Truncated GPNMB, a microglial transmembrane protein, serves as a scavenger receptor for oligomeric ß-amyloid peptide1-42 in primary type 1 microglia.

Glycoprotein non-metastatic melanoma protein B (GPNMB) is up-regulated in one subtype of microglia (MG) surrounding senile plaque depositions of amyloid-beta (Aß) peptides. However, whether the microglial GPNMB can recognize the fibrous Aß peptides as ligands remains unknown. In this study, we report that the truncated form of GPNMB, the antigen for 9F5, serves as a scavenger receptor for oligomeric Aß1-42 (o-Aß1-42 ) in rat primary type 1 MG. 125 I-labeled o-Aß1-42 exhibited specific and saturable endosomal/lysosomal degradation in primary-cultured type 1 MG from GPNMB-expressing wild-type mice, whereas the degradation activity was markedly reduced in cells from Gpnmb-knockout mice. The Gpnmb-siRNA significantly inhibits the degradation of 125 I-o-Aß1-42 by murine microglial MG5 cells. Therefore, GPNMB contributes to mouse MG's o-Aß1-42 clearance. In rat primary type 1 MG, the cell surface expression of truncated GPNMB was confirmed by a flow cytometric analysis using a previously established 9F5 antibody. 125 I-labeled o-Aß1-42 underwent endosomal/lysosomal degradation by rat primary type 1 MG in a dose-dependent fashion, while the 9F5 antibody inhibited the degradation. The binding of 125 I-o-Aß1-42 to the rat primary type 1 MG was inhibited by 42% by excess unlabeled o-Aß1-42 , and by 52% by the 9F5 antibody. Interestingly, the 125 I-o-Aß1-42 degradations by MG-like cells from human-induced pluripotent stem cells was inhibited by the 9F5 antibody, suggesting that truncated GPNMB also serve as a scavenger receptor for o-Aß1-42 in human MG. Our study demonstrates that the truncated GPNMB (the antigen for 9F5) binds to oligomeric form of Aß1-42 and functions as a scavenger receptor on MG, and 9F5 antibody can act as a blocking antibody for the truncated GPNMB.

Deep Learning-based Image Cytometry Using a Bit-pattern Kernel-filtering Algorithm to Avoid Multi-counted Cell Determination.

BACKGROUND/AIM: In pathology, the digitization of tissue slide images and the development of image analysis by deep learning have dramatically increased the amount of information obtainable from tissue slides. This advancement is anticipated to not only aid in pathological diagnosis, but also to enhance patient management. Deep learning-based image cytometry (DL-IC) is a technique that plays a pivotal role in this process, enabling cell identification and counting with precision. Accurate cell determination is essential when using this technique. Herein, we aimed to evaluate the performance of our DL-IC in cell identification. MATERIALS AND METHODS: Cu-Cyto, a DL-IC with a bit-pattern kernel-filtering algorithm designed to help avoid multi-counted cell determination, was developed and evaluated for performance using tumor tissue slide images with immunohistochemical staining (IHC). RESULTS: The performances of three versions of Cu-Cyto were evaluated according to their learning stages. In the early stage of learning, the F1 score for immunostained CD8+ T cells (0.343) was higher than the scores for non-immunostained cells [adenocarcinoma cells (0.040) and lymphocytes (0.002)]. As training and validation progressed, the F1 scores for all cells improved. In the latest stage of learning, the F1 scores for adenocarcinoma cells, lymphocytes, and CD8+ T cells were 0.589, 0.889, and 0.911, respectively. CONCLUSION: Cu-Cyto demonstrated good performance in cell determination. IHC can boost learning efficiencies in the early stages of learning. Its performance is expected to improve even further with continuous learning, and the DL-IC can contribute to the implementation of precision oncology.

Feasibility and safety of robotic surgery for low rectal cancer combined with transanal total mesorectal excision.

