Novel application to evaluate endometrial blood flow using transvaginal superb microvascular imaging: A preliminary study describing physiological changes from ovulation to mid-luteal phase.

INTRODUCTION: We aimed to describe physiological changes in endometrial blood flow (minute arterioles running through the endometrium) from ovulation to the mid-luteal phase using superb microvascular imaging. MATERIAL AND METHODS: The study involved 17 women (median age, 32.5 years; first to third interquartile range, 29.8-40.0 years) with regular menstrual cycles who were managed in our institute from 2020 to 2021. The uterus was delineated at the sagittal section using transvaginal ultrasonography incorporated with superb microvascular imaging. For each participant, a total of 28 cycles were observed; 17 cycles observed within one day of ovulation and the implantation period, 5-7 days (D5-7) after ovulation in the same cycle, and nine cycles in which only ovulation was observed, and two cycles in which only D5-7 was observed. Therefore, 26 and 19 images at ovulation and D5-7, respectively, were acquired. Endometrial blood flow was evaluated by depth of the vascular signal in the endometrium and categorized as follows: signals only in the basal layer of the endometrium (grade 1), reaching up to half the endometrium (grade 2), and covering the whole endometrium (grade 3). Changes in the grade of endometrial blood flow from ovulation to D5-7 after ovulation, and the relationship between the grade of endometrial blood flow and the endometrial thickness on ovulation and D5-7 after ovulation, were analyzed. Statistical significance was set at p < 0.05. RESULTS: The endometrial blood flow from ovulation to D5-7 after ovulation during the same menstrual period showed a downgrade in 14 of 17 cycles (82.3%) and no change in the remaining three cycles (17.6%), indicating a decrease in the endometrial blood flow from ovulation to D5-7 after ovulation (p = 0.001). There were differences between the grade of endometrial blood flow and median endometrial thickness on ovulation (grade 1: 5.9 mm, grade 2: 9.1 mm, and grade 3: 11.2 mm); however, no differences in the endometrial thickness were found between the grades on D5-7 after ovulation. CONCLUSIONS: In the normal menstrual cycle, endometrial blood flow decreased from ovulation to the mid-luteal phase, and the endometrial thickness in the ovulatory phase was related to the endometrial perfusion.

Successful omental flap coverage repair of a rectovaginal fistula after low anterior resection: a case report.

BACKGROUND: Rectovaginal fistula (RVF) is a troublesome and refractory complication after low anterior resection (LAR) for rectal cancer. An omental flap repair was performed for the RVF caused due to Crohn's disease and childbirth trauma. However, there are few cases of an omental flap repair for RVF after LAR. Herein, we present a successfully repaired case of RVF by omental flap coverage after LAR for rectal cancer. CASE PRESENTATION: A 50-year-old female patient with advanced rectal cancer underwent laparoscopic LAR with double-stapling technique anastomosis and achieved curative resection. She complained of a stool from the vagina and was diagnosed with RVF on the postoperative day (POD) 18. Conservative therapy was ineffective. We performed laparoscopic fistula resection and direct closure of the vagina and rectum, designed the omentum that could reach the pelvis, repaired RVF by omental flap coverage, and performed transverse colostomy on POD 25. She was discharged on initial POD 48. Seven months after the initial operation, colostomy closure was administered. There was no recurrence of RVF found 1 year after the initial operation. CONCLUSIONS: The patient achieved an omental flap coverage for RVF. We successfully performed the omental flap coverage repair in patients with RVF after the leakage of LAR. An omental flap may become an alternative treatment for muscle flap or an effective treatment for RVF.

The role of tyrosine hydroxylase as a key player in neuromelanin synthesis and the association of neuromelanin with Parkinson's disease.

The dark pigment neuromelanin (NM) is abundant in cell bodies of dopamine (DA) neurons in the substantia nigra (SN) and norepinephrine (NE) neurons in the locus coeruleus (LC) in the human brain. During the progression of Parkinson's disease (PD), together with the degeneration of the respective catecholamine (CA) neurons, the NM levels in the SN and LC markedly decrease. However, questions remain among others on how NM is associated with PD and how it is synthesized. The biosynthesis pathway of NM in the human brain has been controversial because the presence of tyrosinase in CA neurons in the SN and LC has been elusive. We propose the following NM synthesis pathway in these CA neurons: (1) Tyrosine is converted by tyrosine hydroxylase (TH) to L-3,4-dihydroxyphenylalanine (L-DOPA), which is converted by aromatic L-amino acid decarboxylase to DA, which in LC neurons is converted by dopamine ß-hydroxylase to NE; (2) DA or NE is autoxidized to dopamine quinone (DAQ) or norepinephrine quinone (NEQ); and (3) DAQ or NEQ is converted to eumelanic NM (euNM) and pheomelanic NM (pheoNM) in the absence and presence of cysteine, respectively. This process involves proteins as cysteine source and iron. We also discuss whether the NM amounts per neuromelanin-positive (NM+) CA neuron are higher in PD brain, whether NM quantitatively correlates with neurodegeneration, and whether an active lifestyle may reduce NM formation.

