Spontaneous regression of breast lymphoproliferative disorders after withdrawal of methotrexate in rheumatoid arthritis patients with Epstein-Barr virus infection: a case report and review of the literature.

BACKGROUND: Lymphoproliferative disorder (LPD) has been shown to occur after treatment with methotrexate (MTX). Currently, MTX-LPD has become widely recognized, but its mechanism and prognostic factors remain unclear. CASE PRESENTATION: We report the first case of Epstein-Barr virus (EBV)-associated MTX-LPD of the breast. A 63-year-old Asian woman with long-term rheumatoid arthritis presented to our facility with intermittent fever. A physical examination revealed a 3-cm lump in her left breast. She had been taking MTX for the past 15 years. Laboratory studies revealed slightly elevated levels of EBV-viral capsid antigen antibody immunoglobulin G and EBV nuclear antibody. Contrast-enhanced computer tomography revealed a mass in the left breast, a subcutaneous nodule in the abdomen, a mass in the left lung, and a nodule in the left retroperitoneum. The definitive diagnosis was consistent with MTX-LPD merging into an EBV-positive, diffuse large B-cell lymphoma. Six months following the withdrawal of MTX, the breast mass had markedly shrunk and the patient remained in good health for 1 year with no evidence of relapse of LPD. CONCLUSION: MTX-LPD rarely occurs in the breast, and it is difficult to diagnose because there have only been six reported cases of breast MTX-LPD reported in the literature. EBV-positive MTX-LPD tends to regress spontaneously after MTX withdrawal, and our case also had similar results. It is important to make an appropriate diagnosis of MTX-LPD of the breast based on imaging and pathology to determine the appropriate treatment protocol for this rare disorder.

Plasma Levels of Decorin Increased in Patients during the Progression of Breast Cancer.

Decorin (DCN), an extracellular matrix proteoglycan found in tumor surrounding tissues, is a natural inhibitor of tumor cell proliferation and invasion. We conducted a cross-sectional observation study to evaluate the association of the pathological stage with the levels of DCN in plasma or tumor surrounding tissue. Among 118 patients who underwent breast surgery, 35 were designated as carcinoma in situ (Stage 0), 39 were Stage I, and 44 were Stage II or III. The stromal expression of DCN was quantified using a semiquantitative digital image analysis after immunohistochemical staining. The concentration of DCN was evaluated with a specific ELISA. As we have previously shown, stromal DCN expression was attenuated in the patients with Stage I, whereas stromal and plasma DCN was elevated paradoxically in those with Stage II/III. The elevated plasma DCN is an independent predictive factor of Stage II/III by the multivariate logistic regression analysis. The plasma level of DCN was negatively correlated with stromal DCN expression only in patients with advanced disease (Stage II/III). The plasma level of DCN could become a useful biomarker for patients in the advanced stages. Extensive studies and further assessments are warranted for evaluating the prognostic significance and tumor characteristics to understand the clinical significances of stromal and systemic DCN.

Virtual Navigator Real-Time Ultrasound Fusion Imaging with Positron Emission Tomography/Computed Tomography for Preoperative Breast Cancer.

We used virtual navigator real-time ultrasound (US) fusion imaging with 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) to identify a lesion that could not be detected on the US alone in a preoperative breast cancer patient. Of the patient's two lesions of breast cancer, the calcified lesion could not be identified by US alone. By fusing US with 18F-FDG PET/CT, which had been performed in advance, the location of the lesion could be estimated and marked, which benefited planning an appropriate surgery. The fusion of US and 18F-FDG PET/CT was a simple and noninvasive method for identifying the lesions detected by 18F-FDG PET/CT.

Relationship between Prognostic Stage in Breast Cancer and Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography.

