reviewed. Data collected included age ≤35 years defined as the young, type of operation, pathological data, hormonal receptor (HR) status, human epidermal growth factor receptor-2 (HER-2) expression status, and surgical margin status. Data on adjuvant therapy were also collected. Main outcomes were overall breast cancer recurrence, locoregional, and distant recurrence. Risk factors for each type of recurrence were identified using Cox proportional hazards regression models. RESULTS: There were 294 BCTs in 290 patients during the study period. The overwhelming majority (91%) had early stage (stages I-II) breast cancers. Young age patients constituted 9% of all patients, and triple negative cancers (HR negative and HER-2 negative) were seen in 19%. Involved margins on initial surgery were found in 9% of cases, and after reoperation, only 2% had involved margins. After a median follow-up of 50 months, and a maximum follow-up of 135 months, there were 30 recurrences and 6 deaths. Of the 30 recurrences, 19 included locoregional, 20 included distant, and 13 had in-breast recurrences. The disease-free survival at 10 years was 82.5% (95% CI: 74.8% to 88.1%), and the cumulative in-breast recurrence was 9.3% (95% CI: 4.9% to 17.2%) at 10 years. Multivariable Cox regression analysis revealed that young age, larger tumor size, involved margins, and no breast irradiation were associated with higher risk of locoregional recurrence. Triple negative status, larger tumor size, more positive nodes, and involved margins were associated with higher risk of distant recurrence. CONCLUSIONS: We found young age to be a significant prognosticator of locoregional recurrence, and triple negative status of distant recurrence. Involved surgical margin status was associated with both recurrences. Tumor size was associated with both recurrences, and axillary lymph node metastasis was associated with distant recurrence.