Implementation of First-trimester Screening and Prevention of Preeclampsia: a Stepped Wedge Cluster-randomized Trial in Asia.

BACKGROUND: This trial aimed to assess the efficacy, acceptability and safety of a first-trimester screen-and-prevent strategy for preterm preeclampsia (PE) in Asia. METHODS: Between 1st August 2019 and 28th February 2022, this multicenter stepped wedge cluster randomized trial included maternity/diagnostic units from ten regions in Asia. The trial started with a period where all recruiting centers provided routine antenatal care without study-related intervention. At regular six-week intervals, one cluster was randomized to transit from non-intervention phase to intervention phase. In the intervention phase, women underwent first-trimester screening for preterm PE using a Bayes theorem-based triple-test. High-risk women, with adjusted risk for preterm PE ≥ 1 in 100, received low-dose aspirin from <16 weeks until 36 weeks. RESULTS: Overall, 88.04% (42,897/48,725) of women agreed to undergo first-trimester screening for preterm PE. Among those identified as high-risk in the intervention phase, 82.39% (2,919/3,543) received aspirin prophylaxis. There was no significant difference in the incidence of preterm PE between the intervention and non-intervention phases (adjusted odds ratio [aOR] 1.59; 95% confidence interval [CI] 0.91 to 2.77). However, among high-risk women in the intervention phase, aspirin prophylaxis was significantly associated with a 41% reduction in the incidence of preterm PE (aOR 0.59; 95%CI 0.37 to 0.92). Additionally, it correlated with 54%, 55% and 64% reduction in the incidence of PE with delivery at <34 weeks (aOR 0.46; 95%CI 0.23 to 0.93), spontaneous preterm birth <34 weeks (aOR 0.45; 95%CI 0.22 to 0.92) and perinatal death (aOR 0.34; 95%CI 0.12 to 0.91), respectively. There was no significant between-group difference in the incidence of aspirin-related severe adverse events. CONCLUSIONS: The implementation of the screen-and-prevent strategy for preterm PE is not associated with a significant reduction in the incidence of preterm PE. However, low-dose aspirin effectively reduces the incidence of preterm PE by 41% among high-risk women. The screen-and-prevent strategy for preterm PE is highly accepted by a diverse group of women from various ethnic backgrounds beyond the original population where the strategy was developed. These findings underpin the importance of the widespread implementation of the screen-and-prevent strategy for preterm PE on a global scale.

Prenatal diagnosis of the umbilical cord torsion at the placental cord insertion site: A case report and literature review.

A 35-year-old woman (gravida 1, para 0) was admitted to our hospital at 28 weeks' gestation with vaginal bleeding from placenta previa. Severe fetal bradycardia was observed during fetal heart rate monitoring. Ultrasonography showed widely dilated veins on the fetal surface of the placenta and an extraordinarily low umbilical artery peak systolic velocity in the Doppler study. Umbilical cord torsion was suspected. On the subsequent day, we performed a cesarean section due to worsening fetal heart rate patterns. Umbilical artery blood gas analysis indicated severe acidemia (pH 7.063), and umbilical cord torsion was confirmed at the placental cord insertion site. Diagnosing UCT prenatally is challenging; however, it can be suspected by scanning for the widely dilated veins on the fetal placental surface, termed as the "Sunset Sign," an abnormally low umbilical artery peak systolic velocity, and other fetal Doppler abnormalities.

Inaccessibility, unresponsiveness, inconsistency, and invisibility of informal caregivers of older persons with cognitive impairment: community-based participatory research.

