[Invasive Ductal Carcinoma within a Borderline Malignancy Phyllodes Tumor-A Case Report].

Phyllodes tumors are uncommon breast neoplasms that constitute 1-2% of breast malignancies. Invasive ductal carcinoma in the epithelial component of phyllodes tumor is very rare. When carcinoma is detected within the specimen, the management of treatment changes completely. We report a rare case of invasive ductal carcinoma arising in a giant borderline malignancy phyllodes tumor in a 51-year-old female patient. A painful 20 cm mass was found in her right breast, and a needle biopsy revealed fibroadenoma or benign phyllodes tumor, and a total mastectomy was performed. Pathological results showed that a borderline malignant phyllodes tumor coexisted with invasive ductal carcinoma. We explained that axillary surgery was necessary because invasive cancer was diagnosed after surgery, but the patient requested follow-up using images. Endocrine therapy was performed as postoperative adjuvant therapy, and the follow-up is underway without recurrence.

Population Pharmacokinetic-Pharmacodynamic Target Attainment Analysis of Flomoxef in the Serum and Liver Tissue of Patients Undergoing Hepatic Resection.

The purpose of this study was to investigate the population pharmacokinetics of prophylactic flomoxef based on serum and liver tissue concentrations and to demonstrate a pharmacodynamic target concentration in the serum and liver tissue exceeding the MIC in order to design an effective dosing regimen. Serum samples (n = 210) and liver tissue samples (n = 29) from 43 individuals were analyzed using a nonlinear mixed-effects model. The pharmacodynamics index target value was regarded as the probability of maintaining flomoxef serum trough and liver tissue concentrations exceeding the MIC90 values, 0.5 mg/L and 1.0 mg/L, for Escherichia coli and methicillin-susceptible Staphylococcus aureus, respectively. The final population pharmacokinetic model was a two-compartment model with linear elimination. Creatinine clearance (CLCR) was identified as a significant covariate influencing total clearance when CLCR was less than 60 mL/min. The probability of achieving concentrations in the serum and liver tissue exceeding the MIC90 for E. coli or methicillin-susceptible S. aureus for a 1 g bolus dose was above 90% at 2 h after the initial dose. Our findings suggest that population pharmacokinetic parameters are helpful for evaluating flomoxef pharmacokinetics and determining intraoperative flomoxef redosing intervals.

[Questionnaire Survey of Treatment for Elderly Breast Cancer in Yamaguchi Prefecture].

A questionnaire survey was conducted by 17 doctors from 14 hospitals regarding treating elderly breast cancer in Yamaguchi Prefecture. The survey items are the implementation status of the geriatric assessment(GA)for the elderly, the state at the start of treatment(fit/vulnerable/frail), and the setting of restrictions on the indication of surgery and drug treatment (endocrine therapy/chemotherapy/molecular targeted therapy). Only one institution(6%)was used for GA; the tools used were the G8 and Charlson comorbidity index. Regarding surgical treatment, most facilities did not set restrictions according to age or condition. Endocrine and molecular-targeted therapies(anti-HER drugs)are highly tolerated, and most facilities do not have age restrictions. On the other hand, 40% of the respondents set age restrictions on chemotherapy. Four(24%) therapists said they would limit their age to 70 to 75 if the patient had a frail condition. These results tended to be similar to the reports of NCD-registered elderly breast cancer treatment.

[A Case of Local Recurrence in the Reconstructed Breast Three Years after Reconstructive Surgery and Seven Years after Breast Cancer Surgery].

In recent years, breast reconstruction has been increasingly performed in breast cancer surgery with improving the appearance of the breast. We report a case of local breast cancer recurrence after artificial breast reconstruction. The patient was a 52-year-old woman. She had undergone total mastectomy for left breast cancer 11 years ago, and reconstruction with breast implant 3 years ago. She presented to our hospital with the chief complaint of skin redness and induration of the reconstructed breast. A core needle biopsy was performed, and its results showed in the invasive ductal carcinoma. She had an operation of resection of tumor and reconstruction implant. As a result of histopathological diagnosis, it was a local recurrence of breast cancer 11 years ago. After the surgery, she underwent endocrine therapy and there is no recurrence. As the increase in the number of cases of breast reconstruction, the number of recurrences in the reconstructed breast is expected to increase the future. The treatment strategy for cases of local recurrence after breast reconstruction is currently under review, the accumulation of evidence is necessary.

[Investigation of Patients with Stage â £ Breast Cancer Who Underwent Primary Tumor Resection].

