Adult-Onset Focal Nesidioblastosis With Nodular Formation Mimicking Insulinoma.

Nesidioblastosis is defined as the neoformation of the islets of Langerhans from the pancreatic ductal epithelium and is recognized as the most common cause of hyperinsulinemic hypoglycemia in infants. We herein report an extremely rare case of adult-onset focal nesidioblastosis with the unusual feature of hyperplastic nodular formation. A 55-year-old woman was admitted to our hospital for a tumor detected in the body of the pancreas by magnetic resonance imaging screening. Laboratory examinations showed a high insulin level in the blood. Contrast-enhanced computed tomography and the selective arterial calcium injection test suggested the presence of multiple insulinomas in the body and tail of the pancreas, and, thus, the patient underwent distal pancreatectomy. A histopathological examination of the tumor in the body of the pancreas showed the nodular hyperplasia of islet-like cell clusters. In addition, many small intralobular ductules and islet cells appeared to be budding from the proliferating ductal epithelium, forming "ductuloinsular complexes". No other abnormal lesion was detected in the remainder of the pancreas. The histopathological diagnosis was focal nesidioblastosis. The patient has remained free of the recurrence of hypoglycemic episodes for more than 31 months. The present case of rare adult-onset focal nesidioblastosis with hyperplastic nodular formation was preoperatively identified as an apparent pancreatic tumor mimicking insulinoma. Nesidioblastosis and insulinoma need to be considered in cases of hyperinsulinemic hypoglycemia, even in adult patients.

Optimization of prediction methods for risk assessment of pathogenic germline variants in the Japanese population.

Predicting pathogenic germline variants (PGVs) in breast cancer patients is important for selecting optimal therapeutics and implementing risk reduction strategies. However, PGV risk factors and the performance of prediction methods in the Japanese population remain unclear. We investigated clinicopathological risk factors using the Tyrer-Cuzick (TC) breast cancer risk evaluation tool to predict BRCA PGVs in unselected Japanese breast cancer patients (n = 1,995). Eleven breast cancer susceptibility genes were analyzed using target-capture sequencing in a previous study; the PGV prevalence in BRCA1, BRCA2, and PALB2 was 0.75%, 3.1%, and 0.45%, respectively. Significant associations were found between the presence of BRCA PGVs and early disease onset, number of familial cancer cases (up to third-degree relatives), triple-negative breast cancer patients under the age of 60, and ovarian cancer history (all P < .0001). In total, 816 patients (40.9%) satisfied the National Comprehensive Cancer Network (NCCN) guidelines for recommending multigene testing. The sensitivity and specificity of the NCCN criteria for discriminating PGV carriers from noncarriers were 71.3% and 60.7%, respectively. The TC model showed good discrimination for predicting BRCA PGVs (area under the curve, 0.75; 95% confidence interval, 0.69-0.81). Furthermore, use of the TC model with an optimized cutoff of TC score ≥0.16% in addition to the NCCN guidelines improved the predictive efficiency for high-risk groups (sensitivity, 77.2%; specificity, 54.8%; about 11 genes). Given the influence of ethnic differences on prediction, we consider that further studies are warranted to elucidate the role of environmental and genetic factors for realizing precise prediction.

Genetic and clinical landscape of breast cancers with germline BRCA1/2 variants.

The genetic and clinical characteristics of breast tumors with germline variants, including their association with biallelic inactivation through loss-of-heterozygosity (LOH) and second somatic mutations, remain elusive. We analyzed germline variants of 11 breast cancer susceptibility genes for 1,995 Japanese breast cancer patients, and identified 101 (5.1%) pathogenic variants, including 62 BRCA2 and 15 BRCA1 mutations. Genetic analysis of 64 BRCA1/2-mutated tumors including TCGA dataset tumors, revealed an association of biallelic inactivation with more extensive deletions, copy neutral LOH, gain with LOH and younger onset. Strikingly, TP53 and RB1 mutations were frequently observed in BRCA1- (94%) and BRCA2- (9.7%) mutated tumors with biallelic inactivation. Inactivation of TP53 and RB1 together with BRCA1 and BRCA2, respectively, involved LOH of chromosomes 17 and 13. Notably, BRCA1/2 tumors without biallelic inactivation were indistinguishable from those without germline variants. Our study highlights the heterogeneity and unique clonal selection pattern in breast cancers with germline variants.

[A Case of Anaphylactic Shock after First Administration of Oxaliplatin].

A 48-year-old woman with advanced gastric cancer with peritoneal dissemination was treated with weekly paclitaxel from October 2015 and was then administered the CapeOX regimen. Although she had no adverse event during the 2-hour administration of the first oxaliplatin(L-OHP), sudden wheezing, subsequent decrease in blood pressure, and vomiting occurred after completing the administration. After intravenous injection of epinephrine(1mg)and drip infusion of methylprednisolone( 500mg), she received continuous administration of norepinephrine for 5 days. Hypersensitivity reaction to LOHP typically occurs after several cycles and within 30 minutes of starting the administration. However, we have to recognize that the hypersensitivity can also occur after the first cycle and at a later onset.

