A phase II study of sequential treatment with anthracycline and taxane followed by eribulin in patients with HER2-negative, locally advanced breast cancer (JBCRG-17).

PURPOSE: The sequence of taxanes (T) followed by anthracyclines (A) as neoadjuvant chemotherapy has been the standard of care for almost 20 years for locally advanced breast cancer (LABC). Sequential administration of eribulin (E) following A/T could provide a greater response rate for women with LABC. METHODS: In this single-arm, multicenter, Phase II prospective study, the patients received 4 cycles of the FEC regimen and 4 cycles of taxane. After the A/T-regimen, 4 cycles of E were administered followed by surgical resection. The primary endpoint was the clinical response rate. Eligible patients were women aged 20 years or older, with histologically confirmed invasive breast cancer, clinical Stage IIIA (T2-3 and N2 only), Stage IIIB, and Stage IIIC, HER2-negative. RESULTS: A preplanned interim analysis aimed to validate the trial assumptions was conducted after treatment of 20 patients and demonstrated that clinical progressive disease rates in the E phase were significantly higher (30%) than assumed. Therefore, the Independent Data Monitoring Committee recommended stopping the study. Finally, 53 patients were enrolled, and 26 patients received the A/T/E-regimen. The overall observed clinical response rate (RR) was 73% (19/26); RRs were 77% (20/26) in the AT phase and 23% (6/26) in the E phase. Thirty percent (8/26) of patients had PD in the E phase, 6 of whom had achieved cCR/PR in the AT phase. Reported grade ≥ 3 AEs related to E were neutropenia (42%), white blood cell count decrease (27%), febrile neutropenia (7.6%), weight gain (3.8%), and weight loss (3.8%). CONCLUSION: Sequential administration of eribulin after the A/T-regimen provided no additional effect for LABC patients. Future research should continue to focus on identifying specific molecular biomarkers that can improve response rates.

Efficacy of the eribulin, pertuzumab, and trastuzumab combination therapy for human epidermal growth factor receptor 2-positive advanced or metastatic breast cancer: a multicenter, single arm, phase II study (JBCRG-M03 study).

Purpose To date, it is not clear which anticancer agent is useful in combination with trastuzumab and pertuzumab As the first and second selective regimens for advanced or metastatic breast cancer (AMBC), this multicenter, open-label, phase II trial (JBCRG-M03: UMIN000012232) presents a prespecified analysis of eribulin in combination with pertuzumab and trastuzumab. Methods We enrolled 50 patients with no or single prior chemotherapy for HER2-positive AMBC during November 2013-April 2016. All patients received adjuvant or first-line chemotherapy with trastuzumab and a taxane. The treatment comprised eribulin on days 1 and 8 of a 21-day cycle and trastuzumabplus pertuzumab once every 3 weeks, all administered intravenously. While the primary endpoint was the progression-free survival (PFS), secondary endpoints were the response rate and safety. Results Of 50 patients, 49 were eligible for safety analysis, and the full analysis set (FAS) included 46 patients. We treated 8 (16%) and 41 (84%) patients in first- and second-line settings, respectively. While 11 patients (23.9%) had advanced disease, 35 (76.1%) had metastatic disease. The median PFS was 9.2 months for all patients [95% confidence interval (CI): 7.0-11.4]. In the FAS, 44 patients had the measurable lesions and the complete response rate (CR) was 17.4%, and partial response rate (PR) was 43.5%. The grade 3/4 adverse events were neutropenia (5 patients, 10.2%), including febrile neutropenia (2 patients, 4.1%), hypertension (3 patients, 6.1%), and other (1 patient). The average of the left ventricular ejection fraction did not decline markedly. No symptomatic left ventricular systolic dysfunction was observed. Conclusions In patients with HER2-positive AMBC, eribulin, pertuzumab, and trastuzumab combination therapy exhibited substantial antitumor activity with an acceptable safety profile. Hence, we have started a randomized phase III study comparing eribulin and a taxane in combination with pertuzumab and trastuzumab for the treatment of HER2-positive AMBC. Trial registration ID: UMIN-CTR: UMIN000012232.