PURPOSE: Laparoscopic surgery for low rectal cancer is often challenging. Transanal total mesorectal excision (TaTME) and robotic surgery have been introduced to overcome the technical difficulties in laparoscopic surgery and achieve more favorable outcomes. Hybrid robotic surgery, which combines TaTME with the abdominal robotic approach, incorporates the advantages of each of these surgical techniques and might achieve less invasive and safer surgery. This study evaluated the safety and feasibility of hybrid robotic surgery with TaTME (hybrid TaTME). METHODS: We retrospectively reviewed 162 TaTME cases performed at our department from September 2016 to May 2022. Among them, 92 cases of conventional TaTME and 30 of hybrid TaTME were eligible. We used propensity score matching analysis (PSM) to adjust for patients' characteristics and compared the short-term outcomes of the two treatment groups. RESULTS: Twenty-seven cases in each group were extracted using PSM. The operation time in hybrid TaTME was comparable to that in conventional TaTME. There was no significant difference in the postoperative hospital stay between the two groups. Other intra- and post-operative outcomes were also comparable between the two groups. Furthermore, no significant differences were observed between the two groups in the curative resection and recurrence rates. CONCLUSION: Hybrid TaTME for low rectal cancer was as favorable as conventional TaTME in producing satisfactory short-term outcomes. However, furthermore, larger-scale studies conducted over longer study periods are needed to evaluate the validity of the findings.

Reduced Number and Immune Dysfunction of CD4+ T Cells in Obesity Accelerate Colorectal Cancer Progression.

Obesity, a known risk factor for various types of cancer, reduces the number and function of cytotoxic immune cells in the tumor immune microenvironment (TIME). However, the impact of obesity on CD4+ T cells remains unclear. Therefore, this study aimed to clarify the impact of obesity on CD4+ T cells in the TIME. A tumor-bearing obese mouse model was established by feeding with 45% high-fat diet (HFD), followed by inoculation with a colon cancer cell line MC38. Tumor growth was significantly accelerated compared to that in mice fed a control diet. Tumor CD4+ T cells showed a significant reduction in number and an increased expression of programmed death-1 (PD-1), and decreased CD107a expression and cytokine such as IFN-γ and TNF-α production, indicating dysfunction. We further established CD4+ T cell-depleted HFD-fed model mice, which showed reduced tumor infiltration, increased PD-1 expression in CD8+ T cells, and obesity-induced acceleration of tumor growth in a CD4+ T cell-dependent manner. These findings suggest that the reduced number and dysfunction of CD4+ T cells due to obesity led to a decreased anti-tumor response of both CD4+ and CD8+ T cells to ultimately accelerate the progression of colorectal cancer. Our findings may elucidate the pathogenesis for poor outcomes of colorectal cancer associated with obesity.

Diagnostic challenge of chlamydial Fitz-Hugh-Curtis syndrome and cervicitis complicated by appendicitis: Case report.

Our patient had appendicitis complicated by Chlamydia trachomatis-induced Fitz-Hugh-Curtis syndrome and cervicitis. Differential diagnosis was challenging. A 22-year-old Japanese woman was febrile and presented with vomiting and subsequent abdominal pain. She had unprotected sexual intercourse with multiple partners. She had high Alvarado score and lack of cervical motion pain, despite cervical inflammation. Noncontrast CT showed enlarged appendix. Laparoscopic appendectomy revealed acute suppurative appendicitis and perihepatic adhesion. Cervical PCR assay was positive for C. trachomatis. She remained febrile but defervesced after azithromycin therapy. Clinicians should confirm whether females with abdominal pain are sexually active in view of screening for C. trachomatis.

Mechanical Stimulation-Induced Calcium Signaling by Piezo1 Channel Activation in Human Odontoblast Reduces Dentin Mineralization.