This retrospective study examined the relationship between the standardized uptake value max (SUVmax) of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and the prognostic stage of breast cancer. We examined 358 breast cancers in 334 patients who underwent 18F-FDG PET/CT for initial staging between January 2016 and December 2019. We extracted data including SUVmax of 18F-FDG PET and pathological biomarkers, including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and nuclear grade. Anatomical and prognostic stages were determined per the American Joint Committee on Cancer (eighth edition). We examined whether there were statistical differences in SUVmax between each prognostic stage. The mean SUVmax values for clinical prognostic stages were as follow: stage 0, 2.2 ± 1.4; stage IA, 2.6 ± 2.1; stage IB, 4.2 ± 3.5; stage IIA, 5.2 ± 2.8; stage IIB, 7.7 ± 6.7; and stage III + IV, 7.0 ± 4.5. The SUVmax values for pathological prognostic stages were as follows: stage 0, 2.2 ± 1.4; stage IA, 2.8 ± 2.2; stage IB, 5.4 ± 3.6; stage IIA, 6.3 ± 3.1; stage IIB, 9.2 ± 7.5, and stage III + IV, 6.2 ± 5.2. There were significant differences in mean SUVmax between clinical prognostic stage 0 and ≥II (p < 0.001) and I and ≥II (p < 0.001). There were also significant differences in mean SUVmax between pathological prognostic stage 0 and ≥II (p < 0.001) and I and ≥II (p < 0.001). In conclusion, mean SUVmax increased with all stages up to prognostic stage IIB, and there were significant differences between several stages. The SUVmax of 18F-FDG PET/CT may contribute to prognostic stage stratification, particularly in early cases of breast cancers.

Study of the protocol used to evaluate skin-flap perfusion in mastectomy based on the characteristics of indocyanine green.

BACKGROUND: Indocyanine green angiography enables real-time visualization of blood vessels at depths of up to 10 mm beneath the body surface, thereby aiding the evaluation of the viability of skin flaps and predicting necrosis in surgical fields requiring good tissue perfusion. Although skin-flap necrosis also occurs in mastectomy without reconstruction, most studies have focused on reconstructive plastic surgery. Several patients undergoing mastectomy are eligible for postoperative adjuvant therapy, but complications can lead to delays in treatment and thus require prevention. However, a lack of a standard protocol for evaluating skin-flap perfusion using indocyanine green necessitates the study of its characteristics to facilitate comparison of the perfusion rate among individuals. METHODS: This retrospective study focused on the characteristics of indocyanine green and established a protocol for indocyanine green angiography using laser-assisted imaging (SPY system) to predict postoperative skin-flap necrosis from intraoperative images of 30 patients who underwent mastectomy without reconstruction. RESULTS: Our protocol predicted postoperative skin-flap necrosis as follows. First, the intravenous dose and concentration were set at 2.5 mg/mL and 0.05 mg/kg, respectively. Second, the timing of measurement was set to 100 s after the entry of indocyanine green into the skin (plateau phase); the analysis pattern was set to single frame. Third, comparisons among individuals were made using relative values. CONCLUSIONS: We analyzed the area of postoperative flap necrosis using this protocol. We found that the intraoperative images showed decreased perfusion in that area, which was useful in predicting skin-flap necrosis, as reported by previous breast reconstruction studies.

Clinical usefulness of the fast protocol of breast diffusion-weighted imaging using 3T magnetic resonance imaging with a 16-channel breast coil.

We aimed to evaluate the usefulness of a fast protocol of diffusion-weighted imaging (DWI) with one excitation using 3T magnetic resonance imaging (MRI) and a 16-channel breast coil. We analyzed 30 lesions from 27 women between February 2020 and June 2020. The visibility score (from 1 = extremely poor to 5 = excellent) and apparent diffusion coefficient (ADC) value between one and four excitations were evaluated by two readers. The image acquisition time was 40 s for one excitation and 1 min 52 s for four excitations. The visibility scores were 4.630 ± 0.718 and 4.267 ± 1.015 for one excitation and 4.730 ± 0.691 and 4.200 ± 1.000 for four excitations by the two readers. There was no significant difference in the visibility (P = 0.184 and P = 0.423), mean ADC value (P = 0.918 and P = 0.417), and minimum ADC value (P = 0.936 and P = 0.443) between one and four excitations by the two readers. Despite the short acquisition time, the visibility score and ADC values of one-excitation DWI were comparable to that with four excitations. Our fast DWI protocol could provide reproducible visibility and ADC value, potentially helping radiologists to efficiently diagnose patients.