We investigated whether primary tumor resection performed at our department for the purpose of local control affects the disease progression of Stage Ⅳ breast cancer. Fifteen patients who underwent primary tumor resection between 2009 and 2017 were investigated. The median age at the time of surgery was 63 years. There were two postoperative deaths(1 at<1 year postoperatively and 1 at<2 years postoperatively). The median postoperative stable disease(SD)period was 11 months overall and was 12 months or longer in 7 patients. SD was attained by all patients with the first drug treatment after primary tumor resection. Patients who tended to have a longer postoperative SD period did not receive preoperative drug treatment, were luminal HER2-positive, and had one metastatic organ. Regardless of surgery timing and reason, there were no cases of rapid postoperative disease progression. In all patients, postoperative local control was satisfactory, and continuation of medical treatment was feasible for distant metastatic tumors. These data signify that primary tumor resection can be considered to treat Stage Ⅳ breast cancer for the purpose of local control.

[A Case of Pancreatic Head Cancer Resected after Neoadjuvant Chemotherapy Followed by Pseudocyst].

A 41-year-old man with upper abdominal and back pain was admitted to another hospital. He had a history of recurring acute pancreatitis and pseudocyst. Six months later, abdominal CT revealed a pancreatic head tumor arising from the pseudocyst, and adenocarcinoma was suspected based on endoscopic ultrasound fine needle aspiration(EUS-FNA)findings. We selected neoadjuvant chemotherapy because resection was difficult due to severe inflammation and edema around the tumor. Chemotherapy(FOLFIRINOX followed by gemcitabine plus nab-paclitaxel)was effective, and the tumor almost disappeared on CT. Subtotal stomach-preserving pancreatoduodenectomy(SSPPD)was performed 12 months after starting chemotherapy, and curative resection was successful. The final Stage was ⅡA(T3[CH1]N0M0). Histopathological examination revealed no viable tumor cells. S-1 adjuvant chemotherapy was administered for 6 months. He was still alive 22 months postoperation without any recurrence. Neoadjuvant chemotherapy is effective in cases involving pancreatic cancer with severe inflammation, because pre-operative chemotherapy can reduce tumor size and alleviate the inflammation caused by acute pancreatitis and pseudocysts.

[A Case of Recurrent Gastric Cancer with Clinical Complete Response after Ramucirumab plus Paclitaxel Therapy].

We report a case of a 61-year-old man who underwent open total gastrectomy and D2 lymph node dissection for gastric cancer. The pathological findings were suggestive of pT2N3M0, fStage ⅢA. S -1 was administered for 1 year post-surgery. One year and 9 months after the operation, an epigastralgia was found, and the PET-CT showed an increase of SUVmax 3.80 around the celiac artery. S -1 plus CDDP therapy was initiated. However, due to the occurrence of neutropenia, the therapy was changed to ramucirumab plus paclitaxel. After 20 courses of the same regimen, no PET-CT uptake was observed. We thus considered it cCR and discontinued further chemotherapy. The patient has been alive for 15 months without recurrence. By performing effective chemotherapy at an early stage, cCR could be observed after a secondary treatment. Therefore, longterm survival could be expected for post-operative recurrence of gastric cancer.

[A Case of Gastric Endocrine Carcinoma with a Huge Liver Metastasis].

A-67-year old man was diagnosed with gastric cancer and a liver tumor. Extended left hemihepatectomy combined with caudate lobectomy and distal gastrectomy with lymph node dissection were performed. Histological examination revealed synaptophysin and CD56positive tumor cells with a solid and rosette structure, which was diagnosed as endocrine carcinoma (EC). Additionally, a tubular adenocarcinoma was present in the stomach. The liver tumor presented as EC with tumor thrombus in the left portal vein. Finally, the patient was diagnosed with gastric EC(pT3[SS], pN0, P0, CY0, M1[HEP], Stage Ⅳ, R0). He received 6courses of the adjuvant chemotherapy with cisplatin(CDDP)plus irinotecan(CPT-11), and has been alive without recurrence for 21 months post-operation. Gastric EC is a rare subtype of gastric cancer. The resection of liver metastasis of gastric EC may improve patients' prognosis and QOL. CDDP-based chemotherapy is recommended, due to the regimen for small cell lung cancer.

[A Case of Sigmoid Colon Cancer with Complete Visceral Inversion].

