Gasdermin D represses inflammation-induced colon cancer development by regulating apoptosis.

Chronic inflammation is widely recognized as a major risk factor for cancer formation, but the underlying mechanisms are poorly understood. Recently, it was shown that Gasdermin D (GSDMD) protein drives pyroptotic cell death in macrophages on cleavage by inflammatory caspases. Even though the Gsdmd gene is specifically expressed in the intestinal epithelium, the role of Gsdmd in the intestinal tissues remains poorly characterized. In this study, we examined the biological role of Gsdmd in colorectal cancer (CRC) development, employing an azoxymethane/dextran sulfate sodium carcinogenesis model. Results show that GSDMD deficiency enhances CRC development, probably due to decreased apoptosis caused by downregulation of interferon-gamma (IFNγ)-signal transducer and activator 1 (STAT1) signaling. Furthermore, we show that GSDMD protein is diminished in human colorectal cancer, indicating involvement of GSDMD in repression of CRC development in humans. Our findings provide a new insight into functions of Gsdmd/GSDMD in colonic inflammation and human CRC development.

pfeRNAs-A Novel Class of Small Non-coding RNAs With Real Translational Potential.

Small non-coding RNAs (sncRNAs) are defined by being less than 200 nucleotides (nt) in length, and consequently, have been divided into many different subclasses including mature microRNA (miRNA), small interfering RNA (siRNA), piwi-interacting RNA (piRNA), protein functional effector sncRNA (pfeRNA), precursor miRNA (pre-miRNA), small nucleolar RNA (snoRNA), 5S ribosome RNA (5SrRNA), 5.8SrRNA, and small nuclear RNA (snRNA). Except for the class of pfeRNAs, the discovery, identification, biogenesis, characterization, and function of other sncRNAs have been well documented. Herein, we provide a review, written especially for clinicians, of the least understood class of functional sncRNAs, the pfeRNAs, focusing on their initial discovery, identification, unique features, function, as well as their exciting clinical translational potential.

Double stapling technique versus hemi-double stapling technique for esophagojejunostomy with OrVil™ after laparoscopic total gastrectomy: a single-blind, randomized clinical trial.

BACKGROUND: The transorally inserted anvil (OrVil™) is frequently selected for esophagojejunostomy after laparoscopic total gastrectomy (LTG) because of its versatility. During anastomosis with OrVil™, the double stapling technique (DST) or hemi-double stapling technique (HDST) can be selected by overlapping the linear stapler and the circular stapler. However, no studies have reported the differences between the methods and their clinical significance. METHODS: A randomized controlled clinical trial with a parallel assignment and single-blind outcomes assessment analysis was conducted. Patients with gastric cancer eligible for LTG who met the selection criteria were randomized. Preoperative characteristics and perioperative and postoperative outcomes were compared between the DST and HDST. The primary endpoint was an anastomosis-related complication, and the secondary endpoints were perioperative outcomes and postoperative complications, excluding anastomosis-related complications. RESULTS: Thirty patients with gastric cancer were eligible and randomized. LTG and esophagojejunostomy were successfully performed in all patients, without conversion to laparotomy. Preoperative characteristics, excluding preoperative chemotherapy, were not significantly different between the two groups. One anastomotic leakage of Clavien-Dindo classification grade ≥ IIIa was observed in the DST, although no significant difference was found between the two groups (6.6% vs. 0%, P = 0.30). In the HDST, one case of anastomotic stricture required endoscopic balloon dilation. No significant differences were found in operative time, whereas the anastomosis time was significantly shorter in the HDST than in the DST (47.5 ± 15.8 vs. 38.2 ± 8.8 min, P = 0.028). Except for anastomosis-related complications, postoperative complications (P = 0.282) and postoperative hospital stay for the DST and HDST were not significantly different. CONCLUSIONS: No superiority was found between the DST and HDST with OrVil™ in esophagojejunostomy of LTG for gastric cancer with respect to postoperative complications, whereas the HDST may be preferable in terms of the simplicity of the surgical technique.