A randomized study comparing docetaxel/cyclophosphamide (TC), 5-fluorouracil/epirubicin/cyclophosphamide (FEC) followed by TC, and TC followed by FEC for patients with hormone receptor-positive HER2-negative primary breast cancer.

PURPOSE: Our primary objective was to determine the benefit/risk of anthracycline-free regimens by comparing docetaxel + cyclophosphamide (TC) alone, fluorouracil + epirubicin + cyclophosphamide (FEC) followed by TC, or TC followed by FEC as a primary treatment for patients with HR-positive, HER2-negative BC. METHODS: We randomized patients with stage I-III HR-positive HER2-negative, operable BC to receive either six cycles of TC (TC6), three cycles of FEC followed by three cycles of TC (FEC-TC), or three cycles of TC followed by three cycles of FEC (TC-FEC). The primary endpoint was the pathological response. Secondary endpoints included clinical response, type of surgical procedure, recurrence, death, and adverse events (by NCI-Common Terminology Criteria for Adverse Events v.3.0). We conducted all statistical analyses using SAS Version 9.2. RESULTS: We enrolled 195 patients and analyzed data from 193 as the intention-to-treat population. Pathological complete response rates were numerically higher in the TC6 group than in the other groups (p = 0.321). The breast conservation rate was significantly higher in the TC6 group (73%) than in the other groups (FEC-TC 51%, TC-FEC 45%, p = 0.007). Adverse events with grade > 3 were not common in the treatment groups (p = 0.569). The overall and distant disease-free survivals were similar among the groups with median follow-up of 5.80 years. CONCLUSIONS: Despite similar long-term efficacy and safety profile, the higher breast conservation rate in the TC6 group suggests that preoperative chemotherapy without an anthracycline may benefit patients with HR-positive HER2-negative BC. TRIAL REGISTRATION: UMIN000003283 https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000003873.

Multicenter study of primary systemic therapy with docetaxel, cyclophosphamide and trastuzumab for HER2-positive operable breast cancer: the JBCRG-10 study.

BACKGROUND: The original aim of this study was to evaluate the treatment sequence and anthracycline requirement in docetaxel, cyclophosphamide and trastuzumab therapy. After one death in the anthracycline-containing arm, the protocol was amended to terminate the randomization. The single-docetaxel, cyclophosphamide and trastuzumab arm was continued to examine the efficacy and safety of the anthracycline-free regimen. METHODS: Women with human epidermal growth factor receptor-2-positive, operable and primary breast cancer were randomized to receive 5-fluorouracil, epirubicin and cyclophosphamide (four cycles) followed by docetaxel, cyclophosphamide and trastuzumab (four cycles), or docetaxel, cyclophosphamide and trastuzumab followed by 5-fluorouracil, epirubicin and cyclophosphamide, or docetaxel, cyclophosphamide and trastuzumab (six cycles). After the protocol amendment, patients were allocated to the docetaxel, cyclophosphamide and trastuzumab arm alone. The primary endpoint was a pathological complete response. RESULTS: In total, 103 patients were enrolled between September 2009 and September 2011: 21, 22 and 24 patients in the 5-fluorouracil, epirubicin and cyclophosphamide followed by docetaxel, cyclophosphamide and trastuzumab; docetaxel, cyclophosphamide and trastuzumab followed by 5-fluorouracil, epirubicin and cyclophosphamide and docetaxel, cyclophosphamide and trastuzumab arms, respectively, and 36 patients in the docetaxel, cyclophosphamide and trastuzumab arm after the protocol amendment. In total, 60 patients were allocated to the docetaxel, cyclophosphamide and trastuzumab arm, in which the pathological complete response rate was 45.8%, and disease-free survival at 3 years was 96.6%. Patients with stage I or IIA in the docetaxel, cyclophosphamide and trastuzumab arm showed good disease-free survival (100% at 3 years). The comparison of efficacy among the three arms was statistically underpowered. Left ventricular ejection fraction decreased significantly after 5-fluorouracil, epirubicin and cyclophosphamide followed by docetaxel-docetaxel, cyclophosphamide and trastuzumab (P = 0.017), but not after docetaxel, cyclophosphamide and trastuzumab followed by 5-fluorouracil, epirubicin and cyclophosphamide or docetaxel, cyclophosphamide and trastuzumab. CONCLUSIONS: The pathological complete response rate for docetaxel, cyclophosphamide and trastuzumab was similar to previous reports of anthracycline-containing regimens. Docetaxel, cyclophosphamide and trastuzumab might be an option for primary systemic therapy in human epidermal growth factor receptor-2-positive early breast cancer. A larger confirmatory study is necessary.

