A rare case of neuroendocrine cell tumor mixed with a mucinous component in the ampulla of Vater.

BACKGROUND: A rare case of neuroendocrine cell tumor (NET) having both conventional and mucinous components was reported. Mucinous NET is rarely encountered in the pathological diagnosis of gastrointestinal (GI) tumors. Here we examined the mechanism for transformation of conventional NETs into mucinous NETs. CASE PRESENTATION: Macroscopic examination revealed a tumor with ulceration in the ampulla of Vater that measured 1.7 cm in its largest diameter. Histologically, the tumor comprised two components: a tubular/ribbon-like feature and small nests floating in a mucinous lake. The tumor nests showed sheet, nest and ribbon-like structures of small cells having eosinophilic cytoplasm as well as small-sized nuclei with dense hyperchromatin. Immunohistochemical analysis showed tumor cells positive for pan-endocrine markers (synaptophysin, CD56, INSM1 and chromogranin). Based on the histological findings, the solid and mucinous components were diagnosed as conventional and mucinous NETs, respectively. Grading was NET G2 based on 12.8% and 13.2% Ki-67-positive cells in the solid and mucinous components, respectively. Immunohistochemically, the mucin phenotype of this tumor was gastric and intestinal. Only the mucinous NET component had cytoplasmic CD10 expression. Examination using a customized gene panel detected only a DPC4 mutation, which was limited to the mucinous component. CONCLUSIONS: Coexistence of conventional and mucinous NETs could provide important insight into evaluating the NET subtype histogenesis. Moreover, molecular alterations including cytoplasmic expression of CD10 and the DPC4 mutation can contribute to interpretation of tumor pathogenesis.

Clinical Indicators to Determine the Timing of Surgery for Adhesive Small Bowel Obstruction.

BACKGROUND: Decompression of the intestine with a long tube or nasogastric tube is the first-choice treatment for adhesive small bowel obstruction (ASBO). Scheduling surgery while weighing the risks of surgery against conservative care is a crucial factor in clinical decision-making. Whenever feasible, unnecessary surgeries should be avoided, and it is essential to provide clinical markers for this. This study aimed to obtain evidence regarding the optimal timing of ASBO and when conservative treatment options are not successful. METHODS: The data of patients diagnosed with ASBO and receiving long tube insertion for more than 7 days were reviewed. We investigated transit ileal drainage volume and recurrence. The primary outcomes were the change in the drainage volume from the long tube over time and the percentage of patients who required surgery. We evaluated some cutoff values to determine the indication for surgery based on the insertion duration and volume of long tube drainage. RESULTS: Ninety-nine patients were enrolled in this study. Fifty-one patients showed improvement with conservative treatment, whereas 48 ultimately required surgery. When a daily drainage volume of ≥500 mL was considered an indication for surgery, 13-37 cases (25%-72%) would be judged unnecessary within 6 days of long tube insertion, while 5 cases (9.8%) would be judged unnecessary on day 7. DISCUSSION: Unnecessary surgical interventions for ASBO might be avoided by assessing the drainage volume on day 7 after inserting a long tube.

[A Case of Emergency Radiotherapy for Intramedullary Spinal Cord Metastasis from Breast Cancer].

Intramedullary spinal cord metastasis(ISCM)is rare. However, with advances in diagnostic imaging, the incidence of ISCM is increasing. We herein present a case of breast cancer metastasis in the lower thoracic spinal intramedullary area in a patient who was then successfully treated with emergency radiotherapy. A 56‒year‒old woman with breast cancer was admitted to our hospital due to rapidly progressing weakness in both legs and bladder and rectal disturbance. Spinal MRI revealed a gadolinium‒enhancing intramedullary lesion. The patient was treated with emergency radiotherapy and oral steroids. Although the prognosis of ISCM is extremely poor, emergency radiotherapy could be an effective treatment for ISCM to improve the patient's quality of life(QOL).

Characteristic Radiological Features of Retrospectively Diagnosed Pancreatic Cancers.

OBJECTIVES: The aim of this study was to assess the characteristic radiological features of early-stage pancreatic cancer (PC). METHODS: Between 2009 and 2016, 510 PC patients were selected from our hospital cancer registry database based on International Classification of Diseases for Oncology-3 (C25). Among them, 64 patients (42 males and 22 females; median age, 74 [range, 59-91]) had received repeated abdominal radiological examinations before their diagnosis of PC and were retrospectively investigated for specific radiological findings. The subjects underwent the following imaging examinations: computed tomography, magnetic resonance imaging, and fluoroglucose-positron emission tomography. RESULTS: Characteristic radiological features before diagnosis of PC were classified into the following 9 features: pancreatic duct ectasia (n = 16), focal low-density area (n = 15), change of cyst size (n = 8), localized tissue atrophy (n = 7), distal atrophy (n = 4), mass in pancreatic lipomatosis tissue (n = 2), mass concomitant with the already known cyst (n = 2), protrusion (n = 1), and parenchymal disproportion (n = 1). Fifty-three cases (84%) had more than one characteristic radiological feature before diagnosis of PC, and their median observation period until diagnosis was 24 (range, 1-120) months. CONCLUSIONS: The 9 characteristic radiological features provide an opportunity to diagnose PC at an early stage.

