Patient Preference for Surgical Methods for Ipsilateral Breast Tumor Recurrence.

BACKGROUND: Mastectomy has been the standard surgical treatment for ipsilateral breast tumor recurrence (IBTR). Recently, there has been growing interest in repeat breast-conserving surgery (rBCS) for IBTR among breast surgeons; however, there is currently little information regarding patient preferences for surgical procedure for IBTR. The purpose of this study was to evaluate preference for surgical procedure (mastectomy vs. rBCS) among breast cancer patients who had undergone salvage surgery for IBTR. METHODS: Overall, 100 breast cancer patients who had undergone salvage surgery for IBTR were asked about their preferred surgical methods for IBTR and the reason. The association of patient preference and the reasons related to various clinical and pathological factors were assessed. RESULTS: Of the 100 respondents, only 11 patients (11%) preferred rBCS. Patients who had undergone rBCS and radiotherapy for IBTR were significantly more likely to prefer to undergo rBCS than other groups (p = 0.030). The most frequent reason for choosing rBCS was the patient's desire to minimize breast deformity and surgical wounds. CONCLUSIONS: Our study revealed that there is a low rate of patients who opt to undergo rBCS among patients who had undergone salvage surgery for IBTR. Discrepancies in perceptions regarding the surgical procedure for IBTR between patients and their surgeons may exist.

A comparative, randomised MRI study of the physiological and appetitive responses to gelling (alginate) and non-gelling nasogastric tube feeds in healthy men.

Inclusion in nasogastric tube feeds (NGTF) of acid-sensitive, seaweed-derived alginate, expected to form a reversible gel in the stomach, may create a more normal intragastric state and modified gastrointestinal responses. This may ameliorate NGTF-associated risk of diarrhoea, upper gastrointestinal symptoms and appetite suppression. In a randomised, crossover, comparison study, undertaken in twelve healthy males, an alginate-containing feed (F + ALG) or one that was alginate-free (F-ALG) (300 ml) was given over 1 h with a 7-14-d washout period between treatments. Baseline and for 4-h post-feed initiation, MRI measurements were made to establish small bowel water content (SBWC), gastric contents volume (GCV) and appearance, and superior mesenteric artery blood flux. Blood glucose and gut peptides were measured. Subjective appetite and upper gastrointestinal symptoms scores were obtained. Ad libitum pasta consumption 3-h post-feeding was measured. F + ALG exhibited a gastric appearance consistent with gelling surrounded by a freely mobile water halo. Significant main effects of feed were seen for SBWC (P = 0·03) and peptide YY (PYY) (P = 0·004) which were attributed to generally higher values for SBWC with F + ALG (max difference between adjusted means 72 ml at 210 min) and generally lower values for PYY with F + ALG. GCV showed a faster reduction with F + ALG, less between-participant variation and a feed-by-time interaction (P = 0·04). Feed-by-time interactions were also seen with glucagon-like-peptide 1 (GLP-1) (P = 0·02) and glucose-dependent insulinotropic polypeptide (GIP) (P = 0·002), both showing a blunted response with F + ALG. Apparent intragastric gelling with F + ALG and subsequent differences in gastrointestinal and endocrine responses have been demonstrated between an alginate-containing and alginate-free feed.

Decreased expression of T-cell-associated immune markers predicts poor prognosis in patients with follicular lymphoma.

