Pain-relieving Effects of Autologous Fat Grafting in Breast Cancer Surgery: A Scoping Review.

Background: Chronic pain is relatively common after breast cancer surgery, including breast reconstruction. Autologous fat grafting (AFG) has gained attention as a novel method for breast reconstruction, and recent clinical studies have also shown effects of AFG on alleviation of chronic pain after breast cancer surgery. Our objective was to conduct a scoping review of studies that have examined these effects with clearly defined clinical outcomes. Methods: A literature search was conducted using three databases: PubMed, MEDLINE, and Google Scholar, following PRISMA guidelines and the Arkesy and O'Malley framework. The search focused on clinical studies of the effects of AFG on chronic pain after breast cancer surgery. All studies reporting functional outcomes, return to work, and secondary surgery in a repeat operation were identified. Results: Of the 148 studies identified in the search, 11 studies with a total of 684 patients were included in the review. The average volume of fat grafted was approximately 128 mL over an average of 1.6 sessions. The most common time point for assessment was 1 year post-AFG. In all studies with an evidence level of 3 or lower, AFG showed positive results in alleviating pain after breast cancer surgery. However, one of the three randomized controlled trials did not show clinically significant effects. Conclusions: Most of the studies examined in this review suggested pain-relieving effects of AFG. However, there was one randomized controlled trial in which these effects were not confirmed, indicating a need for further accumulation of cases and performance of new, well-designed randomized controlled trials.

An Effective Approach to Collecting Lymph Vessels Using a Small Diameter Wire for Lymphaticovenous Anastomosis in Upper Limb Lymphedema.

Lymphaticovenous anastomosis (LVA), which involves connecting lymphatic vessels to veins under a microscope, is widely performed around the world as a surgical treatment for lymphedema due to its relatively low patient burden and consistent efficacy. One of the crucial points of LVA is identifying suitable lymphatic vessels from among many lymphatic vessels and connecting them at the most effective site, but in practice, this is not easy to do. To overcome this issue, we have been able to effectively drain lymph by connecting lymphatic vessels to veins just before the occluded site using a lymphatic wire that was just recently developed in Japan. The device guides the subcutaneous deep collecting lymphatic vessels from the peripheral relatively superficial lymphatic vessels. While this special wire is typically adapted in the lower limbs, we have confirmed its effectiveness in upper limb lymphedema as well. Overall, this approach shows promise for improving the accuracy and success rates of LVA procedures, which can have significant benefits for patients with upper limb lymphedema. In this article, we share our experience using lymphatic wire for upper limb lymphedema cases.

Development and implementation of a decision aid for post-mastectomy breast reconstruction for Japanese women with breast cancer: a field-testing study.

INTRODUCTION: Surgical options for post-mastectomy breast reconstruction (PMBR) have increased and become more diverse. These options may cause difficulty and stress for patients in making the best choice, and this also increases the likelihood of postoperative regret over a particular decision. To solve this issue, implementation of shared decision-making (SDM) using a decision aid (DA) has become of increasing interest. We have created the first prototype DA in Japan. The aim of the current field study was to assess the usability of this DA in promoting effective SDM and avoiding regret over a decision to undergo reconstructive surgery. METHODS: A total of 25 consecutive patients who underwent BR were enrolled in the study, including 13 with SDM using the decision aid (DA + group) and 12 who received standard information (DA- group) before their choice of surgery. The Decision Regret Scale (DRS) were completed after PMBR, whereas SDM Questionnaire (SDM-Q-9) was completed before PMBR. Descriptive and summary statistics were compared to identify differences between the two groups to assess the usability of the DA. RESULTS: The DA + group had significantly higher mean total scores on the SDM-Q-9 (90.2 ± 5.3 vs. 84.1 ± 3.5, P = 0.0034) and DRS (90.3 ± 3.8 vs. 84.3 ± 6.7, P = 0.023), compared to those in the DA- group. CONCLUSION: Use of the DA may cause patients to have a higher level of perceived SDM and less regret, which suggests that the DA helps to facilitate smooth and effective implementation of SDM. We conclude that this type of decision-making approach should be recommended for choice of surgery for PMBR.

Characteristics and distribution of chronic pain after mastectomy and breast reconstruction: a long-term prospective cohort study.