Prenatal stress enhances atherosclerosis and telomere shortening in ApoE knockout mouse offspring.

Children born to women who experience stress during pregnancy have an increased risk of atherosclerosis in later life, but few animal models have explored mechanisms. To study this phenomenon, timed-bred ApoE knockout mice were determined pregnant with ultrasound and randomly assigned on gestation day 8.5 to either a control (no stress) or prenatal stress (PS) group using 2 h of restraint for five consecutive days. PS significantly increased plasma corticosterone levels in pregnant mice. The litters from PS mice showed increased neonatal mortality within the first week of life. Body weights (at euthanasia) of adult offspring at 25 wk from the PS group were significantly increased compared with weights of controls. Adult offspring from these pregnancies were serially imaged with ultrasound to measure plaque thickness and were compared with plaque macroscopic and microscopic pathology. PS groups had increased plaque thickness determined by ultrasound, gross, histological evaluation and increased aortic root and valve macrophage infiltration at 25 wk. Five-week-old mice from PS group had significant decrease in mean arterial pressure, yet blood pressure normalized by 10 wk. As prenatal stress induced increased atherosclerosis, and telomeres are susceptible to stress, aortas from 10-wk-old mice were compared for telomere lengths and were found to be significantly shorter in PS mice compared with control mice. These studies support future investigation of how stress impacts telomere shortening in animal models and human aortas. This model could be further used to investigate the role of prenatal stress, telomere biology, and atherosclerosis pathogenesis in adults.

Prenatal stress enhances NNK-induced lung tumors in A/J mice.

Children born to women who experience stress during pregnancy have an increased risk of cancer in later life, but no previous animal studies have tested such a link. We questioned whether prenatal stress (PS) in A/J mice affected the development of lung tumors after postnatal response to tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Timed-bred A/J mice were randomly assigned on gestation day 12.5 to PS by restraint for 5 consecutive days or control (no restraint). Adult offspring of control and stressed pregnancies were all treated with three NNK injections (50 mg/kg every other day) and euthanized 16 weeks later to examine their lungs. Compared with controls, PS dams exhibited significantly increased levels of plasma corticosterone, increased adrenal weights and decreased fetus weights without fetal loss. Prenatally stressed litters had a significantly higher neonatal death rate within first week of life, and surviving male and female offspring developed lung epithelial proliferations with increase multiplicity, increased area and aggressive morphology. PS also induced more advanced atypical adenomatous hyperplasia lesions. We found no difference in lung NNK-derived methyl DNA adducts, but PS did significantly enhance CD3+ T cell and Foxp3+ T cell tumor infiltration. PS significantly increases multiplicity, area of NNK-induced lung tumors and advanced morphology. PS did not affect production of NNK-derived methyl DNA adducts but did increase lymphocytic infiltration of lung tumors. To our knowledge, this is the first animal model of PS with evaluation of cancer development in offspring.

Metabolomic profiling of gastric cancer tissues identified potential biomarkers for predicting peritoneal recurrence.

BACKGROUND: Metabolomics is useful for analyzing the nutrients necessary for cancer progression, as the proliferation is regulated by available nutrients. We studied the metabolomic profile of gastric cancer (GC) tissue to elucidate the associations between metabolism and recurrence. METHODS: Cancer and adjacent non-cancerous tissues were obtained in a pair-wise manner from 140 patients with GC who underwent gastrectomy. Frozen tissues were homogenized and analyzed by capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS). Metabolites were further assessed based on the presence or absence of recurrence. RESULTS: Ninety-three metabolites were quantified. In cancer tissues, the lactate level was significantly higher and the adenylate energy charge was lower than in non-cancerous tissues. The Asp, ß-Ala, GDP, and Gly levels were significantly lower in patients with recurrence than in those without. Based on ROC analyses to determine the cut-off values of the four metabolites, patients were categorized into groups at high risk and low risk of peritoneal recurrence. Logistic regression and Cox proportional hazard analyses identified ß-Ala as an independent predictor of peritoneal recurrence (hazard ratio [HR] 5.21 [95% confidence interval 1.07-35.89], p = 0.029) and an independent prognostic factor for the overall survival (HR 3.44 [95% CI 1.65-7.14], p < 0.001). CONCLUSIONS: The metabolomic profiles of cancer tissues differed from those of non-cancerous tissues. In addition, four metabolites were significantly associated with recurrence in GC. ß-Ala was both a significant predictor of peritoneal recurrence and a prognostic factor.