[Hemorrhagic Colon Cancer with Left Atrial Thrombus Formation after Anticoagulant Therapy Discontinuation-A Case Report].

The patient was a 72-year-old female. She had been taking rivaroxaban for chronic atrial fibrillation; however, she stopped taking it due to anemia and was hospitalized urgently. A contrast-enhanced computed tomography(CT)scan showed a 30 mm mass in the ascending colon, and a colonoscopy revealed ascending colon cancer(cT3, cN0, cM0, cStage Ⅱa). The tumor was hemorrhagic and was thought to have caused the anemia. On day 6 of hospitalization, another contrast- enhanced CT scan showed a poorly contrast-enhanced area in the left atrium, and transesophageal echocardiography revealed 2 left atrial thrombi(27 mm and 17 mm). Since early induction of anticoagulation therapy was considered, an emergency open right colectomy was performed to remove the cause of the bleeding. Intravenous heparin therapy was started the day after surgery and was switched to oral apixaban therapy on the fourth postoperative day. The postoperative course was good, and she was discharged home on the 17th postoperative day. This patient had conflicting clinical problems simultaneously; however, immediate decision-making and initiation of treatment were effective.

Long-range axonal projections of transplanted mouse embryonic stem cell-derived hypothalamic neurons into adult mouse brain.

The hypothalamus is comprised of heterogenous cell populations and includes highly complex neural circuits that regulate the autonomic nerve system. Its dysfunction therefore results in severe endocrine disorders. Although recent experiments have been conducted for in vitro organogenesis of hypothalamic neurons from embryonic stem (ES) or induced pluripotent stem (iPS) cells, whether these stem cell-derived hypothalamic neurons can be useful for regenerative medicine remains unclear. We therefore performed orthotopic transplantation of mouse ES cell (mESC)-derived hypothalamic neurons into adult mouse brains. We generated electrophysiologically functional hypothalamic neurons from mESCs and transplanted them into the supraoptic nucleus of mice. Grafts extended their axons along hypothalamic nerve bundles in host brain, and some of them even projected into the posterior pituitary (PPit), which consists of distal axons of the magnocellular neurons located in hypothalamic supraoptic and paraventricular nuclei. The axonal projections to the PPit were not observed when the mESC-derived hypothalamic neurons were ectopically transplanted into the substantia nigra reticular part. These findings suggest that our stem cell-based orthotopic transplantation approach might contribute to the establishment of regenerative medicine for hypothalamic and pituitary disorders.

EpCAM Is a Surface Marker for Enriching Anterior Pituitary Cells From Human Hypothalamic-Pituitary Organoids.

Human stem cell-derived organoid culture enables the in vitro analysis of the cellular function in three-dimensional aggregates mimicking native organs, and also provides a valuable source of specific cell types in the human body. We previously established organoid models of the hypothalamic-pituitary (HP) complex using human pluripotent stem cells. Although the models are suitable for investigating developmental and functional HP interactions, we consider that isolated pituitary cells are also useful for basic and translational research on the pituitary gland, such as stem cell biology and regenerative medicine. To develop a method for the purification of pituitary cells in HP organoids, we performed surface marker profiling of organoid cells derived from human induced pluripotent stem cells (iPSCs). Screening of 332 human cell surface markers and a subsequent immunohistochemical analysis identified epithelial cell adhesion molecule (EpCAM) as a surface marker of anterior pituitary cells, as well as their ectodermal precursors. EpCAM was not expressed on hypothalamic lineages; thus, anterior pituitary cells were successfully enriched by magnetic separation of EpCAM+ cells from iPSC-derived HP organoids. The enriched pituitary population contained functional corticotrophs and their progenitors; the former responded normally to a corticotropin-releasing hormone stimulus. Our findings would extend the applicability of organoid culture as a novel source of human anterior pituitary cells, including stem/progenitor cells and their endocrine descendants.