Multicentre, phase II study of eribulin in combination with S-1 in patients with advanced breast cancer.

BACKGROUND: We previously reported the synergistic effect of S-1 and eribulin in preclinical models. In addition, our phase I study revealed the recommended dose for the phase II study of the combination therapy in advanced breast cancer (ABC) patients pre-treated with anthracycline and taxane. Our current study reports on the efficacy and safety of the combined use of eribulin and S-1 in patients with ABC and poor prognosis. METHODS: Patients with breast cancer who received prior anthracycline- and/or taxane-based therapy were assigned to receive a combination therapy of eribulin (1.4 mg/m2 on days 1 and 8, every 21 days) and S-1 (65 mg/m2, on days 1 to 14, every 21 days) for advanced/metastatic disease. All patients had at least one clinicopathological factor such as being oestrogen receptor negative, Human Epidermal Growth Factor Receptor 2 (HER2) receptor negative, presence of visceral involvement, presence of three or more metastatic sites, or having a disease-free interval shorter than 2 years. The primary endpoint was the independent-reviewer assessed objective response rate (ORR). Secondary endpoints were clinical benefit rate, disease control rate, progression-free survival (PFS), and overall survival (OS). RESULTS: This study enrolled 33 patients. Confirmed ORR was 33.3% (95% CI: 17.3 to 52.8). Median PFS was 7.5 months (95% CI: 4.0 to 14.3). Median OS time was not reached during the current experimental periods. The most common grade 3/4 adverse event was neutropenia (68.8%). CONCLUSIONS: The combination of eribulin and S-1 is safe and effective for treatment in patients with ABC and poor prognosis. TRIAL REGISTRATION: Current Controlled Trials UMIN000015049 , date of registration: September 5th 2014.

De-escalated neoadjuvant therapy with nanoparticle albumin-bound paclitaxel and trastuzumab for low-risk pure HER2 breast cancer.

PURPOSE: Neoadjuvant trastuzumab combined with anthracycline and taxane is now considered a standard regimen for human epidermal growth factor receptor 2 (HER2)-positive breast cancer. A less toxic, non-anthracycline regimen has been considered as a treatment option for patients with node-negative small tumors. Estrogen receptor-negative and HER2-positive (pure HER2) tumors are more likely to achieve a pathological complete response (pCR). This study evaluates the activity and safety of neoadjuvant nanoparticle albumin-bound paclitaxel (nab-PTX) plus trastuzumab for pure HER2 breast cancer in patients with low risk of relapse. METHODS: We treated patients with tumors measuring ≤ 3 cm, node-negative, pure HER2 breast cancer using neoadjuvant nab-PTX 260 mg/m2 with trastuzumab every 3 weeks for four cycles. The primary endpoint was the pCR rate. The secondary endpoints included the clinical response rate, disease-free survival, pathologic response rate (defined as pCR or minimal residual invasive disease only in the breast), breast-conserving surgery conversion rate, safety, and disease-free survival. Depending on the pathological findings of surgical specimens, the administration of adjuvant anthracycline could be omitted. RESULTS: Eighteen patients were enrolled. No patient required dose delays or reductions; none showed disease progression, and all patients underwent surgery as scheduled. Of the 18 patients, 66.7% achieved pCR, and the adjuvant anthracycline regimen was omitted for all patients. The incidence of severe adverse events was quite low. CONCLUSION: This less toxic, anthracycline-free regimen appears to be a significantly effective neoadjuvant therapy for patients with pure HER2 breast cancer at low relapse risk.

