Real-world effect of bevacizumab and eribulin on metastatic breast cancer using a propensity score matching analysis.

Bevacizumab and eribulin are novel agents for the treatment of HER2-negative metastatic breast cancer (MBC); however, the choice between bevacizumab and eribulin for MBC can be difficult. The present study aimed to compare two treatment strategies, eribulin followed by bevacizumab and paclitaxel (BEV + PTX) versus BEV + PTX followed by eribulin, to determine whether the order of administration affects the outcome of MBC in the real world. A total of 180 patients who started BEV + PTX and eribulin treatment for HER2-negative MBC from August 2011 to June 2018 were selected. Of these, 84 patients were treated with both BEV + PTX and eribulin sequentially. To evaluate the influence of the sequential order, the efficacy of BEV + PTX followed by eribulin (B-E arm) was compared to treatment with the reverse sequence (E-B arm). The propensity score matching method (PSMA) was used to improve the robustness of the findings from the present study. A total of 60 cases analyzed received BEV + PTX or eribulin as either first- or second-line treatment. In the entire cohort, the median time to failure of strategy (TFS) was 16.8 and 9.9 months in the B-E and E-B arms, respectively [hazard ratio (HR)=0.515, 95% CI 0.298-0.889, P=0.017). A similar HR was derived from PSMA for TFS. Using PSMA, TFS was 16.9 and 9.9 months in the B-E and E-B arms, respectively (HR=0.491, 95% CI 0.253-0.952, P=0.031). These results suggested that when both bevacizumab and eribulin are administered, bevacizumab should be administered first and eribulin should be administered later to ensure the most effective use of each drug.

[Is Surgery Really Useful for Breast Cancer Management in Elderly Patients?]

PURPOSE: The Japanese Breast Cancer Society Clinical Practice Guidelines for Breast Cancer 2018 indicated that operation is the standard treatment for breast cancer in elderly patients. This study aimed to assess the safety and efficacy of surgery for elderly patients with breast cancer. METHODS: Between April 2009 and November 2019, 545 patients underwent surgery in our hospital. The medical records of the elderly group(≥80 years, n=62)and the control(55-65 years, n=128)groups were compared and analyzed retrospectively. RESULTS: The elderly group had more comorbidities(p<0.001)than those of the control group. Although no significant difference in the pathological stage was noted between the 2 groups, dermal infiltrations were more common(p=0.003)in the elderly group than those of the other, and 27% of them did not undergo any surgery to the axilla. This group experienced more post-surgery complications than those of the other; however, such complications did not extend beyond the duration of hospital stays. No difference in the recurrence rate between the groups was noted. In the elderly group, 64% died of comorbidities. The 3-year survival rate was 88.3% and 95.4% in the elderly and control groups, respectively(p=0.18). CONCLUSIONS: Our study revealed that surgery was safe for the management of breast cancer in elderly patients. However, their prognosis was poor owing to their comorbidities. Hence, careful therapy for their comorbidity is also important.

[A Case of Stage â £ Cholangiocarcinoma with an Improved Quality of Life after Resection of a Symptomatic Giant Ovarian Teratoma].

An 82‒year‒old female presented to our hospital with abdominal fullness and loss of appetite. Abdominal computed tomography revealed a cholangiocarcinoma(Stage Ⅳ)with liver metastases and multiple lymph node metastases. In addition, we found a left ovarian teratoma(approximately 33 cm in diameter)occupying most of the abdominal cavity. She did not want an aggressive treatment for cholangiocarcinoma, but hoped to receive the best supportive care. She was treated with a fentanyl patch, although there was no symptomatic improvement. We explained that resection of the giant ovarian tumor may improve the symptoms. As a result, she accepted the surgery. The laparotomy was performed, and a left ovarian tumor(approximately 10,600 g in weight)was resected. Operation time was 2 hours and 35 minutes, and the amount of blood loss was small. No postoperative complications were observed. She started oral intake at POD 2. The abdominal symptom was relieved by the surgery, and she was discharged to her own home on POD 12. She was readmitted on POD 46 for general malaise, and died of advanced cholangiocarcinoma on POD 66. It was suggested that the QOL may be improved by resecting symptomatic benign tumors even in terminal cancer patients.

