Absolute Lymphocyte Count as an Independent Prognostic Factor in Metastatic Breast Cancer: A Retrospective Study.

INTRODUCTION: Recently, absolute lymphocyte count (ALC) and neutrophil-to-lymphocyte ratio (NLR) have been reported to be prognostic and/or predictive factors in breast cancer. However, most of the investigations on the relationship between systemic inflammatory markers and prognosis have been conducted perioperatively, with few studies reporting on patients with metastatic or recurrent breast cancer (MBC). Here, we investigated the role of ALC and NLR as prognostic factors of MBC. METHODS: This was a retrospective observational study of patients with MBC treated at the University of Tsukuba Hospital between 2013 and 2020. ALC and NLR clinical data were obtained from the patients' charts. Based on the previous reports, the cutoff value of ALC was set at 1,500/µL and that of NLR, at 3. We investigated the prognostic significance of ALC and NLR. RESULTS: About 80% of the 243 included patients were hormone receptor-positive, 20% were HER2-positive, and 10% were triple negative. The patients were grouped as follows: 114 (46.9%) and 129 (53.1%) in the high and low ALC groups and 145 (59.7%) and 98 (40.3%) in the high and low NLR groups, respectively. The group with high ALC at diagnosis of MBC showed significantly better prognosis (p = 0.002), and the median overall survival (OS) was 70.9 months, as compared with 40.2 months for the low ALC group. On multivariate analysis, visceral metastasis, subtype, and ALC were independent variables for OS; the NLR status was not correlated with OS. CONCLUSIONS: Analysis of real-world data suggests that ALC at diagnosis of MBC is an independent prognostic factor.

Impact of red blood cell distribution width and mean platelet volume in patients with ST-segment elevation myocardial infarction.

The complete blood cell count is one of the most frequently ordered laboratory tests, and many parameters, including red blood cell distribution width (RDW) and mean platelet volume (MPV), are available. The purpose of this study was to investigate the usefulness of the combination of RDW and MPV in patients with ST-segment elevation myocardial infarction (STEMI). Patients with STEMI who underwent primary percutaneous coronary intervention were retrospectively enrolled (n = 229). The association between RDW as well as MPV and cardiovascular events was investigated. The median age was 67 years, and males made up 85% of the sample. Median RDW was 13.6%, and median MPV was 8.2 fL. During a median follow-up period of 528 days (IQR 331.5-920.5), 41 patients died or experienced major adverse cardiac and cerebrovascular events (MACCEs). Patients with RDW ≧ 13.7% had more deaths or MACCEs with marginal significance (p = 0.0799). Patients with MPV ≧ 8.3 fL had significantly more deaths or MACCEs (p = 0.0283). Patients with RDW ≧ 13.7% and MPV ≧ 8.3 fL had significantly more deaths or MACCEs (p = 0.0185). MPV was significantly associated with death or adverse events in patients with STEMI who were treated with primary PCI. RDW had only a weak association with death or adverse events. The results of the combination of MPV and RDW were similar to those of MPV.

Two Cases of Distant Metastasis After Mastectomy for Breast Ductal Carcinoma In Situ.

While the prognosis for ductal carcinoma in situ (DCIS) of the breast is generally excellent, distant metastasis after appropriate local treatment is extremely rare. We experienced two cases of distant metastasis after mastectomy for breast ductal carcinoma in situ. In both cases, the surgical margins were negative, the sentinel nodes were negative for metastasis. The first case was a 67-year-old woman who developed lung metastases four years after mastectomy for high-grade DCIS. The second case was a 34-year-old woman with intermediate-grade DCIS who developed intraductal recurrence localized to the nipple two years after the initial nipple-sparing mastectomy and multiple lung and liver metastases six months later. Both cases developed distant metastases despite appropriate local treatment, without preceding or concurrent invasive local recurrence. Although the probability of distant recurrence is low, it is important to inform patients about the risk of recurrence.

Safety and Efficacy of Compression Therapy to Prevent Chemotherapy-Induced Peripheral Neuropathy in Lower Extremities of Breast Cancer Patients: A Pilot Study.