Efficacy of combined hand exercise intervention in patients with chemotherapy-induced peripheral neuropathy: a pilot randomized controlled trial.

PURPOSE: Previous evidence regarding the impact of exercise interventions on chemotherapy-induced peripheral neuropathy often focuses on lower-extremity functions, such as muscle strength and balance ability, while their effects on upper extremities remain unknown. We aimed to evaluate the efficacy of combined hand exercise intervention on upper-extremity function, symptoms, and quality-of-life in patients with chemotherapy-induced peripheral neuropathy (CIPN). METHODS: After screening 341 patients, 42 were randomly assigned to either the intervention (n = 21) or control (n = 21) group. Participants were evaluated at baseline (T0) and after one (T1) and two (T2) chemotherapy cycles. The primary outcome was upper-extremity function measured using the Michigan Hand Outcomes Questionnaire (MHQ) at T2. The intention-to-treat and as-treated populations were compared using a mixed-effect model. RESULTS: In the intention-to-treat analysis, the decline in activities of daily living of MHQ was significantly suppressed in the intervention group compared with that in the control group at T2 (difference: 7.23; 95% confidence interval: 0.35-14.10). Similarly, in the as-treated analysis, the decline in activities of daily living of MHQ was significantly suppressed in the intervention group compared with that in the control group at T2 (difference: 13.09; 95% confidence interval: 5.68-20.49). Pain also significantly improved in the intervention group compared with that in the control group at T2 (difference: 13.21; 95% confidence interval: - 22.91 to - 3.51). CONCLUSION: The combined hand exercise intervention may improve upper-extremity function, such as by suppressing decline in ADL, and reduce pain in patients with CIPN.

Spontaneous rupture of the umbilical vein associated with liver cirrhosis: A case report.

INTRODUCTION: A decompensated cirrhosis sometimes develops collateral circulation due to severe fibrosis. Rupture of this collateral circulation can induce a fatal situation. CASE PRESENTATION: A 59-year-old man with alcoholic cirrhosis was admitted to our emergency department with a chief complaint of impaired consciousness. The patient had hypotension upon arrival, and enhanced computed tomography (CT) revealed a massive hemoperitoneum. Imaging examinations, including interventional radiography, could not identify the source of bleeding preoperatively; therefore, emergency surgery was performed. Intraoperatively, a collapsed small vessel connecting liver segment 4 and the expanded umbilical vein as collateral circulation due to portal hypertension was detected as the source of bleeding. Ligating the stump of the small vessel and postoperative intensive care saved the patient's life. The patient was discharged from our hospital 14 days after the surgery. CLINICAL DISCUSSION: A rupture of the umbilical vein associated with cirrhosis is rare and causes a critical situation because of the fast blood flow in the collateral circulation caused by portal hypertension. Moreover, the amount of bleeding tends to increase since the abdominal cavity is a free space and patients with cirrhosis have coagulopathies, including thrombocytopenia and prolonged prothrombin time. Although a retrospective review of the enhanced CT image could identify the minute findings, arterial portography was insufficient to detect bleeding from the umbilical vein. Therefore, emergency exploratory laparotomy was required for the diagnosis and treatment. CONCLUSION: Rupture of the reopened umbilical vein can cause idiopathic spontaneous hemoperitoneum in patients with decompensated cirrhosis.

How to do it: endovascular stent and ligament resection during pancreaticoduodenectomy for coeliac axis stenosis in median arcuate ligament syndrome.

To decrease complications associated with the treatment of coeliac axis (CA) stenosis due to median arcuate ligament (MAL) syndrome in pancreaticoduodenectomy, we performed combined preoperative endovascular stenting and intraoperative MAL resection. This technique can secure the CA blood flow to the hepatic artery before surgery in one stage and prevent CA restenosis and stent dislocation because there is no extrinsic compression of the CA after MAL resection.

Comparison of cerebral activation between motor execution and motor imagery of self-feeding activity.