Odontoblasts play critical roles in dentin formation and sensory transduction following stimuli on the dentin surface. Exogenous stimuli to the dentin surface elicit dentinal sensitivity through the movement of fluids in dentinal tubules, resulting in cellular deformation. Recently, Piezo1 channels have been implicated in mechanosensitive processes, as well as Ca2+ signals in odontoblasts. However, in human odontoblasts, the cellular responses induced by mechanical stimulation, Piezo1 channel expression, and its pharmacological properties remain unclear. In the present study, we examined functional expression of the Piezo1 channel by recording direct mechanical stimulation-induced Ca2+ signaling in dentin matrix protein 1 (DMP-1)-, nestin-, and dentin sialophosphoprotein (DSPP)-immunopositive human odontoblasts. Mechanical stimulation of human odontoblasts transiently increased intracellular free calcium concentration ([Ca2+]i). Application of repeated mechanical stimulation to human odontoblasts resulted in repeated transient [Ca2+]i increases, but did not show any desensitizing effects on [Ca2+]i increases. We also observed a transient [Ca2+]i increase in the neighboring odontoblasts to the stimulated cells during mechanical stimulation, showing a decrease in [Ca2+]i with an increasing distance from the mechanically stimulated cells. Application of Yoda1 transiently increased [Ca2+]i. This increase was inhibited by application of Gd3+ and Dooku1, respectively. Mechanical stimulation-induced [Ca2+]i increase was also inhibited by application of Gd3+ or Dooku1. When Piezo1 channels in human odontoblasts were knocked down by gene silencing with short hairpin RNA (shRNA), mechanical stimulation-induced [Ca2+]i responses were almost completely abolished. Piezo1 channel knockdown attenuated the number of Piezo1-immunopositive cells in the immunofluorescence analysis, while no effects were observed in Piezo2-immunopositive cells. Alizarin red staining distinctly showed that pharmacological activation of Piezo1 channels by Yoda1 significantly suppressed mineralization, and shRNA-mediated knockdown of Piezo1 also significantly enhanced mineralization. These results suggest that mechanical stimulation predominantly activates intracellular Ca2+ signaling via Piezo1 channel opening, rather than Piezo2 channels, and the Ca2+ signal establishes intercellular odontoblast-odontoblast communication. In addition, Piezo1 channel activation participates in the reduction of dentinogenesis. Thus, the intracellular Ca2+ signaling pathway mediated by Piezo1 channels could contribute to cellular function in human odontoblasts in two ways: (1) generating dentinal sensitivity and (2) suppressing physiological/reactional dentinogenesis, following cellular deformation induced by hydrodynamic forces inside dentinal tubules.

[A Case of HER2 Positive Unresectable Gastric Cancer Leading to Conversion Therapy with Chemotherapy].

A 72‒year‒old man visited our hospital with a chief complaint of epigastralgia. Upper gastrointestinal endoscopy revealed type 3 advanced gastric cancer at the body of the stomach. Following an investigation, he was diagnosed with human epidermal growth factor receptor 2‒positive gastric cancer with invasion to the pancreas as well as the paraaortic lymph node, and multiple liver metastases were also observed. The cancer was judged to be cT4a, N2M1(H1 LYM: No. 16), cStage Ⅳ and thus was considered suitable for chemotherapy. We performed capecitabine plus cisplatin plus trastuzumab therapy. After 3 courses, the primary lesion and swollen lymph nodes decreased in size. After 20 chemotherapy courses, the primary lesion relapsed, so conversion surgery was performed. The patient underwent total gastrectomy, distal pancreatectomy, and partial resection of the liver. We planned to perform adjuvant chemotherapy, but the patient declined it because of anorexia. At 18 months after the operation, recurrence of the tumor was detected at the celiac artery. Chemotherapy was performed as follows: capecitabine plus trastuzumab 10 courses, ramucirumab plus paclitaxel, irinotecan, and nivolumab. However, the patient eventually died 71 months after the first visit.

ALKBH4 promotes tumourigenesis with a poor prognosis in non-small-cell lung cancer.

The human AlkB homolog family (ALKBH) of proteins play a critical role in some types of cancer. However, the expression and function of the lysine demethylase ALKBH4 in cancer are poorly understood. Here, we examined the expression and function of ALKBH4 in non-small-cell lung cancer (NSCLC) and found that ALKBH4 was highly expressed in NSCLC, as compared to that in adjacent normal lung tissues. ALKBH4 knockdown significantly induced the downregulation of NSCLC cell proliferation via cell cycle arrest at the G1 phase of in vivo tumour growth. ALKBH4 knockdown downregulated E2F transcription factor 1 (E2F1) and its target gene expression in NSCLC cells. ALKBH4 and E2F1 expression was significantly correlated in NSCLC clinical specimens. Moreover, patients with high ALKBH4 expression showed a poor prognosis, suggesting that ALKBH4 plays a pivotal tumour-promoting role in NSCLC.

