BEX2 is poor prognostic factor and required for cancer stemness in gastric cancer.

Gastric cancer is the fifth most common malignancy worldwide. However, targeted therapy for advanced gastric cancer is still limited. Here, we report BEX2 (Brain expressed X-linked 2) as a poor prognostic factor in two gastric cancer cohorts. BEX2 expression was increased in spheroid cells, and its knockdown decreased aldefluor activity and cisplatin resistance. BEX2 was found to upregulate CHRNB2 (Cholinergic Receptor Nicotinic Beta 2 Subunit) expression, a cancer stemness-related gene, in a transcriptional manner, and the knockdown of which also decreases aldefluor activity. Collectively, these data are suggestive of the role of BEX2 in the malignant process of gastric cancer, and as a promising therapeutic target.

Comparison of CEA and CA19-9 as a predictive factor for recurrence after curative gastrectomy in gastric cancer.

BACKGROUND: Our aim of was to compare importance of the tumor markers (TMs) serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 in prediction of recurrence after curative gastrectomy for gastric cancer. METHODS: We reviewed retrospectively the clinical records of 149 patients who underwent curative gastrectomy for stage I-III gastric cancer and whose CEA and CA19-9 levels were determined once preoperatively and for more than 3 years postoperatively. We investigated whether the clinicopathological characteristics of patients including age, sex, pathological disease stage, operative approach, type of gastrectomy, and degree of lymph node dissection as well as preoperative positivity of CEA and CA19-9 were risk factors for recurrence in univariate and multivariate analyses. Rate of recurrence was compared between patients positive and negative for postoperative CEA or CA19-9. We also calculated sensitivity, specificity, positive and negative predictable values of postoperative positivity of CEA and CA19-9 for recurrence. The lead time was compared between CEA and CA19-9 that was defined as the time of the first detection of increases in tumor markers and confirmation of recurrence on imaging modalities. RESULTS: The number of patients positive for preoperative CEA was 25 (17%) and for CA19-9 was 11 (7%). Recurrence was confirmed in 29 (19%) patients. Stage III disease, preoperative positivity for CA19-9 but not CEA, and total gastrectomy were risk factors for recurrence in univariate analysis, but stage III disease was the only risk factor for recurrence in multivariate analysis. Forty and 15 patients were positive for postoperative CEA and CA19-9, respectively. The recurrence rate of 47% (7/15) in patients positive for postoperative CA19-9 was greater than that in negative patients (22/134 = 16%), but it did not differ between patients who were positive or negative for postoperative CEA. Specificity for CA19-9 was greater than that for CEA (P < 0.05). The lead time of CEA (3.9 ± 4.7 months) was not different from that of CA19-9 (6.1 ± 7.1 months). CONCLUSIONS: These results indicate that CA19-9 rather than CEA is likely to be more useful for the detection of recurrence after curative gastrectomy for gastric cancer.

BEX2 is required for maintaining dormant cancer stem cell in hepatocellular carcinoma.

Cancer stem cells (CSCs) are responsible for therapy resistance and share several properties with normal stem cells. Here, we show that brain-expressed X-linked gene 2 (BEX2), which is essential for dormant CSCs in cholangiocarcinoma, is highly expressed in human hepatocellular carcinoma (HCC) lesions compared with the adjacent normal lesions and that in 41 HCC cases the BEX2high expression group is correlated with a poor prognosis. BEX2 localizes to Ki67-negative (nonproliferative) cancer cells in HCC tissues and is highly expressed in the dormant fraction of HCC cell lines. Knockdown of BEX2 attenuates CSC phenotypes, including sphere formation ability and aldefluor activity, and BEX2 overexpression enhances these phenotypes. Moreover, BEX2 knockdown increases cisplatin sensitivity, and BEX2 expression is induced by cisplatin treatment. Taken together, these data suggest that BEX2 induces dormant CSC properties and affects the prognosis of patients with HCC.

Influence of age on postoperative complications especially pneumonia after gastrectomy for gastric cancer.

