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Cervical esophageal adenocarcinoma has a low incidence rate and its treatment involves various strategies. We report a patient with locally advanced cervical to upper esophageal adenocarcinoma who was able to undergo induction chemotherapy and radical surgery. A 55-year-old man was diagnosed with a poorly differentiated adenocarcinoma between the cervical and upper thoracic esophagus. The primary lesion had infiltrated into the tracheal membrane and had metastasized into the cervical lymph nodes. The initial diagnosis was T4bN1M1 stage IVB. The lower edge of the tumor was close to the tracheal bifurcation, making it difficult to create a longitudinal tracheal foramen during surgery. Therefore, when biweekly-DCF therapy was performed as induction chemotherapy, the tumor shrank sufficiently and its infiltration into the tracheal membrane decreased subsequently. We performed total laryngopharyngoesophagectomy with three-field lymph node dissection and reconstruction using free jejunal grafts and subtotal stomach via a posterior mediastinum route and a permanent tracheal foramen as a radical surgery. The pathological diagnosis was T2/MP, N1, and the effect of chemotherapy was grade 2. Cervical esophageal adenocarcinoma was rare, but technically reliable and safe oncologic surgery was possible after induction chemotherapy.

Cancer-associated antigens are not only a good marker for monitoring cancer progression but are also useful for molecular target therapy. In this study, we aimed to generate a monoclonal antibody that preferentially reacts with colorectal cancer cells relative to noncancerous gland cells. We prepared antigens composed of HT-29 colorectal cancer cell lysates that were adsorbed by antibodies to sodium butyrate-induced enterocytically differentiated HT-29 cells. Subsequently, we generated a monoclonal antibody, designated 12G5A, which reacted with HT-29 colon cancer cells, but not with sodium butyrate-induced differentiated HT-29 cells. Immunohistochemical staining revealed 12G5A immunoreactivity in all 73 colon cancer tissue specimens examined at various degrees, but little or no immunoreactivity in noncancerous gland cells. Notably, high 12G5A immunoreactivity, which was determined as more than 50% of colon cancer cells intensively stained with 12G5A antibody, exhibited significantly higher association with a poor overall survival rate of patients with colorectal cancer (P = 0.0196) and unfavorable progression-free survival rate of patients with colorectal cancer (P = 0.0418). Matrix-assisted laser desorption ionization time-of-flight mass spectrometry, si-RNA silencing analysis, enzymatic deglycosylation, and tunicamycin treatment revealed that 12G5A recognized the glycosylated epitope on annexin A2 protein. Our findings indicate that 12G5A identified a cancer-associated glycosylation epitope on annexin A2, whose expression was related to unfavorable colorectal cancer behavior. KEY MESSAGE: • 12G5A monoclonal antibody recognized a colorectal cancer-associated epitope. • 12G5A antibody recognized the N-linked glycosylation epitope on annexin A2. • 12G5A immunoreactivity was related to unfavorable colorectal cancer behavior.

We report a successful case that offered a symbolic therapeutic experience of interventional radiology and surgery collaboration for superior mesenteric artery thrombosis. A 70-year-old man presented with a chief complaint of sudden abdominal pain. Contrast-enhanced computed tomography revealed superior mesenteric artery thrombosis. Interventional radiology was performed, and thrombotic occlusion was observed in the superior mesenteric artery trunk. The abdominal pain disappeared; however, after a while, the thrombus re-formed and the abdominal pain reappeared. Thus, emergency surgery was performed. Before surgery, thrombus aspiration was performed via interventional radiology as much as possible. During surgery, when the blood flow was evaluated using fluorescence with indocyanine green, a region of markedly poor blood flow was detected in the ileum, and the area was excised. The postoperative course was favorable. In this patient, it is possible that preoperative removal of the thrombus via interventional radiology minimized the ischemic area of the intestinal tract, and blood flow evaluation using indocyanine green allowed reliable excision of only the ischemic area. We believe that our case involved a treatment that exploited the advantages of both interventional radiology and surgery using indocyanine green fluorescence.

Patients with advanced gastric cancer, especially diffuse-type gastric cancer, which is often accompanied by stromal fibrosis, commonly exhibit a poor prognosis. This study was designed to unravel the potential roles of C1q/TNF-related protein 6 (CTRP6) in the fibrotic cancer microenvironment of diffuse-type gastric adenocarcinoma. A total of 49 diffuse-type gastric cancer samples were evaluated in this study, and 23 of these samples exhibited focal CTRP6 immunoreactivity. CTRP6 immunoreactivity was found to be correlated with favorable survival outcomes, in terms of both overall and relapse-free survival rates, but this trend did not reach significance (P = 0.15). By contrast, CTRP6 immunoreactivity was significantly correlated with relapse-free survival rates in patients with diffuse-type gastric cancer at a distal site (P = 0.028). Notably, most gastric cancer cells at the cancer invasive front were CTRP6 negative, especially in areas of robust fibrosis. Double immunohistochemical staining demonstrated an inverse expression profile for CTRP6 and the activated fibroblast marker alpha smooth muscle actin (α-sma) in stromal and gastric cancer cells at the cancer invasion front. The addition of recombinant CTRP6 protein attenuated the TGF-β-induced α-sma expression in cultured human fibroblasts but did not alter the proliferation rate or Matrigel-invasion activity of the cultured gastric cancer cells. In addition, CTRP6 did not affect the viability of normal human gastric epithelial cells. This study suggests that CTRP6 may have potential application in combating stromal fibrosis in diffuse-type gastric cancers.