[Two Cases of Metastatic Colorectal Cancer Treated with TAS-102 plus Bevacizumab].

Trifluridine/tipiracil (TAS-102) is an important chemotherapeutic agent recommended by the Japanese guidelines as third- or fourth-line treatment for colorectal cancer. Some studies have reported that administration of TAS-102 concomitant with bevacizumab prolongs progression-free and overall survival in colorectal cancer. We describe 2 patients treated with a chemotherapeutic regimen comprising TAS-102 concomitant with bevacizumab for recurrent colorectal cancer. No adverse events ≥Grade 3(except for hematotoxicity)were observed in these patients. The patient received several courses of chemotherapy with adjustments of the dose and dosing intervals to prevent neutropenia. Combination therapy using TAS-102 and bevacizumab is a feasible Late-line chemotherapeutic regimen for colorectal cancer.

Vaccine Based on Dendritic Cells Electroporated with an Exogenous Ovalbumin Protein and Pulsed with Invariant Natural Killer T Cell Ligands Effectively Induces Antigen-Specific Antitumor Immunity.

(1) Background: Cancer vaccines are administered to induce cytotoxic CD8+ T cells (CTLs) specific for tumor antigens. Invariant natural killer T (iNKT) cells, the specific T cells activated by α-galactosylceramide (α-GalCer), play important roles in this process as they are involved in both innate and adaptive immunity. We developed a new cancer vaccine strategy in which dendritic cells (DCs) were loaded with an exogenous ovalbumin (OVA) protein by electroporation (EP) and pulsed with α-GalCer. (2) Methods: We generated bone marrow-derived DCs from C57BL/6 mice, loaded full-length ovalbumin proteins to the DCs by EP, and pulsed them with α-GalCer (OVA-EP-galDCs). The OVA-EP-galDCs were intravenously administered to C57BL/6 mice as a vaccine. We then investigated subsequent immune responses, such as the induction of iNKT cells, NK cells, intrinsic DCs, and OVA-specific CD8+ T cells, including tissue-resident memory T (TRM) cells. (3) Results: The OVA-EP-galDC vaccine efficiently rejected subcutaneous tumors in a manner primarily dependent on CD8+ T cells. In addition to the OVA-specific CD8+ T cells both in early and late phases, we observed the induction of antigen-specific TRM cells in the skin. (4) Conclusions: The OVA-EP-galDC vaccine efficiently induced antigen-specific antitumor immunity, which was sustained over time, as shown by the TRM cells.

[Case of Peritoneal Dissemination from Gastrointestinal Stromal Tumor of Jejunum Treated with Repeated Non-Curative Surgery].

A 71-year-old male presented with abdominal distension and fever to our hospital. Abdominal CT revealed a huge tumor in abdomen, and non-curative surgery was performed. Peritoneal dissemination was widespread and the tumor invaded the bladder and sigmoid-colon mesenterium. Two months after the initial surgery, CT showed liver metastasis, and oral administration of imatinib mesylate was started. The peritoneal dissemination and liver metastasis showed a decrease, and this was well controlled for 45 months without severe side effects. Abdominal CT revealed peritoneal dissemination in the ileocecum after 43 months since the administration of imatinib. Therefore, sunitinib treatment was initiated. After 3 months of sunitinib administration, the tumor perforated. Emergency operation was performed to resect the ileocecum, and sunitinib was continued for 1 year. In GIST with liver metastasis and peritoneal dissemination, repeated surgical resection combined with chemotherapy is important to improve the patient's survival.

[A Case Report of Sigmoid Colon Cancer with Para-Aortic Lymph Node Metastases and Multiple Liver Metastases Resected after FOLFOX Therapy].