We previously examined the utility of rituximab-bendamustine (RB) in patients with follicular lymphoma (FL) exhibiting less than optimal responses to 2 cycles of the R-CHOP chemotherapy regimen. The aim of this study was to identify molecular biomarkers that can predict prognosis in RB-treated patients in the context of the prospective cohort. We first analyzed the mutational status of 410 genes in diagnostic tumor specimens by target capture and Sanger sequencing. CREBBP, KMT2D, MEF2B, BCL2, EZH2, and CARD11 were recurrently mutated as reported before, however none was predictive for progression-free survival (PFS) in the RB-treated patients (n = 34). A gene expression analysis by nCounter including 800 genes associated with carcinogenesis and/or the immune response showed that expression levels of CD8+ T-cell markers and half of the genes regulating Th1 and Th2 responses were significantly lower in progression of disease within the 24-mo (POD24) group (n = 8) than in the no POD24 group (n = 31). Collectively, we selected 10 genes (TBX21, CXCR3, CCR4, CD8A, CD8B, GZMM, FLT3LG, CD3E, EOMES, GZMK), and generated an immune infiltration score (IIS) for predicting PFS using principal component analysis, which dichotomized the RB-treated patients into immune IIShigh (n = 19) and IISlow (n = 20) groups. The 3-y PFS rate was significantly lower in the IISlow group than in the IIShigh group (50.0% [95% CI: 27.1-69.2%] vs. 84.2% [95% CI: 58.7-94.6%], P = .0237). Furthermore, the IIS was correlates with absolute lymphocyte counts at diagnosis (r = 0.460, P = .00355). These results suggest that the T-cell-associated immune markers could be useful to predict prognosis in RB-treated FL patients. (UMIN:000 013 795, jRCT:051 180 181).

Estimating Distributions of Parameters in Nonlinear State Space Models with Replica Exchange Particle Marginal Metropolis-Hastings Method.

Extracting latent nonlinear dynamics from observed time-series data is important for understanding a dynamic system against the background of the observed data. A state space model is a probabilistic graphical model for time-series data, which describes the probabilistic dependence between latent variables at subsequent times and between latent variables and observations. Since, in many situations, the values of the parameters in the state space model are unknown, estimating the parameters from observations is an important task. The particle marginal Metropolis-Hastings (PMMH) method is a method for estimating the marginal posterior distribution of parameters obtained by marginalization over the distribution of latent variables in the state space model. Although, in principle, we can estimate the marginal posterior distribution of parameters by iterating this method infinitely, the estimated result depends on the initial values for a finite number of times in practice. In this paper, we propose a replica exchange particle marginal Metropolis-Hastings (REPMMH) method as a method to improve this problem by combining the PMMH method with the replica exchange method. By using the proposed method, we simultaneously realize a global search at a high temperature and a local fine search at a low temperature. We evaluate the proposed method using simulated data obtained from the Izhikevich neuron model and Lévy-driven stochastic volatility model, and we show that the proposed REPMMH method improves the problem of the initial value dependence in the PMMH method, and realizes efficient sampling of parameters in the state space models compared with existing methods.

Treadmill running prevents atrophy differently in fast- versus slow-twitch muscles in a rat model of rheumatoid arthritis.

To investigate the effects of treadmill running on two different types of skeletal muscle, we established a rat model of collagen-induced arthritis (CIA). The skeletal muscles studied were the extensor digitorum longus (EDL), which is rich in fast-twitch muscle fibers, and the soleus, which is rich in slow-twitch muscle fibers. The histological and transcriptional changes in these muscles at 14 and 44 days after immunosensitization were compared between rats that were forced to exercise (CIA ex group) and free-reared CIA rats (CIA no group). Change in protein expression was examined on day 14 after a single bout of treadmill running. Treadmill running had different effects on the relative muscle weight and total and fiber cross-sectional areas in each muscle type. In the soleus, it prevented muscle atrophy. Transcriptional analysis revealed increased eukaryotic translation initiation factor 4E (Eif4e) expression on day 14 and increased Atrogin-1 and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) expression on day 44 in the soleus in the CIA ex group, suggesting an interaction between muscle type and exercise. A single bout of treadmill running increased the level of Eif4e and p70S6K and decreased that of Atrogin-1 in the soleus on day 14. Treadmill running prevented muscle atrophy in the soleus in a rat model of rheumatoid arthritis via activation of mitochondrial function, as evidenced by increased PGC-1α expression.

Therapeutic significance of D3 dissection for low rectal cancer: a comparison of dissections between the lateral pelvic lymph nodes and the lymph nodes along the root of the inferior mesenteric artery in a multicenter retrospective cohort study.