A phase II, multicenter, single-arm trial of eribulin as first- or second-line chemotherapy for HER2-negative advanced or metastatic breast cancer: evaluation of efficacy, safety, and patient-reported outcomes.

PURPOSE: Although eribulin is a suitable option for early-line treatment of metastatic breast cancer (MBC), data on first- or second-line use of eribulin for human epidermal growth factor receptor 2 (HER2)-negative MBC are still limited. Therefore, we conducted a phase II trial to investigate the efficacy and safety of eribulin for first- or second-line chemotherapy for HER2-negative MBC. MATERIALS AND METHODS: We performed a phase II, open-label, single-arm, multicenter study in Japan. Eligible patients were women with histologically confirmed HER2-negative MBC without chemotherapy or only one chemotherapy line for MBC. The primary endpoint was the overall response rate (ORR) and the secondary endpoints included the clinical benefit rate (ORR + stable disease for 6 months; CBR), progression-free survival (PFS), overall survival (OS), duration of response (DOR), safety, and health-related quality of life (HRQoL). RESULTS: A total of 35 patients with HER2-negative MBC were enrolled between March 2013 and February 2017 (data cut-off July 31, 2017). The ORR was 37.1% (95% CI 21.1-53.2%). The CBR was 54.3% (95% CI 37.8-70.8%). The median PFS was 6.2 months (95% CI 2.7-9.4 months) and median OS was 21.4 months (95% CI 11.5-32.9 months). Common grade 3/4 adverse events were neutropenia (42.9%) but febrile neutropenia (2.9%). Although the majority of non-hematological adverse events were mild in severity, one patient died of pneumonitis. In HRQoL analysis, eribulin appeared to maintain HRQoL of many patients. CONCLUSIONS: Eribulin as first- or second-line chemotherapy is effective and has manageable toxicity for patients with HER2-negative MBC.

Bi-weekly eribulin therapy for metastatic breast cancer: a multicenter phase II prospective study (JUST-STUDY).

BACKGROUND: This study aimed to investigate whether schedule modification is safe and effective in patients intolerant to the standard eribulin dose and schedule. METHODS: Patients with metastatic breast cancer (MBC) treated with both anthracycline and taxane and ≤ 3 prior regimens of chemotherapy for MBC received eribulin at the standard dose and schedule (1.4 mg/m2 on days 1 and 8 of a 21-day cycle) in the first cycle; change of dosing schedule (1.4 mg/m2 on days 1 and 15 of a 28-day cycle) was determined by change in neutrophil count, platelet count, aspartate aminotransferase, alanine aminotransferase, total bilirubin, serum creatinine, and non-hematological toxicity on day 8 of the first cycle or day 1 of the second cycle. Clinical benefit rate (CBR; primary endpoint), time to treatment failure (TTF), overall survival (OS), and safety were evaluated. RESULTS: Of the 88 patients who were enrolled and received standard eribulin therapy in the first cycle, 42 patients were moved to the bi-weekly therapy group and 40 continued standard therapy. In the bi-weekly and standard therapy groups, mean relative dose intensity was 62.7 and 90.9%, CBR was 31.0 and 25.0%, median TTF was 81.5 and 75 days, and OS was 523 and 412 days, respectively. Neither group reported severe adverse events. CONCLUSION: This is the first study to show that a bi-weekly eribulin schedule is tolerable and has comparable efficacy in patients intolerant to the standard eribulin schedule. CLINICAL TRIAL REGISTRATION: University Hospital Medical Information Network (UMIN) Center (ID: UMIN 000008491).

Randomized phase II study of anastrozole plus tegafur-uracil as neoadjuvant therapy for ER-positive breast cancer in postmenopausal Japanese women (Neo-ACET BC).