Management of an obstructed recurrent inguinal hernia using a hybrid method: a case report.

BACKGROUND: For recurrent incarcerated and strangulated hernias, the optimal treatment strategy for each case is needed. CASE PRESENTATION: The study patient was a 70-year-old man. TAPP repair was performed for a left inguinal hernia (JHS Classification II-1) 7 years earlier. The patient experienced transient pain and swelling of the left inguinal region for 5 months and visited our emergency department for abdominal pain and vomiting. A CT scan showed a recurrent left inguinal hernia and small bowel incarceration, and emergency surgery was performed. Laparoscopic observation of the abdominal cavity revealed recurrent left inguinal hernia (Rec II-1) with small bowel incarceration. The small bowel was reduced after pneumoperitoneum, and no findings suggested intestinal tract necrosis. Adhesions around the herniated sac were dissected using an extraperitoneal approach and then shifted to mesh plug repair. No perioperative complications or hernia recurrence were observed in the 10 months after the surgery. CONCLUSIONS: This report describes a novel, successful surgical treatment for a recurrent incarcerated hernia. In our patient, we could easily perform dissection and understand the positional relationship by hybrid surgery using the TEP method. Additionally, in patients with incarcerated hernias, we believe that performing hybrid surgery by combining the TEP method would be useful because bowel dilation caused by intestinal obstruction would not disturb the operative field.

[A Case of Multiple Laparoscopic Surgeries Performed for Disseminated Peritoneal Recurrence of Primary Peritoneal Carcinoma].

A 61-year-old woman presented to our hospital with abdominal distension. Abdominal CT showed massive ascites and disseminated peritoneal nodules. The patient was diagnosed with primary peritoneal cancer based on ascites and disseminated peritoneal nodules following laparoscopic surgery(initial operation). After receiving neoadjuvant chemotherapy, she underwent hysterectomy, bilateral salpingo-oophorectomy, and omentectomy(2nd operation). During chemotherapy, she experienced small bowel obstruction owing to disseminated peritoneal recurrence and splenic metastasis. Therefore, she underwent a laparoscopic partial small bowel resection(3rd operation)and laparoscopic splenectomy(4th operation). Treatment of primary peritoneal carcinoma consists of debulking surgery and chemotherapy. Laparoscopic debulking surgery may be useful for preventing adhesions and facilitating early postoperative recovery.

Synergistic effect of carbon nuclei and polyaromatic hydrocarbons on respiratory and immune responses.

Particulate matter with aerodynamic diameter ≤2.5 µm (PM2.5 ) is generally composed of carbon nuclei associated with various organic carbons, metals, ions and biological materials. Among these components, polyaromatic hydrocarbons (PAHs) such as benzo(a)pyrene (BaP) and quinones have detrimental effects on airway epithelial cells and immunodisrupting effects, which leads to the exacerbation of respiratory allergies. The effects of PAHs and the carbon nuclei, separately as well as in combination, remain to be established. We investigated the effects of BaP, 9,10-phenanthroquinone (9,10-PQ), and 1,2-napthoquinone (1,2-NQ) and their combined effects with heated diesel exhaust particle (H-DEP) as carbon nuclei of typical PM2.5 . We exposed human airway epithelial cells (BEAS-2B), murine bone marrow-derived antigen-presenting cells (APCs), and murine splenocytes to BaP, 9,10-PQ, or 1,2-NQ in the presence and absence of H-DEP. Several important inflammatory cytokines and cell surface molecules were measured. PAHs alone did not have apparent cytotoxic effects on BEAS-2B, whereas combined exposure with H-DEP induced noticeable detrimental effects which mainly reflected the action of H-DEP itself. BaP increased CD86 expression as an APC surface molecule regardless of the presence or absence of H-DEP. None of the BaP, 9,10-PQ, or 1,2-NQ exposure alone or their combined exposure with H-DEP resulted in any significant activation of splenocytes. These results suggest that PAHs and carbon nuclei show additive effects, and that BaP with the carbon nuclei may contribute to exacerbations of allergic respiratory diseases including asthma by PM2.5 , especially via antigen-presenting cell activation.

