Fumiaki Yotsumoto

Bradykinin involvement in the aggravation of acute pancreatitis in rabbits

This study was designed to investigate the role of bradykinin in the aggravation of acute pancreatitis. After injection of bradykinin 2 micrograms/kg to anesthetized rabbits with cerulein-induced acute pancreatitis, the pancreatic blood flow through gastroduodenal and superior mesenteric arteries (GDAF and SMAF) was determined with electromagnetic blood flow meters, the serum amylase level was measured, and pancreatic tissue was observed histologically. In rabbits treated with a supramaximal dose of cerulein alone (20 micrograms/kg/h), pancreatic blood flow was decreased and the serum amylase level was increased significantly by the early phase, and histological examination showed acute edematous pancreatitis. In rabbits treated with cerulein and bradykinin, GDAF and SMAF were significantly diminished at 300 min (51 +/- 5% and 50 +/- 4%, respectively, p < 0.05), and the serum amylase level rose significantly at 180 and 300 min (730 +/- 130% and 1,190 +/- 200%, respectively, p < 0.01) compared with rabbits treated with cerulein alone, and histological examination revealed pancreatic necrosis and greater inflammatory cell infiltration. These findings suggest that bradykinin has an additive role in the aggravation of acute pancreatitis.

Platelet-Activating Factor Involvement in the Aggravation of Acute Pancreatitis in Rabbits

Platelet activating factor (PAF) was administered to anesthetized rabbits with cerulein-induced acute pancreatitis to investigate the role of PAF in the development of acute pancreatitis. In acute edematous pancreatitis, induced with cerulein 20 micrograms/kg/h i.v. for 5 h, blood flow in the gastroduodenal and superior mesenteric arteries (GDAF and SMAF) had decreased significantly by 30 min and the serum amylase and lipase levels were significantly increased in the early phase. In the cerulein+PAF group, in which PAF was injected 100 ng/kg/min i.v. for 20 min simultaneously with cerulein, GDAF and SMAF declined significantly to 52 +/- 4 and 47 +/- 3% (p < 0.05), serum amylase and lipase levels rose significantly to 1,110 +/- 150 and 1,370 +/- 190% (p < 0.01) at 300 min, much higher than in the cerulein group. Furthermore, scattered hemorrhages and more marked inflammatory cell infiltration were observed histologically. These findings suggest that PAF has an additive role in the aggravation of acute pancreatitis.

Functional Changes of the Exocrine Perfused Rat Pancreas in Cerulein-Induced Pancreatitis

Functional changes of the exocrine pancreas in cerulein-induced pancreatitis were evaluated with the isolated perfused rat pancreas. In control specimens (n = 7), baseline pancreatic juice volume was 0.23 +/- 0.06 microliter/min and after stimulation with CCK-8 (10(-10) M) and secretin (10(-10) M), it was 2.26 +/- 0.45 microliter/min, and in cerulein-induced pancreatitis specimens (n = 8), the corresponding values were 0.11 +/- 0.03 and 0.23 +/- 0.08 microliter/min. The amylase content in the pancreatic juice (IU/min) was 0.73 +/- 0.15 (baseline) and 7.03 +/- 1.66 (stimulated) in the control specimens, and 0.012 +/- 0.002 (baseline) 0.018 +/- 0.004 (stimulated), in the cerulein-induced pancreatitis specimens. Amylase and lipase concentrations in the portal effluents were significantly higher in the cerulein-induced pancreatitis (481.3 +/- 79.4 IU/ml, 283.7 +/- 47.2 BALB U/ml) than in the control specimens (10.7 +/- 1.8 IU/ml, 8.9 +/- 2.9 BALB U/ml). Using the electron microscope fusion of large vacuoles with lateral plasma membrane was observed in cerulein-induced pancreatitis. In cerulein-induced pancreatitis, normal secretion was markedly decreased, and the lateral secretion was suggested to result in the elevation of pancreatic enzyme levels in portal effluents.