PURPOSE: D3 dissection is the standard treatment modality for locally advanced low rectal cancer in Japan. The benefit of lateral pelvic lymph node (LPLN) dissection (LPLND) and lymph nodes along the root of inferior mesenteric artery (253 LN) dissection (253 LND) for low rectal cancer has often been studied separately, and few studies have investigated their benefit in the same cohort. This study aimed to clarify the therapeutic significance of dissection of the LPLN in comparison to that of dissection of the 253 LN for low rectal cancer. METHODS: We retrospectively evaluated 3508 patients with treatment-naïve stage I-III low rectal cancer who underwent mesorectal excision between 1997 and 2012. They were identified from the Japanese Study Group for Postoperative Follow-Up of Colorectal Cancer database. The rates of metastasis, survival, and therapeutic value index (5-year overall survival (OS) rate multiplied by metastatic rate for lymph node metastasis) were compared between LPLN and 253 LN. RESULTS: The rates of LPLN metastasis and 253 LN metastasis were 17.9% and 1.5%, respectively. The 5-year OS was significantly different between patients with and without LPLN metastasis (55.0% vs 85.5%, P < 0.0001) and between patients with and without 253 LN metastasis (36.2% vs 83.3%, P < 0.0001). The therapeutic value indexes of LPLN and 253 LN were 9.85 and 0.54, respectively. CONCLUSIONS: LPLND may have more therapeutic value than 253 LND for patients with treatment-naïve low rectal cancer, although both the patients with LPLN metastasis and those with 253 LN metastasis remained to have poor prognosis.

Clinical outcomes after medial patellofemoral ligament reconstruction: an analysis of changes in the patellofemoral joint alignment.

PURPOSE: Medial patellofemoral ligament (MPFL) reconstruction using the hamstring tendon is widely performed to treat recurrent patellar dislocation. MPFL reconstruction includes a post-operative process of necrosis and reperfusion of the hamstring tendon graft. We hypothesise that the patella gradually shifts laterally because of this process, ultimately affecting the patellofemoral joint alignment. This study aimed to analyse the chronological changes in the patellofemoral joint alignment and the outcomes of MPFL reconstruction. METHODS: In this retrospective case-series study, the Knee Society, Lysholm, and Kujala scores were evaluated in 24 consecutive patients (27 knees). To evaluate patellar tracking defects, radiographic indices including the tilting angle, the lateral shift ratio, and the congruence angle were measured before, immediately after, and three, 12, and 36 months after MPFL reconstruction. RESULTS: Post-operative Kujala, Knee Society, and Lysholm scores for the study population significantly improved relative to the pre-operative scores. The tilting and congruence angles at three months after the operation significantly increased relative to those recorded immediately after the operation. The tilting and congruence angles were not significantly different at three, 12, and 36 months after the operation. CONCLUSIONS: The post-operative outcomes of MPFL reconstruction for recurrent patellar dislocation were favourable. Insufficient union between the bone tunnel and tendon graft, along with an elongation of the necrotic tendon graft, may change the alignment of the patellofemoral joint within three months after the operation. Therefore, we believe it is necessary to refrain from knee rotation that places lateral stress on the patella until three months after the operation.

Sustained Hypoxia Suppresses Joint Destruction in a Rat Model of Rheumatoid Arthritis via Negative Feedback of Hypoxia Inducible Factor-1α.