The patient, a male in his 70s, visited our hospital with a chief complaint of general fatigue and weight loss. Upon a detailed examination, he was diagnosed with sigmoid colon cancer, para-aortic lymph node metastases, and multiple liver metastases, for which he was hospitalized due to a poor performance status(PS). FOLFOX therapy was administered as the symptoms caused by the primary lesion were not recognized and his general condition was considered to be poor and thus he was deemed to be inoperable. After completing 2 courses of the chemotherapy, although his PS improved, laparoscopic sigmoidectomy was carried out with colonic stent placement due to the occurrence of an intestinal obstruction as a result of an enlargement of the primary lesion. Following surgery, 2 courses of FOLFOX therapy and 4 courses of FOLFOX plus bevacizumab therapy were administered and he is alive at 5 months after the operation without progression.

Activation of Mechanosensitive Transient Receptor Potential/Piezo Channels in Odontoblasts Generates Action Potentials in Cocultured Isolectin B4-negative Medium-sized Trigeminal Ganglion Neurons.

INTRODUCTION: Various stimuli to the dentin surface elicit dentinal pain by inducing dentinal fluid movement causing cellular deformation in odontoblasts. Although odontoblasts detect deformation by the activation of mechanosensitive ionic channels, it is still unclear whether odontoblasts are capable of establishing neurotransmission with myelinated A delta (Aδ) neurons. Additionally, it is still unclear whether these neurons evoke action potentials by neurotransmitters from odontoblasts to mediate sensory transduction in dentin. Thus, we investigated evoked inward currents and evoked action potentials form trigeminal ganglion (TG) neurons after odontoblast mechanical stimulation. METHODS: We used patch clamp recordings to identify electrophysiological properties and record evoked responses in TG neurons. RESULTS: We classified TG cells into small-sized and medium-sized neurons. In both types of neurons, we observed voltage-dependent inward currents. The currents from medium-sized neurons showed fast inactivation kinetics. When mechanical stimuli were applied to odontoblasts, evoked inward currents were recorded from medium-sized neurons. Antagonists for the ionotropic adenosine triphosphate receptor (P2X3), transient receptor potential channel subfamilies, and Piezo1 channel significantly inhibited these inward currents. Mechanical stimulation to odontoblasts also generated action potentials in the isolectin B4-negative medium-sized neurons. Action potentials in these isolectin B4-negative medium-sized neurons showed a short duration. Overall, electrophysiological properties of neurons indicate that the TG neurons with recorded evoked responses after odontoblast mechanical stimulation were myelinated Aδ neurons. CONCLUSIONS: Odontoblasts established neurotransmission with myelinated Aδ neurons via P2X3 receptor activation. The results also indicated that mechanosensitive TRP/Piezo1 channels were functionally expressed in odontoblasts. The activation of P2X3 receptors induced an action potential in the Aδ neurons, underlying a sensory generation mechanism of dentinal pain.

[A Super-Elderly Patient with Recurrent Colon Cancer with Metastasis Effectively Treated with Capecitabine plus Bevacizumab Chemotherapy-A Case Report].

The safety and feasibility of chemotherapy for elderly patients is unclear. We report a super-elderly patient with liver metastases from colorectal cancer successfully treated with capecitabine plus bevacizumab chemotherapy. An 87-year-old woman underwent a colectomy for transverse colon. At 4 months postoperatively, she underwent hepatectomy for liver metastases. At 9 months after the first surgery, a new liver metastases(S4)was found. At this time, she rejected another hepatectomy. Therefore, we selected capecitabine plus bevacizumab chemotherapy, considering her age. After 18 courses of administration, the liver metastasis did not progress, and no new metastatic lesions were found on CT examination. Although as adverse events Grade 2 hand-foot syndrome developed, no other adverse event occurred. The patient's PS score was maintained at 0. We suggest capecitabine plus bevacizumab chemotherapy is an effective regimen for super-elderly patients with colorectal cancer.

Gastric lipomatosis treated by total gastrectomy: a case report.