Prognostic Impact of Phosphorylated Discoidin Domain Receptor-1 in Esophageal Cancer.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is common in East Asia and also is often deadly. We sought to determine whether measuring the discoidin domain receptor-1 (DDR1)-both total and phosphorylated proteins-could improve our ability to predict recurrence in ESCC. MATERIALS AND METHODS: Total DDR1 and phosphorylated DDR1 (pDDR1) were measured using semiquantitative immunohistochemistry in a cohort of 60 patients with ESCC. Association between these immunohistochemical measurements and standard clinical-pathological variables such as patient recurrence-free survival was examined using univariate and multivariate analyses. RESULTS: Six patients (10.0%) had regional recurrence and eight patients (13.3%) had distant recurrence. In univariate analysis, early disease recurrence correlated with intense staining of total DDR1 (P = 0.03) as well as intense staining of pDDR1 (P < 0.001). On multivariate analysis, only regional lymph node metastasis (P = 0.04, HR = 4.20) and intensity of pDDR1 immunohistochemistry (P = 0.03, HR = 4.27) emerged as significant independent prognostic factors for recurrence. CONCLUSIONS: This study suggests that immunohistochemical measurements of both the DDR1 protein and pDDR1 can provide prognostic value in ESCC, even when other clinical and pathological factors are also being considered.

DNA methylation genome-wide analysis in remnant and primary gastric cancers.

BACKGROUND: Although primary (PGC) and remnant gastric cancers (RGC) both originate from the same gastrointestinal organ, they have very distinct clinicopathological behaviors. We hypothesized that there would be distinct differences in DNA methylation patterns that would occur during carcinogenesis of RGC and PGC, and that the differences in methylation patterns may help identify the primary factor contributing to chronic inflammation in patients with RGC. METHODS: We investigated the genome-wide DNA methylation patterns of PGC and RGC tissues from 48 patients using the Infinium HumanMethylation450 Beadchip assay. The results were validated by quantitative methylation-specific PCR (qMSP) in separate, independent cohorts. RESULTS: We found that in our training cohort of 48 patients, the most variable genes from the gastric cancer tissues identified by the Infinium HumanMethylation450 Beadchip clustered the resultant heatmap into high and low methylation groups. On multivariate analysis, PGCs contributed significantly to the high methylation group (p = 0.004, OR 12.33), which suggested that the promoter methylation status in PGC is higher than that in RGC. Supporting this conclusion was the finding that in a separate qMSP analysis in a test cohort, the EPB41L3 gene, chosen because of its high ß value on microarray analysis in the gastric cancer tissues, had significantly higher DNA promoter methylation in cancer tissues in the validation PGC tissues than in RGC. CONCLUSIONS: This study demonstrated that promoter methylation status in PGC is higher than in RGC. This result may reflect the effects of the absence of Helicobacter pylori on the reduced DNA methylation in the remnant stomach.

The prognostic value of pfetin: a validation study in gastrointestinal stromal tumors using a commercially available antibody.

