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.

Prevalence of the Academic Research Consortium high bleeding risk criteria in patients undergoing endovascular therapy for peripheral artery disease in lower extremities.

The Academic Research Consortium (ARC) recently published a definition of patients at high bleeding risk (HBR) undergoing percutaneous coronary intervention. However, the prevalence of the ARC-HBR criteria in patients undergoing endovascular therapy (EVT) for peripheral artery disease in lower extremities has not been thoroughly investigated. This study sought to investigate the prevalence and impact of the ARC-HBR criteria in patients undergoing EVT. We analyzed 277 consecutive patients who underwent their first EVT from July 2011 to September 2019. We applied the full ARC-HBR criteria to the study population. The primary end point was a composite outcome of all-cause mortality, Bleeding Academic Research Consortium 3 or 5 bleeding, and lower limb amputation within 12 months of EVT. Among the 277 patients, 193 (69.7%) met the ARC-HBR criteria. HBR patients had worse clinical outcomes compared with non-HBR patients at 12 months after EVT, including a higher incidence of the composite primary outcome (19.2% vs. 3.6%, p < 0.001) and all-cause death (7.8% vs. 0%, p = 0.007). In a multivariate Cox proportional hazards regression analysis, presence of the ARC-HBR criteria [hazard ratio (HR) 4.15, 95% confidence interval (CI) 1.25-13.80, p = 0.020], body mass index (HR 1.13, 95% CI 1.01-1.27, p = 0.042), diabetes mellitus (HR 2.70, 95% CI 1.28-5.69, p = 0.009), hyperlipidemia (HR 0.41, 95% CI 0.21-0.80, p = 0.009), and infrapopliteal lesions (HR 3.51, 95% CI 1.63-7.56, p = 0.001) were independent predictors of the primary composite outcome. Approximately 70% of Japanese patients undergoing EVT met the ARC-HBR criteria, and its presence was strongly associated with adverse outcomes within 12 months of EVT.

A woman complicated by sudden cardiac arrest owing to spontaneous coronary artery dissection after stillbirth.

Spontaneous coronary artery dissection (SCAD) is the most important cause of acute coronary syndrome in pregnant women. Pregnancy-associated SCAD frequently occurs in the third trimester or postpartum period. However, little is known regarding the relationship between the occurrence of SCAD and stillbirth. We describe here a 41-year-old woman complicated by sudden cardiac arrest owing to SCAD in the distal segment of the right coronary artery 13 days after stillbirth. After contacting emergency medical services, she was resuscitated by an automated external defibrillator because the initial electrocardiographic waveform was ventricular fibrillation. After cardiopulmonary resuscitation, the diagnosis of SCAD was confirmed by coronary angiography and intracoronary imaging, including intravascular ultrasound and optical coherence tomography. The patient was managed with conservative medical therapy because the culprit lesion was present in the distal segment of the right coronary artery and coronary blood flow was preserved. No major adverse cardiovascular events, including recurrent ventricular arrhythmia, were observed during hospitalization. Our findings indicate that pregnancy-associated SCAD leading to sudden cardiac arrest may occur in the postpartum period, even after stillbirth. Intravascular imaging plays a pivotal role in diagnosing SCAD. .

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.

[Oral capecitabine as postoperative adjuvant chemotherapy in stage III colon cancer patients].