[Gastrointestinal Stromal Tumor of the Small Intestine with Dissemination Successfully Treated with Surgical Resection and Adjuvant Chemotherapy with Sunitinib-A Case Report].

We report the case of a 73-year-old woman with repeated recurrent small intestinal gastrointestinal stromal tumor(GIST) who was referred to our hospital for best supportive care. She underwent surgical resection 4 times and developed recurrent tumors that were resistant to imatinib. She complained of right lower abdominal pain caused by the recurrent tumor. We performed surgical resection of the tumor and the disseminated tumors synchronously. Histopathological findings of the resected specimen revealed a high-risk GIST. After the operation, she was administered sunitinib(50mg/day)as adjuvant therapy according to a 4-week-on/2-week-off schedule. Due to the resulting adverse effects, the schedule was changed to 1-week-on/1-week-off therapy. She showed no sign of recurrence 38months after the last surgery. Thus, surgical resection and adjuvant molecular targeted therapy may be an effective treatment strategy for recurrent GIST.

Left atrium mass in a patient with breast cancer: a case report.

BACKGROUND: Left atrial thrombi have traditionally been treated with heparin and warfarin, and many physicians have limited experience with direct oral anticoagulants such as apixaban. Furthermore, the efficacy of apixaban for the treatment of left atrial thrombi has not been established. We experienced a case of left atrial thrombus formation before breast cancer surgery, which was resolved by apixaban. CASE PRESENTATION: Computed tomography for a 74-year-old Japanese woman with breast cancer incidentally revealed a left atrial mass with a root before the breast surgery. The mass was surgically removed and determined to be a thrombus. Before the breast surgery, transthoracic echocardiography was performed again, and the left atrial thrombus had recurred within only 14 days. It resolved after administration of apixaban. CONCLUSIONS: A left atrial thrombus might recur within a very short time. Apixaban might be an alternative to warfarin in patients with breast cancer and left atrial thrombus.

Cholangiolocellular carcinoma with rapid progression initially showing abnormally elevated serum alfa-fetoprotein.

Cholangiolocellular carcinoma (CoCC) is a rare malignant liver tumor derived from hepatic progenitor cells, which exist in the canals of Hering. We encountered a case of CoCC with an extremely poor clinical course, initially showing abnormally elevated serum alfa-fetoprotein (AFP). A 72-year-old male presented with a liver tumor and abnormally elevated serum AFP levels (16,399 ng/ml). We preoperatively diagnosed hepatocellular carcinoma and performed extended right hepatectomy, after which the serum AFP levels remarkably decreased to 97 ng/ml. Postoperatively, the disease was pathologically diagnosed as CoCC. Furthermore, immunohistochemical pathological findings were alcian blue negative, cytokeratin (CK) 7 partially positive, CK19 positive, hepatocyte paraffin-1 negative, membranous negative for epithelial membrane antigen, and AFP negative. Fifty-five days later, intra- and extrahepatic recurrence developed, and the patient died 65 days after surgery. Although CoCCs show favorable outcomes, these characteristics of our case were not previously reported. It is necessary to accumulate more information on CoCC.

[A Case of Gastric Cancer with Diffuse Intra-Tumoral Calcifications Showing Pathological Complete Response to Chemotherapy with S-1 plus Docetaxel].

A 70-year-old woman was diagnosed with cStage IV gastric cancer with diffuse intra-tumoral calcifications. She underwent systemic chemotherapy with an S-1/cisplatin regimen. However, as the disease progressed after 5 courses of the regimen, a secondary S-1/docetaxel regimen was administered. The target lesions showed complete response after 6 courses of this regimen, and surgery with curative intent was planned. The patient underwent total gastrectomy because no factors that would compromise the curative intent were observed during laparotomy. Postoperatively, the disease showed pathological complete response to chemotherapy.

Timing of laparoscopic cholecystectomy for mild and moderate acute cholecystitis.