Hypoxia inducible factor (HIF)-1α has been implicated in the pathogenesis of rheumatoid arthritis (RA). HIF-1α, which is expressed in hypoxia, is reversely suppressed in sustained hypoxia. Here, we investigated the inhibitory effect of hypoxia on arthritis by controlling HIF-1α. Rheumatoid fibroblast-like synoviocyte MH7A cells were cultured in a hypoxic incubator for up to 72 h to evaluate the expression of HIF-1. Furthermore, collagen-induced arthritis (CIA) model rats were maintained under 12% hypoxia in a hypoxic chamber for 28 days to evaluate the effect on arthritis. In MH7A cells, HIF-1α protein level increased at 3 h, peaked at 6 h, and subsequently decreased in a time-dependent manner. The transcription of pro-inflammatory cytokines increased at 1 h; however, they decreased after 3 h (p < 0.05). Deferoxamine-mediated activation of HIF-1α abolished the inhibitory effect of sustained hypoxia on pro-inflammatory cytokines. In the rat CIA model, the onset of joint swelling was delayed and arthritis was suppressed in the hypoxia group compared with the normoxia group (p < 0.05). Histologically, joint destruction was suppressed primarily in the cartilage. Thus, sustained hypoxia may represent a new safe, and potent therapeutic approach for high-risk patients with RA by suppressing HIF-1α expression.

Tumour-immune microenvironment in duodenal-type follicular lymphoma.

Despite duodenal-type follicular lymphoma (DTFL) being morphologically, immunophenotypically and genetically indistinguishable from nodal FL (nFL), this entity typically shows a significantly better prognosis. Here, we analysed the tumour immune microenvironments of diagnostic specimens from patients with DTFL (n = 30), limited-stage FL (LSFL; n = 19) and advanced-stage FL (ASFL; n = 31). The mean number of CD8+ tumour-infiltrating lymphocytes (TILs) in the neoplastic follicles was higher in DTFL (1,827/mm2 ) than in LSFL (1,150/mm2 ) and ASFL (1,188/mm2 ) (P = 0·002, P = 0·002, respectively). In addition, CD8+ PD1-  T cells with non-exhausting phenotype were more abundant in the peripheral blood (PB) of DTFL than in LSFL and ASFL, indicating that DTFL may exhibit a better and longer-lasting T cell-mediated immune response. Moreover, whereas FOXP3+ CTLA-4+ effector regulatory T cells (eTregs) were rarely observed in the neoplastic follicles of DTFL (mean: 12/mm2 ), they were more abundant in LSFL (78/mm2 ) and ASFL (109/mm2 ) (P = 2·80 × 10-5 , P = 4·74 × 10-8 , respectively), and the numbers of eTregs correlated inversely with those of CD8+ TILs (r = -0267; P = 0·018). Furthermore, DTFL showed significantly fewer circulating FOXP3hi CD45RA- CD25hi eTregs (0·146%) than ASFL (0·497%) and healthy controls (0·639%) (P = 0·0003, P = 6·79 × 10-7 , respectively). These results suggest that the augmented anti-tumour immune reactions may contribute to a better prognosis on DTFL.

Nadir lymphocytopenia as a risk factor of bloodstream infection during molecular targeting pharmacotherapy in multiple myeloma.

OBJECTIVE: Molecular targeting pharmacotherapy (MTP) with proteasome inhibitors and immunomodulatory drugs has led to a remarkable improvement in the effectiveness of multiple myeloma (MM) therapy. However, the effect of MTP on the occurrence of infections in patients with MM remains unclear. We aimed to identify the incidence of and risk factors for bloodstream infection (BSI) in patients with MM undergoing MTP. MATERIALS AND METHODS: We conducted a retrospective cohort study. We reviewed the medical records of 108 inpatients with MM at the National Defense Medical College Hospital between January 2010 and January 2017. Univariate and multivariate analyses were conducted to identify risk factors for BSI. RESULTS: The incidence of BSI in patients with MM receiving MTP (n = 188) was 6.9%, which was significantly lower than the 52.6% in patients receiving cytotoxic chemotherapy (n = 57). We found that the most important risk factor for BSI in patients receiving MTP was lymphocytopenia at nadir (< 200/µL). In contrast, the risk factor for BSI in patients receiving cytotoxic chemotherapy was the number of regimens performed. CONCLUSION: Our study suggests that the incidence of BSI is lower in patients with MM receiving MTP than in those receiving cytotoxic chemotherapy and that lymphocytopenia at nadir may be a risk factor for BSI in patients with MM receiving MTP. Since previous clinical trials with MTP showed that the frequency of myelosuppression and infections was high in the Japanese population, these findings might provide novel insights into MTP for Japanese patients with MM.
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Treadmill Running in Established Phase Arthritis Inhibits Joint Destruction in Rat Rheumatoid Arthritis Models.