PURPOSE: This phase II study evaluated the efficacy and safety of anastrozole concurrent with tegafur/uracil (UFT) as neoadjuvant therapy for ER-positive postmenopausal breast cancer. METHODS: Postmenopausal Japanese women with ER-positive, HER2-negative, T2,N0-1,M0 breast cancer seen at tertiary hospitals were eligible for this open-label, randomized, multicenter study. Patients were randomized 1:1 by minimization to orally receive either anastrozole (1 mg once daily) plus UFT (tegafur/uracil combination in 1:4 molar ratio; 270 mg/m2/day in two divided doses) or anastrozole (as above) alone for 24 weeks. Tumor response was assessed by investigator and central review as per RECIST v1.1. The primary endpoint was the proportion of patients with best overall response of CR or PR [clinical response rate (RR)] determined by central radiologic review. RESULTS: The study was prematurely terminated due to Grade ≥ 3 liver dysfunction reported in 3 patients receiving anastrozole/UFT. Of 57 patients randomized before termination (29 anastrozole/UFT, 28 anastrozole), all were analyzed for safety and 56 (28 each group) for tumor response. Compared with anastrozole alone, anastrozole/UFT did not achieve significantly higher RR [39.3% (90% CI 23.8-56.5%) vs 14.3% (90% CI 5.0-29.8%); p = 0.0683, Fisher's exact test], but produced significantly greater tumor shrinkage (mean tumor reduction rate 31.0 vs. 14.2%; p = 0.0181, unpaired t-test). Grade ≥ 3 adverse events were more common with anastrozole/UFT than with anastrozole (17.2 vs. 0%). CONCLUSION: Although the study was terminated owing to the altered liver function, it showed that there was a trend to greater shrinkage of tumor in the combination group for ER-positive, HER2-negative postmenopausal breast cancer.

Gemcitabine and Vinorelbine Combination Chemotherapy in Taxane-Pretreated Patients with Metastatic Breast Cancer: A Phase II Study of the Kinki Multidisciplinary Breast Oncology Group (KMBOG) 1015.

BACKGROUND: This phase II study was conducted to evaluate the efficacy and safety of the chemotherapy combination of gemcitabine and vinorelbine in taxane-pretreated Japanese metastatic breast cancer patients. METHODS: In this multicenter, phase II, single-arm study, patients with recurrent or metastatic HER2-negative breast cancer were administered gemcitabine (1,200 mg/m2) and vinorelbine (25 mg/m2) intravenously on days 1 and 8 every 3 weeks. The primary endpoint was the objective response rate, and other endpoints included progression-free survival, overall survival, and safety. RESULTS: A total of 42 patients were enrolled in this study. The objective response rate and clinical benefit rate were 24 and 43%, respectively. The median progression-free survival was 4.0 months. The median overall survival was 11.1 months. Grade 3/4 neutropenia was the most common hematologic toxicity, occurring in 22 patients (54%). Nonhematologic toxicity was moderate and transient, with fatigue (48%) being the most common condition and no severe adverse event reported. CONCLUSION: The combination of gemcitabine and vinorelbine is an effective and tolerable regimen for HER2-negative, taxane-pretreated, metastatic breast cancer patients in Japan.

[A Case of Metastatic Colorectal Cancer Refractory to Standard Chemotherapies Treated with TAS-102 with Bevacizumab].

A 51-year-oldwoman with lung, liver, andd istant lymph node metastases from sigmoidcolon cancer was treatedusing TAS-102 with bevacizumab as fourth-line chemotherapy. There was a 35%decrease in the size of target lesions after the first 4 cycles of therapy, and disease control has been maintained for 9 months. The only Grade 3 or worse adverse event experiencedwas neutropenia. In patients with refractory colorectal cancer, the combination of TAS-102 with bevacizumab might be an effective andsafe treatment.

[A Case of Multiple Pancreatic Metastases from Renal Cell Carcinoma Diagnosed Using EUS-FNA].