BACKGROUND: The aim of this study was to investigate the influence of patients' age on postoperative morbidities including pneumonia. METHODS: We reviewed the clinical records of 211 patients with stages I - III gastric cancer undergoing curative distal gastrectomy (DG) or total gastrectomy (TG). Patients were classified into an elderly (≧80 y.o.) or a control (< 80 y.o.) group. We compared patient characteristics (sex ratio, disease stage, degree of lymph node dissection, number of retrieved lymph nodes, and type of reconstruction) and early postoperative outcomes (operation time, intra-operative blood loss, and postoperative morbidity including pneumonia, and mortality) between the two groups separately in DG and TG. RESULTS: There were 134 and 77 patients who underwent DG and TG, respectively. The numbers of patients in the elderly and control groups were 25 and 109 in DG and 12 and 65 in TG. The percentage of female patients in the elderly group was greater than that in the control group in both DG and TG. The extent of lymph node dissection did not differ between two groups in TG; in contrast in DG, the rate of a D1 dissection was greater in the elderly group than in the control group. There were no differences between the two groups in distribution of disease stage, number of retrieved lymph nodes, operation time, and blood loss in DG and in TG. Overall postoperative morbidity did not differ between two groups after DG and after TG. The rate of infectious complications in the elderly group was not different from that in the control group after DG and after TG. The incidence of pneumonia was more frequent in the elderly group compared to the control group after DG (8% vs. 1%, P < 0.05) but not after TG (17% vs. 5%). When patients were compared between the elderly and the control groups regardless of type of gastrectomy, the incidence of pneumonia in the elderly group (4/37 (11%)) was greater than that in the control group (4/174 (2%), P < 0.05). CONCLUSIONS: These results suggest that pneumonia is increased in patients older than 80 years after DG.

NDRG2, suppressed expression associates with poor prognosis in pancreatic cancer, is hypermethylated in the second promoter in human gastrointestinal cancers.

Although N-myc downstream regulated gene 2 (NDRG2) is frequently downregulated in various cancers and is considered to be a candidate tumor suppressor gene, molecular mechanisms of the expressional suppression that lead to cancers are largely unknown. Recent studies indicated that epigenetic suppression of NDRG2 involved carcinogenesis and progression in several tumor types, and we demonstrated positive association with NDRG2 suppression and poor prognosis in pancreatic cancer. In this study, we analyzed mRNA and protein expressions of NDRG2 in 26 cancer cell lines (20 colorectal and 6 gastric cancers) and found that many cell lines showed variously reduced NDRG2 expressions. Furthermore, NDRG2 expressions were significantly reduced in primary resected cancer tissues compared to corresponding normal tissues immunohistochemically (19 of 20 colorectal and 14 of 17 gastric cancers). Treatment with 5-Aza-2' deoxycytidine predominantly upregulated NDRG2 expressions in NDRG2 low-expressing cell lines. Bisulfite sequencing analyses and methylation specific PCR revealed that methylation status at one of the two promoters (around exon 2) correlated well with the suppressed expression, and this is the major promoter in colorectal and gastric cancer cell lines. Our present results suggest that hypermethylation in promoter around exon 2 is functioning as essential factors of NDRG2 silencing in gastrointestinal cancers.

Optimal timing of cholecystectomy after percutaneous gallbladder drainage for severe cholecystitis.

BACKGROUND: The Tokyo guideline for acute cholecystitis recommended percutaneous transhepatic gallbladder drainage followed by cholecystectomy for severe acute cholecystitis, but the optimal timing for the subsequent cholecystectomy remains controversial. METHODS: Sixty-seven patients who underwent either laparoscopic or open cholecystectomy after percutaneous transhepatic gallbladder drainage for severe acute cholecystitis were enrolled and divided into difficult cholecystectomy (group A) and non-difficult cholecystectomy (group B). Patients who had one of these conditions were placed in group A: 1) conversion from laparoscopic to open cholecystectomy; 2) subtotal cholecystectomy and/or mucoclasis; 3) necrotizing cholecystitis or pericholecystic abscess formation; 4) tight adhesions around the gallbladder neck; and 5) unsuccessfully treated using PTGBD. Preoperative characteristics and postoperative outcomes were analyzed. RESULTS: The interval between percutaneous transhepatic gallbladder drainage and cholecystectomy in Group B was longer than that in Group A (631 h vs. 325 h; p = 0.031). Postoperative complications occurred more frequently when the interval was less than 216 h compared to when it was more than 216 h (35.7 vs. 7.6%; p = 0.006). CONCLUSIONS: Cholecystectomy for severe acute cholecystitis was technically difficult when performed within 216 h after percutaneous transhepatic gallbladder drainage.