Background/Aim: This study aimed to assess the association of the modified albumin-bilirubin (mALBI) grade with the endoscopic findings of gastroesophageal varices (GEVs). Patients and Methods: A total of 141 patients with histologically proven cirrhosis who underwent a liver biopsy and esophagogastroduodenoscopy were enrolled. The relationships between the mALBI grade and endoscopic findings were evaluated. Results: The incidence of GEVs and high-risk GEVs differed among mALBI grades. Patients with mALBI grades of 2b-3 had higher rates of GEVs and high-risk GEVs in comparison to those with mALBI grades of 1-2a (p

Background/aim At present, there are no biomarkers to predict the effects of molecular targeted drugs in patients with CRC with liver metastasis. Thus, we performed this study to explore potential biomarkers for these patients. Materials and methods We obtained cancer tissue specimens from liver metastasis-bearing CRC patients who received the following preoperative neoadjuvant chemotherapies with molecular targeted drugs: i) no therapy (n=3), ii) 5-FU+oxaliplatin+anti-EGFR (n=3), iii) and 5-FU+oxaliplatin+anti-VEGF (n=3). Results We investigated the RNA expression of 84 genes related to cancer drug resistance using an RT-PCR array. The MYC gene was the only gene that was significantly up-regulated in CRC tissue specimens from anti-EGFR group in comparison to the anti-VEGF group. Conclusion MYC up-regulation in the primary CRC tissues may be a potentially useful biomarker for selecting anti-EGFR combination therapy in neoadjuvant chemotherapy for CRC with liver metastasis.

This study was designed to unravel the pathobiological role of impaired ARID1A expression in gastric carcinogenesis. We examined ARID1A expression immunohistochemically in 98 gastric cancer tissue specimens with regard to the clinicopathological features. Based on the proportion and intensity of ARID1A immunoreactivity at the cancer invasion front, we subdivided the specimens into low- and high-expression ARID1A groups. Notably, low ARID1A expression was significantly correlated with overall survival of the patients. Subsequently, we determined the molecular signature that distinguished ARID1A low/poor prognosis from ARID1A high/good prognosis gastric cancers. A comprehensive gene profiling analysis followed by immunoblotting revealed that a mitochondrial apoptosis mediator, Harakiri, was less expressed in ARID1A low/poor prognosis than ARID1A high/good prognosis gastric cancers. siRNA-mediated ARID1A downregulation significantly reduced expression of the Harakiri molecule in cultured gastric cancer cells. Interestingly, downregulation of ARID1A conferred resistance to apoptosis induced by the mitochondrial metabolism inhibitor, devimistat. In contrast, enforced Harakiri expression restored sensitivity to devimistat-induced apoptosis in ARID1A downregulated gastric cancer cells. The present findings indicate that impaired ARID1A expression might lead to gastric carcinogenesis, putatively through gaining resistance to the Harakiri-mediated apoptosis pathway.

A 75-year-old woman was diagnosed with anemia during hospitalization for the treatment of right superior ophthalmic arteriovenous fistula. Colonoscopy revealed an entire circumference of type 2 tumor in the ascending colon. Computed tomography showed ascending colon wall thickening, a tumor with a maximum diameter of 32 mm on the right external iliac artery and multiple low-density nodules in the spleen. We performed right hemicolectomy with D3 lymph node dissection, splenectomy and right external iliac lymph node dissection. Histopathological finding revealed moderately-differentiated adenocarcinoma in ascending colon and right external iliac lymph node. The lesion of spleen was diagnosed as splenic lymphangioma. The patient was discharged on postoperative day 18. Additional treatments, including chemotherapy, were not performed, and no recurrences were seen up to 66 months after surgery. We herein report an uncommon event of ascending colon cancer with synchronous right external iliac lymph node metastasis, which was successfully treated by surgical resection, made feasible when the distant lymph node metastasis is localized.

Aim To elucidate the common and different points between sarcopenia and frailty in chronic liver damage (CLD). Patients and methods Patients with both grip strength decline and skeletal muscle index decline were regarded as sarcopenia. Frailty was defined as a syndrome in which 3 or more of the following criteria were met: i) exhaustion, ii) body weight loss, iii) slow walking speed, iv) muscle weakness, and v) low physical activity. Results Sarcopenia and frailty were identified in 52 patients (15.2%) and 46 (13.5%), respectively. The prevalence of sarcopenia and frailty was well stratified according to age and the liver cirrhosis (LC) status. In the multivariate analysis, we identified significant factors for sarcopenia: i) age, ii) LC, iii) body mass index and iv) extracellular water (ECW) to total body water (TBW) ratio, while only the ECW to TBW ratio was significant for frailty. Conclusion Sarcopenia and frailty in CLD should be separately evaluated.

Postoperative chylothorax after esophagectomy is a relatively rare complication, but treatment can sometimes be complicated. We report 3 cases of Lipiodol lymphangiography via inguinal lymph node puncture that was effective for chyle leakage occurring after esophagectomy. Case 1: A 67-year-old man with stage IIIA esophageal squamous cell carcinoma underwent radical esophagectomy by video-assisted thoracic surgery (VATS) following neoadjuvant chemotherapy (NAC). After enteral feeding, right pleural effusion drainage increased sharply and changed to white color that was diagnosed as chylothorax. Conservative treatment was started on postoperative day (POD) 15. On POD 50, intranodal Lipiodol lymphangiography and thoracic duct ligation were performed, resulting in complete improvement by the next day. Case 2: A 69-year-old man with stage IIIC esophageal cancer was treated salvage operation following chemoradiation. Postoperative chylothorax was diagnosed on POD 6. Despite conservative treatment, the pleural fluid volume did not decrease. Intranodal Lipiodol lymphangiography performed on POD 13 showed contrast medium draining from the thoracic duct near the tracheal bifurcation. Thoracotomy for thoracic duct ligation was performed on POD 15. Thereafter, drainage from the thoracic drain decreased significantly, and the right thoracic drain was removed 4 days later. Case 3: A 65-year-old man with Stage IVA hypopharyngeal cancer and Stage IIIA esophageal cancer underwent total pharyngopharyngeal esophagectomy by VATS following NAC. Postoperative chylothorax was diagnosed on POD 7. Despite conservative treatment, the pleural fluid volume did not decrease. Intranodal Lipiodol lymphangiography performed on POD 19 completely visualized the thoracic duct and showed no outflow of contrast from the main thoracic duct into the mediastinum. Pleural fluid decreased remarkably after lymphangiography. Intranodal Lipiodol lymphangiography for postoperative chylothorax accurately visualizes flow within the thoracic duct and clearly depicts its positional relationship with other organs. Besides lymphangiography is not only helps to determine the site of chyle leakage but can also be effective for curing chylothorax by less invasive and safer method.