PURPOSE: Chronic pain following breast surgery is a concern for breast cancer survivors; however, few studies have investigated the localization of persistent postoperative pain. We conducted this study to identify the location of pain following breast reconstruction. METHODS: A total of 213 Japanese women undergoing mastectomy only or breast reconstruction with a tissue expander/implant (TE/Imp) or a deep inferior epigastric perforator (DIEP) flap were enrolled in the study. Questionnaires related to pain location were sent to patients at the end of postoperative year (POY) 1 and POY 5. Multiple comparisons of the types of operation and cross-tabulation were made between the two time points. RESULTS: Surveys were completed by 107 of the women. Severe pain in the upper medial breast was significantly more common in POY 1 after DIEP reconstruction than after mastectomy only (P = 0.01), whereas abdominal pain was worse in POY 5 after DIEP reconstruction than after mastectomy only (P = 0.04). Pain in the medial arm and axilla had resolved better after TE/Imp (P = 0.03) and DIEP reconstruction (P = 0.01) than after mastectomy only by POY 5, but the difference between TE/Imp and DIEP reconstruction was not significant. CONCLUSIONS: These results show that localization of prolonged postoperative pain following breast reconstruction differs depending on the surgical strategy.

Risk factors associated with chronic pain after mastectomy: a prospective study with a 5-year follow-up in Japan.

BACKGROUND: Chronic pain is a major complication following breast surgery including breast reconstruction. We previously examined prospective patient-specific and medical/surgical factors that predict chronic pain a year after breast surgery in the Japanese population. Five-year survivorship is essential for breast cancer patients. This report is a 4-year follow-up study following the previous research. METHODS: A follow-up observation study was performed 5 years after breast operations. The subjects were patients who underwent breast surgery, including tissue expander/implant (TE/implant), DIEP procedures and mastectomy only. Pain at 5 years was assessed using the Japanese Version of the Short-Form McGill Pain Questionnaire (SF-MPQ-JV). A multiple linear regression model was used to examine the relationships of clinical factors with chronic pain. RESULTS: Questionnaires were completed by 132 subjects. No factor related to chronic pain was significantly related to the MPQ pain ratings. Among patient characteristics, a psychotic or neurological medical history was related to significantly lower visual analog scale (p = 0.02) and present pain index (p = 0.04) scores. A history of chemotherapy and/or hormone therapy was significantly associated with the frequency of use of pain medication postoperatively (p = 0.05) and effect on the social life of the patients (p = 0.02). CONCLUSIONS: A psychotic or neurological history and a history of chemotherapy and/or hormone therapy were identified as risk factors for chronic pain after breast surgery, but the type of operation was not associated with chronic pain.

Effectiveness of eribulin as first-line or second-line chemotherapy for HER2-negative hormone-resistant advanced or metastatic breast cancer: findings from the multi-institutional, prospective, observational KBCRN A001: E-SPEC study.

BACKGROUND: The optimal positioning of eribulin treatment remains unclear. This study aimed to investigate the effectiveness of eribulin administration as first- and second-line chemotherapy in patients with endocrine-resistant advanced or metastatic breast cancer (AMBC) in the real-world clinical setting. METHODS: This multi-institutional prospective cohort study enrolled patients with triple-negative AMBC or estrogen receptor-positive AMBC refractory to at least one previous endocrine therapy. The overall survival (OS) from the start of first-line (OS1) and second-line chemotherapy (OS2) was assessed. Data analysis included real-world chemotherapy sequences of first- to third-line chemotherapy regimens. The adjusted hazard ratio (HR) with 95% confidence interval (CI) for treatment regimen comparison was calculated using a stratified proportional hazards model. RESULTS: Among 201 patients enrolled, 180 were included in the final analysis. Eribulin was administered as first- and second-line chemotherapy to 46 (26.6%) and 70 (47.9%) patients, respectively. Median OS1 and OS2 were 2.25 (95% CI 1.07-2.68) and 1.75 (95% CI, 1.28-2.45) years for first- and second-line eribulin, respectively. Oral 5-FU followed by eribulin had a numerically longer OS1 (2.84 years) than the other sequences. Among patients who proceeded to second-line or later chemotherapy, the median OS1 for those treated with anthracycline or taxane as first- or second-line (n = 98) was 2.56 years (95% CI 2.27-2.74), while it was 2.87 years (95% CI 2.20-4.32) for those who avoided anthracycline and taxane as first- and second-line (n = 48) (adjusted HR, 1.20; 95% CI 0.70-2.06). In the exploratory analysis, OS1 was 2.55 (95% CI 2.14-2.75) and 2.91 years (95% CI 2.61-4.32) for those aged < 65 and ≥ 65 years, respectively (adjusted HR of ≥ 65, 0.91; 95% CI 0.56-1.46). CONCLUSIONS: Eribulin or oral 5-FU administration in first- and second-line chemotherapy without anthracycline/taxane was acceptable in the real-world setting. TRIAL REGISTRATION: This study is registered with Clinical Trials.gov (NCT 02,551,263).