Complete visceral inversion occurs in 1/5,000 individuals. In 64%of cases, complete visceral inversion is complicated by the malformation of other organs. Careful attention is required when performing surgeries. In recent years, with the development of laparoscopic surgery, some cases of laparoscopic surgery with complete visceral inversion have been reported. Herein, we report a case of safely performed laparoscopic surgery for sigmoid colon cancer with complete visceral inversion along with a relevant discussion.

[Chemoradiotherapy with S-1 for Recurrence Cases of Colorectal Cancer].

INTRODUCTION: Although chemotherapy is the main treatment for recurrent colorectal cancer, the utility of radiotherapy as a local treatment has been widely reported. We performed chemoradiotherapy with S-1 for cases with recurrence after surgery, and the outcomes are reported herein. MATERIALS AND METHODS: Chemoradiotherapy with S-1 was performed in 4 cases. S-1 was administered for 2 weeks during the irradiation period, and the off period provided was 1 week. RESULTS: X-ray irradiation was performed in 2 cases and proton beam irradiation in the other 2. The progression free periods of the 2 cases receiving proton beam irradiation were 31 months and 36 months. In contrast, the progression free periods of the 2 cases given X-ray irradiation were 24 months and 21 months. DISCUSSION: It is known that S-1 not only achieves a high anticancer effect via dihydropyrimidine dehydrogenase(DPD)inhibition, which is a major metabolic pathway of 5-FU, but also increases the radiation susceptibility of malignancies. S-1 is regarded as an ideal anticancer agent when used in combination with radiation therapy. Since the local control achieved in our 4 cases was good, chemoradiotherapy with S-1 was considered to be a useful treatment.

[A Case of Recurrent Breast Cancer with Bone Metastasis Successfully Treated with Everolimus and Exemestane Therapy].

We report a case of a patient treated with everolimus and exemestane combination therapy for bone metastasis after breast surgery.The patient, a 58-year-old woman, consulted our department for back pain in October 2014.S he was diagnosed with left breast cancer when she was 41 years old.She had received Bt+Ax for left breast cancer and administered tamoxifen for 5 years.We decided on everolimus and exemestane combination therapy after observing an abnormal uptake in the 7th to 8th thoracic vertebrae on a PET-CT scan.The pain was controlled using oxycodone and fentanyl orally disintegrating tablet with zoledronic acid.After receiving treatment, the patient experienced pruritus and a Grade 2 rash, but they were managed with antihistamine administration and the treatment was continued.Four months later, the abnormal uptake on the right thoracic vertebrae shrunk; the pain almost disappeared, and oxycodone and fentanyl orally disintegrating tablet were discontinued.Subsequently, exemestane was used alone.Six months later, the range of abnormal uptake on the thoracic vertebrae progressed, and the disease was evaluated as PD.Four months later, everolimus and exemestane combination therapy was resumed, and the abnormal uptake on the thoracic vertebrae almost disappeared as observed on a PET scan.The effectiveness of the treatment was evaluated as CR because other local recurrence and new metastases were not found. Everolimus might exhibit bone resorption inhibiting effects and bone protection effects, but the decision regarding the periods of suitable use and the effects of long-term continuation of treatment are controversial, and further discussion based on experience of increasing use is required.

[Efficacy and Safety of Everolimus plus Exemetane in Postmenopausal Endocrine-Responsive Metastatic Breast Cancer Patients].

Everolimus and exemestane combination therapy represents a treatment option for estrogen receptor(ER)-positive metastatic breast cancer. We evaluated the efficacy and safety of everolimus and exemestane therapy, retrospectively. After a median follow-up of 10.5 months, the median progression-free survivalin patients was 4.7 months. The clinicalbenefit rate was 27%and the disease controlrate was 64%. The most common all-grade adverse events(AEs)were stomatitis(82%) and non-infectious lung disease(27%). The most commonB3 grade AEs were cellulitis(18%)and hyperglycemia(18%). The AEs reported were mostly grade 1 and 2, and manageable with appropriate intervention. Combination therapy with everolimus and exemestane appears to be a useful addition for ER-positive metastatic breast cancer, with carefulmanage- ment of specific AEs.

[Effect of Pegfilgrastim Primary Prophylactic Administration on Relative Dose Intensity(RDI)in Postoperative Adjuvant Chemotherapy(TC Therapy)for Breast Cancer - A Single-Center, Retrospective Study].