Risk factors for difficulty of laparoscopic cholecystectomy in grade II acute cholecystitis according to the Tokyo guidelines 2013.

BACKGROUND: The Tokyo Guidelines 2013 classifies acute cholecystitis (AC) into three grades and recommends appropriate therapy for each grade. For grade II AC, either early laparoscopic cholecystectomy (LC) or percutaneous transhepatic gallbladder drainage (PTGBD) should be performed. This study aimed to identify the risk factors for difficulty of LC for treating grade II AC. METHODS: Totally, 122 patients who underwent LC for grade II AC were enrolled and divided into difficult LC (DLC) and nondifficult LC (NDLC) groups. The DLC group included patients who experienced one of the following conditions: conversion from LC to open cholecystectomy, operating time ≥ 180 min, or blood loss ≥300 ml. Preoperative characteristics and postoperative outcomes were analyzed. RESULTS: In univariate analysis, risk factors included male sex, interval between symptom onset and admission, interval between symptom onset and LC, and anticoagulant therapy. The incidence of postoperative complications was higher in the DLC group than in the NDLC group (23.5% vs. 4.6%, p = 0.0016). According to receiver operating characteristic curves, the optimal cutoff value was calculated, and multivariate analysis showed that male sex [odds ratio (OR), 5.76; 95% confidence interval (CI), 1.979-19.51; p = 0.0009) and interval between symptom onset and LC of over 96 h (OR, 6.32; 95% CI, 2.126-20.15; p = 0.0009) were independent risk factors for difficulty of LC. CONCLUSIONS: In patients with grade II AC, LC was technically difficult when performed over 96 h after symptom onset. Moreover, male sex was a risk factor. Therefore, PTGBD should be considered in these patients.

G-cell hyperplasia of the stomach induces ECL-cell proliferation in the pyloric glands in a paracrinal manner.

An inhibitory mechanism toward gastrin hypersecretion is significantly different between G-cell hyperplasia and gastrinoma despite the common clinical manifestations; hypergastrinemia and its related persistent gastric ulcers. We recenlty studied the G-cell, d-cell and ECL-cell density in a case of G-cell hyperplasia. The 70-year-old patient has been treated for persistent gastric ulcers with a markedly increased plasma gastrin (5600 pg/mL). The stomach was surgically resected because of the obstruction associated with ulcer scars. The number of G-cells in the pyloric glands was quantified on the surgical specimens and G-cell hyperplasia was histolopathologically identified. Immunostainig of histidine decarboxylate revealed the presence of ECL-cell hyperplasia in the pyloric glands and its density was significantly and positively correlated with G-cell density. Somatostatin immunoreactive cells (D-cells) increased in their number in the oxyntic glands. These results all indicated that hypersecretion of gastrin in G-cell hyperplasia could induce ECL-cell proliferation in a paracrinal manner. In addition, relatively non-prominent endocrinological features in the G-cell hyperplasia compared to gastrinoma could be also related to the paracrinal somatostatin inhibitory effects upon ECL-cells in the pyloric glands.

Usefulness of alternate-day administration of S-1 and leucovorin in a xenograft mouse model of colorectal cancer: a shorter drug-free interval leads to more efficient antitumor effects.

BACKGROUND: A clinical trial of S-1 with leucovorin (S-1/LV) in metastatic colorectal cancer (CRC) patients demonstrated promising efficacy; however, the gastrointestinal toxicities were so severe that it has not been applied in the clinical setting. On the other hand, alternate-day administration of S-1 has been proposed to attenuate the adverse events without reducing its anticancer activity. Our present study was conducted to confirm the feasibility of alternate-day administration of S-1/LV in in vivo xenograft tumor models. METHODS: Mice were treated with S-1/LV in a daily group (2 weeks of administration followed by 2 weeks of withdrawal) or an alternate-day group (administration on alternate days for 4 weeks), then the mice were killed and the xenograft tumors were resected. We compared body weight changes, condition of feces, mucosal injury and myelosuppression and assessed adverse reactions, tumor volume, tumor growth inhibition (TGI) and expression of Ki67, TUNEL, cIAP2 and XIAP to evaluate the antitumor activity and tumor apoptosis. RESULTS: Severe weight loss, diarrhea, mucosal injury and myelosuppression were observed only in the daily group; however, some myelosuppression was also observed in the alternate-day group. The TGI in the alternate-day group was better than in the daily group, possibly resulting from apoptosis due to the suppression of cIAP2 but not XIAP. CONCLUSION: Our findings suggest that alternate-day administration of S-1/LV for CRC treatment can achieve high antitumor activity without severe adverse reactions, and we propose that clinical trials with this regimen should be conducted in CRC patients.