[Clinical Efficacy of Paclitaxel plus Bevacizumab Combination Therapy for Bone Marrow Carcinomatosis Arising from Breast Cancer - A Case Report].

We report a case of a 42-year-old woman with bone marrow carcinomatosis in the course of metastatic breast cancer who responded well to paclitaxel plus bevacizumab(PTX plus Bev)combination therapy. Four years after initial breast conserving surgery, she was admitted to our hospital with back pain and general malaise and was diagnosed as multiple bone metastases with bone marrow carcinomatosis originating from previous breast cancer(ER+/HER2-). While administering denosumab, we initiated systemic chemotherapy with PTX plus Bev. There has been no sign of progression at 1 year after beginning the treatment. Therefore, we conclude that PTX plus Bev combination therapy could be effective and sustainable treatment for bone marrow carcinomatosis arising from metastatic breast cancer.

[Clinical Efficacy of Alternate-Day S-1/Letrozole Combination Therapy for Advanced Breast Cancer with Gastric Metastasis--A Case Report].

We report a case of Stage IV breast cancer in a 62-year-old woman who responded well to alternate-day S-1/letrozole combination therapy. She was admitted to our hospital because of appetite loss and vomiting, and was diagnosed with invasive lobular carcinoma (ER+/HER2-) with gastric metastasis. After gastrointestinal stenting was performed, we initiated oral administration of S-1 (100 mg/body) and letrozole (2.5 mg) as systemic therapy. To reduce adverse effects, we administered S-1 on alternate days. Computed tomography and endoscopic examination revealed that the patient has been showing partial response since 1 year after initiating treatment. Therefore, we conclude that alternate-day S-1/letrozole combination therapy could be an effective and sustainable treatment for advanced ER-positive, HER2-negative breast cancer.

Prevalence and risk factors of bone metastasis and skeletal related events in patients with primary breast cancer in Japan.

BACKGROUND: Bone metastasis (BM) is important for studying systemic spread of breast cancer. It often causes skeletal-related events (SREs) that worsen quality of life. We investigated the prevalence and risk factors for BM and SRE using a dataset from the Breast Oncology Research Network (BORN) in Japan. PATIENTS AND METHODS: We collected data on primary breast cancer patients with node-positive or node-negative disease at intermediate to high risk of recurrence. The risk factors affecting the BM-free rate, SRE-free rate and overall survival were analyzed by using the Cox proportional hazard model. RESULTS: Data of 1,779 patients who were diagnosed with breast cancer during 2003-2005 were collected from the BORN and 1,708 cases were used for analysis. The median follow-up duration was 5.71 years. BM developed in 193 cases (11.3 %) and the BM-free rate at 5 years was 89.2 %. The annual hazard ratio of BM development differs remarkably according to the tumor subtype. SREs occurred in 133 (68.9 %) out of 193 patients and the SRE-free rate at 5 years was 92.6 %. In the multivariate analysis, clinical stage (P < 0.0001), number of lymph node (LN) metastases (P = 0.0029), tumor subtype (P = 0.034) and progesterone receptor status (P = 0.038) were independently significant risk factors for BM-free rate, but only clinical stage (P < 0.0001) and number of LN metastases (P = 0.0004) significantly correlated with SRE-free rate. CONCLUSIONS: This retrospective study clarifies the prevalence and risk factors for BM and SRE in Japanese breast cancer patients. Our results show the importance of considering subtype in the care of BM and SRE.

The first symbiont-free genome sequence of marine red alga, Susabi-nori (Pyropia yezoensis).