Motor imagery is defined as an act wherein an individual contemplates a mental action of motor execution without apparent action. Mental practice executed by repetitive motor imagery can improve motor performance without simultaneous sensory input or overt output. We aimed to investigate cerebral hemodynamics during motor imagery and motor execution of a self-feeding activity using chopsticks. This study included 21 healthy right-handed volunteers. The self-feeding activity task comprised either motor imagery or motor execution of eating sliced cucumber pickles with chopsticks to examine eight regions of interest: pre-supplementary motor area, supplementary motor area, bilateral prefrontal cortex, premotor area, and sensorimotor cortex. The mean oxyhemoglobin levels were detected using near-infrared spectroscopy to reflect cerebral activation. The mean oxyhemoglobin levels during motor execution were significantly higher in the left sensorimotor cortex than in the supplementary motor area and the left premotor area. Moreover, significantly higher oxyhemoglobin levels were detected in the supplementary motor area and the left premotor area during motor imagery, compared to motor execution. Supplementary motor area and premotor area had important roles in the motor imagery of self-feeding activity. Moreover, the activation levels of the supplementary motor area and the premotor area during motor execution and motor imagery are likely affected by intentional cognitive processes. Levels of cerebral activation differed in some areas during motor execution and motor imagery of a self-feeding activity. This study was approved by the Ethical Review Committee of Nagasaki University (approval No. 18110801) on December 10, 2018.

Identification by nano-LC-MS/MS of NT5DC2 as a protein binding to tyrosine hydroxylase: Down-regulation of NT5DC2 by siRNA increases catecholamine synthesis in PC12D cells.

Tyrosine hydroxylase (TH), which catalyzes the conversion of l-tyrosine to l-DOPA, is the rate-limiting enzyme in the biosynthesis of catecholamines. It is well known that both α-synuclein and 14-3-3 protein family members bind to the TH molecule and regulate phosphorylation of its N-terminus by kinases to control the catalytic activity. In this present study we investigated whether other proteins aside from these 2 proteins might also bind to TH molecules. Nano-LC-MS/MS analysis revealed that 5'-nucleotidase domain-containing protein 2 (NT5DC2), belonging to a family of haloacid dehalogenase-type (HAD) phosphatases, was detected in the immunoprecipitate of PC12D cell lysates that had been reacted with Dynabeads protein G-anti-TH antibody conjugate. Surprisingly, NT5DC2 had already been revealed by Genome-Wide Association Studies (GWAS) as a gene implicated in neuropsychiatric disorders such as schizophrenia, bipolar disorder, which are diseases related to the abnormality of dopamine activity in the brain, although the role that NT5DC2 plays in these diseases remains unknown. Therefore, we investigated the effect of NT5DC2 on the TH molecule. The down-regulation of NT5DC2 by siRNA increased the synthesis of catecholamines (dopamine, noradrenaline, and adrenaline) in PC12D cells. These increases might be attributed to the catalytic activity of TH and not to the intracellular stability of TH, because the intracellular content of TH assessed by Western blotting was not changed by the down-regulation of NT5DC2. Collectively, our results indicate that NT5DC2 inhibited the synthesis of dopamine by decreasing the enzymatic activity of TH.

Successful surgical management of non-perforating acute appendicitis with septic disseminated intravascular coagulation: A case report and review of the literature.

INTRODUCTION: Perforating appendicitis and abscess-forming appendicitis may cause septic disseminated intravascular coagulation (DIC). However, non-perforating acute appendicitis with septic DIC is extremely rare. PRESENTATION OF CASE: A 67-year-old man was referred to our hospital one day after starting oral antibiotic treatment for acute appendicitis. Physical examination revealed only slight spontaneous abdominal pain without tenderness and peritoneal irritation. Contrast-enhanced computed tomography demonstrated an enlarged appendix (10 mm in diameter) without fecalith, ascites, intraperitoneal free air, and abscess. There was no evidence of perforating appendicitis. Laboratory analysis revealed septic DIC. The patient was diagnosed with non-perforating acute appendicitis with septic DIC. The patient was distressed regarding whether he should be treated conservatively with an antibiotics-first strategy or undergo an appendectomy. Ultimately, a laparoscopic appendectomy was performed. Histopathological examination showed non-perforating gangrenous appendicitis. He required DIC therapy for 2 days postoperatively. He was discharged on postoperative day 9, and remained in good health 1 month after surgery. DISCUSSION: There is no absolute index of conversion to surgery with an antibiotics-first strategy of appendicitis treatment. Judging the limit of conservative treatment and determining the best moment to perform surgery is a critically important matter for patients with acute appendicitis. CONCLUSIONS: The incidence of conservative treatment preceding an antibiotics-first strategy for acute appendicitis is increasing. However, it is thought that appendectomy should be performed when acute appendicitis is complicated with septic DIC, even if it is a non-perforating appendicitis in which improvement with conservative treatment is anticipated.