This study assessed the effect of pegfilgrastim in patients with early stage breast cancer who were receiving docetaxel and cyclophosphamide(TC)therapy(75mg/m / 2 docetaxel plus 600 mg/m2 cyclophosphamide). In total, 17 patients who were to receive 4 planned cycles of TC therapy every 3 weeks were included in this study. Of the 17 patients, 10 who received pegfilgrastim after January 2016 formed the Peg-G group and 7 who did not receive pegfilgrastim until December 2015 formed the control group. We observed a high successful execution rate and relative dose intensity(RDI)with docetaxel in both groups. The successful execution rates were 100% in the Peg-G group and 42.8% in the control group. The RDI was 86.5%(65.4-100%)in the Peg-G group and 52.5%(48.0-58.0%)in the control group. This study showed that the use of pegfilgrastim results in a high successful execution rate and RDI in patients with early stage breast cancer undergoing TC therapy.

[Examination of Cases of Hepatectomy for Metastatic Colorectal Cancer].

OBJECTIVES: Resection of liver metastasis from colorectal cancer is known to improve prognosis; therefore, surgical treatment is recommended for resectable metastases in the Japanese Society for Cancer of the Colon and Rectum Guidelines for the Treatment of Colorectal Cancer. In this study, we investigated factors that affect the prognosis of resection of such metastatic liver tumors. RESULTS: Thirty-three cases of liver resection performed during the period from 1998 to 2017 were investigated. The 5-year overall survival rate after liver resection was 47.3%, and the 5-year recurrence-free survival rate after liver resection was 29.9%. Univariate analysis identified CA19-9(p=0.02)and operative procedure(p=0.0046)as prognostic factors, while multivariate analysis revealed operative procedure(p=0.03)to be a prognostic factor. When prognosis was examined in terms of operative procedure(ie, lobectomy, segmental resection, or partial resection), the prognosis of patients undergoing lobectomy was significantly poorer compared to those undergoing segmental resection(p=0.0092, RR=28.94)and partial resection(p=0.0092, RR=25.37). CONCLUSION: In this study, operative procedure was identified as a poor prognostic factor. The prognosis of liver metastasis requiring lobectomy is considered to be poor. Further accumulation of cases is needed to investigate the effects of other factors in the choice of operative procedure.

Multicenter Prospective Cohort Study of Neoadjuvant Chemotherapy for Borderline Resectable Pancreatic Cancer (YPB-001).

OBJECTIVES: The present multicenter prospective observational study investigated the effectiveness and safety of neoadjuvant chemotherapy (NAC) for patients with borderline resectable pancreatic cancer (BRPC) and those with RPC contacting major vessels, with respect to a historical control of upfront surgery. MATERIALS AND METHODS: Patients with BRPC and RPC contacting major vessels were prospectively registered and administered NAC with durations and regimens determined by the corresponding treating physician. Our primary aim was to assess the R0 resection rate, and secondary aim was to evaluate safety, resection rate, time to treatment failure, overall survival, and response rate. RESULTS: Fifty of 52 enrolled patients were analyzed; 2 with serious comorbidities died during treatment. Thirty-one patients underwent resection, with R0 resection being achieved in 26 (52% of total and 84% of all resected cases). Univariate and multivariate analyses indicated age (≥75 years) as the only independent predictor of nonresection. Median progression-free survival and median survival time were longer in the prospective cohort than in the historical cohort. CONCLUSIONS: Overall, NAC for BRPC in real-world setting might yield R0 resection rates similar to those reported in previous clinical studies. Development of safe regimens and management strategies that can maintain treatment intensity in geriatric patients is warranted.

[Solitary ectopic thymoma at ligamentum arteriosum; report of a case].

We report a case of solitary ectopic thymoma at the ligamentum arteriosum, which was resected with thoracoscopic surgery. A 62-year-old male patient received chemoradiation therapy for laryngeal cancer approximately 1 year before. The present computed tomography scan indicated a mass (diameter, 2 cm) at the ligamentum arteriosum. Furthermore, positron emission tomography showed an abnormal accumulation on the mass. Malignant lymphoma and laryngeal cancer with lymph node metastasis were suspected, and thoracoscopic surgery was performed. The tumor had a clear margin;therefore, it could be extirpated easily. The results of the postoperative pathological examination indicated that the tumor was an ectopic thymoma. The patient was discharged 3 days after the surgery because he showed good clinical course and was kept under careful observation.

[Long-term survival of a case of juvenile colon cancer with multiple liver metastases successfully treated by multidisciplinary therapy].