Nori, a marine red alga, is one of the most profitable mariculture crops in the world. However, the biological properties of this macroalga are poorly understood at the molecular level. In this study, we determined the draft genome sequence of susabi-nori (Pyropia yezoensis) using next-generation sequencing platforms. For sequencing, thalli of P. yezoensis were washed to remove bacteria attached on the cell surface and enzymatically prepared as purified protoplasts. The assembled contig size of the P. yezoensis nuclear genome was approximately 43 megabases (Mb), which is an order of magnitude smaller than the previously estimated genome size. A total of 10,327 gene models were predicted and about 60% of the genes validated lack introns and the other genes have shorter introns compared to large-genome algae, which is consistent with the compact size of the P. yezoensis genome. A sequence homology search showed that 3,611 genes (35%) are functionally unknown and only 2,069 gene groups are in common with those of the unicellular red alga, Cyanidioschyzon merolae. As color trait determinants of red algae, light-harvesting genes involved in the phycobilisome were predicted from the P. yezoensis nuclear genome. In particular, we found a second homolog of phycobilisome-degradation gene, which is usually chloroplast-encoded, possibly providing a novel target for color fading of susabi-nori in aquaculture. These findings shed light on unexplained features of macroalgal genes and genomes, and suggest that the genome of P. yezoensis is a promising model genome of marine red algae.

A second generation genetic linkage map of Japanese flounder (Paralichthys olivaceus).

BACKGROUND: Japanese flounder (Paralichthys olivaceus) is one of the most economically important marine species in Northeast Asia. Information on genetic markers associated with quantitative trait loci (QTL) can be used in breeding programs to identify and select individuals carrying desired traits. Commercial production of Japanese flounder could be increased by developing disease-resistant fish and improving commercially important traits. Previous maps have been constructed with AFLP markers and a limited number of microsatellite markers. In this study, improved genetic linkage maps are presented. In contrast with previous studies, these maps were built mainly with a large number of codominant markers so they can potentially be used to analyze different families and populations. RESULTS: Sex-specific genetic linkage maps were constructed for the Japanese flounder including a total of 1,375 markers [1,268 microsatellites, 105 single nucleotide polymorphisms (SNPs) and two genes]; 1,167 markers are linked to the male map and 1,067 markers are linked to the female map. The lengths of the male and female maps are 1,147.7 cM and 833.8 cM, respectively. Based on estimations of map lengths, the female and male maps covered 79 and 82% of the genome, respectively. Recombination ratio in the new maps revealed F:M of 1:0.7. All linkage groups in the maps presented large differences in the location of sex-specific recombination hot-spots. CONCLUSIONS: The improved genetic linkage maps are very useful for QTL analyses and marker-assisted selection (MAS) breeding programs for economically important traits in Japanese flounder. In addition, SNP flanking sequences were blasted against Tetraodon nigroviridis (puffer fish) and Danio rerio (zebrafish), and synteny analysis has been carried out. The ability to detect synteny among species or genera based on homology analysis of SNP flanking sequences may provide opportunities to complement initial QTL experiments with candidate gene approaches from homologous chromosomal locations identified in related model organisms.

Genetic linkage map of the loach Misgurnus anguillicaudatus (Teleostei: Cobitidae).

In the present study, the first genetic linkage map of the loach Misgurnus anguillicaudatus was constructed with 164 microsatellite markers and a color locus, and it included 155 newly developed markers. A total of 159 microsatellite markers and a color locus were mapped in 27 linkage groups (LGs). The female map covered 784.5 cM with 153 microsatellite markers and a color locus, whereas the male map covered 662.2 cM with 119 microsatellite markers. The centromeric position in each LG was estimated by marker-centromere mapping based on half-tetrad analysis. In 4 LGs (LG2, LG3, LG4, and LG5), the centromere was estimated at the intermediate region. In LG1, LG11, and LG12, the centromere was estimated to shift from the sub-intermediate region to the end (telomeric). The number of these LGs (7) was identical to the collective number of bi-arm metacentric (5) and sub-metacentric chromosome (2) of the haploid chromosome set (n = 5) of the loach. In the other LGs, the position of the centromere was estimated at the end or outside. These results indicate satisfactory compliance between the linkage map and the chromosome set. Our map would cover approximately almost the entire loach genome because most markers were successfully mapped.

Endometrial carcinosarcoma presenting as a tibial metastasis.

Metastasis to a lower-extremity bone is an extremely rare event in patients with endometrial carcinoma. A 64-year-old woman presented with progressive right leg pain but no gynecologic complaints. A diagnostic workup revealed primary endometrial carcinosarcoma with an isolated tibial metastasis. Though the patient received only local irradiation to the tibial lesion, complete resolution of symptoms resulted. Six months after the radiotherapy, the intraabdominal disease progressed and the patient died. We note that tibial metastasis is one of the possible presenting symptoms in patients with endometrial malignant tumors. Irradiation can improve their quality of life and so may be effective in the management of symptomatic tibial metastasis.