BACKGROUND: Gastric lipomatosis is characterized by multiple gastric lipomas or a diffuse gastric infiltration of the submucosal or subserosal layer by the adipose tissue; diffuse-type gastric lipomatosis is an extremely rare condition. Here, we present the case of a patient with gastric lipomatosis treated by total gastrectomy. CASE PRESENTATION: A 54-year-old man diagnosed with gastric submucosal tumor in 2008 was referred to our hospital for further examination and treatment in September 2016. Upper gastrointestinal endoscopy revealed a submucosal tumor with an associated ulcer on the anterior wall of the lower body of the stomach. A compressing mass was observed on the anterior wall of the greater curvature and the posterior wall of the stomach. Following a biopsy of the submucosal tumor and ulcer, lipoma without malignancy was diagnosed by microscopy. A giant gastric lipoma was suspected because endoscopic ultrasound revealed a high-echoic lesion on the antral wall that extended to the stomach. Therefore, total gastrectomy was performed, and gastric lipomatosis was confirmed by a histological examination of the resected specimen. CONCLUSIONS: Surgical treatment is a highly effective treatment for symptomatic gastric lipomatosis with extensive involvement or multiple lipomas and can be used for patient diagnosis.

Phase II study of bevacizumab and irinotecan as second-line therapy for patients with metastatic colorectal cancer previously treated with fluoropyrimidines, oxaliplatin, and bevacizumab.

PURPOSE: Fluorouracil and folinic acid with irinotecan (FOLFIRI) plus bevacizumab (BV) is widely used as second-line chemotherapy for patients with metastatic colorectal cancer (mCRC) previously treated with fluoropyrimidines, oxaliplatin, and BV. FOLFIRI requires a CV catheter and an infusion pump, which are inconvenient for patients. Sufficient data are not available for characterizing the effectiveness of fluoropyrimidines beyond first disease progression. In this study, we evaluated the efficacy and safety of irinotecan (CPT-11) plus BV as second-line therapy. METHODS: Patients with mCRC previously treated with at least four courses of a fluoropyrimidine, oxaliplatin, and BV were designated to receive 150 mg/m2 of CPT-11 and 10 mg/kg of BV every 2 weeks as second-line therapy. The primary endpoint was progression-free survival (PFS), and secondary endpoints included response rate (RR), overall survival (OS), and adverse events. RESULTS: Thirty patients from six institutes were enrolled from March 2011 to January 2014. The median PFS was 5.7 months (95% CI 4.2-7.3 months), and the RR was 6.7% (range 0.8-22.1%). Grades 3-4 adverse events included leucopenia (36.7%), neutropenia (50%), thrombocytopenia (26.7%), anemia (30%), diarrhea (3.3%), anorexia (6.7%), and hypertension (3.3%). Relative dose intensities were 94.5 and 96.3% for CPT-11 and BV, respectively. The median OS was 11.8 months (6.3 months-not reached). CONCLUSIONS: Administration of CPT-11 plus BV to patients with mCRC achieved comparable efficacies with relatively lower toxicities compared with the results of previous studies using FOLFIRI plus BV as second-line therapy. The dose intensity of CPT-11 was judged as satisfactory. CLINICAL TRIAL INFORMATION: UMIN000005228.

Potassium Currents Activated by Depolarization in Odontoblasts.

Increased intracellular free Ca2+ concentrations elicit plasma membrane depolarization, which leads to the activation of K+ currents. However, the precise properties of K+ currents activated by depolarization in odontoblasts remain to be elucidated. The present study identified biophysical and pharmacological characteristics of time-dependent and voltage-activated K+ currents in freshly dissociated rat odontoblasts using patch-clamp recordings in a whole-cell configuration. Using a holding potential of -70 mV, outwardly rectifying time- and voltage-dependent currents were activated by depolarizing voltage. To record pure K+ conductance, we substituted Cl- in both the extracellular and intracellular solutions with gluconate-. Under these conditions, observation of K+ concentration changes in the extracellular solution showed that reversal potentials of tail currents shifted according to the K+ equilibrium potential. The activation kinetics of outward K+ currents were relatively slow and depended on the membrane potential. Kinetics of steady-state inactivation were fitted by a Boltzmann function. The half-maximal inactivation potential was -38 mV. Tetraethylammonium chloride, 4-aminopyridine, and α-dendrotoxin inhibited outward currents in odontoblasts in a concentration-dependent manner, suggesting that rat odontoblasts express the α-subunit of the time- and voltage-dependent K+ channel (Kv) subtypes Kv1.1, 1.2, and/or 1.6. We further examined the effects of Kv activity on mineralization by alizarin red and von Kossa staining. Continuous application of tetraethylammonium chloride to human odontoblasts grown in a mineralization medium over a 21-day period exhibited a dose-dependent decrease in mineralization efficiency compared to cells without tetraethylammonium chloride. This suggests that odontoblasts functionally express voltage-dependent K+ channels that play important roles in dentin formation.