BACKGROUND: Studies on informal caregivers in Japan have been limited to family caregivers and largely conducted where family caregivers generally gather. Family caregivers who do not visit such places or non-family caregivers are generally overlooked, and data on these informal caregivers remains scant. Consequently, a framework is needed through which healthcare professionals can approach the informal caregivers of community-dwelling older persons. Therefore, this study approaches such informal caregivers and proposes a classification system for them from the starting point of older persons living in the community with cognitive impairment. METHODS: In 2016, we conducted an epidemiological survey of 7000 + community-dwelling older persons and identified 198 residents with Mini-mental state examination scores less than 23. A team of healthcare professionals contacted them regularly. By 2022, 92 people were still living in the community, and we systematically asked them about their informal caregivers. After approaching the caregivers and obtaining informed consent, we mailed separate questionnaires to older persons and informal caregivers. RESULTS: Among the caregivers, 59%, 34%, and 3% were the child, spouse, and sibling of the older person, while the remaining 4% were non-family caregivers. Except for two daughters-in-laws, all children were biological children of the older person. Male caregivers (46%) tended to have full-time jobs, whereas female caregivers (54%) tended to face financial difficulties. Only 3% of the caregivers had joined a family caregivers' association. Caregivers' reason for not joining such organizations was a lack of time and knowledge. A 3-tiered classification system was developed for these informal caregivers: (1) the household form, (2) accessibility, and (3) the reciprocal awareness of caregiving. Furthermore, family caregivers who lived with the older person or visited them more than once a week with reciprocal awareness of caring and being cared, or "traditional caregivers," accounted for 68% of the caregivers in this study. CONCLUSION: Core family caregivers can be easily approached at places where such caregivers generally gather. However, there also exists a group of informal caregivers who are sometimes inaccessible, unresponsive, and invisible to healthcare professionals. Moreover, their awareness of caregiving is sometimes inconsistent.

Association of Neutrophil Extracellular Traps with Plaque Instability in Patient with Carotid Artery Stenosis.

BACKGROUND: Vulnerable carotid plaques are related to cerebral thromboembolic and ischemic events. Neutrophil extracellular traps (NETs) can induce endothelial dysfunction and induce inflammation and coagulation. The aim of the present study was to investigate NETs in patients with carotid artery plaques. METHODS: Carotid plaques were collected by carotid endarterectomy (CEA) from 26 symptomatic and 8 asymptomatic patients between August 2017 and January 2021. The specimens were stained with hematoxylin-eosin and Elastica-van Gieson. Immunohistochemistry was performed staining by CD31 for identifying endothelial cells. NETs were detected by digoxigenin-labeled antihistone H3 (HH3) (citrulline R2+R8+R17). The relationships between the presence of NETs and patient profile and histopathological findings were assessed. RESULTS: HH3-positive cells were detected in 17 (asymptomatic = 2 symptomatic = 15) of 34 carotid plaques (median = 9.7/mm). The number of NETs was correlated with the number of diffusion-weighted imaging high-intensity lesions [P = 0.01], plaque rupture [P = 0.001], intraplaque hemorrhage [P = 0.02], intra luminal thrombus [P = 0.001], and thin fibrous cap [P = 0.001]. CONCLUSIONS: The presence of NETs was associated with the instability of carotid plaques, intraluminal thrombus, which may lead to subsequent cerebral infarction. Clarifying the roles of NETs in carotid plaques may improve the treatment of carotid artery disease.

Clinical significance of immunohistochemical lymphovascular evaluation to determine additional surgery after endoscopic submucosal dissection for colorectal T1 carcinoma.

PURPOSE: The Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines indicate lymphovascular invasion-evaluated by hematoxylin and eosin (HE) staining-as a surgical requirement after endoscopic submucosal dissection (ESD) in T1 colorectal carcinoma (CRC) patients; however, immunohistochemical evaluation may be superior. This study aimed to clarify the significance of immunohistochemical lymphovascular evaluation as an indicator for additional surgery of T1 CRC after ESD, and assessed the guidelines' adequacy, even when evaluating through immunostaining. METHODS: Patients with T1 CRC who underwent ESD were enrolled across three institutions between January 2012 and December 2017. Immunohistochemical lymphovascular evaluation was performed. Clinicopathological features, pathological evaluations, and surgery indications were recorded. Univariate and multivariate logistic regression identified risk factors for lymph node (LN) metastasis of T1 CRC after ESD. RESULTS: Among 370 patients with T1 CRC, recurrence, 5-year overall survival, and 5-year disease specific survival rates were 1.6%, 94.6%, and 99.5%, respectively. Six patients (1.6%) experienced recurrence, five of whom underwent additional surgery. Those with no risk factors did not exhibit recurrence. A total of 215 (58.1%) patients underwent additional surgery after ESD, 21 (9.7%) of whom exhibited LN metastasis. Among 16 patients who underwent additional surgery due to lymphovascular invasion, three (18.8%) had LN metastasis. Multivariate logistic regression analysis identified lymphatic invasion as a significant risk factor for LN metastasis (odds ratio 3.9, 95% confidence interval 1.0-14.6, P = 0.0421). CONCLUSIONS: The JSCCR guidelines have clinical validity, and immunohistochemical lymphatic evaluation findings potentially predict LN metastasis for T1 CRC after ESD.