Background Chemotherapy-induced peripheral neuropathy (CIPN) is a problematic adverse event for breast cancer patients receiving taxane antimitotic agents. We evaluated the effectiveness of compression therapy against CIPN in the lower extremities of breast cancer patients receiving taxanes. Methods Eligible patients scheduled for perioperative treatment with taxanes for early-stage breast cancer were enrolled. Each patient wore latex-free surgical gloves and compression socks, putting on two layers of each 15 minutes before the administration of taxanes and removing them 15 minutes after administration. Peripheral neuropathy (PN) was evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 and the Patient Neurotoxicity Questionnaire (PNQ). The primary endpoint was the incidence of CTCAE version 4.0 grade 2 or higher CIPN in the lower extremities during the entire period of perioperative chemotherapy with taxanes. Results PN assessment by CTCAE in the lower extremities, the primary outcome, showed that 13.3% developed grade 2 sensory disturbances, and 8.3% developed grade 2 motor disturbances. The incidence of CTCAE grade 2 or higher PN in the hands was 26.7% for sensory disturbances and 13.3% for motor disturbances during the entire study period. No patient had grade 3 or higher PN. No adverse events due to compression therapy were observed. Conclusion Compression of the lower extremities with compression socks tended to reduce the incidence of CIPN compared to the general incidence. Compression therapy may help prevent the development of CIPN.

Recurrent severe hypocalcemia following chemotherapy regimen changes in advanced breast cancer: two case reports.

BACKGROUND: As an oncologic emergency related to abnormalities in calcium metabolism, hypercalcemia associated with paraneoplastic syndrome and bone metastases is well known. Meanwhile, the incidence of hypocalcemia is low, except in cases associated with bone-modifying agents used for bone metastases. Hypocalcemia induced by bone-modifying agents typically occurs early after the initial administration, and its incidence can be significantly reduced by preventive administration of calcium and vitamin D3 supplements. CASE REPORT: We report two cases of recurrent severe hypocalcemia occurring during chemotherapy for metastatic breast cancer with multiple bone metastases. Case 1: A 35-year-old Japanese woman developed metastases in the bone, liver, and ovaries during postoperative endocrine therapy for invasive lobular carcinoma of the breast. She underwent chemotherapy and treatment with denosumab. She experienced recurrent episodes of severe hypocalcemia subsequent to a change in the chemotherapy regimen. Case 2: A 65-year-old Japanese woman encountered multiple bone metastases after postoperative anti-human epidermal growth factor receptor 2 therapy and during endocrine therapy for invasive ductal carcinoma of the breast. She underwent anti-human epidermal growth factor receptor 2 therapy and treatment with denosumab. She experienced recurrent severe hypocalcemia subsequent to a change in the chemotherapy regimen to letrozole + lapatinib, trastuzumab emtansine, and lapatinib + capecitabine. CONCLUSIONS: We observed two cases of recurrent severe hypocalcemia in patients with advanced breast cancer and bone metastases after modifications to their therapy regimens. These cases differed from the typical hypocalcemia induced by bone-modifying agents. It is possible that antitumor drugs affect calcium and bone metabolism associated with bone metastases. While these cases are rare, it is crucial for oncologists to be aware of hypocalcemia not only at the initiation of bone-modifying agents but also throughout the entire antitumor therapy, as hypocalcemia can lead to fatal outcomes.

Intestinal ultrasound for intestinal Behçet disease reflects endoscopic activity and histopathological findings.

BACKGROUND/AIMS: Intestinal Behçet disease is typically associated with ileocecal punched-out ulcers and significant morbidity and mortality. Intestinal ultrasound is a noninvasive imaging technique for disease monitoring. However, no previous reports have compared intestinal ultrasound with endoscopic ulcer activity or histopathological findings for intestinal Behçet disease. We evaluated the usefulness of intestinal ultrasound for assessing the activity of ileocecal ulcers in intestinal Behçet disease. METHODS: We retrospectively compared intestinal ultrasound findings with 73 corresponding endoscopic images and 6 resected specimens. The intestinal ultrasound findings were assessed for 7 parameters (bowel wall thickness, vascularity [evaluated using the modified Limberg score with color Doppler], bowel wall stratification, white-plaque sign [strong hyperechogenic lines or spots], mesenteric lymphadenopathy, extramural phlegmons, and fistulas), and endoscopic ulcer activity was classified into active, healing, and scar stages. Histopathological findings were evaluated by consensus among experienced pathologists. RESULTS: Bowel wall thickness (P< 0.001), vascularity (P< 0.001), loss of bowel wall stratification (P= 0.015), and white-plague sign (P= 0.013) were significantly exacerbated in the endoscopic active ulcer stage. Receiver operating characteristic curve analysis revealed that a bowel wall thickness of > 5.5 mm (sensitivity 89.7%, specificity 85.3%) was potentially useful for detecting active lesions. When compared with histopathological findings, an increase in bowel wall thickness reflected the ulcer marginal ridge, and the white-plaque sign reflected the ulcer bottom. CONCLUSIONS: Intestinal ultrasound is useful for monitoring intestinal ulcer activity in intestinal Behçet disease.