A Multicenter, Randomized, Controlled Trial Comparing Reinforced Staplers with Bare Staplers During Distal Pancreatectomy (HiSCO-07 Trial).

BACKGROUND: Although distal pancreatectomy (DP) using a reinforced stapler is expected to reduce PF, no multicenter RCT has been performed. To investigate whether reinforced staplers reduce the incidence of clinically relevant pancreatic fistula (PF) after DP compared with staplers without reinforcement. METHODS: Between July 2016 and December 2017, patients scheduled for DP were enrolled in a multicenter, randomized, controlled trial (RCT) at nine hospitals in Hiroshima Japan. Patients were randomized either to reinforced stapler or bare stapler. The primary endpoint was incidence of clinically relevant PF. This RCT was registered with UMIN Clinical Trial Registry (UMIN000022341). RESULTS: A total of 122 patients were assigned to reinforced stapler (n = 61) or bare stapler (n = 61), and 119 patients (61 reinforced stapler and 59 bare stapler) were analyzed. There was no significant difference in the incidence of clinically relevant PF between the reinforced stapler and bare stapler groups (16.3% vs. 27.1%, p = 0.15). Furthermore, the rates of major complication (16.3% vs. 18.6%, p = 0.74), postpancreatectomy hemorrhage (0% vs. 3.4%, p = 0.08), and median postoperative in-hospital days (19 days vs. 20 days, p = 0.78) did not differ between the two groups. Within a subset of 82 patients in whom the thickness of pancreatic transection line was less than 14 mm, a significant difference was found in the incidence of clinically relevant PF (4.5% vs. 21.0% in the reinforced stapler vs. bare stapler groups, respectively, p = 0.01). CONCLUSIONS: Reinforced stapler for pancreatic transection during DP does not reduce the incidence of clinically relevant PF compared to stapler without reinforcement.

Appendiceal neurofibroma with low-grade appendiceal mucinous neoplasm in neurofibromatosis type 1 patient: A case report.

INTRODUCTION: Neurofibromas are a characteristic of the autosomal dominant disorder Neurofibromatosis type 1 (NF1), also known as von Recklinghausen's disease. Appendiceal neurofibromas are extremely rare, and low-grade appendiceal mucinous neoplasms (LAMNs) have not previously been reported in NF1. PRESENTATION OF CASE: A 62-year-old man with NF1 was scheduled for elective surgical treatment of an asymptomatic, enlarged and diffusely thickened appendix that remained after curative antimicrobial treatment of acute appendicitis. Laboratory analysis revealed all normal. Colonoscopy showed thickened appendiceal mucosa projecting into the cecum. A sample of the mucosa was found to be pathologically benign. The patient was preoperatively diagnosed with treated acute appendicitis with chronic appendiceal inflammation versus appendiceal neoplasms. Laparoscopic cecectomy was performed. Multiple neurofibromas were observed in the muscle layer, submucosa, and mucosa of the appendix on histopathological examination. Immunohistochemical examination showed positive staining for S-100. Pathologically, the patient was diagnosed with appendiceal neurofibroma consistent with NF1 with LAMNs. His postoperative course was unremarkable. He was discharged on post-operative day 3 and remained in good health 7 month after surgery. CONCLUSIONS: Appendiceal neurofibromas are often preoperatively diagnosed as appendicitis. Appendiceal neurofibromas should be considered in patients with NF1 who are suspected of having appendicitis.

Intestinal obstruction caused by low-grade appendiceal mucinous neoplasm: A case report and review of the literature.

