A nomogram to predict the pathological complete response in patients with breast cancer based on the TILs-US score.

BACKGROUND: The tumor-infiltrating lymphocytes-ultrasonography score is a calculation system for predicting lymphocyte-predominant breast cancers in surgical specimens. A nomogram based on the tumor-infiltrating lymphocytes-ultrasonography score was developed to predict the pathological complete response in breast cancer treated with neoadjuvant chemotherapy. METHODS: A retrospective evaluation was conducted on 118 patients with breast cancer treated with neoadjuvant chemotherapy at Hiroshima University Hospital. Tumor-infiltrating lymphocytes-ultrasonography scores ≥4 were classified as high. A nomogram was developed using a stepwise logistic regression model for pathological complete response (ypT0 ypN0), based on the smallest Akaike information criterion. The predictive ability and clinical usefulness of the nomogram were also evaluated. RESULTS: Among 118 patients, 34 (28.8%) achieved a pathological complete response, and 52 (44.1%) exhibited high tumor-infiltrating lymphocytes-ultrasonography. In multivariate logistic regression analysis, high tumor-infiltrating lymphocytes-ultrasonography (odds ratio, 6.01; P < 0.001), clinical complete response (odds ratio, 4.83; P = 0.004) and hormone receptor (odds ratio, 3.48; P = 0.038) were independent predictors of pathological complete response. A nomogram based on tumor-infiltrating lymphocytes-ultrasonography score, clinical complete response, hormone receptor and clinical N status was developed. The nomogram showed an area under the curve of 0.831 and a bias-corrected area under the curve of 0.809. The calibration plot showed a good fit between the expected and actual pathological complete response values. Decision curve analysis also showed the clinical utility of the nomogram for predicting pathological complete responses. CONCLUSIONS: A nomogram based on the tumor-infiltrating lymphocytes-ultrasonography score exhibited a favorable predictive ability for pathological complete response in patients with breast cancer, which can be useful in predicting the residual disease status after neoadjuvant chemotherapy.

Successful omental flap coverage repair of a rectovaginal fistula after low anterior resection: a case report.

BACKGROUND: Rectovaginal fistula (RVF) is a troublesome and refractory complication after low anterior resection (LAR) for rectal cancer. An omental flap repair was performed for the RVF caused due to Crohn's disease and childbirth trauma. However, there are few cases of an omental flap repair for RVF after LAR. Herein, we present a successfully repaired case of RVF by omental flap coverage after LAR for rectal cancer. CASE PRESENTATION: A 50-year-old female patient with advanced rectal cancer underwent laparoscopic LAR with double-stapling technique anastomosis and achieved curative resection. She complained of a stool from the vagina and was diagnosed with RVF on the postoperative day (POD) 18. Conservative therapy was ineffective. We performed laparoscopic fistula resection and direct closure of the vagina and rectum, designed the omentum that could reach the pelvis, repaired RVF by omental flap coverage, and performed transverse colostomy on POD 25. She was discharged on initial POD 48. Seven months after the initial operation, colostomy closure was administered. There was no recurrence of RVF found 1 year after the initial operation. CONCLUSIONS: The patient achieved an omental flap coverage for RVF. We successfully performed the omental flap coverage repair in patients with RVF after the leakage of LAR. An omental flap may become an alternative treatment for muscle flap or an effective treatment for RVF.

[Hemorrhagic Colon Cancer with Left Atrial Thrombus Formation after Anticoagulant Therapy Discontinuation-A Case Report].

The patient was a 72-year-old female. She had been taking rivaroxaban for chronic atrial fibrillation; however, she stopped taking it due to anemia and was hospitalized urgently. A contrast-enhanced computed tomography(CT)scan showed a 30 mm mass in the ascending colon, and a colonoscopy revealed ascending colon cancer(cT3, cN0, cM0, cStage Ⅱa). The tumor was hemorrhagic and was thought to have caused the anemia. On day 6 of hospitalization, another contrast- enhanced CT scan showed a poorly contrast-enhanced area in the left atrium, and transesophageal echocardiography revealed 2 left atrial thrombi(27 mm and 17 mm). Since early induction of anticoagulation therapy was considered, an emergency open right colectomy was performed to remove the cause of the bleeding. Intravenous heparin therapy was started the day after surgery and was switched to oral apixaban therapy on the fourth postoperative day. The postoperative course was good, and she was discharged home on the 17th postoperative day. This patient had conflicting clinical problems simultaneously; however, immediate decision-making and initiation of treatment were effective.

Effect of Wnt5a on drug resistance in estrogen receptor-positive breast cancer.