OBJECTIVE: Adjuvant treatment with imatinib mesylate is an effective treatment for gastrointestinal stromal tumor. However, 50% of patients with gastrointestinal stromal tumor can be cured by surgery alone; hence, risk stratification for therapy with imatinib mesylate is the next challenge. Previously, using a proteomic approach, we discovered a potential prognostic biomarker for gastrointestinal stromal tumor, pfetin, and immunohistochemically validated its clinical utility using our original monoclonal antibody. In the present study, we examine the usefulness of a commercially available polyclonal antibody against pfetin. METHODS: Western blotting and immunohistochemistry were performed using surgical specimens of primary tissues from gastrointestinal stromal tumor patients using a polyclonal antibody against pfetin and our original monoclonal antibody. Formalin-fixed and paraffin-embedded primary tissue sections from 112 gastrointestinal stromal tumor patients were subjected to immunohistochemistry. The immunohistochemistry results were integrated with the clinico-pathological observations. RESULTS: Western blotting revealed that both antibodies recognized multiple post-translationally modified pfetin isoforms. The immunohistochemical study with the commercial antibody demonstrated that the disease-free survival rate was 88 and 56% for pfetin-positive and pfetin-negative patients, respectively. Univariate and multivariate analyses showed that pfetin expression as measured by the commercial antibody was a significant and independent prognostic factor among the clinico-pathological parameters examined. Of the 112 gastrointestinal stromal tumor cases examined, 13 yielded discordant results between the commercial antibody and our original antibody, and there were no significantly different clinical or pathological factors to account for this discrepancy. CONCLUSIONS: Our observations suggest that the pfetin expression level assessed by the commercial antibody could be a prognostic biomarker in gastrointestinal stromal tumors.

Analysis of the efficacy of direct hemoperfusion with polymyxin B-immobilized fiber (PMX-DHP) according to the prognostic factors in patients with colorectal perforation.

PURPOSE: Direct hemoperfusion with polymyxin B-immobilized fiber (PMX-DHP) has been reported to improve the outcomes in patients with colorectal perforation. We retrospectively identified prognostic factors in patients with colorectal perforation and considered the efficacy of PMX-DHP based on these prognostic factors. METHODS: One hundred and fifty-six patients who underwent surgery for colorectal perforation in our department between November 1995 and March 2011 were enrolled in this study. The clinicopathological factors were compared between the survivor and non-survivor groups. RESULTS: There were 28 patients (17.9 %) who died within 28 days after surgery. According to the multivariate analysis, an Acute Physiology and Chronic Health Evaluation II (APACHE II) score of 17 or more was a significant independent prognostic factor (P = 0.002, odds ratio = 5.39). There was a significant difference in the survival rates between the patients with APACHE II scores of 16 or less and those with scores of 17 or more who had received the PMX-DHP (+) (P < 0.0001). CONCLUSION: The APACHE II score is useful as a prognostic factor in patients with colorectal perforation, and the survival rate was 50 % or lower among the patients with APACHE II scores of 17 or higher. Therefore, PMX-DHP appears to have limited efficacy in serious cases.

Pathological complete response with nivolumab for recurrence of liver metastasis after gastrectomy of gastric cancer.

BACKGROUND: Advanced gastric cancer has an unfavorable prognosis and poor curability. Immune checkpoint inhibitors, such as nivolumab, have recently emerged as a potential solution for this aggressive disease. However, there is a lack of established evidence on the clinical efficacy of these agents, particularly in the perioperative period for advanced gastric cancer patients who are unresectable, recurrent, or preoperative. Despite the limited data available, there have been rare cases of dramatic therapeutic effects. In this study, we present a successful case of nivolumab treatment along with surgery. CASE PRESENTATION: A 69-year-old female presented with pericardial discomfort and was diagnosed with advanced gastric cancer following upper gastrointestinal endoscopy. Laparoscopic distal gastrectomy with D2 lymph node dissection was performed, resulting in a final pathological diagnosis of Stage IIIA. The patient received postoperative adjuvant chemotherapy with oral S-1 therapy, but was found to have multiple liver metastases at 8 months postsurgery. Weekly paclitaxel and ramucirumab therapy was initiated, but the patient experienced adverse side effects, leading to the discontinuation of treatment. Nivolumab monotherapy was then administered for 18 cycles, resulting in a partial therapeutic response and PET-CT revealed a complete metabolic response. However, the patient developed a Grade 3 pemphigoid as an immune-related adverse event, leading to the cessation of nivolumab. The patient underwent laparoscopic partial hepatectomy. Postoperative pathology showed no residual tumor cells, indicating a complete response. At present, 25 months after surgery, the patient was alive without recurrence. CONCLUSION: In this report, we present a case of gastric cancer with liver metastatic recurrence, in which a complete pathological response was achieved with nivolumab treatment. Although determining whether surgical intervention is necessary following successful drug treatment can be challenging, PET-CT imaging may be useful in decision-making regarding surgical treatment.