The patient was a 79-year-old man, who underwent left nephrectomy for left renal cell carcinoma in 2007. In March 2015, he complained ofthirst, polydipsia, and polyuria. A slight elevation ofamylase levels was detected following laboratory testing. Abdominal CT revealed well-enhanced tumors in the pancreatic head and tail. MPD was dilated in the pancreatic body and tail. Endoscopic ultrasound-guided fine-needle aspiration(EUS-FNA)was used to obtain additional pathological findings. We diagnosed multiple pancreatic metastases from renal cell carcinoma using cell block sections from EUS-FNA ofthe pancreatic head tumor. We also identified worsening of diabetes control due to pancreatic disease. A subtotal stomachsparing pancreaticoduodenectomy and a distal pancreatectomy were performed in June 2015. Histological examination confirmed clear cell carcinoma metastases from RCC in both tumors. The patient remains alive without recurrence approximately 1 year after surgery. Glycemic control has improved with a decrease in insulin levels. Cell block sections from EUS-FNA are useful in the diagnosis of pancreatic disease. Although postoperative follow-up ofthe remnant pancreas is important, preservation ofthe pancreas should be considered for multiple pancreatic metastases when complete tumor removal is possible.

Phase II Study of Neoadjuvant Anthracycline-Based Regimens Combined With Nanoparticle Albumin-Bound Paclitaxel and Trastuzumab for Human Epidermal Growth Factor Receptor 2-Positive Operable Breast Cancer.

UNLABELLED: We treated patients with operable human epidermal growth factor receptor 2-positive breast cancer with neoadjuvant anthracycline regimens followed by nanoparticle albumin-bound paclitaxel plus trastuzumab. Of the 44 patients, 49% achieved a pathologic complete response (pCR). The pCR rate was 36% and 71% in the patients with estrogen receptor-positive and -negative cancer, respectively. Neoadjuvant therapy using this combination appears to be effective and safe. Introduction: Neoadjuvant chemotherapy plus trastuzumab. INTRODUCTION: Neoadjuvant chemotherapy plus trastuzumab results in a 30% to 50% pathologic complete response (pCR) rate in human epidermal growth factor receptor 2 (HER2)-positive breast cancer and has been associated with improved therapeutic outcomes. Thus, the pCR rate can be useful in evaluating novel agents in this patient population. Nanoparticle albumin-bound (nab)-paclitaxel (PTX) can reduce the toxicity of PTX while maintaining its efficacy. The present study evaluated the activity and safety of nab-PTX as a neoadjuvant treatment of HER2(+) breast cancer. PATIENTS AND METHODS: We treated patients with stage I to IIIA breast cancer using neoadjuvant epirubicin/cyclophosphamide (EC) or 5-fluorouracil/epirubicin/cyclophosphamide every 3 weeks (q3w) for 4 cycles, followed by nab-PTX (260 mg/m(2)) plus trastuzumab q3w for 4 cycles. The primary endpoint was the pCR rate. The secondary endpoints included the clinical response rate, disease-free survival, pathologic response rate (defined as pCR or minimal residual invasive disease only in the breast), breast-conserving surgery rate, and safety. RESULTS: Forty-six patients were enrolled. One patient met the exclusion criteria because of the coexistence of another malignant disease; therefore, we evaluated 45 patients in the entire study. One patient experienced rapid disease progression during EC therapy, leaving 44 patients evaluable for nab-PTX treatment. Of the 45 patients, 49% achieved a pCR. The pCR rate was 36% and 71% in those with estrogen receptor-positive and -negative cancer, respectively. Of all the study treatments, the most frequent reason for delay or dose reduction was hematologic toxicity; only 1 patient required a dose reduction for nab-PTX because of peripheral neuropathy. CONCLUSION: Neoadjuvant therapy using this combination appears to be effective and safe.

[A Case of Extrahepatic Hepatocellular Cancer Discovered during Gynecological Laparoscopic Surgery].

Recently, laparoscopic surgery has become increasingly popular because of its lesser invasiveness, including smaller incisions, and fewer post-operative complications. It is also possible to observe the abdominal cavity by laparoscopy. We report a hepatocellular carcinoma arising in an accessory liver lobe detected during gynecological laparoscopic surgery. A 48-year-old woman who was undergoing laparoscopic hysterectomy for uterine fibroids was found to have a protruding, extrahepatic pedunculated tumor by intraoperative observation of the abdominal cavity during the fibroid procedure. We suspected FNH based on preoperative imaging findings, including abdominal ultrasound, computed tomographic scanning, and magnetic resonance imaging. We performed a laparoscopic partial hepatectomy. The cut surface of the tumor was similar to normal liver tissue. The pathological findings identified normal liver tissue and vessels, suggesting it was the accessory liver lobe. It also included a well-differentiated hepatocellular carcinoma. The final diagnosis was hepatocellular carcinoma arising in the accessory liver lobe. There have been no prior reports of extrahepatic liver tissue detected during gynecological surgery. This case reminded us of the importance of intra-abdominal observation during laparoscopic procedures. The opportunities to discover other cases of extrahepatic liver tissue by laparoscopy will increase.