BACKGROUND: Previously, we reported that Wnt5a-positive breast cancer can be classified as estrogen receptor (ER)-positive breast cancer; its prognosis is worse than that of Wnt5a-negative breast cancer. This study aimed to investigate the mechanisms underlying the poor prognosis in Wnt5a-positive breast cancer patients. METHODS: In total, 151 consecutive ER-positive breast cancer patients who underwent resection between January 2011 and February 2014 were enrolled. DNA microarray and pathway analyses were conducted using MCF-7 cells stably expressing Wnt5a [MCF-7/Wnt5a (+)]. Based on the outcomes, cell viability/drug sensitivity assays, and mutation analysis were performed using cell cultures and breast cancer tissues. The relationship between Wnt5a and the PI3K-AKT-mTOR signaling pathway was also examined. RESULTS: The relapse-free survival rate in patients with Wnt5a-positive breast cancer was significantly lower than that in patients with Wnt5a-negative breast cancer (P = 0.047). DNA microarray data suggest that only the cytochrome P450 (CYP) pathway was significantly upregulated in MCF-7/Wnt5a (+) cells (P = 0.0440). Additionally, MCF-7/Wnt5a (+) cells displayed reduced sensitivity to the metabolic substrates of CYP, tamoxifen (P < 0.001), paclitaxel (P < 0.001), and cyclophosphamide (P < 0.001). Of note, PIK3CA mutations were not associated with the expression of Wnt5a in breast cancer tissue and culture cells. CONCLUSIONS: In ER-positive breast cancer, Wnt5a upregulates the CYP metabolic pathway and suppresses tamoxifen, paclitaxel, and cyclophosphamide resistance, all of the three, standard treatment methods for ER-positive breast cancer. Wnt5a is thus potentially involved in the poor prognosis of ER-positive breast cancer independently of the PI3K-AKT-mTOR signaling pathway.

Wnt5a-induced cell migration is associated with the aggressiveness of estrogen receptor-positive breast cancer.

Elevated expression of Wnt5a is associated with malignancy, cell invasion, and metastasis. The role of Wnt5a expression in breast cancer remains elusive. We investigated the significance of Wnt5a expression in breast cancer. The relationship between Wnt5a expression and clinicopathologic factors was assessed in invasive breast cancer (n = 178) resected at Hiroshima University Hospital between January 2011 and February 2014. Wnt5a was expressed in 69 of 178 cases (39%) of invasive breast cancer and correlated strongly with estrogen receptor (ER) expression (P < 0.001). Wnt5a expression in ER-positive breast cancer correlated significantly with lymph node metastasis, nuclear grade, and lymphatic invasion. The recurrence-free survival was shorter in breast cancer patients with Wnt5a expression than in those without (P = 0.024). The migratory capacity of ER-positive breast cancer cells increased with constitutive expression of Wnt5a and decreased with Wnt5a knockdown. DNA microarray analysis identified activated leukocyte cell adhesion molecule (ALCAM) as the primary gene induced by Wnt5a. ALCAM was expressed in 69% of Wnt5a-positive but only 27% of Wnt5a-negative cancers (κ = 0.444; P < 0.001). The inhibition of ALCAM reversed the enhanced migratory effect of Wnt5a, confirming the importance of this protein in the migration of ER-positive breast cancer cells. Wnt5a expression is related to high malignancy and a poor prognosis in ER-positive breast cancer. We suspect that Wnt5a expression increases the malignancy of breast cancer by increasing the migratory capacity of cancer cells through the induction of ALCAM expression.

Ability of contrast-enhanced ultrasonography to determine clinical responses of breast cancer to neoadjuvant chemotherapy.

OBJECTIVE: We aimed to determine whether contrast-enhanced ultrasonography can predict the effects of neoadjuvant chemotherapy on breast cancer. METHODS: The clinical responses of 63 consecutive patients with breast cancer (T1-4, N0-1, M0) to neoadjuvant chemotherapy between October 2012 and May 2015 were assessed using contrast-enhanced magnetic resonance imaging, positron emission tomography/computed tomography and contrast-enhanced ultrasonography. Perfusion parameters for contrast-enhanced ultrasonography were created from time-intensity curves based on enhancement intensity and temporal changes to objectively evaluate contrast-enhanced ultrasonography findings. The sensitivity, specificity and accuracy of contrast-enhanced ultrasonography, magnetic resonance imaging and positron emission tomography/computed tomography to predict a pathological complete response were compared after confirming the pathological findings of surgical specimens. RESULTS: Twenty-three (36.5%) of the 63 patients achieved pathological complete response. The sensitivity, specificity and accuracy of contrast-enhanced ultrasonography for predicting pathological complete response were 95.7% (82.5-99.2%), 77.5% (69.9-79.5%) and 84.1% (74.5-86.7%). The sensitivity of contrast-enhanced ultrasonography was significantly greater than that of magnetic resonance imaging (95.7 vs. 69.6%, P = 0.047). The specificity and accuracy were significantly greater and tended to be greater, respectively, for contrast-enhanced ultrasonography than positron emission tomography/computed tomography (specificity, 77.5 vs. 52.5%, P = 0.02; accuracy, 84.1 vs. 69.8%, P = 0.057). CONCLUSIONS: Contrast-enhanced ultrasonography might serve as a new diagnostic modality when planning therapeutic strategies for patients with breast cancer after neoadjuvant chemotherapy.