INTRODUCTION: Intestinal obstructions due to appendiceal pathology are rare. Obstructions caused by low-grade appendiceal mucinous neoplasms (LAMNs) are rarer still. PRESENTATION OF CASE: A 79-year-old woman was referred to our hospital for mechanical small intestinal obstruction. The patient had undergone prior left oophorectomy via a lower abdominal incision. Physical examination revealed abdominal distension and slight tenderness. Laboratory analysis was unremarkable. Contrast enhanced computed tomography (CT) demonstrated dilation of an obstructed small intestinal loop without evidence of strangulation. There appeared to be a low density mass measuring 3.0 × 1.5 cm with a potential twist in the mesentery near the transition point in the small intestine. The patient was diagnosed with mechanical small intestinal obstruction and was treated conservatively with nasogastric tube decompression for one week. After no clinical improvement, we elected to surgically explore her. Intraoperative findings revealed that the ileum was compressed by the appendix, which had a cystic mass on its tip. There was no evidence of intestinal ischemia. Laparotomy appendectomy alone was performed. Pathology revealed a LAMN measuring 3.0 × 1.5 cm. She remains disease-free with 18 months of postoperative follow-up. DISCUSSION: Intestinal obstruction due to external compression by an appendiceal mass is rare, and is often difficult to preoperatively diagnose with CT. CONCLUSIONS: The etiology of small intestinal obstruction with a transition point in the right lower quadrant of abdomen includes an appendiceal mass on the broad differential for this common problem.

Pancreatobiliary fistula associated with intraductal papillary mucinous carcinoma accompanying obstructive jaundice: A case report.

INTRODUCTION: Intraductal papillary mucinous neoplasms (IPMNs) occasionally involve formation of fistulas with other adjacent organs. Pancreatobiliary fistulas associated with IPMNs are rare, but affected patients often develop obstructive jaundice and cholangitis. PRESENTATION OF CASE: A 79-year-old man was referred to our hospital for evaluation of abnormal biliary enzymes. Contrast-enhanced computed tomography and endoscopic retrograde cholangiopancreatography demonstrated multiple cystic lesions with septa in the pancreatic head and fistulas between the cystic lesions and common bile duct. The clinical diagnosis was pancreatobiliary fistula associated with a mixed-type IPMN and accompanying obstructive jaundice. The patient underwent subtotal stomach-preserving pancreaticoduodenectomy. The resected specimen showed fistulas between the cystic lesions and common bile duct. Histopathological examination showed that the main and branch ducts of the pancreatic head were dilated and filled with mucus. The epithelia of the pancreatic ducts revealed papillary proliferation and an invasive adenocarcinoma arising from an intraductal neoplasm. Immunohistochemistry examination showed CDX2- and MUC2-positive reactions. The final diagnosis was an intraductal papillary mucinous carcinoma of the intestinal-type. The patient remained disease-free for 9 months postoperatively. DISCUSSION: The causes of death in patients who have pancreatobiliary fistulas associated with IPMNs without resection are cholangitis or hepatic insufficiency. Nonoperative treatment is limited for cases with obstructive jaundice. It is necessary to prevent obstructive jaundice and cholangitis due to a large quantity of mucinous material. CONCLUSIONS: Surgical resection should be considered, if possible, in patients with pancreatobiliary fistulas associated with IPMNs. A better prognosis is expected with prevention of obstructive jaundice or cholangitis.

Mixed adenoneuroendocrine carcinoma of the distal bile duct: A case report.

INTRODUCTION: Mixed adenoneuroendocrine carcinomas (MANECs) of the distal bile duct are extremely rare, and only a few cases have been reported in the English literature. PRESENTATION OF CASE: An 82-year-old man was referred to our hospital for increasing biliary enzymes. Abdominal computed tomography (CT) showed enlargement of the intrahepatic bile ducts and stenosis of the distal bile duct. Endoscopic retrograde cholangiopancreatography showed stenosis of the distal bile duct and a high-density signal at the same site on diffusion weighted imaging. PET-CT showed increased FDG accumulation (SUVmax: 4.5) at the distal bile duct stenosis. Biopsy specimens obtained by endoscopic ultrasonography-guided fine-needle aspiration revealed adenocarcinoma. The patient was diagnosed with adenocarcinoma of the distal bile duct and underwent subtotal stomach-preserving pancreaticoduodenectomy with regional lymph node dissection. The resected distal bile duct tumor was 18×14×12mm in diameter. Hematoxylin and eosin staining revealed a composite carcinoma with adenocarcinoma and non-adenocarcinoma elements. The non-adenocarcinoma component stained positive for synaptophysin and chromogranin A. The Ki-67 labeling index was 37%. The non-adenocarcinoma component was therefore diagnosed as a neuroendocrine carcinoma. The two composite carcinoma was diagnosed as MANEC of the distal bile duct. The patient was treated with surgery alone and he remained disease-free for 7 months after the surgery. DISCUSSION: The treatment of MANECs of the bile duct remains controversial and the prognosis is poor. CONCLUSIONS: There is no standard treatment for MANECs of the bile duct. Larger studies are required to establish standard treatment regimens.