The best surgical approach for perforated gastric cancer: one-stage vs. two-stage gastrectomy.

BACKGROUND: Surgery for perforated gastric cancer has a dual purpose: treating life-threatening peritonitis and curing gastric cancer. An emergent one-stage gastrectomy may place an undue burden on patients with a poor general status and could impair long-term survival even if the gastric malignancy is curable. A two-stage gastrectomy, in which the initial treatment of peritonitis is followed by elective gastrectomy, can accomplish both desired purposes. METHODS: We retrospectively analyzed 514 Japanese cases of perforated gastric cancer. 376 patients underwent a one-stage gastrectomy and 54 patients underwent a two-stage gastrectomy. We evaluated patient characteristics, surgical outcomes, postoperative complications, and survival rates in both groups. RESULTS: The two-stage gastrectomy group saw a 78.4% rate of curative R0 resection and 1.9% hospital mortality rate, while corresponding rates in the one-stage gastrectomy group were 50 and 11.4%, respectively. Among cases in which curative R0 resection was performed, there was no significant difference in overall survival between 136 one-stage gastrostomies and 40 two-stage gastrostomies. In a multivariate analysis, curative R0 resection [hazard ratio (HR) 2.937, p = 0.001] and depth of tumor invasion (HR 1.179, p = 0.016) were identified as independent prognostic factors. CONCLUSIONS: Regardless of whether patients underwent a one-stage or two-stage gastrectomy, curative R0 resection improved survival in patients with perforated gastric cancer. When curative R0 resection cannot be performed in the initial treatment phase due to diffuse peritonitis, non-curative and palliative gastrectomy should be avoided, and a two-stage gastrectomy should be planned following peritonitis recovery and detailed examinations.

Role of the intraluminal contents and the continuity of intrinsic neurons in intracolonic capsaicin-induced contraction and defecation in dogs.

PURPOSE: We, herein, examined the role of the intraluminal contents and continuity of colonic intrinsic neurons in intracolonic capsaicin-induced enhancement of colonic motility and defecation. METHODS: Five beagle dogs were equipped with three strain gauge force transducers throughout the colon. The colonic contractile activity in response to intracolonic capsaicin was studied in intact dogs, dogs after colonic cleansing and dogs with transection/re-anastomosis (T/R) between the proximal and middle colon. The effects of intravenous yohimbine, a α2 adrenergic antagonist, on the colonic motility and defecation were also studied in the same models. RESULTS: In intact dogs, capsaicin (10 mg) and yohimbine (2 mg/kg) immediately induced contractions throughout the colon, with defecation occurring in all experiments. In dogs after colonic cleansing and T/R, the capsaicin (10 mg)-induced enhancement of colonic motility was decreased in the middle and distal colon, and capsaicin-induced defecation was observed in 0-20 % of experiments (p < 0.05 compared to intact dogs). The effect of yohimbine (2 mg/kg) in inducing colonic contractions was unaltered after colonic cleansing and T/R; in contrast, yohimbine-induced defecation was not observed after colonic cleansing, but was unchanged after T/R. CONCLUSIONS: The continuity of the colonic intrinsic nerves as well as the intraluminal contents appear to play an important role in the colonic motor response to intracolonic capsaicin.

Effects of duodeno-jejunal bypass on glucose metabolism in obese rats with type 2 diabetes.