[A Resected Case of Acinar Cell Carcinoma Diagnosed by Endoscopic Ultrasound Guided Fine-Needle Aspiration Prior to Surgical Treatment].

Acinar cell carcinoma (ACC) of the pancreas is an extremely rare tumor type, accounting for approximately 1% of all pancreatic neoplasm. Here, we report a rare case of ACC of the pancreas diagnosed on the basis of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) findings prior to surgical treatment. A 73-years-old woman was being followed-up for chronic hepatitis C at our institution. Abdominal enhanced computed tomography showed an enhanced region, 16 mm in size, near the head of the pancreas on early-phase images. Magnetic resonance cholangiopancreatography did not show interruption or dilatation of the main pancreatic duct. Fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography showed an increased FDG uptake in the mass (SUVmax=12.7). EUS-FNA indicated a diagnosis of ACC, and pancreaticoduodenectomy was performed. Pathological examination confirmed the diagnosis of ACC. The patient was discharged after an 18-day hospital stay. Two years later, the patient has not shown any sings of recurrence.

Rapid on-site cytologic examination of 1500 breast lesions using the modified Shorr's stain.

BACKGROUND: Rapid on-site evaluation (ROSE) cytology enables sample quality assessment in the procedure room and facilitates the process of examination. While its use for mammary lesions in one-stop breast clinics has been reported, its usefulness as a cytologic diagnostic tool has not been fully explored. METHODS: A total of 1500 examinations of core-needle biopsy imprint/fine-needle aspiration cytology were performed for outpatients with breast lesions. The slides were immediately processed with modified Shorr's stain, which can be completed within a few minutes yet produces specimens of similar staining quality as the Papanicolaou (Pap) stain. The adequacy of sampling was evaluated on site, and a cytologic diagnosis was also made. ROSE cytologic findings were classified into five grades: class 1, inadequate; class 2, benign; class 3, indeterminate; class 4, suspicious for malignancy; class 5, malignant. If enough epithelial cells could not be obtained despite repeated examinations, the sample was scored as ineligible. These scores were utilized for patient management. Final cytologic diagnoses were made with conventional Pap stains. RESULTS: Reproducibility of scores between both staining methods was excellent (weighted κ statistic = 0.985). When compared class by class, concordance of cytologic diagnoses was particularly high in class 2 and 5 Shorr scores, in which the agreement with Pap diagnoses was 92.8 and 93.6 %, respectively. CONCLUSIONS: Our modified Shorr's staining protocol was useful to reduce the time for the diagnosis and treatment planning of breast lesions suspected of being breast cancer. It is beneficial for both the patients and clinicians.

Cosmetic evaluation following volume replacement using lateral tissue flap in breast-conserving surgery.

BACKGROUND: We examined the effectiveness of volume replacement using a lateral tissue flap (LTF) in breast-conserving surgery for a good cosmetic outcome. METHODS: We analyzed the results of 130 patients with breast cancer who underwent breast-conserving surgery with replacement using an LTF from 2006 to 2010 with cosmetic evaluations performed according to the criteria of the Japanese Breast Cancer Society. We examined scores with regard to the following possible contributing factors: partial resection (Bp) or quadrantectomy (Bq), diameter of the specimen, body mass index (BMI), axillary lymphadenectomy, postoperative irradiation, and position of the tumor. RESULTS: The scores for cases with Bp and non-postoperative irradiation were higher than those for Bq and postoperative irradiation cases, though they were not significant factors in multivariate analysis. A negative correlation was seen between score and diameter of the specimen, whereas there was no significant correlation with BMI. There was no significant difference between scores of cases with or without an axillary lymphadenectomy. However, the score for the extended upper-outer area including the upper and outer borders was significantly higher than scores for other portions. In multiple regression analysis, cases with a tumor diameter less than 4 cm in the extended upper-outer area or less than 2 cm in other areas showed good adaptation. CONCLUSION: Tumor location and diameter are important factors for cosmetic evaluation of volume replacement using an LTF.