Background/Aim: This study aimed to assess the clinical significance of measuring the arm skeletal muscle mass in patients with cirrhosis. Patients and Methods: Using body composition data measured with the bioimpedance analysis (BIA) method, the skeletal muscle mass index (SMI) values of the arm (arm skeletal muscle mass/height(2)) and leg (leg skeletal mass muscle/height(2)) were calculated for 353 patients with cirrhosis, and the relationships of these indices to their prognosis were assessed. In addition, overhydration of the upper and lower limbs was compared. Results: Arm SMI was significantly positively associated with the prognosis of patients with cirrhosis (p=0.0002) but leg SMI was not (p=0.0829). The rate of overhydration in the lower limbs was significantly higher than that in the upper limbs (p

Background/aim A bioimpedance analysis (BIA) can indicate an overhydrated state as the extracellular water/total body water (ECW/TBW) value. This study aimed to assess the clinical significance of this value in patients with chronic liver diseases (CLDs). Patients and methods A total of 552 CLD patients who received a liver biopsy and underwent anthropometric assessment and BIA-based body composition analysis were enrolled. The association of the ECW/TBW value with the liver fibrosis and nutritional status was assessed. The relationship between the ECW/TBW value and the prognosis of cirrhotic patients (N=209) was also evaluated. Results The ECW/TBW value increased as liver fibrosis progressed and was also related to decreased muscle mass/sarcopenia. The presence of overhydration was associated with a poor prognosis of cirrhotic patients. Conclusion An increased ECW/TBW value was associated with progressive liver fibrosis and malnutrition and related to the prognosis of cirrhotic patients.

Background/Aim: The bioimpedance analysis (BIA) can provide anthropometric data on patients. The aim of the study is to evaluate the clinical relevance of these automatically obtained values. Patients and Methods: We studied the arm circumference (AC) and arm muscle circumference (AMC) of 197 histologically proven cirrhotic patients. The BIA-based anthropometric data were compared to the manually measured data. In addition, we evaluated whether or not the BIA-based anthropometric data were associated with the prognosis of the patients. Results: The data of %AC and %AMC obtained using the two methods were well correlated (p

Endoscopic ultrasound-guided tissue acquisition (EUS-TA) plays a crucial role in the diagnosis of pancreatic tumors. The present study aimed to investigate the current status of needle tract seeding (NTS) after EUS-TA of pancreatic tumors based on a nationwide survey in Japan.Patients who underwent surgical resection of primary pancreatic tumors after EUS-TA performed between April 2010 and March 2018 were surveyed. The incidence rates of NTS were determined, and compared in patients with pancreatic ductal adenocarcinomas (PDACs) and other tumors, and in patients who underwent transgastric and transduodenal EUS-TA of PDACs. The detailed features and prognosis of patients with NTS were also assessed.A total of 12,109 patients underwent surgical resection of primary pancreatic tumors after EUS-TA. The overall incidence rate of NTS was 0.330%, and the NTS rate was significantly higher in patients with PDAC than in those with other tumors (0.409% vs. 0.071%, P=0.004). NTS was observed in 0.857% of patients who underwent transgastric EUS-TA, but in none of those who underwent transduodenal EUS-TA. Of the patients with NTS of PDACs, the median time from EUS-TA to occurrence of NTS and median patient survival were 19.3 and 44.7 months, respectively, with 97.4% of NTS located in the gastric wall and 65.8% of NTS resected. The patient survival was significantly longer in patients who underwent NTS resection than in those without NTS resection (P=0.037).NTS appeared only after transgastric not after transduodenal EUS-TA. Careful follow-up provides an opportunity to remove localized NTS lesions by gastrectomy.