PURPOSE: To evaluate the foregut and hindgut hypotheses for metabolic surgery in obese rats with diabetes. METHODS: Otsuka Long-Evans Tokushima fatty rats were divided into a sham operation group, a partial duodeno-jejunal bypass (P-DJB) group, and a complete DJB (C-DJB) group. P-DJB is a model to test foregut hypothesis, whereas C-DJB is a model to test both hypotheses. We performed oral glucose tolerance tests (OGTT) on all groups at baseline, and then 4 and 8 weeks postoperatively. The rats were killed thereafter and the plasma levels of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) were measured. A separate sub-group of C-DJB rats underwent OGTT after treatment with the GLP-1 antagonist, the PYY antagonist, or saline. RESULTS: Marked improvement of the blood glucose control during the OGTT was noted 8 weeks after C-DJB, but not 8 weeks after P-DJB or the sham operation. The serum GLP-1 and PYY levels were higher in the C-DJB group than in the other two groups. Pretreatment with the GLP-1 antagonist increased the blood glucose levels 30 min after the OGTT in the C-DJB rats. CONCLUSIONS: Improvement in glucose metabolism after DJB was associated with the inflow of bile and pancreatic juice into the ileum, supporting validity of the hindgut hypothesis. GLP-1 appears to play a role in this improvement.

Treatment Strategies for Locoregional Recurrence in Esophageal Squamous-Cell Carcinoma: An Updated Review.

Emerging evidence has shown remarkable advances in the multimodal treatment of esophageal squamous-cell carcinoma. Despite these advances, the oncological outcomes for advanced esophageal cancer remain controversial due to the frequent observation of local recurrence in the regional or other lymph nodes and distant metastasis after curative treatment. For cases of locoregional recurrence in the cervical lymph nodes alone, salvage surgery with lymph node dissection generally provides a good prognosis. However, if recurrence occurs in multiple regions, the oncological efficacy of surgery may be limited. Radiotherapy/chemoradiotherapy can be employed for unresectable or recurrent cases, as well as for selected cases in neo- or adjuvant settings. Dose escalation and toxicity are potential issues with conventional three-dimensional conformal radiotherapy; however, more precise therapeutic efficacy can be obtained using technical modifications with improved targeting and conformality, or with the use of proton beam therapy. The introduction of immune checkpoint inhibitors, including pembrolizumab or nivolumab, in addition to chemotherapy, has been shown to improve the overall survival in unresectable, advanced/recurrent cases. For patients with lymph node recurrence in multiple regions, chemotherapy (5-fluorouracil [5-FU] plus cisplatin) and combination therapy with nivolumab and ipilimumab have shown comparable oncological efficacy. Further prospective studies are needed to improve the treatment outcomes in patients with esophageal cancer with locoregional recurrence.

Endoscopic Mini- or Less-Open Sublay operation with transversus abdominis muscle release using a single-port platform for incisional hernia: A video vignette.

TECHNIQUE: The Endoscopic Mini- or Less-open Sublay operation (EMILOS) is a transhernial repair that allows endoscopic dissection and mesh placement in the retrorectus/retromuscular space, and simultaneous transversus abdominis release (TAR) for larger hernias. The operative summary is as follows. 1 A 7-cm longitudinal skin incision was made immediately above the hernial orifice. 2 The hernial sac was circumferentially dissected to the border of the defect, and the abdomen was opened. 3 The posterior rectus sheath (PRS) was incised approximately 5 mm lateral to the medial border of the rectus sheath to enter the retrorectus space. 4 Exploratory laparoscopy was performed, and the peritoneum was closed. 5 A single port platform was attached to the wound, and the abdominal wall was insufflated. The retrorectal space was dissected laterally to the outer edge of the rectus abdominis muscle. The linea alba was incised at least 5 cm cranially and caudally from the border of the hernia defect to obtain sufficient mesh overlap. 6 The TAR was added to the left side to facilitate medial advancement of the PRS. (7) The PRS was approximated with continuous suture. A self-gripping mesh was trimmed and implanted in the retrorectus space. The mesh was secured with 3-0 absorbable sutures (8) A closed-suction drain was placed on the mesh, and the wound was trimmed and closed. RESULTS: The postoperative course was uneventful. No recurrence was observed at 6-month follow-up. CONCLUSIONS: This technique may be advantageous because it allows minimal skin incision with physiological reconstruction of abdominal wall.

A retrospective study examining the association between polypharmacy and complications after laparoscopic surgery for colorectal cancer.