[Four Patients Who Underwent Proton Beam Therapy after Debulking Surgery and Omental Wrapping of the Residual Tumor as a Spacer for Unresectable Local Recurrence of Rectal Cancer].

We report 4 patients who underwent proton beam therapy after debulking surgery for unresectable local recurrence of rectal cancer. Case 1: A 55-year-old man underwent radiotherapy and systemic chemotherapy for local recurrence; however, the lesion exhibited evident regrowth. Combination therapy of debulking surgery, omental wrapping of the residual tumor as a spacer, and postoperative proton beam therapy was performed. He died of lung metastasis after 24 months. Case 2: A 79- year-old woman who underwent surgical resections and radiotherapy twice in a previous hospital was referred to our hospital. Similar to that in case 1, proton beam therapy after debulking surgery and omental wrapping was performed. She died of lymph node metastasis after 31 months. Case 3: A 75-year-old man was diagnosed with unresectable local recurrence of rectal cancer. He underwent combination therapy and is doing well without any recurrence for 43 months. Case 4: A 57-yearold woman was also diagnosed with unresectable local recurrence. She underwent the same combination therapy after systemic chemotherapy. She died of lymph node metastasis after 11 months.

Abscopal effect following radiation monotherapy in breast cancer: A case report.

Radiotherapy has been found to be valuable for the control and eradication of local foci in various malignant tumors. The abscopal effect is determined as a systemic antitumor response at a distance from the irradiation site invoked by local irradiation. We herein present an extremely rare case of breast cancer in a 64-year-old woman, in whom the abscopal effect was observed after radiotherapy induced an antitumor response in all metastatic lesions, without any combination therapy. The patient was admitted to our hospital complaining of a breast mass and pain at the left hip, and was diagnosed with breast cancer with multiple bone, lung and lymph node metastases. She received treatment with local radiotherapy delivered to the breast tumor and some of the bone metastases but did not receive chemotherapy due to her poor performance status. However, 10 months after radiotherapy, spontaneous regression was observed, not only within the irradiated field, but also in the non-irradiated areas. All signs of cancer throughout the body disappeared, and the patient's performance status drastically improved. To the best of our knowledge, there have been no reports of advanced breast cancer cases in which the abscopal effect was observed after radiation monotherapy; therefore, this case report is extremely rare and highly valuable.

[Indication for Radiotherapy for Breast Cancer Metastasis to the Skull Base Accompanied by Cranial Nerve Palsies].

Distant metastasis to the skull base region frequently manifests various cranial nerve symptoms and reduces patients' quality of life(QOL). We report a 62-year-old woman with skull base metastasis of breast cancer, whose condition clinically improved following palliative radiotherapy. The patient presented to our hospital with hoarseness. CT screening revealed a tumor in the right breast, axial lymph node swelling, and osteoblastic change at multiple sites. A core needle biopsy of the breast tumor revealed invasive lobular carcinoma. She also had nausea, anorexia, vertigo, lower left angle of the mouth, apraxia of lid closing, and dysphagia owing to several cranial nerve palsies. MRI T1- and T2-weighted images showed a diffuse low-signal intensity of the skull base region, and the patient was diagnosed as having breast cancer with symptomatic skull base metastases. Her cranial nerve symptoms improved after 1 week of palliative irradiation to the skull base. We conclude that, even among terminal-stage patients, palliative radiotherapy to the skull base region is an effective treatment option to improve patients' QOL.

Neuroendocrine tumor of the extrahepatic bile duct: A case report.

INTRODUCTION: Neuroendocrine tumors (NETs) of the extrahepatic bile ducts are extremely rare neoplasms arising from endocrine cells and have variable malignant potential. They most commonly occur in young females and usually present with painless jaundice. PRESENTATION OF CASE: Here we present the case of an asymptomatic 57-year-old woman with NET of the common bile duct that was incidentally discovered on abdominal ultrasound during a medical examination. She was admitted to our hospital with a diagnosis of hepatic hilar tumor. Computed tomography revealed the tumor surrounding the hepatic hilum and duodenum. Magnetic resonance cholangiopancreatography revealed a filling defect of the common bile duct with morphology suggestive of external compression. Endoscopic ultrasound confirmed a submucosal tumor of the duodenal bulb measuring 30×20mm in size. The patient qualified for surgery with a preoperative diagnosis of submucosal tumor of the duodenal bulb. Intraoperative examination revealed that the tumor location involved the common bile duct and/or cystic duct with no signs of invasion to other organs or metastatic lymph nodes. Excision of the biliary ducts and tumor was followed by Roux-en-Y anastomosis. Histological results showed NET grade 1. DISCUSSION: Preoperative diagnosis of NETs is difficult because of their rarity. A definitive diagnosis is usually established intraoperatively or after histopathological evaluation. CONCLUSION: For these tumors, surgical resection is currently the only treatment modality for achieving a potentially curative effect and prolonged disease-free survival.