A vanished gastric gastrointestinal stromal tumor.

BACKGROUND: Local resection is the standard treatment for gastrointestinal stromal tumors (GISTs). Laparoscopic and endoscopic cooperative surgery (LECS) is a minimally invasive surgery used to resect GISTs. Herein, we report an extremely rare case of a gastric GIST that grossly vanished during LECS. CASE PRESENTATION: A 50-year-old Japanese female was referred to our hospital after an abnormality was detected during an esophagogastroduodenoscopy (EGD) at her annual health checkup. Based on EGD, endoscopic ultrasound (EUS), and computer tomography (CT) findings, the patient was diagnosed with a 50-mm submucosal tumor (SMT) with intraluminal growth on the anterior wall of the lesser curvature of the upper body of the stomach. We routinely use LECS to treat the intraluminal growth type of GISTs. During the intraoperative endoscopy, the intraluminal submucosal tumor, which was detected preoperatively, had vanished. A red-white scar was observed in the regressed tumor region. LECS was performed by resecting at a distance away from the scar tissue and closing the gastric wall with intracavitary sutures. In the evaluation from the tumor section view of the original resected specimen, a 22 × 14 × 8 mm lobular neoplasm was observed that was predominantly located in the gastric submucosa to the muscularis propia. Pathological findings confirmed the diagnosis of GIST with intermediate risk indicated by the Fletcher classification. The patient continued postoperative adjuvant chemotherapy with imatinib and no recurrence was detected over 12 months after surgery. CONCLUSION: LECS was performed on the vanished gastric GIST, providing the best surgical treatment and leading to an accurate diagnosis and optimal postoperative care.

Totally Laparoscopic Pylorus-Preserving Gastrectomy (TLPPG) is Safe and Effective for Early Gastric Cancer Treatment.

Background: Compared to distal gastrectomy (DG), pylorus-preserving gastrectomy (PPG), a peristaltic function-preserving surgery for early gastric cancer (EGC), is advantageous as it leads to a more improved nutritional status and quality of life (QOL) of patients. In recent years, total laparoscopic PPG (TLPPG), an anastomosis which is performed intracorporeally, has increasingly replaced laparoscopic-assisted PPG (LAPPG) due to its minimal invasiveness. Aim: To evaluate the safety and feasibility of TLPPG in terms of perioperative efficacy. Patients: Three patients underwent TLPPG in the Affiliated Hospital of Changzhi Medical College from September 2021 to March 2022. Methods: Surgical safety analysis: Our three cases (TLPPG group) were compared to data from the CLASS-02 study, which collected data from multiple centers across China for the laparoscopic total gastrectomy (LTG group). The CLASS-02 study provides data from the most invasive type of gastric surgery, providing solid comparative data to our own.Postoperative short-term efficacy analysis: Patient questionnaire responses provided data on postoperative nutritional and QOL status. Results from our three cases were compared to the Japanese multicenter data PGSAS-37 (PGSAS group). Results: There were no complications or deaths occurred during or after operation in our cases. Compared to the PGSAS group, our cases scored lower for abdominal pain, dyspepsia, and weight loss. Conclusion: Although more case information is needed, our findings demonstrate that TLPPG may be a possible and effective treatment for EGC in China, similar to that in Japan.

Eosinophils Exert Antitumorigenic Effects in the Development of Esophageal Squamous Cell Carcinoma.