BACKGROUND/AIMS: The timing of a laparoscopic cholecystectomy (LC) for acute cholecystitis (AC) remains controversial. Traditionally, LC for AC is performed within 3 days. We designed this study so that the cut-off time of LC for AC was within 7 days of admission, based on severity. METHODOLOGY: A total of 103 patients were divided into 2 groups: patients undergoing LC within 7 days of admission [early LC (ELC), n = 41] and patients undergoing LC between 8 days and 5 weeks of admission [delayed LC (DLC), n = 62]. The outcomes compared were complication rate, conversion rate, postoperative hospital days, and operation time. Statistical analyses were performed in mild, moderate and all AC cases. Results: Of all AC cases, successful LC was performed in 93 patients, and no significant difference was observed between the 2 groups. In DLC for moderate AC, percutaneous cholecystectomy (PC) with or without endoscopic nasal bile drainage (ENBD) was performed more frequently than ELC. CONCLUSIONS: DLC had no advantage over ELC. ELC for AC is preferable in cost­effect. Even if the operation cannot be scheduled early, proper initial treatment, including percutaneous cholecystectomy with or without endoscopic nasal bile drainage for moderate AC, enables DLC a safe option.

A large retroperitoneal malignant solitary fibrous tumor.

We report on a large, retroperitoneal, malignant, solitary fibrous tumor (SFT) with high proliferation activity. A 43-year-old man was admitted to our department complaining of a palpable mass. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a large retroperitoneal tumor occupying the entire abdominal cavity. A laparotomy was performed for diagnosis and treatment, which revealed a tumor in the retroperitoneum but with no invasion to the surrounding organs, thereby allowing safe macroscopic excision. Histologically, the tumor was composed of spindle-shaped cells with patternless pattern and a hemangiopericytomatous appearance. Moreover, immunohistochemical staining was positive for CD34, vimentin, Bcl-2, and CD99 and negative for desmin, S-100p, and smooth muscle actin (AMA). The tumor exhibited high cellularity, moderate mitotic activity, pleomorphism, necrosis, and hemorrhagic changes. In addition, the Ki-67 labeling index was 37%. These findings confirmed the diagnosis of malignant SFT with high proliferation activity. Subsequently, adjuvant doxorubicin plus ifosfamide chemotherapy was performed. No signs of recurrence were observed 12 months after the surgery.

Divided saphenectomy for varicose vein in ambulatory surgery.

We performed divided saphenectomy (DS) for varicose vein in ambulatory surgery with minimal incisions. Under tumescent local anesthesia, this procedure ligates all perforators in the thigh, preserving a route of venous drainage, and reduces bruising by ligating all tributaries. Also, DS does not need any special surgical instrument. Subcutaneous inguinal hemorrhage was observed in 4.9% (3/61), mild bruises were observed in 19.7% (12/61), and saphenous nerve neuralgia was 1.6% (1/61). Wound infection, deep venous thrombosis, and edema were not observed. DS is a minimally invasive, simple, and cost-effective procedure.

Multicystic biliary hamartoma mimicking intrahepatic cholangiocarcinoma: report of a case.

Multicystic biliary hamartoma (MCBH) is a rare cystic disease of the liver. A 69-year-old man was referred to our hospital with radiographic abnormality. Physical examination of the patient was unremarkable, and he denied any previous medical, travel, or surgical history. An abdominal computed tomography (CT) scan demonstrated a 3-cm low-density lesion in segment 3 of the liver, with dilation of the intrahepatic bile duct. The peripheral site of this lesion was slightly enhanced in the arterial phase. In the portal phase, the peripheral site was enhanced more clearly and showed a honeycomb-like dilated bile duct. Ultrasonography also revealed that the lesion was an irregularly shaped mass. On magnetic resonance imaging (MRI), T1-weighted images revealed a low-density mass and T2-weighted images revealed a dappled-density mass with honeycomb-like dilated bile duct and dilation of major intrahepatic bile duct. The patient was diagnosed with intrahepatic cholangiocarcinoma (ICC) and underwent left hepatectomy. However, pathological findings revealed that the lesion was MCBH. Our case highlights the potential difficulties in differentiating between MCBH and ICC under such circumstances.

Prevalence and risk factors of bone metastasis and skeletal related events in patients with primary breast cancer in Japan.

BACKGROUND: Bone metastasis (BM) is important for studying systemic spread of breast cancer. It often causes skeletal-related events (SREs) that worsen quality of life. We investigated the prevalence and risk factors for BM and SRE using a dataset from the Breast Oncology Research Network (BORN) in Japan. PATIENTS AND METHODS: We collected data on primary breast cancer patients with node-positive or node-negative disease at intermediate to high risk of recurrence. The risk factors affecting the BM-free rate, SRE-free rate and overall survival were analyzed by using the Cox proportional hazard model. RESULTS: Data of 1,779 patients who were diagnosed with breast cancer during 2003-2005 were collected from the BORN and 1,708 cases were used for analysis. The median follow-up duration was 5.71 years. BM developed in 193 cases (11.3 %) and the BM-free rate at 5 years was 89.2 %. The annual hazard ratio of BM development differs remarkably according to the tumor subtype. SREs occurred in 133 (68.9 %) out of 193 patients and the SRE-free rate at 5 years was 92.6 %. In the multivariate analysis, clinical stage (P < 0.0001), number of lymph node (LN) metastases (P = 0.0029), tumor subtype (P = 0.034) and progesterone receptor status (P = 0.038) were independently significant risk factors for BM-free rate, but only clinical stage (P < 0.0001) and number of LN metastases (P = 0.0004) significantly correlated with SRE-free rate. CONCLUSIONS: This retrospective study clarifies the prevalence and risk factors for BM and SRE in Japanese breast cancer patients. Our results show the importance of considering subtype in the care of BM and SRE.