Capecitabine(Xeloda®)has been a global standard drug for the treatment of colon cancer since large randomized controlled trials demonstrated its efficacy and safety in treating patients suffering from the disease. Few studies have been conducted to assess the effects of oral capecitabine treatment on Japanese patients. Therefore, we conducted this study to evaluate oral capecitabine as postoperative adjuvant chemotherapy in 50 patients who underwent surgery for stage III colon cancer at our department. Patients received an 8 courses treatment with capecitabine during the study, and the incidence of adverse events, treatment completion rate, and treatment compliance were assessed. Adverse events were reported in a total of 46 patients(92%). The most common adverse event was hand foot syndrome(HFS), reported in 39 patients(78%), whereas bone-marrow toxicity and diarrhea were reported in as few as 2(4%)and 3(6%)patients, respectively. Both these events were mild in severity, and no patients required hospitalization, nor were they associated with treatment-related deaths. The median treatment duration was 8 courses ranging from 3 to 8 courses, and the 8 courses treatment completion rate was 96%. The relative dose intensity, which was used as a treatment compliance index, is expressed as the actual dose taken by the patient divided by the dose planned at baseline. The median and mean of the relative dose intensity were 100%(ranging from 37% to 100%)and 93%, respectively. The results of this study showed that the safety profile of oral capecitabine therapy was generally favorable, with a lower incidence and lesser severity of life-threatening bone-marrow toxicity and diarrhea, although the treatment is still associated with frequent HFS. This is the great advantage of capecitabine when it is used as postoperative adjuvant chemotherapy for gastrointestinal cancer. Indeed, a satisfactory treatment completion rate was achieved in this study while maintaining a sufficient dose and treating HFS, by reducing the dose, interrupting treatment, or providing appropriate corrective measures.

Lymphoepithelial cyst of the pancreas associated with elevated CA 19-9 levels.

An extremely rare case of a lymphoepithelial cyst associated with persistent elevation of serum carbohydrate antigen (CA) 19-9 levels is described. A 72-year-old man was incidentally found to have a cystic tumor in the uncus of the pancreas and to have a high serum CA 19-9 level. At 2-year follow up, the tumor size had gradually increased and the high CA 19-9 level persisted. Because the malignant potential of the tumor could not be ruled out, a laparotomy was performed. The tumor was excised from the pancreas. On pathological examination, the tumor was proven to be a lymphoepithelial cyst. After the operation, the patient's serum CA 19-9 level decreased to the normal range. Lymphoepithelial cysts of the pancreas are a rare, benign entity. They are true pancreatic cysts, characterized by a mature, keratinizing, squamous lining surrounded by lymphoid tissue. Because the treatment options and the prognosis of these entities are quite different from those of other cystic neoplasms of the pancreas, preoperative differential diagnosis is the main issue. Thus, although they are rare, lymphoepithelial cysts should be considered in the differential diagnosis of cystic tumors of the pancreas.

Surgical resection combined with CHOP chemotherapy plus rituximab for a patient with advanced mesenteric diffuse large B cell lymphoma.

Herein is described a mesenteric diffuse large B cell lymphoma (DLBCL) case with a bulky mass which had achieved a complete remission by the combination therapy of a surgical resection and the CHOP chemotherapy with rituximab. A 78 year old man was referred to the Rakuwakai-Otowa Hospital due to a left lower abdominal tumor. Abdominal CT and MRI showed a bowel-like mass in the left lower abdominal cavity. Abdominal US revealed lymph node swellings at the paraaortic region. By the gastro-duodenoscopy, DLBCL of non-Hodgkin's lymphoma was proven at the 2nd portion of the duodenum. On laparotomy, a mass of 8x8cm in size was found at the mesenterium of the ileum, which directly invaded the ileum and the sigmoid mesocolon. A partial resection of the ileum and the sigmoid colon was performed. After the operation, it was determined to be Stage IV DLBCL and the chemotherapy based on the R-CHOP regimen was performed. The regimen was repeated to the 6th course. During the chemotherapy, he was confirmed to have achieved a complete remission. The present case is a rare case in which a Stage IV mesenteric DLBCL with extensive bulky masses had a favorable prognosis. Stage IV mesenteric DLBCLs with extensive bulky masses are thought to be the indication for the combination therapy of surgical resection and multiagent chemotherapy with rituximab.

The role of prophylactic bilateral oophorectomy at the time of initial diagnosis of a unilateral ovarian metastasis in cases with colorectal adenocarcinoma.