Evaluation of Malignancy Grade of Breast Cancer Using Perflubutane-Enhanced Ultrasonography.

Whether the contrast effects of perflubutane on contrast-enhanced ultrasonography can predict the malignancy grade of breast cancer is unknown. We analyzed associations between perfusion parameters created from time-intensity curves based on enhancement intensity and temporal changes in contrast-enhanced ultrasonography and clinicopathologic factors in 100 consecutive patients with invasive breast cancer. Values of perfusion parameters were significantly greater in estrogen receptor-negative than -positive tumors (peak intensity, p = 0.0002; ascending slope, p = 0.006; area under the curve, p = 0.0006). Variations in the peak intensity of Ki-67 were significantly correlated in all tumors (r = 0.54, p < 0.0001) and in luminal (r = 0.43, p = 0.0002), human epidermal growth factor receptor type 2-positive (r = 0.47, p = 0.047) and triple-negative (r = 0.55, p = 0.043) tumors. Perfusion parameters on contrast-enhanced ultrasonography can provide excellent predictive value for high-grade malignancy and might help to determine appropriate therapeutic strategies.

Role of FDG-PET/CT in prediction of underestimation of invasive breast cancer in cases of ductal carcinoma in situ diagnosed at needle biopsy.

BACKGROUND: The aim of this study was to evaluate the significance of FDG-PET/CT for predicting the underestimation of invasive breast cancer in cases of DCIS at needle biopsy. PATIENTS AND METHODS: Of 83 consecutive cases with diagnoses of DCIS at primary needle biopsy who underwent curative surgery between 2010 and 2013, the association between the SUVmax on FDG-PET/CT before excision and the underestimation of invasive breast cancer was examined. RESULTS: There were 29 (34.9%) cases diagnosed to have invasive breast cancer at excision. Receiver operating characteristics curve analysis showed the cutoff value of the SUVmax to predict underestimation of invasive breast cancer was 1.6. The rates of underestimation were 61.5% for patients with a tumor of SUVmax > 1.6 and 11.4% for patients with a tumor of SUVmax ≤ 1.6 (P < .001). A high value of SUVmax was significantly associated with symptomatic presentation (P < .001), palpability (P < .001), mass formation (P = .013), high Breast Imaging Reporting and Data System category (P = .011), and core needle biopsy (P = .007). In multivariate analysis, high SUVmax was only a significant predictive factor of underestimation of invasive breast cancer (hazard ratio, 11.7; 95% confidence interval, 3.70-37.0; P < .001). CONCLUSION: SUVmax on FDG-PET/CT is useful for predicting the underestimation of invasive breast cancer in cases of DCIS at needle biopsy.

A case of an acute cervicomediastinal hematoma secondary to the spontaneous rupture of a parathyroid adenoma.

We herein report the case of a patient with an acute cervicomediastinal hematoma secondary to the spontaneous rupture of a parathyroid adenoma. A 47-year-old female presented with swelling and pain in the neck. She had no history of trauma or of having undergone any medical or odontological procedures. An ultrasound examination revealed the presence of an obscure mass located behind the right lobe of the thyroid gland. A computed tomography scan showed the presence of a low-density lesion extending from the retropharynx to the mediastinum, a high-density lesion located behind the right lobe of the thyroid gland and a right pleural effusion. Because the patient's neck swelling and anemia gradually worsened, she underwent emergency surgery. The neck was found to be swollen due to a hematoma; however, no abscesses were detected in the operative field.Thoracoscopy of the right chest showed no active bleeding. The fragmented mass was histopathologically diagnosed as a parathyroid adenoma with acute hemorrhage, which is quite rare. Our experience suggests that, in patients with severe cervicomediastinal hematomas without any trauma or trigger, a diagnosis of spontaneous rupture of a parathyroid gland lesion should be considered.