[A case of metastatic acsending colon cancer showing sustained complete response to chemotherapy with SOX and followed UFT].

A 72-year-old woman was diagnosed as Stage IV ascending colon cancer, with metastasis of lung and para-aortic lymph node. She received laparoscopic assisted right hemicolectomy for the local control. After the operation, we performed chemotherapy. We report a case of metastatic ascending colon cancer showing complete response(CR)to 3 courses of S-1/ oxaliplatin(SOX)regimen, and maintaining a CR status while being followed with UFT for 20 months.

Laparoscopic splenectomy for a large multilocular splenic cyst with elevated CA19-9: Report of a case.

INTRODUCTION: Because splenic cysts are rare, a definitive treatment regime for these cysts remains unclear. We report a case of a large multilocular splenic cyst with elevated carbohydrate antigen 19-9 (CA19-9) levels, which was successfully treated with laparoscopic splenectomy. PRESENTATION OF CASE: A 22-year-old female was admitted to our hospital with severe left upper abdominal pain. Serum CA19-9 level was mildly elevated (65U/ml). Computed tomography revealed a 25-cm long spleen with multilocular cystic lesions, for which an emergency laparoscopic splenectomy was performed. Histological findings revealed that the lesion was a benign true cyst, and immunostaining analyses showed that the epithelium was CA19-9-positive. DISCUSSION: Although some spleen-preserving approaches have been reportedly used, splenic cyst recurrence usually occurs in true cyst cases, wherein the cyst is incompletely removed. Most reported cases of splenic cysts producing CA19-9 are true cysts. CONCLUSION: The treatment approach should be decided on the basis of the type, shape, location, and even CA19-9 levels of the splenic cyst.

[A case of stage IV gastric cancer with multiple liver metastases responding to chemotherapy with weekly PTX after failure of chemotherapy with S-1 and CDDP combination].

A 65-year-old male with type 5 gastric cancer and two lesions of liver metastases was initially treated with S-1/CDDP. After completion of the second course, however, the progression of liver metastases and appearance of massive ascites were detected with CT scan, and dysphagia appeared. Total gastrectomy was performed to improve the symptoms. Later, chemotherapy with weekly PTX was performed, demonstrating the regression of liver metastases and disappearance of ascites after 2 courses. Thus, partial liver resection for liver metastases was performed. PTX has been readministered weekly, and the patient is currently attending the outpatient clinic without recurrence, although two years have passed since his first examination.

Laryngeal carcinoma in a non-smoker female patient with thyroid carcinoma: report of a case.

Laryngeal carcinoma is usually encountered in smoker men, and thyroid carcinoma is sometimes discovered incidentally during treatment for these patients. However, this coexistence of malignancies could occur in non-smoker female. We report an unusual case of multiple primary malignancies in the larynx and the thyroid gland. The laryngeal carcinoma was suspected to be related to the malignant transformation of the papillomas. The case suggests the importance of meticulous examination in the head and neck region for treatment of cervical metastatic lymph nodes with negative cytology in non-smoker female.

Dynamic helical CT mammography of breast cancer.

PURPOSE: The purpose of this study was to determine whether dynamic helical computed tomography (CT)-mammography could assist in selecting the most appropriate surgical method in women with breast cancer. MATERIALS AND METHODS: Preoperative contrast-enhanced helical CT scanning of the breast was performed on 133 female patients with suspicion of breast cancer at the same time as clinical, mammographic, and/or ultrasonographic examinations. The patients were scanned in the prone position with a specially designed CT-compatible device. A helical scan was made with rapid intravenous bolus injection (3 ml/s) of 100 ml of iodine contrast material. Three-dimensional maximum intensity projection (MIP) images were reconstructed, and CT findings were correlated with surgical and histopathological findings. RESULTS: Histopathological analysis revealed 84 malignant lesions and seven benign lesions. The sensitivity, specificity, and accuracy levels of the CT scanning were 94.6%, 58.6%, and 78.9%. Helical scanning alone revealed additional contralateral carcinomas in three of four patients and additional ipsilateral carcinomas in three of five patients. However, the technique gave false-positive readings in 24 patients. The preoperative CT-mammogram altered the surgical method in six patients. CONCLUSION: Dynamic helical CT-mammography in the prone position may be one of the choices of adjunct imaging in patients with suspected breast cancer scheduled for surgery.