Effects of Components of PM2.5 Collected in Japan on the Respiratory and Immune Systems.

Epidemiologic studies have reported that particulate matter with aerodynamic diameters ≤2.5 µm (PM2.5) affect respiratory diseases, including asthma. The components and/or factors of PM2.5 that contribute to the exacerbation of asthma have not been identified. We investigated the effects of extracts of PM2.5 collected in Japan on the respiratory and immune systems. PM2.5 was collected from an industrial area and an urban area in December 2013. Airway epithelial cells and immune cells were exposed to aqueous or organic extracts of PM2.5. Exposure to extracts from both areas, especially to organic extracts rather than aqueous extracts, caused a pro-inflammatory response via interleukin (IL) 6 production from airway epithelial cells, and it induced the maturation/activation of bone marrow-derived antigen-presenting cells via dendritic and epithelial cell (DEC) 205 and cluster of differentiation (CD) 86 expression and proportional changes in the constitution of the splenocytes. The extracts collected from the industrial area tended to show greater effects than those from the urban area. These results suggest that organic components of PM2.5 affect the respiratory and immune systems. These effects can differ by the collection areas. In addition, IL-6, DEC205, and CD86 can be predictive biomarkers for the respiratory and immune effects of ambient PM2.5.

Biological factor related to Asian sand dust particles contributes to the exacerbation of asthma.

Epidemiologic studies have revealed that Asian sand dust particles (ASDs) can affect respiratory and immune health represented by asthma. Factors responsible for the exacerbation of asthma remain unclear. The fungus Bjerkandera adusta (B.ad) and polycyclic aromatic hydrocarbons such as benzo[a]pyrene (BaP) have been identified in ASDs collected from the atmosphere when an ASD event occurred. We investigated the effects of B.ad and BaP related to ASDs on respiratory and immune systems. Bone marrow-derived antigen-presenting cells (APCs) and splenocytes from atopic prone NC/Nga mice and human airway epithelial cells were exposed to the B.ad or to BaP in the presence and absence of heated-ASDs (H-ASDs). B.ad and BaP in both the presence and absence of H-ASDs increased the expression of cell surface molecules on APCs. H-ASDs alone slightly activated APCs. The expressions induced by B.ad were higher than those induced by BaP in the presence and absence of H-ASDs. There were no remarkable effects on the activation of splenocytes or the proinflammatory responses in airway epithelial cells. These results suggest that B.ad rather than BaP contributes to the exacerbation of asthma regardless of the presence or absence of sand particles, particularly by the activation of the immune system via APCs. Copyright © 2016 John Wiley & Sons, Ltd.

[A Study of Patients with Regional Lymph Node Recurrence after Breast Surgery].

Regional lymph node recurrence without distant metastasis after the initial treatment of breast cancer is a relatively rare event. The optimal management for regional lymph node recurrence is poorly understood. We retrospectively evaluated 21 patients who developed regional lymph node recurrence between January 1, 2003 and December 31, 2014. The median interval between regional lymph node recurrence and distant metastasis was 1.0 years(range, 0.4 to 2.5 years). On followup, 15 cases(71.4%)were found to eventually develop distant metastases. Median follow-up time after lymph node recurrence was 1.8 years(range, 0.4 to 20.3 years). The 2-year survival rate after regional lymph node recurrence was 65.5%. The mean distant-disease-free interval was 2.2 years in patients with estrogen receptor(ER)-positive tumor(n=10)and 0.7 years in patients with ER-negative tumor(n=11). The distant-disease-free interval after regional lymph node recurrence was significantly shorter in patients with ER-negative tumor than in patients with ER-positive tumor(p=0.008). The 2-year survival rate after regional lymph node recurrence was significantly lower in patients with ER-negative tumor(33.3%)than in patients with ER-positive tumor(100%, p=0.016). This study revealed that regional lymph node recurrence after initial treatment is associated with an increased risk of distant metastasis and death and ER-negative tumors are indicative of a poor prognosis.

[A Case of Gastrointestinal Stromal Tumor(GIST)Originating in the Anal Canal].