Background/aim We report the end results of a study evaluating the safety and efficacy of preoperative chemoradiotherapy with S-1 plus oxaliplatin. Patients and methods Eligible patients had histopathologically confirmed locally advanced rectal carcinoma (LARC; cT3-T4, any N). They received oral S-1 (80 mg/m2/day on days 1-5, 8-12, 22-26, and 29-33) and oxaliplatin by infusion (50 mg/m2/day on days 1, 8, 22, and 29) along with radiotherapy (1.8 Gy/day, total dose: 45 Gy/25 fractions). A chemotherapy gap was included in the third week of radiotherapy. The study endpoint was pathological response rate (Grade 2, 3). Secondary endpoints included rates of pathologic complete response (pCR), R0 resection, disease-free survival (DFS), overall survival (OS), local and distant recurrence, and safety and relative dose intensity. Results The study enrolled 23 patients at three Centres in Gifu, Japan. All patients received chemoradiotherapy, and 22 underwent surgery. Rates of pathological response, R0 resection, and pathological down-staging were 56.5% (13/23), 95.7% (22/23), and 63.6% (14/22), respectively. There were no grade 4 adverse events, but grade 3 events occurred in 21.7% of patients. The cumulative 3-year local recurrence rate was 8.7%. Distant metastasis occurred in 10 (43.5%) patients, 2 (8.7%) from local recurrence and 2 from secondary pancreatic cancer and lung cancer. There were 8 patients with lung metastasis, 2 with liver metastasis, one with ovarian metastasis, and one with bone metastasis. Three-year rates of DFS and OS were 51.1% (median follow-up 34.3 months) and 91.1% (45.2 months), respectively. Conclusion The study showed high pathological response rate without severe toxicity and good follow-up results. Unexpectedly, however, this regimen could not control local recurrence and distant metastasis. Nevertheless, adding oxaliplatin to preoperative chemoradiotherapy with S-1 in patients with LARC appears feasible and may safely result in better local control than standard treatment. The study suggests adding treatment with induction chemotherapy in consideration of CEA level and N factor.

AIM We aimed to compare the well-established liver fibrosis (LF) markers in Japanese patients with chronic hepatitis B (CHB, n = 331) and chronic hepatitis C (CHC, n = 886) and to discuss possible causes of differences in results between CHB patients and CHC patients. METHODS Virtual touch quantification (VTQ) in acoustic radiation force impulse, Fibrosis-4 (Fib-4) index, aspartate aminotransferase to platelet ratio index (APRI), and hyaluronic acid (HA) were compared between the two cohorts. As an additional investigation, total collagen proportional area (TCPA, %) was tested using liver pathological samples (n = 83). RESULTS Significant LF (F2 or greater) and advanced LF (F3 or greater) were identified in 153 (46.2%) and 76 (23.0%) patients in the CHB cohort and 579 (65.3%) and 396 (44.7%) patients in the CHC cohort. The median VTQ, Fib-4 index, APRI, and HA values in the CHB cohort were 1.20 m/s, 1.36, 0.44, and 25 ng/mL; those in the CHC cohort were 1.32 m/s, 2.60, 0.74, and 65.5 ng/mL (P-values, all

AIM Transient elastography (TE) is the gold standard for measurement of liver stiffness. The usefulness of shear wave elastographies (SWE) is well accepted. However, the measurement values cannot be equivalently compared because cut-off values for the diagnosis of liver fibrosis are different among those devices. We aimed to clarify correlations, to generate the regression equations between TE and SWEs, and to compare the diagnostic ability of each device to diagnose liver fibrosis. METHODS A total of 109 patients with chronic liver disease who underwent liver biopsy and same-day evaluation of liver stiffness using six ultrasound devices were analyzed. The diagnostic ability of liver stiffness from each ultrasound device and correlations between TE and each SWE were analyzed. RESULTS Liver stiffness measured by all six ultrasound devices increased significantly as liver fibrosis stage advanced (P

Fluorouracil (5FU) is converted to its active metabolite fluoro-deoxyuridine monophosphate (FdUMP) through the orotate phosphoribosyl transferase (OPRT)-ribonucleotide reductase (RR) pathway and thymidine phosphatase (TP)-thymidine kinase (TK) pathway and inhibits thymidylate synthase (TS), leading to inhibition of thymidine monophosphate (dTMP) synthesis through a de novo pathway. We investigated the mechanism of 5FU resistance and strategies to overcome it by focusing on 5FU metabolism. Colon cancer cell lines SW48 and LS174T and 5FU-resistant cell lines SW48/5FUR and LS174T/5FUR were used. FdUMP amount was measured by western blotting. The FdUMP synthetic pathway was investigated by combining TP inhibitor (tipiracil hydrochloride; TPI) or RR inhibitor (hydroxyurea; HU) with 5FU. Drug cytotoxicity was observed by crystal violet staining assay. FdUMP was synthesized through the OPRT-RR pathway in SW48 cells but was scarcely synthesized through either the OPRT-RR or TP-TK pathway in SW48/5FUR cells. FdUMP amount in SW48/5FUR cells was reduced by 87% vs. SW48 cells. Expression levels of OPRT and TP were lower in SW48/5FUR when compared with these levels in the SW48 cells, indicating decreased synthesis of FdUMP-led 5FU resistance. These results indicated that fluoro-deoxyuridine (FdU) rather than 5FU promotes FdUMP synthesis and overcomes 5FU resistance. Contrastingly, FdUMP was synthesized through the OPRT-RR and TP-TK pathways in LS174T cells but mainly through the TP-TK pathway in LS174T/5FUR cells. FdUMP amount was similar in LS174T/5FUR vs. the LS174T cells. OPRT and RR expression was lower and TK expression was higher in LS174T/5FUR vs. the LS174T cells, indicating that dTMP synthesis increased through the salvage pathway, thus leading to 5FU resistance. LS174T/5FUR cells also showed cross-resistance to FdU and TS inhibitor, suggesting that nucleoside analogs such as trifluoro-thymidine should be used to overcome 5FU resistance in these cells. 5FU metabolism and mechanisms of 5FU resistance are different in each cell line. Both synthesized FdUMP amount and FdUMP sensitivity should be considered in 5FU-resistant cells.