Exercise therapy inhibits joint destruction by suppressing pro-inflammatory cytokines. The efficacy of pharmacotherapy for rheumatoid arthritis differs depending on the phase of the disease, but that of exercise therapy for each phase is unknown. We assessed the differences in the efficacy of treadmill running on rheumatoid arthritis at various phases, using rat rheumatoid arthritis models. Rats with collagen-induced arthritis were used as rheumatoid arthritis models, and the phase after immunization was divided as pre-arthritis and established phases. Histologically, the groups with forced treadmill running in the established phase had significantly inhibited joint destruction compared with the other groups. The group with forced treadmill running in only the established phase had significantly better bone morphometry and reduced expression of connexin 43 and tumor necrosis factor α in the synovial membranes compared with the no treadmill group. Furthermore, few cells were positive for cathepsin K immunostaining in the groups with forced treadmill running in the established phase. Our results suggest that the efficacy of exercise therapy may differ depending on rheumatoid arthritis disease activity. Active exercise during phases of decreased disease activity may effectively inhibit arthritis and joint destruction.

[Complete Remission of Advanced Gastric Cancer with Tumor Embolism in the Right Gastric Vein Treated with Radical Resection after Chemotherapy].

A 74-year-old man presented to our hospital with the chief complaint of epigastric pain; upper gastrointestinal endoscopy revealed a 7-cm-sized type 3 gastric cancer in the lesser curvature of the lower part of the stomach. Abdominal contrast computed tomography revealed a tumor embolus in the right gastric vein; the preoperative diagnosis was cT4a(SE) N3aH0P0M0, cStage ⅢC. Because the cancer could spread during surgical manipulation, performing a safe radical resection was difficult; therefore, we decided to initiate chemotherapy. The patient received 3 courses of trastuzumab plus CapeOX, which led to reduction of the primarylesion, peri-gastric lymph node, and right gastric vein tumor embolus. Partial remission was achieved after chemotherapy; therefore, distal gastrectomy, D2 lymph node dissection, and Roux-en-Y reconstruction were performed. Histopathological examination did not reveal viable tumor cells in the primarylesion, lymph nodes, or tumor embolus, and the histological effect was Grade 3. Currently, the patient is alive without relapse at 9 months post operation. Advanced gastric cancer accompanied with tumor embolism in the gastric vein is commonly observed in patients with liver metastasis and in those with severely progressed state of cancer; many of these patients have poor prognosis. Preoperative chemotherapymaybe effective in cases in which tumor embolism in the gastric vein is identified through preoperative diagnostic imaging.

[Ethinyl Estradiol Therapy for Postmenopausal Women with Heavily Pre-Treated Endocrine-Responsive Metastatic Breast Cancer].

Ethinyl estradiol(EE2)therapy has been reported to be an effective endocrine therapy for postmenopausal hormone receptor-positive advanced breast cancer, especially in the supposed acquired resistance state. The current study retrospectively investigated the efficacy and safety of EE2 therapy in postmenopausal women with hormone receptor-positive advanced breast cancer who had previously undergone multiple endocrine therapies. Twelve patients were enrolled; median lines of endocrine therapies were seven before EE2. Median PFS was 4.8 months and median overall survival was 10.0 months. Grade 3 adverse event comprised of anorexia in only one patient. EE2 therapy may be considered effective and safe in hormone receptor-positive advanced breast cancer even in late-stage endocrine therapy.

[A Case of Breast Carcinoma with Cartilaginous Differentiation and Distant Metastasis with Complete Response to Post-Operative Chemotherapy].