BACKGROUND: Polypharmacy is an escalating public health concern across various healthcare settings worldwide. We aimed to comprehensively investigate postoperative complications after laparoscopic surgery for colorectal cancer and explore their association with polypharmacy. As laparoscopic surgery is widespread, clarifying the association between polypharmacy and postoperative complications is clinically important. METHODS: We retrospectively surveyed the medical charts of adult inpatients who underwent laparoscopic surgery for colorectal cancer at Tohoku Medical and Pharmaceutical University Hospital between April 2019 and March 2023. Postoperative complications were determined using the Clavien-Dindo classification. We explored the factors related to postoperative complications and calculated the cut-off values for the number of medication ingredients. RESULTS: Among the 236 patients, 32 (13.6%) developed postoperative complications. On multivariable logistic regression analysis, the number of regularly used medication ingredients (odds ratio = 1.160, 95% confidence interval 1.050-1.270, p = 0.002) was identified as a factor related to postoperative complications. The identified cut-off value for complications was 10 ingredients. Patients using 10 or more ingredients had approximately 3.5 times higher occurrence of postoperative complications than those using fewer than 10 ingredients (33.3% vs. 9.3%, p < 0.001, Fisher's exact test). CONCLUSIONS: Our study comprehensively investigated postoperative complications and examined their association with polypharmacy. We found that the number of regularly used medication ingredients may be linked to complications following laparoscopic surgery for colorectal cancer. These findings have important implications for perioperative management and patient care, providing valuable insights that may influence clinical practices and enhance patient outcomes.

Mesorectal thromboembolism with increased 18F-fluorodeoxyglucose uptake during positron emission tomography/computed tomography in a patient with non-small cell lung cancer.

This study presents a case of a 72-year-old man diagnosed with non-small cell lung cancer (cT4N0M0) referred to our hospital for possible surgical treatment of a solitary nodule detected in the mesorectum. The patient had received combined chemoradiotherapy and achieved a complete response 13 months before the presentation. On examination, the mesorectal nodule was incidentally detected during surveillance computed tomography, and the maximum standardized uptake value of the nodule was 10.3. Because of the potential malignancy and need for en-bloc resection of the nodule, we performed laparoscopically assisted high anterior resection of the rectum. The postoperative course was uneventful. Notably, while pathological examination revealed that the mesorectal nodule comprised an intravenous organized thromboembolism, malignancy was not observed. These findings suggest that although positron emission tomography/computed tomography with 18F-fluorodeoxyglucose is useful for the diagnosis of malignant diseases, surgical resection might be the most reliable option for complex cases such as ours.

Surgical indication and management of obstructive colonic metastasis from primary lung adenocarcinoma: report of a case and review of the literature.

BACKGROUND: Colonic metastasis from lung cancer is very rare and is typically associated with poor prognosis. Herein, we report the case of a patient who achieved intermediate-term survival using a multimodal treatment approach, including chemotherapy, immunotherapy, radiotherapy, and surgical resection for obstructive colonic metastasis from primary lung adenocarcinoma. CASE PRESENTATION: A woman in her 50s presented with anemia and a positive fecal occult blood test. Computed tomography revealed a tumor in the right upper lobe of the lung with mediastinal lymphadenopathy and wall thickening in the transverse colon. Colonoscopy revealed a stricture involving 50% of the colonic lumen. Biopsy revealed a poorly differentiated adenocarcinoma positive for CK-7 and TTF-1, very focally positive for napsin A, and negative for CK-20 and CDX-2. Furthermore, positron emission tomography/CT (PET/CT) showed a high maximum standardized uptake value (SUVmax) of 8.2 in the iliac bone. Based on these findings, the patient was diagnosed with primary lung adenocarcinoma with simultaneous metastasis to the transverse colon and iliac bone (cT4N3M1c, cStage IVB). After receiving first-line chemotherapy with atezolizumab, pemetrexed, and carboplatin, the tumors shrank after 4 courses. Subsequently, the patient received maintenance therapy with atezolizumab and pemetrexed. However, the tumor enlarged after 10 courses. Second-line chemotherapy with docetaxel and ramucirumab (3 courses) failed to achieve tumor reduction. Colonoscopy revealed an impassable colonic tumor. Nineteen months after diagnosis, surgery was planned for imminent intestinal obstruction. We determined that the colonic tumor was resectable, because laparoscopic exploration revealed no other metastases. The tumor was resected by partial colectomy with ileocolonic anastomosis. The postoperative course was uneventful. Pathological examination revealed a resection margin that was negative for malignancy, and the histological type was consistent with metastatic lung adenocarcinoma. The patient then received nab-paclitaxel therapy; however, she developed symptoms of superior vena cava syndrome after 3 courses. The patient received palliative irradiation (30 Gy/10 fr) followed by nivolumab. She soon developed a solitary brain metastasis, and stereotactic irradiation was planned. After 3 courses of nivolumab, the metastasis was reduced significantly, and stereotactic brain irradiation was canceled. The lung tumor and mediastinal lymphadenopathy gradually shrank, and the patient survived for 13 months after surgery without disease progression. CONCLUSIONS: In this case, surgical resection of colonic metastasis from primary lung adenocarcinoma may have contributed to the short-term prognosis as a bridge-to-next available multimodal treatment.