We report a case of a gastrointestinal stromal tumor(GIST)that originated in the anal canal. A 70's woman with a subcutaneous tumor reaching from the anal canal was referred to our hospital. After a thorough examination, the tumor was resected percutaneously in the jackknife position. Histopathological examination showed proliferation of spindle-shaped tumor cells arranged in irregular bundles. Immunohistochemical staining showed that the tumor was positive for c-kit and CD34, and negative for a-SMA and S-100, so the tumor was diagnosed as GIST. As a-SMA-positive smooth muscle cells were seen around the tumor, we suspected that this tumor originated from the internal sphincter muscle.

Massive pneumoretroperitoneum arising from emphysematous cholecystitis: a case report and the literature review.

BACKGROUND: Emphysematous cholecystitis is a severe variant of acute cholecystitis caused by anaerobic bacteria. Although intraperitoneal air as a complication has been described in association with emphysematous cholecystitis, pneumoretroperitoneum arising from emphysematous cholecystitis is extremely rare. Herein, we describe a rare case of pneumoretroperitoneum arising from emphysematous cholecystitis that was successfully treated with emergency surgery. CASE PRESENTATION: An 84-year-old male was transported to the Emergency Department of our hospital for acute abdomen. Computed tomography revealed acute cholecystitis accompanied by emphysematous change. Computed tomography also revealed massive pneumoretroperitoneum complicated with pneumobilia and gas in the hepatoduodenal ligament. Clinical findings fulfilled the diagnostic criteria for systemic inflammatory response syndrome and sepsis. Emergency surgery was carried out with a diagnosis of both emphysematous cholecystitis and gastrointestinal perforation. Intraoperative findings revealed acute gangrenous cholecystitis and pneumoretroperitoneum presenting with an odor-free foamy abscess along the loose connective tissue behind the ascending colon and mesocolon. No evidence of gastrointestinal perforation was found during surgery. Therefore, cholecystectomy and lavage drainage were performed. Bacterial culture examination isolated a single species of anaerobe, Klebsiella pneumoniae, which was considered to be the cause of emphysematous cholecystitis, pneumobilia, and pneumoretroperitoneum. CONCLUSIONS: Emphysematous cholecystitis should be considered as a possible cause of pneumoretroperitoneum. The present case is the first report of massive pneumoretroperitoneum extending to the dorsal side of the ascending mesocolon as a complication of emphysematous cholecystitis.

Effects of air pollution-related heavy metals on the viability and inflammatory responses of human airway epithelial cells.

Various metals produced from human activity are ubiquitously detected in ambient air. The metals may lead to induction and/or exacerbation of respiratory diseases, but the significant metals and factors contributing to such diseases have not been identified. To compare the effects of each metal and different oxidation states of metals on human airway, we examined the viability and production of interleukin (IL)-6 and IL-8 using BEAS-2B cell line, derived from human airway epithelial cells. Airway epithelial cells were exposed to Mn(2+), V(4+), V(5+), Cr(3+), Cr(6+), Zn(2+), Ni(2+), and Pb(2+) at a concentration of 0.5, 5, 50, or 500 µmol/L for 24 hours. Mn and V decreased the cell viability in a concentration-dependent manner, and V(5+) tended to have a greater effect than V(4+). The Cr decreased the cell viability, and (Cr(+6)) at concentrations of 50 and 500 µmol/L was more toxic than (Cr(+3)). Zn at a concentration of 500 µmol/L greatly decreased the cell viability, whereas Ni at the same concentration increased it. Pb produced fewer changes. Mn and Ni at a concentration of 500 µmol/L induced the significant production of IL-6 and IL-8. However, most of the metals including (V(+4), V(+5)), (Cr(+3), Cr(+6)), Zn, and Pb inhibited the production of both IL-6 and IL-8. The present results indicate that various heavy metals have different effects on toxicity and the proinflammatory responses of airway epithelial cells, and those influences also depend on the oxidation states of the metals.

Metastatic gastric carcinoma from breast cancer mimicking primary linitis plastica: A case report.