Local recurrence of breast cancer histologically resembling Paget disease presumably due to needle tract seeding: a case report.

Seeding of cancer cells along the needle tract during core needle biopsy is a well-known phenomenon, with a reported frequency of between 22 and 50% [Hoorntje et al. in Eur J Surg Oncol 30:520-525, 2004;Liebens et al. in Maturitas 62:113-123, 2009;Diaz et al. in AJR Am J Roentgenol 173:1303-1313, 1999;]. Local recurrence due to needle tract seeding is rare because the immune system eliminates the cancer cells in most cases. In addition, most local recurrences due to needle tract seeding occur as invasive carcinoma after diagnosis of invasive ductal carcinoma of the breast or mucinous carcinoma, and needle tract seeding due to noninvasive carcinoma is uncommon. We herein report a rare case of local breast cancer recurrence histologically resembling Paget disease, presumably due to needle tract seeding after core needle biopsy for diagnosis of ductal carcinoma in situ of the breast. After receiving a diagnosis of ductal carcinoma in situ, the patient underwent skin-sparing mastectomy and breast reconstruction with a latissimus dorsi musculocutaneous flap. The pathological study showed ER/PgR-negative ductal carcinoma in situ, and no postoperative radiation therapy or systemic therapy was administered. Six months after the surgery, the patient had a breast cancer recurrence histologically resembling Paget disease, presumably in the scar of her core needle biopsy. The pathological study showed Paget disease localized in the epidermis, no invasive carcinoma, and no lymph node metastasis. It was morphologically similar to the primary lesion and was diagnosed as a local recurrence due to needle tract seeding.

Doublet or Triplet Antiemetic Prophylaxis for Nausea and Vomiting Induced by Trastuzumab Deruxtecan: an Open-Label, Randomized, and Multicenter Exploratory Phase 2 Study.

Background: Trastuzumab deruxtecan is classified as an anticancer agent that poses a moderate emetic risk in the international guidelines for antiemetic therapy. The guidelines recommend emesis prophylaxis using a two-drug combination therapy comprising a 5-hydroxytryptamine-3 receptor antagonist (5-HT3RA) and dexamethasone (DEX). However, the high incidence of nausea and vomiting associated with trastuzumab deruxtecan is problematic. The National Comprehensive Cancer Network guideline version 1.2023 classified trastuzumab deruxtecan as having a high risk of emesis and changed its recommendation to a triplet regimen including a neurokinin-1 receptor antagonist (NK1RA). However, the emetogenic potential of trastuzumab-deruxtecan and the optimal antiemetic prophylaxis are controversial. Hence, this exploratory phase 2 study aimed to assess the efficacy and safety of treatment comprising 5-HT3RA and DEX with or without a NK1RA in preventing trastuzumab deruxtecan-induced nausea and vomiting. Methods: We conducted an open-label and randomized exploratory phase 2 study at 14 centers in Japan. Patients with breast cancer who were scheduled to receive trastuzumab deruxtecan were enrolled in this study. The patients were randomly assigned to receive granisetron and DEX (arm GD) or granisetron, DEX, and aprepitant (fosaprepitant; arm GDA). The primary endpoint was complete response (CR; no emesis or no rescue therapy) during the overall phase (120 h after the start of trastuzumab deruxtecan). Results: Between September 2020 and March 2023, 40 patients were randomly assigned to the GD (n = 19) or GDA (n = 21) arm. In the GDA arm, one patient who did not complete the use of the rescue medication listed in the diary was excluded from the efficacy analysis, which included the use of rescue medication. The CR rates during the overall phase were 36.8% and 70.0% in the GD and GDA arms, respectively (odds ratio 0.1334; 95% confidence interval [CI]: 0.0232-0.7672; P = 0.0190), with a difference of 33.2%. No grade 3 or 4 toxicity related to antiemetic therapy was observed. Conclusions: Patients receiving trastuzumab deruxtecan require triple therapy, including mandatory NK1RA administration.

Investigation of the significance of population-based breast cancer screening among women aged under 40 years.