Splenic hamartoma associated with thrombocytopenia: A case report.

INTRODUCTION: Hamartomas are rare, benign tumors of the spleen. Few cases of splenic hamartomas associated with thrombocytopenia have been reported. PRESENTATION OF CASE: An asymptomatic 64-year-old man with myelodysplastic syndrome was found to have a splenic tumor. Laboratory tests were significant for thrombocytopenia, with a platelet count of 7.8×104/µL. Ultrasonography showed splenomegaly (10.8×6.6cm), and a hypoechoic splenic mass (8.0×7.0cm). Color doppler ultrasound revealed blood flow within the mass, and the mass density was homogeneous on abdominal computed tomography (CT). Contrast-enhanced CT showed heterogeneous enhancement of the splenic mass during the arterial phase. Positron emission tomography (PET)-CT showed no significant fludeoxyglucose (FDG) accumulation within the mass. The differential diagnosis included splenic hamartoma, splenic hemangioma, splenomegaly associated with extramedullary hematopoiesis, and malignant tumor, including solitary splenic metastasis. A laparoscopic splenectomy was performed due to the possibility of malignancy, the presence of thrombocytopenia, and the risk of splenic rupture. The resected specimen showed a localized, well-demarcated, 8.0×7.0cm splenic mass. Histological examination revealed abnormal red pulp proliferation and the absence of normal splenic structures. The patient's post-operative course was uneventful. His platelet count improved on post-operative day 1 and he was discharged on post-operative day 9. He remained in good health with a normal platelet count one month after surgery. DISCUSSION: Making definitive preoperative diagnosis is difficult in splenic hamartomas. Surgery is necessary for diagnosis when malignancy cannot be ruled out. CONCLUSIONS: Surgery may also improve symptoms of hypersplenism, including thrombocytopenia.

[Abdominoperineal Resection for Anal Metastasis of Rectal Cancer].

Anal metastasis of colorectal cancer is rare, and no standardized effective therapeutic strategy exists. We report a case of abdominoperineal resection for anal metastasis of rectal cancer. A 65-year-old man underwent laparoscopic low anterior resection for rectal cancer in August 2013. Histopathological examination revealed a moderately differentiated adenocarcinoma( tub2, pSS, ly3, v2, pN1, H0, P0, M0, Stage III a, Cur A). In February 2015, he complained of anal discomfort, and tumor markers were elevated. Enhanced CT revealed a 15-mm high-density solid tumor in the anal canal. The results of needle biopsy indicated a moderately differentiated adenocarcinoma. This tumor was suspected to be metastasis from rectal cancer, and we performed abdominoperineal resection. Histopathological examination revealed a moderately differentiated adenocarcinoma, which was the same histological type as the primary rectal cancer and was covered with normal anal epithelium. Collectively, the findings indicated anal metastasis from rectal cancer. The patient is alive without recurrence for 18 months after resection. Anal metastasis should be considered as a differential diagnosis in patients with anal discomfort who have a history of colon/rectal cancer. Abdominoperineal resection may be an effective treatment modality for this condition.

Injury to the endometrium prior to the frozen-thawed embryo transfer cycle improves pregnancy rates in patients with repeated implantation failure.

AIM: This retrospective cohort study evaluated the effectiveness of injury to the endometrium prior to the frozen-thawed embryo transfer (FET) cycle in patients with repeated implantation failure (RIF) in our clinic. METHODS: Included in this study were 173 patients, aged ≤ 41 years, who failed to become pregnant after repeating fair and/or good embryo transfer more than twice between February 2012 and February 2015. The patients were divided into three groups: Group A (n = 38) underwent soft curettage to the endometrium twice, prior to the FET cycle; Group B (n = 45) underwent hysteroscopy prior to the FET cycle, with no significant factors, such as endometrial polyp; and Group C (n = 90) was the no-treatment group. RESULTS: The clinical pregnancy rate per transfer was found to be statistically significant between Group A at 42.1% (16/38) and Group C at 22.2% (20/90). The crude and adjusted odds ratios (OR) were 2.55 and 2.49 (95% confidence intervals 1.13-5.78, P = 0.03 and 1.01-6.17, P = 0.048) respectively. Group B with only hysteroscopy had a higher pregnancy rate of 35.6% (16/45) than Group C, but showed no statistical significance (P = 0.103). CONCLUSION: These results suggest that injuring the endometrium has a positive effect on pregnancy.