Background: Patients with liver metastases from colorectal cancer (CRLMs) frequently receive chemotherapy prior to liver resection. Histopathological assessment of the resected specimen can evaluate the response to chemotherapy. This study analyzed the correlation between histopathological changes in the primary site and liver metastases. Patients and Methods: This study comprised 45 patients with resectable CRLMs at the Surgical Oncology Department of Gifu University School of Medicine from January 2006 to August 2015. Results: The study included 24 men and 21 women. The primary colonic tumor was located in the right side in 13 (28.9%) patients and the left side in 32 (71.9%) patients. We evaluated patients with metastatic colorectal cancer (31/45) after excluding those in whom histopathological heterogeneity between the primary and liver metastasis changed to grade 3 after chemotherapy. We compared the group which underwent hepatectomy after chemotherapy (n=25) with that underwent hepatectomy alone (n=6). In 16 (53.3%) out of 25 patients, histopathological heterogeneity of the liver metastasis was lost (p=0.04). Conclusion: Chemotherapy appears to change histopathological heterogeneity.Our study suggests that the change of intratumoral heterogeneity reflect by the response of chemotherapy.

BackgroundCervical esophageal adenocarcinoma has a low incidence rate and its treatment involves various strategies. We report a patient with locally advanced cervical to upper esophageal adenocarcinoma, able to undergo induction chemotherapy and radical surgery. We report our case as a valuable clinical experience.Case presentationThe patient complained of throat stuffiness. We found a poorly differentiated adenocarcinoma between the cervical esophagus and the upper thoracic esophagus. The primary lesion had infiltrated into the tracheal membrane and had metastatized into the cervical lymph nodes. The initial diagnosis was T4bN1M0 stage IVA. The lower edge of the tumor was close to the tracheal bifurcation, making it difficult to create a longitudinal tracheal foramen during surgery. Therefore, when biweekly-DCF therapy was performed as induction chemotherapy, the tumor shrank sufficiently. Furthermore, tumor infiltration into the tracheal membrane decreased, allowing us to perform total laryngopharyngoesophagectomy with three-field lymph node dissection and reconstruction using free jejunal grafts and subtotal stomach via a posterior mediastinum route and a permanent tracheal foramen as a radical surgery. The pathological diagnosis was T2/MP, N1, and the effect of chemotherapy was grade 2. The patient is followed-up regularly.ConclusionsCervical esophageal adenocarcinoma was rare, but technically reliable and safe oncologic surgery was possible after induction chemotherapy.

The need for adjuvant therapy after radical resection for patients with stage II–III thoracic esophageal squamous cell carcinoma (TESCC) who have undergone neoadjuvant chemotherapy (NAC) has not been determined. Since recurrence can occur after radical resection and since the prognosis is still poor, it is necessary to consider additional treatment strategies, including adjuvant chemotherapy. We retrospectively investigated the significance of adjuvant therapy after NAC followed by radical resection for TESCC. Between 2008 and 2018, 115 patients with clinical stage II–III underwent radical subtotal esophagectomy after neoadjuvant therapy. Among them, 62 were analyzed, excluding patients with T4 tumors and patients who had undergone R plus resection or who were receiving preoperative chemoradiotherapy. We compared patients who received adjuvant chemotherapy with those who only received observation; we examined overall survival (OS) and recurrence rates. Twenty-nine patients (46.7%) had lymph node metastasis, 12 of whom received adjuvant chemotherapy (41.3%). The recurrence rates for patients with and without lymph node metastasis were 55.1 % and 15.1%, respectively (p = 0.0022). Among patients with lymph node metastasis, there was no significant difference in the recurrence rate (p = 0.9270) or OS (p = 0.5416) based on the administration of adjuvant chemotherapy. However, in 15 patients with two or more positive lymph nodes, adjuvant chemotherapy increased OS (p = 0.0404). Adjuvant chemotherapy was associated with improved OS in clinical stage II–III TESCC patients with two or more pathological positive lymph nodes after NAC followed by radical surgery. Supplementary Information The online version contains supplementary material available at 10.1007/s13193-021-01419-0.

Purpose Malignant large-bowel obstruction (MLBO) is a highly urgent condition in colorectal cancer with high complication rates. Self-expandable metal stent (SEMS) placement in MLBO is a new decompression treatment in Japan. Preoperative stent placement (bridge to surgery: BTS) avoids emergency surgery, but oncological influences of stent placement and post-BTS surgical approach remain unclear. We examined short- and long-term results of surgery for MLBO after SEMS placement in our hospital. Methods We retrospectively reviewed 75 patients with MLBO who underwent resection after SEMS placement at our hospital from June 2013 to December 2018. Postoperative morbidity and mortality were evaluated by comparison with the surgical approach. Results Tumor location was significantly higher in the left-side colon and rectum (n = 59, 78.7%) than right-side colon (n = 16, 21.3%). Technical and clinical success rates for SEMS placement were 97.3% and 96.0%, respectively. Laparoscopic surgery was performed in 54 patients (69.0%), and one-stage anastomosis was performed in 73 (97.3%). Postoperative complications were similar in the open surgery (open) group (n = 5, 23.8%) and laparoscopic surgery (lap) group (n = 7, 13.0%), with no severe complications requiring reoperation. Three-year overall survival (OS) and relapse-free survival (RFS) rates were not significantly different in the lap vs open group (67.5% vs 66.4%; 82.2% vs 62.5%). Conclusion Preoperative stent treatment avoids stoma construction but allows anastomosis. One-time surgery was performed safely contributing to minimally invasive treatment and acceptable short- and long-term results.