Low neutrophil-lymphocyte ratio correlates with extended survival in patients with metastatic breast cancer who achieved clinically complete response following multidisciplinary therapy: A retrospective study

The prognosis of patients with metastatic or recurrent breast cancer (MBC) is improving as novel treatments are developed. The present study compared the clinical characteristics of patients with MBC with or without a complete clinical response (cCR) and identified the survival-associated factors. This was a retrospective study, which included 171 patients treated for MBC between 2011 and 2017 at the Shiga Medical Center for Adults. Neutrophil to lymphocytes ratios (NLRs) were determined in blood samples. The median follow-up period following diagnosis of MBC was 44 months (range, 0-217 months). A total of 32 patients (18.7%) achieved a cCR. Compared with the non-cCR group, the cCR group had significantly fewer metastases or recurrences (P<0.001), significantly fewer visceral metastases (P<0.001), a significantly lower NLR (P<0.001) and were diagnosed with primary breast cancer at a significantly earlier stage (P=0.003). Prognosis was significantly improved in the cCR group compared with the non-cCR group (P<0.001) and a high NLR (≥19) independently predicted worse survival in a multivariate analysis (P=0.0218; hazard ratio, 1.75; 95% confidence interval, 1.09-2.85). In conclusion, the present study determined that achieving a cCR and having a low NLR are important for the long-term survival of patients with MBC.

Patients who achieved long-term clinical complete response and subsequently terminated multidisciplinary and anti-HER2 therapy for metastatic breast cancer: A case series

Highlights • Breast cancers that are positive for human epidermal growth factor receptor 2 (HER2) are aggressive and typically associated with a poor prognosis.• Novel anti-HER2 therapies have recently improved the outcomes in these cases.• We report a case series in which women were treated for metastatic HER2-positive breast cancer using trastuzumab and various chemotherapies.• These patients ultimately achieved clinical complete response, and subsequently terminated their systemic therapy after maintenance therapy.• Our findings indicate that select patients may be suitable for treatment termination if they have achieved a prolonged period of complete response.

Multidisciplinary treatment for locally advanced breast cancer with internal mammary lymph node metastasis in an elderly patient

Internal mammary lymph node (IMLN) metastasis is one of the important prognostic indicators in breast cancer. However, the management for IMLN metastasis is not established. The dissection for IMLN metastasis is not recommended in the National Comprehensive Cancer Network guidelines version3. 2015. Furthermore, radiotherapy including IMLN region and biopsy have attendant risks and hence should be performed with caution. Here, we describe our experience of multidisciplinary treatment for locally advanced breast cancer with IMLN metastasis in an elderly patient. Core-needle biopsy of the breast tumor histologically diagnosed the tumor as estrogen receptor positive, progesterone receptor positive, human epidermal growth factor receptor-2 negative, and high Ki-67 labeling index. IMLN swelling was detected by ultrasonography and breast cancer metastasis was diagnosed by fine-needle aspiration cytology. The patient underwent mastectomy and axillary lymph node dissection, followed by postmastectomy radiation therapy. Systemic therapy using tegafur plus uracil (UFT®; Taiho Pharmaceutical Co., Ltd, Tokyo, Japan) and letrozole was beneficial treatment for disease control.

Overall survival of elderly patients with breast cancer is not related to breast-cancer specific survival: A single institution experience in Japan

BACKGROUND As the aging population grows, the number of elderly breast cancer patients has rapidly increased especially in Japan; a suitable treatment for elderly patients, considering chronic comorbidities and treatment tolerance, is urgently needed. METHODS In this retrospective study, 286 elderly breast cancer patients were investigated. Tumor characteristics and survival outcome were compared between 70-79-year-old and ≥ 80-year-old groups. Disease-free survival, overall survival, and breast cancer-specific survival were compared, and the effect of variables was analyzed statistically. For resectable cases, prognoses were compared based on treatment (standard therapy or undertreated). RESULTS Tumor characteristics were similar between groups, but the Ki-67 labeling index tended to be higher in older patients. Elderly patients with resectable cancer tended to be undertreated. During the median 59-month follow-up period, overall survival was significantly worse in the ≥80-year-old than in the 70-79-year-old group (p < 0.001), but disease-free and breast cancer-specific survivals were equivalent. Recurrence or death event hazard rates tended to be lower in patients receiving standard treatment. CONCLUSIONS Standard multidisciplinary treatment for breast cancer prevents recurrence and metastasis and tends to extend breast cancer-specific survival even in elderly patients.