[A Case of Perianal Squamous Cell Carcinoma with Left Inguinal Lymph Node Metastasis That Showed a Complete Response More Than Five Years after Chemotherapy and Concomitant Proton Beam Therapy].

We report a case of perianal squamous cell carcinoma and left inguinal lymph node metastasis that showed a complete response more than 5 years after chemotherapy and concomitant proton beam therapy. A 34-year-old woman was referred to our hospital for an anal tumor and a left inguinal tumor. A digital rectal examination revealed a tumor in the anterior wall of the anal canal. In addition, the left inguinal lymph nodes were swollen, leading us to suspect metastases. Biopsy specimens confirmed poorly differentiated squamous cell carcinoma. We made a diagnosis of squamous cell carcinoma T4bN2M0, Stage III b. The patient was treated with chemotherapy consisting of 5-FU(700mg/m / 2/day; continuous intravenous administra- tion)on days 1-5, and CDDP(70mg/m / 2/day)on day 1, along with concomitant proton beam therapy. A total of 45 Gy of X-ray irradiation was administered to the primary lesion, pelvis, and groin area. Furthermore, 24.2 Gy of proton beam therapy was administered to the primary lesion, and 28.6 Gy to the left inguinal lymph nodes. The patient tolerated this treatment with no severe adverse effects. The tumor disappeared completely 1 month after this treatment, and biopsy specimens confirmed the absence of any viable cancer cells. The patient has been alive with no sign of recurrence for 5 years.

[An Autopsy Case of Pulmonary Tumor Thrombotic Microangiopathy That Progressed Slowly during Chemotherapy for Advanced Gastric Cancer].

A man in his 50s presented to our hospital for anemia and was diagnosed with advanced gastric cancer with para-aortic lymph node metastases. He underwent gastrojejunostomy and received postoperative chemotherapy. Despite stable disease with chemotherapy, he complained of cough and respiratory discomfort and was subsequently admitted with progressive respiratory distress. Pulmonary hypertension and right-sided heart failure developed, and he died of sudden cardiopulmonary arrest 9 days after admission. An autopsy revealed widespread tumor metastasis, and he was diagnosed with pulmonary tumor thrombotic microangiopathy(PTTM)associated with gastric cancer. Although PTTM is a rare clinicopathological entity that causes severe pulmonary hypertension, it should be considered in the differential diagnosis of acute dyspnea in patients with carcinoma, regardless of clinical improvement.

[A Case of an Abdominal Desmoplastic Small Round Cell Tumor with Metastasis in the Medulla Oblongata].

A desmoplastic small round cell tumor(DSRCT)is a very rare malignant tumor that mainly occurs in the intra-abdominal cavity in young adults.This neoplasm has an extremely poor prognosis, with a clinical course characterized by rapid progression and metastasis.We present a 31-year-old man who presented with chief complaints of dysphagia, ataxic gait, and hoarseness.He first underwent surgical resection of a tumor in the medulla oblongata; however, the lesion was suspected to be a metastatic neoplasm.Following a thorough medical examination, the patient was diagnosed with retroperitoneal DSRCT with multiple metastatic lesions.He received multidisciplinary treatment including debulking surgery for the primary lesion; radiotherapy for metastatic lesions in the brain, abdomen, and cervical lymph nodes; hepatic artery embolization for liver metastasis; and systemic chemotherapy.The patient died of progressive disease 17 months after the initial diagnosis.

Arteriovenous malformation of the pancreas: a case report.

Arteriovenous malformation (AVM) of the pancreas is uncommon in the gastrointestinal tract. We present a case of AVM of the pancreatic head in a 59-year-old male. He was admitted to a hospital with hematemesis and tarry stool and referred to our hospital in March 2014 on the diagnosis of pancreatic artery pseudoaneurysm. A computed tomography scan showed the presence of irregular dilated and/or stenotic vessels with meandering in the pancreatic head. Magnetic resonance imaging showed strong enhancement of the conglomeration in the pancreatic head. Selective angiography showed the proliferation of a vascular network in the pancreatic head and an early visualization of the portal vein at the arterial phase. The patient qualified for surgery with a preoperative diagnosis of AVM of the pancreatic head. We performed pylorus-preserving pancreaticoduodenectomy. The histological results confirmed the presence of irregular dilated tortuous arteries and veins in the pancreatic head. Surgical treatment may represent definitive management of symptomatic AVM.