A 35-year-old woman underwent hemicolectomy and RFA for ascending colon cancer with multiple liver metastases in February, 2005. She received postoperative hepaticarterial infusion chemotherapy with 5-FU, and systemic hemotherapy with UFT for 10 months after the operation. A local recurrence of the anastomosis was detected in March, 2006, and she underwent a resection for it. This was followed by 6 courses of adjuvant chemotherapy with modified FOLFOX6. Because multiple liver metastases and lymph node metastases were detected in March, 2007, she received RFA and 6 courses of adjuvant chemotherapy with modified FOLFOX6 again. Liver metastases disappeared but lymph node metastases still remained. Therefore, she received 4 courses of bevacizumab plus modified FOLFOX6. The metastatic lesions disappeared and were judged to be CR. Therefore, she was followed-up with the oral administration of UFT. Metastases of liver and lymph nodes of the mediastinum were detected in May, 2008, for which she received 4 courses of bevacizumab plus FOLFIRI2. Because the effects of the chemotherapy were judged to be CR, she continued with 4 courses of the same regimen. The regimen was discontinued due to diarrhea, and she therefore began to receive 4 courses of bevacizumab plus LV/5-FU regimens. CR has been maintained at present, over 7 years after the initial surgery.

[A case wherein bevacizumab/XELOX combination therapy was remarkably effective for the treatment of extensive dissemination in advanced colon cancer, and the primary lesion could be resected].

Here, we report a case wherein bevacizumab/XELOX combination therapy was remarkably effective for the treatment of a patient with unresectable advanced cecum cancer and carcinomatous peritonitis. A 52-year-old man was diagnosed with cecum cancer with extensive carcinomatous dissemination. He underwent open laparotomy, and the findings indicated a unresectable cecal tumor attached to the retroperitoneum; therefore, ileo-transverse colostomy was performed. After 6 courses of bevacizumab and XELOX therapy, the primary tumor as well as ascites and carcinomatous dissemination had disappeared, and a marked decrease in the serum carcinoembryonic antigen(CEA)level was noted. However, subsequently, positive emission tomography/computed tomography(PET/CT)indicated a recurrence of the primary tumor. Therefore, ileocecalectomy and D2 lymph node dissection were performed. Thus, we believe that bevacizumab/XELOX therapy may be useful as neoadjuvant chemotherapy for the treatment of advanced colon cancer with peritonitis carcinomatosa.

[A case of advanced esophageal cancer revealed a pathological complete response and survived more than 8 years, treated by radiation therapy combined with nedaplatin and 5-FU chemotherapy].

We report here the long-term survival case of advanced esophageal cancer treated with definitive chemoradiotherapy (CRT). A 61-year-old woman visited our hospital because of a disturbance in her swallowing in September, 2003. She was diagnosed with a middle esophageal type 3 tumor, which was 9 cm in length by endoscopy. Squamous cell carcinoma was diagnosed by pre-operative endoscopic biopsy. CT revealed the tumor with direct invasion to the aorta, and multiple metastases of the lymph nodes(T4, N1, M0: Stage IVa). CRT(combination of 5-FU and nedaplatin with 40 Gy of radiation)was administered. After the completion of CRT, the tumor size was remarkably reduced, but stenosis of the lumen of the esophagus remained partially. Therefore, we performed sub-total esophagectomy in February, 2004. A pathological complete response was diagnosed with no carcinoma cells evident in the resected specimen. Pathological therapeutic evaluation of the esophageal cancer was grade 3. The patient had received no adjuvant chemotherapy, but she is alive and healthy now with no relapse of carcinoma for more than 8 years after operation.

[A case of pathologically by complete response in advanced sigmoid colon cancer with multiple metastases of lung and Liver, left hydronephrosis after chemotherapy including bevacizumab/FOLFOX6].

A 61-year-old complaining of anorexia and general fatigue was admitted to our hospital for further examination. She was diagnosed as advanced sigmoid colon cancer with multiple metastases of lung, liver, and left hydronephrosis. Since curative surgery was not deemed possible, we started chemotherapy with bevacizumab/FOLFOX6 (bi-weekly drip infusion). After the 6th course, colonoscopy revealed a significant tumor reduction and changes to the scar tissues. CT did not reveal a complete disappearance, but found some reductions in metastases of lung and liver. Sigmoidectomy and lymph node resection (D1) were performed. We did not disappeared any dissemination and the histological diagnosis revealed a complete disappearance of cancer cells in the main tumor. She was discharged 13 days after surgery, following chemotherapy which included bevacizumab and XELOX. The chemotherapy using bevacizumab/FOLFOX6 is a candidate for the standard treatment strategy for inoperable advanced colon cancer. Herein we report this rare case with a review of the literature.