Peribiliary Gland Hyperplasia That Required Differentiation from Extrahepatic Bile Duct Cancer: A Case Report.

Introduction: The peribiliary gland is an accessory bile duct gland. Hyperplasia of these tissues may lead to elevation of the mucosa in the bile ducts and bile duct stenosis. We herein report a case of peribiliary gland hyperplasia that required preoperative differentiation from bile duct cancer, with a discussion of the literature. Case Presentation: The patient had an adenomatous lesion in the ascending colon that was difficult to treat endoscopically; therefore, surgery was planned. Preoperative abdominal ultrasonography revealed a bile duct tumor, and endoscopic ultrasonography revealed a mass lesion around the confluence of the cystic duct. Computed tomography revealed localized wall thickening in the middle bile duct, and the upstream bile ducts were slightly dilated. In addition, continuous thickening of the bile duct wall from the gallbladder to the confluence of the cystic duct was observed. No distant metastases, such as liver metastases, or nearby enlarged lymph nodes were observed. Endoscopic retrograde cholangiopancreatography and magnetic resonance cholangiopancreatography revealed a papillary-like elevated lesion in the bile duct near the confluence of the cystic duct, and a biopsy and bile cytology from the same area showed no malignant findings. As a result, the possibility that the patient had gallbladder or bile duct cancer could not be ruled out; therefore, a policy of surgery together with the ascending colon tumor was decided after receiving sufficient informed consent. During surgery, the patient underwent extrahepatic bile duct resection, reconstruction of the biliary tract using the Roux-en-Y method, and right hemicolectomy. Both duodenal and hilar bile duct transects were subjected to a fast frozen section analysis during surgery, and the results were negative for cancer. A histopathological examination of the resected specimen revealed no malignant findings in the bile duct lesions, and a diagnosis of peribiliary gland hyperplasia with chronic inflammatory cell infiltration and fibrosis of the extrahepatic bile duct wall was made. Conclusions: We encountered a case of peribiliary gland hyperplasia that was difficult to distinguish from bile duct cancer.

Suppressed expression of NDRG2 correlates with poor prognosis in pancreatic cancer.

Pancreatic cancer is a highly lethal disease with a poor prognosis; the molecular mechanisms of the development of this disease have not yet been fully elucidated. N-myc downstream regulated gene 2 (NDRG2), one of the candidate tumor suppressor genes, is frequently downregulated in pancreatic cancer, but there has been little information regarding its expression in surgically resected pancreatic cancer specimens. We investigated an association between NDRG2 expression and prognosis in 69 primary resected pancreatic cancer specimens by immunohistochemistry and observed a significant association between poor prognosis and NDRG2-negative staining (P=0.038). Treatment with trichostatin A, a histone deacetylase inhibitor, predominantly up-regulated NDRG2 expression in the NDRG2 low-expressing cell lines (PANC-1, PCI-35, PK-45P, and AsPC-1). In contrast, no increased NDRG2 expression was observed after treatment with 5-aza-2' deoxycytidine, a DNA demethylating agent, and no hypermethylation was detected in either pancreatic cancer cell lines or surgically resected specimens by methylation specific PCR. Our present results suggest that (1) NDRG2 is functioning as one of the candidate tumor-suppressor genes in pancreatic carcinogenesis, (2) epigenetic mechanisms such as histone modifications play an essential role in NDRG2 silencing, and (3) the expression of NDRG2 is an independent prognostic factor in pancreatic cancer.