Magnetic resonance vessel wall imaging predicts morphological deterioration in unruptured intracranial artery dissection.

OBJECTIVE: The mechanism involved in progression of unruptured intracranial artery dissection (IAD) is poorly understood. We investigated the relationship between contrast enhancement of dissecting lesions on magnetic resonance vessel wall imaging (MR-VWI) and unruptured IAD progression on the hypothesis that this finding might predict its instability. METHODS: A total of 49 unruptured IADs were investigated retrospectively. Three-dimensional T1-weighted fast spin-echo sequences were obtained before and after injection of contrast medium, and the dissecting lesion/pituitary stalk contrast enhancement ratio (CRstalk) was calculated. Unruptured IAD progression was defined as morphological deterioration; progressive dilatation or stenosis. The relations between unruptured IAD progression and potential risk factors were statistically investigated. RESULTS: Morphological deterioration was demonstrated in eleven of 49 unruptured IADs (22 %). The CRstalk value and male predominance was significantly higher in progressed IADs than stable ones (1.0 vs. 0.65; p = 0.0035, 82% vs 37%; p= 0.015, respectively). On stepwise multivariable logistic regression analysis, the CRstalk value was independently associated with unruptured IAD progression with odds ratio of 102.5 (95% CI, 2.59-4059, P=0.0013). The optimal cutoff value of CRstalk to estimate IADs with progression was 0.87 (sensitivity, 0.82; specificity, 0.74). Multimodalic images showed contrast enhancement on VWI corresponded to residual stagnant flow in dissecting lesions. CONCLUSIONS: Quantitative analysis of contrast enhancement on VWI could predict instability of unruptured IADs. Contrast enhancement in dissecting lesions would be a clue to understand the mechanism of unruptured IAD progression.

Vessel Wall Imaging of Evolving Unruptured Intracranial Aneurysms.

Background and Purpose- Unruptured intracranial aneurysms (UIAs) have various scenarios of growth and rupture. Magnetic resonance vessel wall imaging can detect aneurysmal wall thickening with inflammation and neovascularization. This study was performed to explore the vessel wall imaging findings of UIAs with consecutive follow-up. Methods- A total of 60 aneurysms with serial angiography over 2 years (mean period, 49 months, range, 24-192 months) were evaluated by vessel wall imaging. UIAs were morphologically categorized into 3 patterns: stable, whole sac expansion, or daughter sac formation. Aneurysm wall enhancement (AWE) was evaluated after administration of gadolinium. Results- Thirty-three of the 60 UIAs (55%) demonstrated no morphological changes, whereas 16 UIAS (27%) showed whole sac expansion and 11 UIAs (18%) demonstrated daughter sac formation. AWE was significantly less frequent in stable UIAs compared with UIAs showing morphological changes ( P<0.01). Aneurysms with daughter sac formation showed a significantly higher frequency of AWE than those demonstrating whole sac expansion. In the majority of UIAs with daughter sac formation, AWE was detected in the main aneurysm and not in the developing component. Conclusions- UIAs demonstrate various modes of growth. The pattern of AWE might be useful for identifying unfavorable morphological changes of UIAs.

Management and risk factors for incomplete resection associated with jumbo forceps polypectomy for diminutive colorectal polyps: a single-institution retrospective study.