Hydronephrosis Caused by Metastatic Breast Cancer.

Breast cancer metastasizes mainly to organs such as bone, lung, and liver, whereas metastases to the peritoneum and urinary tract are rare. Metastasis to the peritoneum or urinary tract may result in renal dysfunction, infection, and painful hydronephrosis. In our hospital, 1,409 breast cancer surgeries were performed between January 2004 and December 2015, and 7 cases of hydronephrosis associated with recurrence were observed. The median age of patients was 69 years (57-79 years). The median time from surgery to diagnosis of hydronephrosis was 47 months (20-70 months). Histology was invasive ductal carcinoma (IDC) in 6 cases and invasive lobular carcinoma (ILC) in 1 case. There were 6 bilateral cases and 1 unilateral case of hydronephrosis. The causes were retroperitoneal metastasis in 5 cases and lymph node metastasis in 2 cases. The hydronephrosis was untreated in 2 cases, and treated with a ureteral stent in 2 cases, nephrostomy in 1 case, and nephrostomy due to ureteral stent failure in 2 cases. The median survival from the onset of hydronephrosis was 12 months (3-57 months). Although the probability of hydronephrosis in breast cancer recurrence was not high, care must be taken to avoid renal dysfunction, infection, or pain, which may require treatment.

Predictors for upstaging of ductal carcinoma in situ (DCIS) to invasive carcinoma in non-mass-type DCIS.

Preoperatively diagnosed ductal carcinoma in situ (DCIS) is sometimes upstaged to invasive cancer by postoperative pathological examination. Various preoperative factors associated with upstaging to invasive cancer have been reported; however, this subject remains to be clarified. DCIS takes various forms on imaging, but many cases show non-mass-type lesions. In non-mass-type DCIS, recognizing the presence of invasion is difficult. To investigate predictors associated with upstaging to invasive cancer more precisely, we examined only non-mass-type DCIS. The present study retrospectively analyzed 101 patients diagnosed with non-mass-type DCIS preoperatively on breast biopsy at our institution between 2007 and 2017. Data were analyzed using Fisher's exact probability test and two-sample t-tests. Multivariate analysis was performed using logistic regression. The results showed that 27 patients (27%) were finally diagnosed with invasive cancer. Univariate analysis revealed abnormal result of palpation on breast examination (P=0.05), comedo necrosis (P=0.05), and HER2 status (P=0.02) as significant predictors. Multivariate analysis revealed an abnormal result of palpation as an independent predictor of invasive cancer underestimation (odds ratio 4.76; confidence interval 1.44-15.7; P=0.01). In conclusion, preoperatively diagnosed non-mass-type DCIS represented an underestimation in approximately 27% of cases. In particular, the presence of a clinically abnormal palpation increases the chance of upstaging to invasive cancer.

[Totally Laparoscopic Stomach-Partitioning Gastrojejunostomy for Gastroduodenal Outlet Obstruction for Elderly Cancer Patients].

We have performed totally laparoscopic stomach-partitioning gastrojejunostomy for gastroduodenal outlet obstruction caused by advanced malignancies in 14 cases. We divided 14 patients into 2 groups according to age at surgery: those<80 years of age and thoseB80 years of age. We compared these 2 groups regarding preoperative status, operative findings, and postoperative course. We found that the stage of cancer in the older group was lower than in the younger group, the number of unresectable factors in the older group were fewer than in the younger group, and the postoperative stay in the older group was shorter than in the younger group. There were no serious postoperative complications in either group and all 14 patients were able to drink or eat the day after surgery. These results suggest that palliative, totally laparoscopic stomachpartitioning gastrojejunostomy may be the best option for elderly cancer patients with gastroduodenal outlet obstruction caused by advanced malignancies, even when their general conditions is poor. We should consider this surgical procedure as soon as possible when the patient decides on palliative treatment.