[A case of long-term survival in rectal cancer with late lung and kidney metastases treated with combined multimodality therapy].

A 59-year-old man was diagnosed with rectal cancer and a low anterior resection was performed. Bilateral lung metastases appeared 4 years and 4 months after the primary surgery. The lung metastases were resected and FOLFOX6 neoadjuvant chemotherapy was administered. An abdominal computed tomography (CT) scan 7 years and 11 months after the primary surgery revealed bilateral multiple lung metastases, a left renal tumor, and swelling in the surrounding lymph node. A left nephrectomy and lymph node dissection were performed. A diagnosis of renal tumor from rectal cancer metastasis was made. For the lung metastases, chemotherapy (sLV/5FU2+Bmab) was administered in 26 courses and stable disease was achieved. It is important to combine adequate surgical resection and systemic chemotherapy for long survival.

Low dose capecitabine plus weekly paclitaxel in patients with metastatic breast cancer: a multicenter phase II study KBCSG-0609.

PURPOSE: The combination of capecitabine and paclitaxel (XP) has demonstrated synergistic antitumor activity in preclinical models. The purpose of this phase II study was to evaluate the efficacy and safety of a monthly XP regimen in patients with metastatic breast cancer (MBC). METHODS: Eligible patients had received one or fewer prior chemotherapy regimens for MBC. Patients received oral capecitabine of low dose (828 mg/m(2) twice daily, days 1-21) plus paclitaxel (80 mg/m(2), i.v., over 60 min, days 1, 8 and 15) every 28 days until disease progression or unacceptable toxicity. The primary endpoint was overall response rate (ORR). Progression-free survival (PFS), overall survival (OS) and safety were secondary endpoints. An exploratory analysis of efficacy according to hormone receptor (HR) status was performed. RESULTS: Forty-four patients were enrolled, and 43 patients were evaluable. ORR was 46.5%. PFS and OS were 8.3 and 22.9 months, respectively. ORR was 45.5% in patients with HR-positive tumors and 50% in HR-negative cases. The most frequently observed grade 3/4 adverse events were neutropenia (27.9%), leukopenia (11.6%), hand-foot syndrome (HFS, 9.3%) and fatigue (7.0%). There were no discontinuations due to HFS. CONCLUSIONS: Monthly XP was an effective and well-tolerated regimen for the first- or second-line treatment for MBC.

Ultrasound-guided infraclavicular axillary vein puncture is effective to avoid pinch-off syndrome: a long-term follow-up study.

PURPOSE: Pinch-off syndrome (POS) is a serious complication encountered during the long-term management of totally implantable access ports (TIAPs). The aim of this study was to examine the effect of ultrasound-guided infraclavicular axillary vein puncture to avoid POS in patients with long-term use of a TIAP. METHODS: This was a retrospective review of 207 consecutive TIAPs: one hundred devices implanted using an anatomical landmark technique were used as historical controls (Landmark group), while 107 devices were implanted using an ultrasound (US)-guided puncture method (US group). The pinch-off grade (POG) was determined using chest X-ray findings following the definition of Hinke, and the progression of POG during the follow-up period of the Landmark and US groups was compared. RESULTS: Sixteen cases in the Landmark group were POG-1 and 3 were POG-2, while all cases in the US group were POG-0 at the time of venipuncture (p < 0.001). Eleven patients in the Landmark group showed some degree of progression of the POG during the follow-up period. In contrast, there were no cases showing progression of the POG in the US group (p = 0.002). CONCLUSIONS: US-guided infraclavicular axillary vein puncture was found to effectively make it possible to avoid POS for the long-term management of TIAPs, as well as at the time of implantation.