BACKGROUND: Cold forceps polypectomy is simple and widely used in clinical practice. However, there are concerns about the risk of incomplete resection using this technique. In recent years, it has been reported that polypectomy with jumbo forceps (JF) is an effective treatment modality for diminutive polyps (DPs) because JF are able to remove large tissue samples with the combined advantage of a higher complete histological resection rate for DPs than standard forceps. To our knowledge, no studies have evaluated the risk factors for incomplete resection when polypectomy with JF is performed for DPs. METHODS: From among 1129 DPs resected using JF at Hiroshima City Asa Citizens Hospital between November 2015 and December 2016, we retrospectively evaluated the clinical outcomes of 999 tumors with known histopathology and investigated the relationship between incomplete resection and clinicopathological factors. RESULTS: Most lesions [985 (87%)] were low-grade dysplasia and 14 (1%) were high-grade dysplasia. The en bloc resection rate was 92% (918/999) and the histological en bloc resection rate was 78% (777/999). Multivariate analysis showed that the significant independent predictors of incomplete resection were tumor size ≥ 4 mm [odds ratio (OR) 3.8; 95% confidence interval (CI) 2.65-5.37; p < 0.01], non-tangential direction of forceps in relation to the tumor (OR 1.73; 95% CI 1.21-2.45; p < 0.01), and lack of muscularis mucosae in the pathological specimen (OR 15.7; 95% CI 9.16-27.7; p < 0.01). CONCLUSIONS: This study identified significant independent predictors of incomplete resection of DPs which may be helpful when planning polypectomy with JF.

Gastrectomy for invasive micropapillary carcinoma is associated with poorer disease-free and disease-specific survival.

BACKGROUND: Invasive micropapillary carcinoma (IMPC) is a relatively rare subtype of gastric adenocarcinoma and has aggressive histopathologic characteristics, including lymphatic and vascular invasion. However, the associated long-term survival outcomes remain unclear. This study aimed to compare the clinicopathological characteristics and prognosis of gastric adenocarcinoma with and without IMPC using propensity score-matched (PSM) analysis. METHODS: Patients with gastric adenocarcinoma who underwent gastrectomy between 2006 and 2015 were included in the analysis. PSM analysis was performed to compensate for the background heterogeneity between the groups. The primary endpoint was disease-free survival (DFS) after gastrectomy, and the secondary endpoints were disease-specific survival (DSS) and recurrence pattern. RESULTS: Of 882 patients who underwent gastrectomy for gastric adenocarcinoma, with a follow-up duration greater than 36 months, 35 were diagnosed as having gastric adenocarcinoma with IMPC. After PSM, 70 patients, including 35 with IMPC and 35 without IMPC, were selected. Gastric adenocarcinoma with IMPC is characterized by lymphatic invasion (94% versus 69%, p = 0.012). Patients with IMPC had significantly poorer DFS than those without IMPC, with 3-year DFS rates of 62.2% and 93.4% (p = 0.003), respectively. Furthermore, a significant difference was also observed in DSS (p = 0.016); patients with IMPC more frequently developed liver metastasis (20%) than those without IMPC (3%, p = 0.006). CONCLUSIONS: Resected gastric carcinoma with IMPC was associated with poorer DFS and DSS; furthermore, an increased rate of lymphatic invasion and liver metastasis was noted than in cases without IMPC.

[A Case of Primary Small Cell Carcinoma in the Breast with Neoadjuvant Chemotherapy That Were Difficult to Select Chemotherapy].

Primary small cell carcinoma in the breast is a rare and aggressive tumor, and a standard treatment strategy has not been established. Herein, we report a 35-year-old woman with primary small cell carcinoma in the breast. She had an 8 cm diameter tumor in the right breast. She was diagnosed with small cell carcinoma(cT3N1M0, cStage ⅢA)in the right breast, and neoadjuvant chemotherapy was planned. She received a combination chemotherapy of cisplatin(CDDP)and etoposide(VP- 16)based on the regimen for pulmonary small cell carcinoma; however, the disease showed progression. Therefore, 5-FU plus epirubicin plus cyclophosphamide(FEC)and weekly paclitaxel(PTX)chemotherapy based on a regimen for breast cancer were administered, and the tumor was partially reduced in size. Modified radical mastectomy followed by radiotherapy and hormonal therapy was performed. Ten months after the surgery, multiple liver and bone metastases occurred, and the patient died the following month. Further studies in other such patients are needed.

Clinicopathological Insights From Vessel Wall Imaging of Unruptured Intracranial Aneurysms.