Metastases to the gastrointestinal tract rarely occur in breast cancer except in invasive lobular carcinoma. The present study reports a rare case of metastatic gastric cancer from invasive ductal carcinoma (IDC) of the breast mimicking primary gastric linitis plastica. A 51-year-old premenopausal female, who had a history of partial mastectomy for right breast cancer at the age of 40, was referred to Toyama City Hospital (Toyoma, Japan) for an endoscopic diagnosis of gastric linitis plastica. Abdominal computed tomography (CT) revealed left hydronephrosis, while peritoneal metastasis and malignant ascites were not detected. Chest CT detected a left lung tumor, which had invaded the left upper bronchus. Biopsy specimens were obtained and the histopathological findings on both the gastric tumor and lung tumor demonstrated poorly differentiated adenocarcinoma, whereas the histology of the original breast cancer was IDC with a solid-tubular type. Immunohistochemistry revealed that the biopsied specimens of the gastric and lung tumors were positive for estrogen receptor (ER), progesterone receptor (PgR) and negative for human epithelial growth factor receptor-2 (HER2). These molecular characteristics indicated the case was metastatic gastric carcinoma from the breast cancer with lung metastasis, since the statuses of ER, PgR and HER2 were concordant with those of the original breast cancer. However, the possibility of primary gastric cancer could not be completely ruled out. Therefore, a total gastrectomy was performed for the purpose of both diagnosis and treatment. Pathological examination of the resected specimen provided a definite diagnosis of multiple metastatic gastric carcinomas from the breast. To the best of our knowledge, metastatic gastric cancer derived from the breast presenting as linitis plastica 11 years following the surgical removal of IDC has not been described previously.

Sigmoid colon cancer arising in a diverticulum of the colon with involvement of the urinary bladder: a case report and review of the literature.

BACKGROUND: Colon cancer can arise from the mucosa in a colonic diverticulum. Although colon diverticulum is a common disease, few cases have been previously reported on colon cancer associated with a diverticulum. We report a rare case of sigmoid colon cancer arising in a diverticulum with involvement of the urinary bladder, which presented characteristic radiographic images. CASE PRESENTATION: A 73-year-old man was admitted to our hospital for macroscopic hematuria. Computed tomography and magnetic resonance imaging revealed a sigmoid colon tumor that protruded into the urinary bladder lumen. The radiographs showed a tumor with a characteristic dumbbell-shaped appearance. Colonoscopy showed a type 1 cancer and multiple diverticula in the sigmoid colon. A diagnosis of sigmoid colon cancer with involvement of the urinary bladder was made based on the pathological findings of the biopsied specimens. We performed sigmoidectomy and total resection of the urinary bladder with colostomy and urinary tract diversion. Histopathological findings showed the presence of a colovesical fistula due to extramurally growing colon cancer. Around the colon cancer, the normal colon mucosa was depressed sharply with lack of the muscular layer, suggesting that the colon cancer was arising from a colon diverticulum. CONCLUSION: The present case is the first report of sigmoid colon cancer arising in a diverticulum with involvement of the urinary bladder. Due to an accurate preoperative radiological diagnosis, we were able to successfully perform a curative resection for sigmoid colon cancer arising in a diverticulum with involvement of the urinary bladder.

Currarino syndrome in an adult presenting with a presacral abscess: a case report.

INTRODUCTION: Currarino syndrome (Currarino triad) was described in 1981 as a triad syndrome with a common embryogenesis in infants and with three characteristics: anorectal stenosis, a defect in the sacral bone, and a presacral mass. We describe here an unusual case of Currarino syndrome in an adult presenting with a presacral abscess but no meningitis. CASE PRESENTATION: A 32-year-old Japanese man presented with fever, arthralgia and buttock pain. A digital rectal examination showed mild rectal stenosis with local warmth and tenderness in the posterior wall of his rectum. Computed tomography showed a scimitar-shaped deformity of his sacrum and an 8cm presacral mass, which continued to a pedicle of his deformed sacrum. This was diagnosed as Currarino syndrome with a presacral abscess. The abscess was drained by a perianal approach with our patient treated with antibiotics. His symptoms soon disappeared. After three months, an excision was performed through a posterior sagittal approach. His postoperative course was uneventful and he was discharged 10 days after surgery. A histopathological examination revealed an infected epidermoid cyst. He has been free from recurrence as of four years and six months after surgery. CONCLUSIONS: We report a case of Currarino syndrome in an adult who presented with a presacral abscess but no meningitis. Abscess drainage followed by radical surgery resulted in a successful outcome.