We report a case of breast cancer with cartilaginous differentiation that responded well to chemotherapy, which completely eliminated distant metastasis. A 63-year-old woman visited our hospital complaining of a large hemorrhagic mass measuring 15 cm in diameter with ulceration of the left breast. Palpation revealed swelling of the left axillary and right supraclavicular (SC)lymph nodes, suggesting breast cancer metastasis. A CT scan revealed metastasis in the right lung measuring 2.5 cm in size. She underwent a total mastectomy with axillary dissection. The pathological findings were as follows; breast carcinoma with cartilaginous differentiation accompanied by a single lymph node metastasi(s 1/21)and skin involvement, ly0, v0, ER(-), PgR(-), HER2 0, Ki-67 80%. Four courses of AC therapy were administered as postoperative chemotherapy, which resulted in a decrease in the size of the SC lymph node to 1 cm. Subsequently, 12 courses of weekly paclitaxel yielded a complete response of the lung and SC lymph node metastasis. Oral administration of S-1 after paclitaxel therapy resulted in no recur- rence for 16 months after the operation.

Outcome of Low-Invasive Local Split-Thickness Lengthening for Iliotibial Band Friction Syndrome.

Conventional surgical methods for iliotibial band friction syndrome (ITBFS) may affect the iliotibial band (ITB), delaying return to sports activities or impeding performance. We have developed a minimally invasive method. This study retrospectively analyzed the outcomes of this procedure in individuals with ITBFS. This study included 34 knees of 31 individuals. Surgery involved lengthening the central part of the ITB by splitting it into a superficial and a deep layer, maintaining the anterior and posterior fibers immediately above the lateral epicondyle. Outcomes included time to resume sports activity, personal best times to run a 5000-m race before and after surgery, and 2-month post-surgery muscle strengths. The mean postoperative time to return to competition was 5.8 weeks. Personal best times of 5000-m race improved in 13 of 17 runners. Two months post-surgery, the mean extensor muscle strengths on the healthy and affected sides did not significantly differ nor did the flexor muscle strengths. In ITBFS, the ITB itself is normal. Lengthening the limited region of the ITB immediately above the lateral femoral epicondyle removes the cause of ITBFS, with a reduction in inflammation. This technique resulted in early return to competition without degrading performance.

Length change patterns and shape of a grafted tendon after anatomical medial patellofemoral ligament reconstruction differs from that in a healthy knee.

PURPOSE: Recurrent patellar dislocation is currently treated with anatomical reconstruction of the medial patellofemoral ligament (MPFL), and favourable postoperative outcomes have been reported. However, it is uncertain if healthy MPFL function is restored by anatomical reconstruction. The hypothesis in this study was that stabilization of the patella following MPFL reconstruction would be improved compared with that before surgery, but that function of the grafted tendon would differ from that of a healthy MPFL. The objective was to analyse the length change patterns of the MPFL before surgery and the grafted tendon after surgery in patients with recurrent patellar dislocation treated with anatomical MPFL reconstruction. METHODS: The subjects were 12 patients (13 knees) in whom recurrent patellar dislocation was treated with anatomical MPFL reconstruction. The length change patterns of the MPFL and reconstructed ligament were analysed at extension and flexion of the knee joint using open MRI. RESULTS: The postoperative grafted tendon length was significantly shorter than that of the preoperative MPFL at knee extension, and significantly longer at 90° and 120° of knee flexion. The postoperative length of the grafted tendon only changed slightly from 0° to 30° of knee flexion, and then significantly decreased at flexion of 30° or more. The morphology of the grafted tendon was linear until 60° knee flexion, but became convex toward the extraarticular side at flexion of 90° or more. CONCLUSION: The grafted tendon length at knee extension was shorter than that of the preoperative MPFL, but there was no significant difference at 30° flexion. These findings suggest that the effect of damping of the patella with a grafted tendon after MPFL reconstruction may differ from that in a healthy knee. In addition, the morphology at 60° knee flexion was improved to linear after surgery, suggesting that ligament morphology at this flexion was normalized by MPFL reconstruction. LEVEL OF EVIDENCE: III.