Background and Purpose- The clinical significance of vessel wall imaging (VWI) remains unclear in patients with unruptured intracranial aneurysms. This study was performed to investigate the correlations between aneurysm wall imaging findings and histopathologic aneurysm wall architectures. Methods- A total of 9 aneurysms was evaluated by VWI and subsequently characterized with histopathology. We used VWI to visualize the aneurysm wall and determine if there was aneurysm wall enhancement after gadolinium contrast administration. Results- Aneurysm wall structures were identified in 6 of 9 unruptured intracranial aneurysms by native VWI, and wall enhancement was identified in 5 of these 6 aneurysms. Histopathologic studies revealed that wall thickening accompanied by atherosclerosis, neovascularization, and macrophage infiltration corresponded to visualization of the aneurysm wall by native VWI and to aneurysm wall enhancement. Conclusions- VWI can visualize thickening of the aneurysm wall, and wall enhancement corresponded to histologically confirmed degenerative changes accompanied by neovascularization and prominent macrophage infiltration.

Coexistence of gastrointestinal stromal tumor and leiomyosarcoma of the stomach presenting as a collision tumor: A case report and review of literature.

Collision tumor of the stomach is rare. We report a rare case of a gastric collision tumor consisting of gastrointestinal stromal tumors (GISTs) and leiomyosarcoma (LMS). Computed tomography scan revealed a 15 cm sized mass in the posterior wall of the body of the stomach. Gross examination of the wedge resection specimen showed the tumor located in the muscularis propria with extramural protrusion into the peritoneal cavity and the gastric cavity with geographic necrosis, hemorrhage, and mucosal ulceration. Histologically, the majority of the tumor consisted of the GIST component and the minor area in the submucosal region consisted of the LMS component. The tumor showed an abrupt transition between GIST and LMS by histologically and immunohistochemically, suggesting a collision tumor. Furthermore, the GIST components exhibited a c-kit exon 11 mutation. On the other hand, LMS component exhibited neither c-kit nor platelet-derived growth factor receptor-alpha (PDGFRA) mutation. Here we describe a case of the collision tumor consisting of GIST and LMS and its literature review.

Invasive micropapillary carcinoma component is an independent prognosticator of poorer survival in Stage III colorectal cancer patients.

BACKGROUND: Invasive micropapillary carcinoma (IMPC) is an aggressive variant of adenocarcinoma found in several organs. Recent studies showed that IMPC in colorectal cancer leads to poorer prognosis than conventional colorectal cancer; however, the influence of IMPC on outcomes remains unclear. The present study aimed to identify the clinicopathological characteristics of colorectal cancers with IMPCs, and to evaluate the prognostic significance of IMPCs per se. METHODS: We retrospectively analyzed data from 837 patients with colorectal cancer who underwent surgical treatment. We compared the clinicopathological characteristics and survival outcomes of colorectal cancer patients with IMPCs to those without. RESULTS: Among 837 patients, 130 (16%) had an IMPC component, including 0 (0%) of 18, 9 (4.2%) of 215, 34 (13%) of 254, 59 (24%) of 249 and 28 (27%) of 101 patients with TNM Stages 0, I, II, III and IV, respectively. The 3-year disease-free survival (DFS) rates were significantly worse for Stage III patients with IMPC than for those without (55.3% vs. 78.7% respectively, P < 0.001), but not in patients with other stages. Multivariate analyses of patients with Stage III colorectal cancer found IMPC to be associated with significantly worse DFS (P = 0.026), as were high CEA levels, tumor budding and TNM staging. IMPC was only significantly associated with tumor invasion (P = 0.045) and venous invasion (P = 0.045) in Stage III tumors. CONCLUSIONS: Identifying IMPC components in Stage III colorectal cancer is crucial, as their presence is significantly associated with poorer survival.

Morphology and clinical importance of epidural membrane and periradicular fibrous tissue in lumbar spinal stenosis.