Background: Complete recovery from retroperitoneal squamous cell carcinoma of unknown primary site treated by multidisciplinary therapy is extremely rare.Case presentation: A 78-year-old man was referred to our hospital due to a mass measuring 8 cm in size in the left pelvic retroperitoneal area, which was diagnosed as a cancer of unknown primary site. The pathological type was squamous cell carcinoma. The left iliac artery/vein and ureter were involved in the tumor, and the tumor caused severe left leg pain. Although inflammation and symptoms were severe, palliative radiotherapy was considered. After that, biweekly combined therapy with docetaxel, cisplatin, and fluorouracil was planned. After 5 courses of chemotherapy, the tumor diameter reduced from 11.6 cm to 4 cm in size. In addition, the border between the iliac vessels, urinary tract and tumor became apparent. The patient underwent radical resection of the tumor 8 months after the treatment started. The left ureter and the external/internal iliac artery were preserved, but the external iliac vein was sacrificed because of the possibility of tumor invasion. The postoperative course was free of complications, and the patient was discharged 10 days after the operation. The histopathological findings showed no residual viable tumor cells or foreign body-type giant cells with necrosis. The pathological effect of chemotherapy was defined as Grade 3 (pathological complete response). The patient has experienced no recurrence or distant metastasis for 4 years.Conclusions: Multidisciplinary therapy succeeded in treating a retroperitoneal squamous cell carcinoma of unknown primary site with preservation of organ function.

Purpose Malignant large-bowel obstruction (MLBO) is a highly urgent condition in colorectal cancer with high complication rates. Self-expandable metal stent (SEMS) placement in MLBO is a new decompression treatment in Japan. Preoperative stent placement (bridge to surgery: BTS) avoids emergency surgery, but oncological influences of stent placement and post-BTS surgical approach remain unclear. We examined short- and long-term results of surgery for MLBO after SEMS placement in our hospital.Methods We retrospectively reviewed 75 patients with MLBO who underwent resection after SEMS placement at our hospital from June 2013 to December 2018. Postoperative morbidity and mortality were evaluated by comparison with the surgical approach.Results Tumor location was significantly higher in the left-side colon and rectum (n=59, 78.7%) than right-side colon (n=16, 21.3%). Technical and clinical success rates for SEMS placement were 97.3% and 96.0%, respectively. Laparoscopic surgery was performed in 54 patients (69.0%), and one-stage anastomosis was performed in 73 (97.3%). Postoperative complications were similar in the open surgery (Open) group (n=5, 23.8%) and laparoscopic surgery (Lap) group (n=7, 13.0%), with no severe complications requiring reoperation. Three-year overall survival (OS) and relapse-free survival (RFS) rates were not significantly different in the Lap vs Open group (67.5% vs 66.4%; 82.2% vs 62.5%).Conclusion Preoperative stent treatment avoids stoma construction but allows anastomosis. One-time surgery was performed safely contributing to minimally invasive treatment and acceptable short- and long-term results.

We aimed to investigate the association in frailty and sleep disorder as assessed by the Japanese version of Pittsburgh Sleep Quality Index (PSQI-J) in patients with chronic liver diseases (CLDs, n = 317, 141 males). Frailty was determined using the following five phenotypes: unintentional body weight loss, self-reported exhaustion, muscle weakness, slow walking speed, and low physical activity. Sleep disorder was defined as patients with PSQI-J score 6 or greater. Robust (phenotype, 0), prefrail (1 or 2 phenotypes) and frailty (3 phenotypes or greater) were observed in 101 (31.9%), 174 (54.9%) and 42 (13.2%), respectively. The median (interquartile range (IQR)) PSQI-J score was 4 (3, 7). Sleep disorder was found in 115 patients (36.3%). The median (IQR) PSQI-J scores in patients of the robust, prefrail, and frail groups were 3 (2, 5), 5 (3, 7), and 8 (4.75, 10.25), respectively (P &lt, 0.0001 between any two groups and overall P &lt, 0.0001). The ratios of sleep disorder in patients with robust, prefrail and frailty were 15.8% (16/101), 39.1% (68/174), and 73.8% (31/42), respectively (overall P &lt, 0.0001). In conclusion, CLD patients with frailty can involve poorer sleep quality. As sleep disorder in CLDs is potentially remediable, future frailty-preventive strategies must take sleep complaints into account.

Background The GOD VISION wireless smart glass-shaped monitor (INBYTE) was used in the treatment of an elderly patient with mixed breathing disorder undergoing transanal minimally invasive surgery (TAMIS) for low rectal cancer under lumbar anesthesia. Method After wearing the GOD VISION wireless smart glass-shaped monitor, we attached it to the Gel POINT Path® (Applied Medical). The tumor was surgically removed from all layers of the rectum using an ENDOPATH Electrosurgery PROBE PLUS II System® (a spatula-type electric scalpel) and the site was closed after sufficient washing. Results The total operation time was 93 min, and the estimated blood loss was 6 mL. The patient was discharged without complications on postoperative day 14. No local recurrence or distant metastasis in the 7 months after the operation. The patient remained in a good condition with the preservation of the anal function. Conclusions It is necessary to accumulate cases and to perform long-term follow-up. In addition, the anal side operators are able to operate without discomfort. In the present case, the GOD VISION wireless smart glass-shaped monitor allowed the TAMIS operation to be performed more comfortably.

The aim of the study described here was to clarify the diagnostic value of the fluttering sign, a new sign that characterizes hepatic hemangiomas in gray-scale ultrasonography (US). It refers to a phenomenon in which the speckled echogenicity inside the hemangioma changes continuously and seems to be moving. A total of 172 hemangiomas diagnosed with contrast-enhanced US were evaluated. The fluttering sign was found in 123 of 172 hemangiomas (71.5%). Its prevalence was significantly higher than that of the marginal strong echo (89/172, 51.7%, p < 0.001), posterior acoustic enhancement (103/172, 59.9%, p = 0.031) and chameleon sign (100/172, 58.1%, p = 0.013). In addition, the fluttering sign was observed significantly more frequently in mixed or hypo-echoic tumors than in hyper-echoic tumors (p < 0.001), relatively large tumors (p < 0.001) and tumors that were less than 5 cm from the body surface (p = 0.015). The fluttering sign in gray-scale US has great potential to be a new complementary sign for the diagnosis of hemangioma.