Efficiency of fluorodeoxyglucose positron emission tomography/computed tomography to predict prognosis in breast cancer patients received neoadjuvant chemotherapy.

Neoadjuvant chemotherapy (NAC) has become a standard therapy for patients with advanced breast cancer. Pathological complete response (pCR) after NAC is an important prognostic indicator, but some patients with pCR continue to experience recurrence. So new predictive and prognostic markers in addition to pCR are needed following NAC for breast cancer. Fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) can evaluate metastases in the entire body simultaneously, and has several potential advantages over conventional imaging modalities. The purpose of this study was to evaluate whether FDG-PET/CT can determine NAC response and whether FDG-PET/CT can be a new prognostic marker. We imaged 83 breast cancer tumors with FDG-PET/CT, ultrasound (US), and magnetic resonance imaging (MRI) to evaluate NAC efficacy. As we previously analyzed 110 breast cancers with FDG PET/CT, we defined a threshold of >1.7 maximum standardized uptake value (SUVmax) as abnormal fluorodeoxyglucose (FDG) uptake. After NAC, 16 (19.3 %) tumors had a complete response, 54 (65.1 %) had a partial response, 11 (13.3 %) showed stable disease, and 2 (2.4 %) showed progressive disease. One of the two patients with progressive disease had bone metastasis detected by FDG-PET/CT and was not operated on. Remote metastases were evident in 2.4 % of patients after NAC as determined by FDG-PET/CT. Overall, 17 patients had pathological complete response (pCR). The sensitivity of abnormal FDG uptake after NAC for non-pCR was 20.3 % and the specificity was 94.7 %. Patients with abnormal FDG uptake after NAC experienced significantly more recurrences (P = 0.004) and more of them died (P = 0.010). Moreover, the difference in disease-free survival was more significant in the estrogen receptor (ER)-negative group. FDG-PET after NAC may be more effective for predicting prognosis than for evaluating treatment response. This tendency was particularly remarkable in ER-negative breast cancer tumors. FDG-PET/CT is useful for reevaluating surgical applicability after NAC.

[Seven Cases of Surgery for Breast Cancer under Tumescent Local Anesthesia].

BACKGROUND: Surgical procedures for breast cancer are usually performed under general anesthesia. However, general anesthesia needs to be avoided in some cases due to patient-related factors such as the presence of comorbid diseases. In these cases, we perform surgery under tumescent local anesthesia(TLA)in our department. SUBJECTS: Seven patients who were diagnosed with breast cancer underwent surgery under TLA instead of general anesthesia due to their comorbidities. RESULTS: The planned surgical procedures were successfully completed under TLA. A shift to general anesthesia could be avoided in all cases. The operative procedures for the breasts included modified radical mastectomy (Bt) in 3 cases and wide excision (Bp) in 4 cases. In addition, axillary lymph node dissection was performed in 2 cases; sampling, in 1 case; sentinel lymph node biopsy, in 2 cases; and no procedure for the axilla, in 2 cases. In terms of anesthesia, 2 cases were managed under TLA alone and 5 cases were managed under TLA combined with epidural anesthesia. Lidocaine was used for local anesthesia and did not reach the maximal permissive dose in all cases. No postoperative complication was observed. No local recurrence or new metastasis was observed during the observation period, which ranged from 1 to 67 months after the surgery. CONCLUSION: These findings demonstrate that surgery for breast cancer under TLA is safe and offers high curability for patients at high risk for complications of general anesthesia.