Intrahepatic splenosis in a chronic hepatitis C patient with no history of splenic trauma mimicking hepatocellular carcinoma.

BACKGROUND: Intrahepatic splenosis (IHS) is the autotransplantation of splenic tissue that mostly develops after abdominal injury and is often misdiagnosed as hepatocellular carcinoma (HCC) because of similarities in radiological features. We had an opportunity to treat an extremely rare case of intrahepatic splenosis, which were found in a patient without any history of splenic injury. To the best of our knowledge, this is the first such case report in the world. CASE REPORT: A 58-year-old man with chronic hepatitis C was referred to our hospital for further examination of liver function abnormality. Abdominal ultrasonography incidentally revealed a low echoic tumor in the posterior segment of the liver, with high echoic capsule, which is possibly different from tumor capsule of HCC, known as halo. Abdominal contrast-enhanced computed tomography and gadoxetic acid-enhanced magnetic resonance imaging showed that the tumor had an inhomogeneous enhancement in the arterial phase and diminished enhancement in the equilibrium phase, diagnosed as HCC. The patient underwent right lateral segmentectomy of the liver, and histopathological study confirmed a diagnosis of intrahepatic splenosis. CONCLUSIONS: This case presents a new understanding of IHS in a patient without any splenic injury. We also focused on the differences in echo patterns of the tumor capsule between HCC and IHS, which can be used to efficiently diagnose IHS.

A case of diaphragmatic clear cell carcinoma in a patient with a medical history of ovarian endometriosis.

We present a case of clear cell carcinoma located in the diaphragm in a patient with a medical history of ovarian endometriosis. Ultrasonography revealed the presence of a 2.5-cm nodule on the surface of the liver in a 65-year-old woman. She had undergone right salpingo-oophorectomy for treatment of an endometrial cyst of the right ovary at the age of 43 years and hysterectomy for treatment of a myoma of the uterus at the age of 51 years. We performed laparotomy and found that the tumor had originated from the diaphragm and invaded the liver. The diaphragm and liver were partially resected. Histopathological examination revealed the presence of clear cells and hobnail cells. The clear cells contained pale or eosinophilic cytoplasm and were arranged in a solid pattern. The hobnail cells lined the lumen and papillae. Immunohistochemical examination of the tumor cells showed positive staining for CK-7 and CA-125; negative staining for CK-20, TTF-1, and CA19-9; and weak positive staining for CEA. The findings were compatible with those of ovarian clear cell carcinoma. After 1 year, the patient had metastasis in the lung, and right lower lobectomy was performed.

Characterization of circulating DNA in healthy human plasma.

BACKGROUND: The importance of circulating DNA has been recognized since the detection of mutated oncogene products in cancer patients; however, there is little information about circulating DNA in normal human plasma. We characterized circulating DNA in normal human plasma to obtain basic information. METHODS: Circulating DNA was purified from plasma samples obtained from 10 healthy donors and examined. Purified DNA was cloned and their sequence determined and analyzed. The terminal structure was examined by a labeling method. RESULTS: The DNA levels in normal plasma samples were quite low (3.6-5.0 ng/ml). All 556 clones analyzed were independent, and obtained from various chromosomes and various regions of the gene. The mean values of their length and GC content were 176 bp and 53.7%, respectively. Their 5' and 3' ends were rich in C and G, respectively, and they presented as 5' protruding forms of double-stranded DNA in plasma. CONCLUSION: Circulating DNA in normal human plasma is derived from apoptotic cells but not from necrotic cells. Structural characteristics of the circulating DNA might be associated with their stability in plasma.

Rational design, synthesis, and structure-activity relationships of novel factor Xa inhibitors: (2-substituted-4-amidinophenyl)pyruvic and -propionic acids.

An inhibitor of factor Xa (fXa), the m-substituted benzamidine AXC1578 (1a), was structurally modified with the aim of increasing its potency. In particular, pyruvic acid and propionic acid substituents were incorporated into the P1 benzamidine moiety to introduce a favorable interaction with the oxy-anion hole in the catalytic triad region of fXa. This strategy was based on computational docking studies using the extracted active site of fXa. The validity of the computational model was supported by the acquisition of X-ray crystal structures of the 1a-trypsin and 3b-trypsin complexes (the homology around the active sites of fXa and trypsin is high). The above modifications significantly increased the inhibitory activity toward fXa, whereas the high selectivity for fXa versus thrombin was maintained or enhanced. Compounds 3b, 3c, 3e, and 4b are considered to be potential lead compounds for the development of orally active anticoagulant drugs because they demonstrated potent activity when administered orally to cynomolgus monkeys.