BACKGROUND: Owing to low incidence rates, population-based breast cancer screening is not recommended by many municipalities in Japan for women aged < 40 years. To evaluate the usefulness of screening in women aged < 40 years, we investigated the results of population-based breast cancer screening among young women performed in the Ibaraki Prefecture. METHODS: Data regarding histological characteristics, recall rates, cancer detection rates, positive predictive values, tumor categories, and status of lymph node metastases were obtained from population-based screening data from Ibaraki Health Service Association Institute. The "number needing to be screened" (NNS) was determined; using Pearson's chi-squared test, these data were compared between women aged < 40 years and > 40 years. RESULTS: The data of 428,560 women were evaluated. Cancer detection rates were significantly lower and the NNS and proportion of women with tumor category T2 or higher was significantly increased in women aged < 40 years than in those aged > 40 years (0.06% vs. 0.21%, 1505 vs. 281-439, and 28.9% vs. 6.3%, respectively; all, p < 0.05). The proportion of early-stage cancers was lower in women aged < 40 years than in those > 40 years, but this was not significant. CONCLUSIONS: These results suggest that population-based breast cancer screening should not be recommended for women aged < 40 years. To reduce the breast cancer-related mortality rate in young women and ensure efficient use of limited medical resources in Japan, a more efficient surveillance system, based on genetic propensity and family history, needs to be established.

Four cases of Trousseau syndrome associated with breast cancer that exhibited central nervous system manifestations.

Cancer-associated thrombosis is known as Trousseau syndrome (TS). Here, we report 4 cases of TS associated with advanced breast cancer that caused central nervous system (CNS) vascular events. All 4 patients experienced sudden onset of CNS symptoms. Imaging revealed multiple brain infarctions or intracranial hemorrhage and all 4 patients had leptomeningeal or brain metastasis. Laboratory findings showed hypercoagulability at diagnosis of TS. Of the 4 patients, 2 patients were treated with unfractionated heparin, while 2 patients could not undergo anticoagulant therapy. In all patients, once the TS occurred, the CNS symptoms progressed rapidly and the prognosis was very poor, 3 patients dying within about a month of diagnosis of TS. Therefore, the predictive factors of TS are important and standards and guidelines for administration of anticoagulants are needed.

Use of human senses as sensors.

This paper is an overview of our recent findings obtained by the use of human senses as sensors, suggesting that human senses might be indispensable sensors, not only for practical uses but also for gaining a deeper understanding of humans. From this point of view, two kinds of studies, both based on semantic responses of participants, deserve emphasis. One study assessed the efficacy of the photocatalytic elimination of stains or bio-aerosols from an air environment using TiO(2) as well as the photocatalytic deodorizing efficacy of a TiO(2)-type deodorizer; the other study evaluated the changes in perception of a given aroma while inhaling the fragrance of essential oils. In the latter study, we employed a sensory test for evaluating changes in perception of a given aroma. Sensory tests were conducted twice, when participants were undergoing the Kraepelin mental performance test (mental arithmetic) or an auditory task (listening to environmental natural sounds), once before the task (pre-task) and once after the task (post-task). The perception of fragrance was assessed by 13 contrasting pairs of adjectives as a function of the task assigned to participants. The obtained findings illustrate subtle nuances regarding how essential oils manifest their potency and how olfactory discrimination and responses occur in humans.

A case of hemorrhagic cystitis caused by nab-paclitaxel.

Nab-paclitaxel (nab-PTX) is a nanoparticle albumin-bound paclitaxel and, as such, is free of solvents like ethanol and polyoxyethylene castor oil. The absence of solvents from this formulation has several practical advantages: it has a shorter infusion time, it negates the need for premedications for hypersensitivity reactions, and it can be administered to patients with alcoholic hypersensitivity. It is thought that nab-paclitaxel will be in widespread use in the near future because of its convenience and efficacy. Here, we report the case of a breast cancer patient who developed hemorrhagic cystitis potentially due to treatment with nab-paclitaxel. The patient was 69-year old lady with stage IIB left breast cancer. She was due to undergo neoadjuvant chemotherapy and started weekly treatment with nab-paclitaxel. On the second day of the first cycle of treatment, she experienced symptoms of cystitis, but was not hemorrhagic and the symptoms were managed with antibiotics. After the third cycle, the symptoms of cystitis became severe, and she was diagnosed with hemorrhagic cystitis and discontinued chemotherapy with nab-paclitaxel. This is the first case report of hemorrhagic cystitis associated with nab-paclitaxel.