Chondrolipoma of the breast as a rare variant of myofibroblastoma: an immunohistochemical study of two cases

Chondrolipoma of the breast is a very rare tumor whose histogenesis remains obscure. We report two cases (56-year-old and 43-year-old women) and present the results of an immunohistochemical study which strongly suggests that this tumor is a variant of myofibroblastoma. The tumors predominantly consisted of lipoma-like, mature adipose tissue, and many islands of hyaline cartilage. A proliferation of spindle cells associated with the deposition of collagen fibers was also seen. On immunohistochemical examination, spindle cells showed cytoplasmic reactivity for vimentin, desmin, bcl-2, and α-smooth muscle actin, as well as nuclear reactivity for estrogen receptor (ER) and progesterone receptor (PgR). Chondrocytes were immunoreactive for ER, PgR, S-100 protein, and Sox9. The nuclei of adipocytes, chondrocytes, and spindle cells were not immunoreactive for Rb (retinoblastoma) protein. The immunoreactivity of spindle cells for muscle markers indicates myofibroblastic differentiation, and the lack of the nuclear expression of Rb protein suggests the close relationship of this tumor with myofibroblastoma and spindle cell lipoma. The immunoreactivity of chondrocytes for ER and PgR suggests that they are derived from metaplasia of hormone-sensitive spindle cells. These findings support the concept that chondrolipoma of the breast could be a lipomatous variant of myofibroblastoma associated with cartilaginous metaplasia and that it should be added to members of the “13q/Rb family of tumors.”

Palliative surgery for giant mucinous carcinoma of the breast in an elderly patient: A rare case report

Mucinous breast carcinoma (MBC) is relatively rare, accounting for <10% of all breast cancers in women. These tumors are usually slow-growing and exhibit less aggressive characteristics compared with other types of breast cancer. Between 1989 and 2016, 55 patients underwent surgery for MBC at the Shiga Medical Center for Adults (Moriyama, Japan). The 10-year disease-free survival (DFS) and overall survival rates were 94.5 and 100.0%, respectively. Specifically, the 10-year DFS rates of pure MBC (PMBC) and mixed MBC were 97.7 and 83.3%, respectively. We herein report the case of a sizeable mucinous carcinoma causing rupture of the skin and bleeding due to tumor pressure. Palliative surgery was performed in order to remove the bleeding source after a total of 5 months of preoperative endocrine-based therapy. In conclusion, palliative surgery improved the patients quality of life and may be a viable option for PMBC patients. The aim of the present study was to review the characteristics and management of these tumors, particularly in elderly patients.

Localized primary amyloidosis of the breast: a case report and review of the literature.

BackgroundPrimary amyloidosis of the breast is an unusual benign disease that mostly occurs in postmenopausal elderly women. Amyloidosis is the deposition of amorphous protein within tissues. Breast biopsy is necessary to make a definite diagnosis in order to avoid unnecessary surgical methods. Localized primary amyloidosis of the breast has a good prognosis. However, secondary amyloidosis is a systemic disease and has a poor prognosis.Case presentationWe report the case of a 77-year-old female with primary amyloidosis of the breast. She noticed a lump in her left breast. Mammographic and ultrasonographic examinations indicated breast cancer. However, core needle biopsy showed amyloidosis, not cancer of the breast. For further examinations, the patient visited the outpatient clinics of the hematology, dermatology, and gastroenterology departments. She underwent bone marrow aspiration, computed tomography, cardiac ultrasonography, random skin biopsy, gastrofiberscopy, and colonofiberscopy. Plasma cell myeloma and systemic amyloidosis were ruled out, and localized breast amyloidosis was highly suspected. Lumpectomy was performed to make a definite diagnosis, and histological evaluations revealed that this patient had localized amyloidosis of the breast, and the deposited amyloid protein was of the amyloid light chain kappa type.ConclusionsBreast biopsy is necessary in order to avoid unnecessary surgical technique. A diagnosis should be achieved only through a histological evaluation. The main treatment of localized primary amyloidosis of the breast is surgical removal.