BACKGROUND/AIMS: In cases with a macroscopic unilateral ovarian metastasis of colorectal adenocarcinoma, a clear therapeutic policy regarding a prophylactic bilateral oophorectomy is lacking. METHODOLOGY: Four cases of ovarian metastases of colorectal adenocarcinoma are presented. RESULTS: Case 1 is a 63-year-old with ascending colon carcinoma, Dukes' C, and right oophorectomy due to metachronous ovarian metastasis. Case 2 is a 28-year-old with transverse colon carcinoma, Dukes' D, and right oophorectomy due to synchronous ovarian metastasis. Case 3 is a 40-year-old with rectal carcinoma, Dukes' B, and right oophorectomy due to metachronous ovarian metastasis. Case 4 is a 32-year-old with rectal carcinoma, Dukes' D, and bilateral oophorectomy due to synchronous and metachronous ovarian metastases. Later, in cases 1 and 3, in which a unilateral ovary was preserved, ovarian metastases to the preserved ovary were found and caused severe clinical symptoms. However, by that time their general condition did not permit any additional laparotomy. CONCLUSIONS: Without other extensive metastases, if demonstrable diseases are found in a unilateral ovary, a prophylactic bilateral oophorectomy is recommended.

Synchronous mucosa-associated lymphoid tissue lymphoma and gastrointestinal stromal tumor of the stomach presenting with gastric bleeding.

We report an extraordinarily rare case of synchronous mucosa-associated lymphoid tissue lymphoma and gastrointestinal stromal tumor of the stomach. An 80-year-old man presented with gastric bleeding. Gastroscopy showed an ulcerative lesion and a submucosal tumor at the upper corpus of the stomach. The ulcerative lesion was proven by biopsy to be mucosa-associated lymphoid tissue lymphoma, but the submucosal tumor could not be diagnosed. Due to the repeating episodes of massive gastric bleeding, a total gastrectomy with lymphadenectomy was performed. After the operation, the submucosal tumor was pathologically proven to be a gastrointestinal stromal tumor. In this case, synchronous occurrence of mucosa-associated lymphoid tissue lymphoma and gastrointestinal stromal tumor seems to be coincidental rather than related with the same pathogenic triggering. Surgical resection of the stomach provided an accurate diagnosis and an effective treatment.

Successful sphincter-sparing local excision for mucinous adenocarcinoma associated with chronic fistula in ano using preoperative MRI evaluation.

A 78-year-old man with a 10-year history of ischiorectal abscess was referred to our hospital because purulent drainage from an external opening changed to mucoid drainage. By the brushing cytology of fistula ano, mucinous adenocarcinoma was found. T2-weighted magnetic resonance imaging (MRI) indicated that a mucinous adenocarcinoma was localized within the abscess and the fistula, and was not invasive neoplasm. He underwent a sphincter-sparing local excision of the ischiorectal abscess including the fistula and openings. The pathological findings indicated that mucinous adenocarcinoma arose from anal glands, developed lining the preexisting abscess and fistula wall. Five years after the resection, he remains asymptomatic and free of disease. From the present case, it is advisable that a high index of clinical suspicion in any elderly patient presenting with perirectal abscess and a major impact of the MRI evaluation on the perioperative assessment of perianal diseases should be emphasized.

Successfully-treated mesenteric non-Hodgkin's lymphoma involving hepatic mass--a case report.

A mesenteric diffuse large B-cell lymphoma which also involves the liver is very rare. We describe herein a mesenteric diffuse large B-cell lymphoma with hepatic involvement successfully treated by the combination of surgical resection and multiagent chemotherapy. A 77-year-old man was referred to our hospital because of a right lower abdominal tumor. Abdominal computed tomography showed a mass in the mesenterium at the ileocoecal region and multiple mass in the liver. Gallium scintigram showed focal hot uptake at the ileocoecal region and multiple areas of increased Gallium uptake in the liver. With the diagnosis of a mesenteric tumor with liver metastases, a laparotomy was performed. By an intraoperative pathological examination, non-Hodgkin's lymphoma was suggested. The mesenteric mass was completely resected, but additional operative procedures were not done to the liver. After the operation, the patient was determined to have Stage IVB diffuse large B-cell lymphoma, and chemotherapy based on the CHOP-like regimen was given. After the 8th course of such chemotherapy, he was confirmed to have achieved a complete remission by abdominal computed tomography and Gallium scintigram.The Stage IV mesenteric diffuse large B-cell lymphoma involving the liver seems to be an indication for combination therapy of surgical resection and multiagent chemotherapy.