PURPOSE: Compared to the ligamentum flavum (LF), morphology of the epidural membrane (EM) and the periradicular fibrous tissue (PRFT) has been largely ignored in studies of lumbar spinal stenosis (LSS). The aim of this prospective study was to elucidate the morphologies and clinical importance of the EM and PRFT in LSS. METHODS: Before starting this study, neural compressive EM (c-EM) and PRFT (c-PRFT) were defined as follows based on our microsurgical experience and a literature review. The c-EM is a constriction band or membrane obstructing dural tube expansion, and the c-PRFT is a fibrous tissue that compresses the nerve root and/or restricts its mobility. This study enrolled 134 patients who underwent microscopic decompression at L4/5. The morphologies of each patient's EM and PRFT were observed and recorded. Specimens were obtained from randomly selected patients for histological evaluation. RESULTS: The EM and PRFT exhibited a wide morphological spectrum, from a fine strand to a substantial membrane. The c-EM alone was observed in four cases, the c-PRFT alone in 37 cases, and both in three cases. The c-PRFT was more frequently observed in patients with degenerative spondylolisthesis than in those without olisthesis (P < 0.05). Several cases exhibited interesting histological findings including many small arteries, chondrometaplasia, ganglion-like cyst formation, and hyalinized collagen fibers. CONCLUSIONS: Some EM and PRFT transform into degenerative and substantial fibrous tissues during the process of symptomatic LSS development. Such morphological and histological changes can cause dural tear, symptomatic epidural hematoma, and/or inadequate decompression.

Chronic kidney disease as a risk factor for recurrence and progression in patients with primary non-muscle-invasive bladder cancer.

OBJECTIVES: To investigate the relationship between chronic kidney disease and primary non-muscle-invasive bladder cancer. METHODS: Disease outcomes were analyzed in 418 patients treated with transurethral resection for primary non-muscle-invasive bladder cancer, and were correlated to traditional risk factors as well as chronic kidney disease stage according to estimated glomerular filtration rate: ≥60 (G1-2), 45-59 (G3a) or <45 (G3b-5). RESULTS: The median follow-up time was 40.0 months. There were 287 (68.7%), 98 (23.4%), and 33 (7.9%) patients with G1-2, G3a and G3b-5 chronic kidney disease, respectively. T1 tumor was present in 29.6% of G1-2, 43.9% of G3a and 51.4% of G3b-5 chronic kidney disease (P = 0.004). The proportion of histological grade 3 non-muscle-invasive bladder cancer was higher in G3a and G3b-5 than G1-2 (P < 0.001). Higher chronic kidney disease stage was associated with worse recurrence-free (P < 0.001) and progression-free survival (P = 0.017). In multivariable analysis, G3b-5 was found to be an independent predictor for recurrence (hazard ratio 1.87; P = 0.004) and progression (hazard ratio 2.96; P = 0.019). Chronic kidney disease stage was also strongly associated with the European Association of Urology bladder cancer risk groups (P < 0.001), and with shorter time to recurrence and progression in each group. CONCLUSIONS: Chronic kidney disease predicts the clinical outcome of primary non-muscle-invasive bladder cancer. Adding chronic kidney disease to the conventional risk factors might increase the accuracy of risk stratification.

[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.

[Pathological Complete Response to SOX plus Bevacizumab for Treating Stage IV Sigmoid Colon Cancer].

Advanced sigmoid colon cancer with stenosis was discovered in a man in his 50's who presented with constipation. A radiological examination revealed peritoneal dissemination. Transverse colostomy was scheduled for the treatment of bowel obstruction. Multiple disseminated nodules were confirmed, and adenocarcinoma was detected from a nodule in the omentum. Eight courses of SOX plus bevacizumab caused the primary tumor to shrink and disseminated nodules to become radiologically undetectable. The patient underwent sigmoid colectomy 8 weeks after the last bevacizumab administration, and no disseminated nodules were found during the procedure. Histological assessment revealed no evidence of cancer cells in the colon and lymph nodes, and the histological effect was judged as Grade 3.

[A case report of hepatocellular carcinoma with metastases to the lip, stomach, and colorectum].

A 79-year-old man was diagnosed with hepatocellular carcinoma in 2000 and treated with partial hepatectomy. Intrahepatic carcinoma recurred with lung metastases 7 years later. Several transcatheter arterial chemoembolizations were performed to treat the recurrence, and a right lower lobectomy was performed for lung metastasis. Twelve years after the original carcinoma diagnosis, lip and lung metastases were detected, and he was hospitalized for radiotherapy of the lung metastasis; an oral molecular-targeting drug was initiated. During the therapy, hematochezia was observed, and a colonoscopy was performed. A submucosal lesion with a blood clot measuring approximately 4mm in diameter was found in the sigmoid colon, and endoscopic mucosal resection was performed. Furthermore, an elevated lesion with a 5-mm diameter recess was observed on upper gastrointestinal endoscopy. Both lesions were diagnosed histopathologically as hepatocellular carcinoma metastases.