[A Study of Therapy for Locally Advanced Breast Cancer with Metastasis].

We reviewed 21 patients with locally advanced breast cancer with distant metastasis.The median age was 61 years.The median time to presentation at hospital was 13 months, and the median neoplasm diameter on the first visit was 10 cm.The main histological type was scirrhous carcinoma.Sixteen cases tested positive for hormone receptor(76%), 4 tested positive for HER2(19%), and 3 were triple negative(14%).Four patients underwent surgery.The techniques performed included mastectomy and axillary lymph node dissection.Three patients experienced local recurrence.The first-line treatment was surgery for 1 patient, chemotherapy for 12 patients, hormonal therapy for 7 patients, and trastuzumab for the HER2 positive patients.The median follow-up period was 49 months.The patients for where an operation was performed were 49 months and the operation not- enforcement patients were 54 months.If treatment is possible for patients with locally advanced breast cancer with distant metastasis, multidisciplinary treatment according to individual patient characteristics is recommended. In the case of surgical treatment, careful consideration must also be given to these characteristics.

[Resection of Paraaortic Lymph Node Recurrence Wherein Complete Response to Bevacizumab Was Observed after Surgery for Sigmoid Colon Cancer].

We report a case of resection of a paraaortic lymph node recurrence, wherein complete response to bevacizumab was observed. Our patient was a 50-year-old woman who had a paraaortic lymph node recurrence during adjuvant chemotherapy with FOLFOX 6 months after surgery for sigmoid colon cancer. She was treated with chemotherapy consisting of FOLFOX plus bevacizumab/FOLFIRI plus bevacizumab, which suppressed progression of the periaortic lymph node recurrence. She underwent surgery for the paraaortic lymph node recurrence, and the pathologic result was complete response. We report that bevacizumab was effective for her paraaortic lymph node recurrence.

An exploratory trial of intravenous immunoglobulin therapy for idiopathic pulmonary fibrosis: a preliminary multicenter report.

BACKGROUND AND AIMS: Idiopathic pulmonary fibrosis (IPF) is a fatal disorder without specific treatments. Although the efficacy of intravenous immunoglobulin (IVIG) therapy for autoimmune diseases has been reported, that for IPF remains unknown. This study aims to determine the efficacy and safety of IVIG for IPF. METHODS: In an exploratory, multicenter, non-randomized and prospective trial, patients with progressive IPF were enrolled. Patients were treated with IVIG for five consecutive days (5-day IVIG) or once monthly for five consecutive months (5-month IVIG). Changes in the vital capacity (VC), diffusion capacity of the lung for carbon monoxide (DLCO), 6-min walk test (6MWT) and high-resolution computed tomography (HRCT) findings were evaluated. RESULTS: A total of 10 patients with IPF were treated with IVIG: 6 were in 5-day IVIG and 4 were in 5-month IVIG group. In 5-day IVIG group, the treatment effects were temporal, and physiological and HRCT findings deteriorated in three of six patients. In 5-month IVIG group, changes in %VC, %DLCO and walk distance in 6MWT at 6 months were -0.9 ± 5.3%, 6.9 ± 12.6% and 79 ± 58 m (mean ± standard deviation), respectively, and the treatment effects were long lasting. The change in VC 6 months after starting IVIG was smaller than that of 6-12 months after starting IVIG (after cessation of IVIG) (-0.02 ± 0.15 vs -0.33 ± 0.14 L, P = 0.022). Ground glass opacities were diminished in two of four patients. Adverse events were mild and tolerable. CONCLUSION: This preliminary study shows that once-monthly IVIG treatment may be effective and tolerable in patients with IPF.