Background/aim Hepatoma-derived growth factor (HDGF) is involved in the progression of hepatocellular carcinoma (HCC). The present study assessed the epigenomic changes in hepatoma-derived cells through HDGF stimulation. Materials and methods We used two hepatoma-derived cell lines (HepG2 and SK-Hep1) and searched for microRNAs whose expression commonly changed in response to HDGF administration. We further explored a genetic database to investigate the association of the candidate microRNAs with the survival of HCC patients. Results Despite both HepG2 and SK-Hep1 cells being categorized as hepatoma-derived cells, the microRNA profile differed between these two lines. However, HepG2 and SK-Hep1 cells shared 30 up-regulated and 2 down-regulated microRNAs. Of these, miR-6072 and miR-3137 were significantly associated with a poor prognosis in HCC patients. Conclusion We identified two candidate microRNAs whose expression increased in response to HDGF stimulation. Both these molecules were associated with a poor prognosis of HCC patients.

Background/Aim: To elucidate the influence of calf circumference (CC) on sarcopenia in patients with chronic liver damages (CLDs, n=525, 255 men). Patients and Methods: Anthropometry parameters including arm circumference, arm muscle circumference, CC, arm muscle area, triceps skinfold thickness, waist circumference and body mass index were measured. Patients with both grip strength (GS) decline and skeletal muscle index (SMI) decline were diagnosed as sarcopenic. Results: Liver cirrhosis was identified in 103 cases (40.4%) in males and 87 cases (32.2%) in females. Sarcopenia was identified in 23 male patients (9.0%) and 38 female patients (14.1%). CC had the strong positive correlation with SMI both in male (r=0.79, p

We sought to examine the serum zinc (Zn) level and frailty in patients with chronic liver diseases (CLDs, n = 285, 107 liver cirrhosis cases, median age = 66 years). Frailty was defined as a clinical syndrome in which three or more of the following criteria were met (frailty score 3, 4, or 5): unintentional body weight loss, self-reported exhaustion, muscle weakness (grip strength: &lt, 26 kg in men and &lt, 18 kg in women), slow walking speed (&lt, 1.0 m/s), and low physical activity. Robust (frailty score 0), prefrail (frailty score 1 or 2), and frailty were found in 90 (31.6%), 157 (55.1%), and 38 (13.3%), respectively. The median serum Zn levels in patients with frailty, prefrailty, and robust were 59.7 &mu, g/dL, 72.8 &mu, g/dL, and 76.9 &mu, g/dL, respectively (p-values: frailty vs. prefrail, p &lt, 0.0001, prefrail vs. robust, p = 0.0063, frailty vs. robust, p &lt, overall p &lt, 0.0001). For all cases, variables with absolute values of correlation coefficient with frailty score (0&ndash, 5) &ge, 0.3 were age (rs = 0.3570, p &lt, 0.0001), serum albumin (rs = &minus, 0.3212, p &lt, 0.0001), extracellular water to total body water ratio using bioimpedance analysis (rs = 0.4386, p &lt, 0.0001), and serum Zn level (rs = &minus, 0.3406, p &lt, 0.0001). In conclusion, decreased serum Zn level in patients with CLDs can be closely associated with the presence of frailty.

Lifestyle changes have led to an increase in the number of patients with nonalcoholic fatty liver disease (NAFLD). However, the effects of NAFLD-associated single-nucleotide gene polymorphisms (SNPs) in HBV-infected patients have not been adequately investigated. Methods: We investigated the association of the NAFLD-related SNPs patatin-like phospholipase domain-containing protein 3 (PNPLA3, rs738409), transmembrane 6 superfamily member 2 (TM6SF2, rs58542926), 17-beta hydroxysteroid dehydrogenase 13 (HSD17B13, rs72613567, rs6834314 and rs62305723), membrane-bound O-acyltransferase domain containing 7 (MBOAT7, rs641738) and glucokinase regulatory protein (GCKR, rs1260326) with the presence of histologically proven hepatic steatosis (HS) in HBV-infected patients (n = 224). We also investigated tolloid-like 1 (TLL1) SNP (rs17047200), which has been reported to be involved in the disease progression in Japanese NAFLD patients, and evaluated the association of HS and various SNPs with the treatment efficacy of pegylated-interferon (PEG-IFN) monotherapy following nucleotide/nucleoside (NA) treatment (NA/PEG-IFN sequential therapy, n = 64). Among NAFLD-associated SNPs evaluated, only the PNPLA3 SNP was significantly associated with the presence of hepatic steatosis in a total of 224 HBV-infected patients (P = 1.0&times, 10-4). Regarding the sequential therapy, PNPLA3 SNP and TLL1 SNP were related to the treatment efficacy, and patients without minor alleles of these SNPs showed favorable results with a high virologic response and significant reduction in their HBsAg titer. A multivariate analysis showed that HBeAg positivity (odds ratio 5.810, p = 0.016) and the absence of a risk allele in PNPLA3 and TLL1 SNPs (odds ratio 8.664, p = 0.0042) were significantly associated with treatment efficacy. The PNPLA3 SNP might be associated with the presence of HS, and the combination of the PNPLA3 and TLL1 SNPs might be related to the efficacy of PEG-IFN monotherapy following NA treatment.