Treadmill Running Ameliorates Destruction of Articular Cartilage and Subchondral Bone, Not Only Synovitis, in a Rheumatoid Arthritis Rat Model.

We analyzed the influence of treadmill running on rheumatoid arthritis (RA) joints using a collagen-induced arthritis (CIA) rat model. Eight-week-old male Dark Agouti rats were randomly divided into four groups: The control group, treadmill group (30 min/day for 4 weeks from 10-weeks-old), CIA group (induced CIA at 8-weeks-old), and CIA + treadmill group. Destruction of the ankle joint was evaluated by histological analyses. Morphological changes of subchondral bone were analyzed by µ-CT. CIA treatment-induced synovial membrane invasion, articular cartilage destruction, and bone erosion. Treadmill running improved these changes. The synovial membrane in CIA rats produced a large amount of tumor necrosis factor-α and Connexin 43; production was significantly suppressed by treadmill running. On µ-CT of the talus, bone volume fraction (BV/TV) was significantly decreased in the CIA group. Marrow star volume (MSV), an index of bone loss, was significantly increased. These changes were significantly improved by treadmill running. Bone destruction in the talus was significantly increased with CIA and was suppressed by treadmill running. On tartrate-resistant acid phosphate and alkaline phosphatase (TRAP/ALP) staining, the number of osteoclasts around the pannus was decreased by treadmill running. These findings indicate that treadmill running in CIA rats inhibited synovial hyperplasia and joint destruction.

[Bilateral Metastatic Lung Tumor with Different Primary Organs].

A 72-year-old woman with a history of surgery for left breast cancer was found to have sigmoid colon cancer and solitary pulmonary tumor of left upper lobe. We diagnosed adenocarcinoma of the unknown origin by a transbronchial biopsy. We performed left upper segmentectomy and sigmoidectomy. Left pulmonary tumor was diagnosed metastatic lung tumor from breast cancer. A right pulmonary tumor was confirmed by chest computed tomography(CT) after sigmoidectomy. It was also considered to be metastasis from breast cancer and treated with vinorelbine ditartrate. Since no effect was observed by chemotherapy, tumor was surgically removed by wedge resection. Right pulmonary tumor was pathologically diagnosed as metastasis from sigmoid colon cancer. In suspicious case of pulmonary metastases from double cancer, the possibility of different lesions from different primary site should be kept in mind.

[HER2-Positive Breast Cancer with Severe Infusion Reaction to Pertuzumab plus Trastuzumab-A Case Report].

A 64-year-old woman detected a tumor in her left breast in July 2015, and the tumor became exposed and ulcerated in January 2016. Subsequently, the tumor began to bleed, and the patient was admitted to our hospital on an emergency basis in March 2016. A CT scan revealed the presence of a giant tumor in the left breast, accompanied by chest wall infiltration, left axillary lymph node metastasis, and multiple liver and bone metastases. Following needle biopsy, the specimen was diagnosed as Luminal-HER2-type invasive ductal carcinoma, and pertuzumab plus trastuzumab plus docetaxel was administered. Upon administration of 2/3 of the pertuzumab, the patient developed chills. Therefore, the administration rate was reduced; however, the patient experienced palpitations, nausea, tachycardia, and decreased blood pressure at the end of the administration. Pertuzumab was temporarily discontinued, a replenisher was infused, and the symptoms improved within approximately 20 minutes. However, the patient again experienced chills, tachycardia, and decreased blood pressure immediately after reinitiating trastuzumab administration and complained of strong pain at the tumor site. Continuation of chemotherapy was deemed dangerous, and administration was discontinued. It has been reported that infusion reactions to trastuzumab are associated with clinical stage. In this case, the symptoms of the infusion reaction were severe because of the large tumor volume. It is necessary to consider administration of premedication and the administration time of anti-HER2 drugs in cases with high tumor burden such as the current case.