Huge pseudocyst of the pancreas caused by poorly differentiated invasive ductal adenocarcinoma with osteoclast-like giant cells: report of a case.

A 72-year-old man presented with several week's abdominal distension and jaundice. Under the tentative diagnosis of pancreatic pseudocyst of 22cm in diameter, a percutaneous drainage was performed. Despite the reduction of the pseudocyst, his serum total bilirubin level was increased. At this time, abdominal computed tomography scan showed a tumor at the uncinate process of the pancreas. After the biliary decompression, a total pancreatectomy with the resection of pseudocyst walls and splenectomy was performed. It was histologically proven to be poorly differentiated ductal adenocarcinoma in combination with osteoclast-like giant cells. The pseudocyst was considered to be due to the stenosis of the main pancreatic duct caused by carcinoma of the uncinate process. Five months later, he died of recurrent carcinomatous peritonitis. Osteoclast-like giant cell tumor is a very rare neoplasm, the origin and prognosis of which still remain obscure. However, it has to be considered in the differential diagnosis of cystic changes of the pancreas, especially of pseudocyst. Furthermore, detailed surveys are needed in cases of pseudocyst of the pancreas without chronic pancreatitis, in order to identify small carcinoma of the pancreas.

Nonfunctioning pancreatic endocrine tumor presenting with hemorrhage from isolated gastric varices.

Hemorrhage from gastric varices due to left-sided portal hypertension is an unusual presentation for pancreatic endocrine tumor. A case of pancreatic endocrine tumor presenting with gastric variceal hemorrhage secondary to left-sided portal hypertension associated with splenic vein occlusion is presented. A 53-year-old man with hemorrhage from isolated gastric varices was referred to our hospital. Laboratory studies revealed normal liver function. Surveys to identify the cause of gastric varices by an abdominal CT, MRCP, and abdominal angiography revealed splenic vein occlusion secondarily attributed to the pancreatic tail tumor and splenomegaly. The pancreatic tumor was suspected to be a resectable endocrine tumor. A distal pancreatectomy, splenectomy, partial resection of the gastric fundus, and limited lymph node dissection were performed. By the histological examination, the diagnosis of nonfunctioning pancreatic endocrine tumor with malignant potential was determined. Three years after the surgery, the patient is doing well and reveals no sign of recurrence. In this case, the unusual presentation for pancreatic endocrine tumors such as a gastric variceal hemorrhage had an advantage that led to early presentation prior to the development of metastases with possible curative surgery.

[Postoperative adjuvant immunochemotherapy using Lentinan for advanced gastric carcinoma patients with metastasis in the regional lymph nodes and serosal invasion].

Six patients with gastric cancer, stage IIIA to IV, received intraabdominal cisplatin (CDDP) at laporotomy. This was followed by postoperative intravenous infusion of mitomycin C (MMC), CDDP or fluorouracil (5-FU). When these patients recovered to the extent that permitted oral medication, an immunochemotherapeutic regimen containing either oral UFT (uracil and tegafur) or 5'-deoxy-5-fluorouridine (5'-DFUR), plus intravenous Lentinan (LNT) was administered for a period ranging from one and a half to two years. This postoperative immunochemotherapy was successful in all 6 patients. No relapse has been observed in any of them for at least 4 years. These findings indicate that the chemotherapeutic strategy of administering intraabdominal CDDP immediately after surgery, followed by postoperative immunochemotherapy with pyrimidine-fluoride products plus Lentinan on an outpatient basis may be useful in the treatment of T3 or T4 gastric carcinoma with metastasis in the regional lymph nodes.