Effects of hydrogen peroxide on mucociliary transport in human airway epithelial cells.

The effects of environmental pollutants on airway clearance have not been well elucidated. This study examined mucociliary transport using different sized-fluorescent particles on polarized human airway epithelial cells which were maintained in an air-liquid interface (ALI) culture system. The effects of hydrogen peroxide (H2O2) exposure on mucociliary transport were also investigated. The movement of fluorescent particles with diameters of 10-14 and 2.5-4.5 µm was observed by fluorescent microscopy as an index of the mucociliary transport. The mixture of the particles with two different sizes was propelled concentrically on the apical surface by the interaction of ciliary activity and mucus in the control condition, whereas H2O2 exposure for 24 h significantly inhibited the movement of the particles. The particle sizes did not affect their movement after the control or H2O2 exposure. These results suggest that particle tracking on polarized human airway epithelial cells is a useful experimental tool for the evaluation of the effect of environmental pollutants on mucociliary transport. In addition, reactive oxygen species may impair mucociliary transport, leading to the airway damage and exacerbation of respiratory diseases.

[Analysis of factors associated with quality of life for older adult patients with non-small cell lung cancer receiving outpatient gemcitabine therapy as an alternative inpatient therapy].

An increasing number of patients with lung cancer are undergoing outpatient chemotherapy as an alternative to inpatient therapy. To investigate the factors influencing the quality of life (QOL) for these patients, we administered a QOL questionnaire, The QOL Questionnaire for Cancer Patients Treated with Anticancer Drugs (QOL-ACD) to 8 older adult patients with non-small cell lung cancer. The medical factors related to the overall QOL scores and other categories indicating activity, physical condition, psychological condition, social relationship, psychological condition and face scale were analyzed. No significant decrease in each factor was observed in this study.

[A case of synchronous triple cancer involving lung, stomach and bladder, responding to combination chemotherapy of S-1 and cisplatin].

A 77-year-old man was admitted to our hospital complaining of general malaise, loss of appetite and hemoptysis. Chest X-ray film and computed tomography (CT) scan showed right-sided pleural effusion with lung tumor. Succeeding upper gastro-intestinal fiberscopy and cystoscopy revealed poorly-differentiated adenocarcinoma of the stomach and urothelial carcinoma of the bladder. Repeated treatment with 100 mg/body of S-1 on day 1 followed by 60 mg/m(2) of cisplatin on day 8 was effective in this patient.

Detection of incidental breast tumors by noncontrast spiral computed tomography of the chest.

PURPOSE: The aim of this study was to investigate the frequency of breast tumors and breast cancers with noncontrast spiral chest computed tomography (CT). MATERIAL AND METHODS: A clinical study was conducted to evaluate findings in the mammary region of 1008 consecutive patients with no mammary symptoms or signs who underwent noncontrast spiral CT of the chest from April 2003 to March 2006. RESULTS: Six cases of breast abnormality were detected among the 1008 women. Three were primary breast cancers, one was metastatic breast cancer, and two were benign tumors. All four breast cancer patients were over 70 years old. The characteristics of the tumor margins on CT scans corresponded to the mammography and ultrasonography findings. The mammographic background density ranged from inhomogeneous high-density breast to fatty breast. The detection rate of primary breast cancer by noncontrast spiral CT was 0.30%. CONCLUSION: Noncontrast spiral chest CT occasionally detects nonsymptomatic breast cancers, especially in elderly patients.

[Analysis of factors associated with quality of life for patients with non-small lung cancer receiving outpatient vinorelbine therapy as alternative inpatient therapy].

An increasing number of patients with lung cancer are undergoing outpatient chemotherapy as an alternative inpatient therapy. To investigate the factors influencing the quality of life (QOL) for these patients,we used a QOL questionnaire, "The QOL Questionnaire for Cancer Patients Treated with Anticancer Drugs" (QOL-ACD) for 8 patients with non-small cell lung cancer. The medical factors related to the overall QOL scores and other categories indicating "activity," "physical condition," "psychological condition," "social relationship" and "face scale" were analyzed. Significant improvements in the factors indicating "psychological condition" were observed in this study.