We aimed to clarify the impact of the serum zinc (Zn) level grading system proposed by the Japanese society of clinical nutrition (JSCN: 80 &mu, g/dL &lt, serum Zn level &lt, 130 &mu, g/dL (type A), 60 &mu, 80 &mu, g/dL (type B), and serum Zn level &lt, 60 &mu, g/dL (type C)) in patients with hepatitis C virus (HCV)-related liver cirrhosis (LC) on the incidence of composite hepatic events (Com-HEs) compared with Child&ndash, Pugh (C&ndash, P) classification or albumin-bilirubin (ALBI) grade. (n = 275, median age = 67 years). The Akaike information criterion (AIC) was compared among three prognostic models. Factors associated with the incidence of Com-HEs were also studied. The first incidence of any HE was confirmed in 112 patients (40.7%). The AIC value for Com-HEs by the Zn level grading system was the lowest among the three prognostic models (AIC: 301.788 in Zn level grading system, 303.372 in ALBI grade, and 333.953 in C&ndash, P classification). In the multivariate analysis, male (p = 0.0031), ALBI grade 3 (p = 0.0041), type B (p = 0.0238), type C (p = 0.0004), and persistent viremia (p &lt, 0.0001) were significant factors associated with the incidence of Com-HEs. In conclusion, the serum Zn level grading system proposed by JSCN can be helpful for estimating the incidence of Com-HEs in HCV-related LC patients.

We sought to clarify the correlation between non-protein respiratory quotient (npRQ) in indirect calorimetry and serum zinc (Zn) level in chronic liver diseases (CLDs, n = 586, 309 liver cirrhosis (LC) patients, median age = 63 years). Clinical parameters potentially linked to npRQ &lt, 0.85 (best cutoff point for the prognosis in LC patients) were also examined in receiver operating characteristic curve (ROC) analyses. The median npRQ was 0.86. The median serum Zn level was 64 &mu, g/dL. The median npRQ in patients with non-LC, Child&ndash, Pugh A, Child&ndash, Pugh B and Child&ndash, Pugh C were 0.89, 0.85, 0.83 and 0.82 (overall p &lt, 0.0001)). The median serum Zn level in patients with npRQ &lt, 0.85 (58 &mu, g/dL) was significantly lower than that in patients with npRQ &ge, 0.85 (68 &mu, g/dL) (p &lt, 0.0001). The correlation coefficient (r) between npRQ level and serum Zn level for all cases was 0.40 (p &lt, 0.0001). Similar tendencies were observed in all subgroup analyses. The highest correlation coefficient between serum Zn level and npRQ was found in patients with Child&ndash, Pugh C (n = 22, r = 0.69). In ROC analyses for npRQ &lt, 0.85, serum Zn level had the highest area under the ROC (AUC) among baseline laboratory parameters (AUC = 0.69). In conclusion, serum Zn level can be helpful for npRQ in patients with CLDs.

AIM We sought to create a prediction model for intrahepatic covalently closed circular DNA (IH-cccDNA) level in chronic hepatitis B (CHB) patients and to validate the model's predictive accuracy. METHODS Patients who did not receive previous nucleoside analogue (NA) therapy were assigned to the training cohort (n = 57), and those who received previous NA therapy were assigned to the validation cohort (n = 69). Factors linked to IH-cccDNA levels in the training cohort were analyzed and a formula to predict IH-cccDNA levels was constructed. Next, the reproducibility of that formula was assessed. RESULTS In the multivariate analysis for the prediction of IH-cccDNA level in the training cohort, fasting blood sugar (FBS) (P = 0.0227), hepatitis B e antigen (HBeAg) (P = 0.0067) and log10 (HB surface antigen [HBsAg]) (P = 0.0497) were significant, whereas HB core-related antigen (HBcrAg) tended to be significant (P = 0.0562). The formula was constructed and named the FBS-cres score based on the variables used (FBS, HBcrAg, HBeAg, and HBsAg). The FBS-cres score was calculated as: 3.1686 - (0.0148 × FBS) + (0.1982 × HBcrAg) + (0.0008168 × HBeAg) + (0.1761 × log10 (HBsAg)). In the training cohort, a significant correlation was noted between HBcrAg and IH-cccDNA levels (P

Whether direct-acting antiviral (DAA) therapy can reduce liver fibrosis and steatosis in patients with chronic hepatitis C virus (HCV) infection remains unclear. We evaluated sequential changes in liver stiffness and steatosis using transient elastography (TE) and the TE-based controlled attenuation parameter (CAP) in patients with HCV who received DAA therapy.A total of 57 patients with HCV who received DAA therapy and achieved sustained virological response (SVR) were analyzed. Liver stiffness as evaluated with TE, steatosis as evaluated with CAP, and laboratory data were assessed before treatment (baseline), at end of treatment (EOT), 24 weeks after EOT (SVR24), and 48 weeks after EOT (SVR48).Alanine aminotransferase levels, corresponding to the presence of necroinflammatory activity, significantly decreased overall, with significant differences between baseline and EOT, EOT, and SVR24, and baseline and SVR48. However, alanine aminotransferase levels showed no significant changes between SVR24 and SVR48. Median (interquartile range) liver stiffness values at baseline, EOT, SVR24, and SVR48 were 8.3 (5.0-14.8), 7.4 (4.6-14.7), 5.3 (4.1-11.8), and 5.4 (4.0-13.4) kPa, respectively (baseline vs. EOT, P=0.044; EOT vs. SVR24, P=0.011; and SVR24 vs. SVR48, P=0.054). In patients with fatty liver (CAP≥236 dB/m, n=14), CAP values at baseline and SVR48 were 253 (245-278) and 229 (209-249) dB/m, respectively (P=0.020).Liver stiffness at SVR24 might reflect liver fibrosis in the patients who received DAA therapy and achieved SVR. In addition, liver steatosis reduces in the same cohort with fatty liver.