BACKGROUND AND AIMS: Eosinophils are present in several solid tumors and have context-dependent function. Our aim is to define the contribution of eosinophils in esophageal squamous cell carcinoma (ESCC), as their role in ESCC is unknown. METHODS: Eosinophils were enumerated in tissues from 2 ESCC cohorts. Mice were treated with 4-NQO for 8 weeks to induce precancer or 16 weeks to induce carcinoma. The eosinophil number was modified by a monoclonal antibody to interleukin-5 (IL5mAb), recombinant IL-5 (rIL-5), or genetically with eosinophil-deficient (ΔdblGATA) mice or mice deficient in eosinophil chemoattractant eotaxin-1 (Ccl11-/-). Esophageal tissue and eosinophil-specific RNA sequencing was performed to understand eosinophil function. Three-dimensional coculturing of eosinophils with precancer or cancer cells was done to ascertain direct effects of eosinophils. RESULTS: Activated eosinophils are present in higher numbers in early-stage vs late-stage ESCC. Mice treated with 4-NQO exhibit more esophageal eosinophils in precancer vs cancer. Correspondingly, epithelial cell Ccl11 expression is higher in mice with precancer. Eosinophil depletion using 3 mouse models (Ccl11-/- mice, ΔdblGATA mice, IL5mAb treatment) all display exacerbated 4-NQO tumorigenesis. Conversely, treatment with rIL-5 increases esophageal eosinophilia and protects against precancer and carcinoma. Tissue and eosinophil RNA sequencing revealed eosinophils drive oxidative stress in precancer. In vitro coculturing of eosinophils with precancer or cancer cells resulted in increased apoptosis in the presence of a degranulating agent, which is reversed with NAC, a reactive oxygen species scavenger. ΔdblGATA mice exhibited increased CD4 T cell infiltration, IL-17, and enrichment of IL-17 protumorigenic pathways. CONCLUSION: Eosinophils likely protect against ESCC through reactive oxygen species release during degranulation and suppression of IL-17.

Eosinophils exert direct and indirect anti-tumorigenic effects in the development of esophageal squamous cell carcinoma.

Background/Aims: Eosinophils are present in several solid tumors and have context-dependent function. Our aim is to define the contribution of eosinophils in esophageal squamous cell carcinoma (ESCC), since their role in ESCC is unknown. Methods: Eosinophils were enumerated in tissues from two ESCC cohorts. Mice were treated with 4-nitroquinolone-1-oxide (4-NQO) for 8 weeks to induce pre-cancer or 16 weeks to induce carcinoma. Eosinophil number was modified by monoclonal antibody to IL-5 (IL5mAb), recombinant IL-5 (rIL-5), or genetically with eosinophil-deficient (ΔdblGATA) mice or mice deficient in eosinophil chemoattractant eotaxin-1 ( Ccl11 -/- ). Esophageal tissue and eosinophil specific RNA-sequencing was performed to understand eosinophil function. 3-D co-culturing of eosinophils with pre-cancer or cancer cells was done to ascertain direct effects of eosinophils. Results: Activated eosinophils are present in higher numbers in early stage versus late stage ESCC. Mice treated with 4-NQO exhibit more esophageal eosinophils in pre-cancer versus cancer. Correspondingly, epithelial cell Ccl11 expression is higher in mice with pre-cancer. Eosinophil depletion using three mouse models ( Ccl11 -/- mice, ΔdblGATA mice, IL5mAb treatment) all display exacerbated 4-NQO tumorigenesis. Conversely, treatment with rIL-5 increases esophageal eosinophilia and protects against pre-cancer and carcinoma. Tissue and eosinophil RNA-sequencing revealed eosinophils drive oxidative stress in pre-cancer. In vitro co-culturing of eosinophils with pre-cancer or cancer cells resulted in increased apoptosis in the presence of a degranulating agent, which is reversed with N-acetylcysteine, a reactive oxygen species (ROS) scavenger. ΔdblGATA mice exhibited increased CD4 T cell infiltration, IL-17, and enrichment of IL-17 pro-tumorigenic pathways. Conclusion: Eosinophils likely protect against ESCC through ROS release during degranulation and suppression of IL-17.

Intraoperative blood transfusion contributes to decreased long-term survival of patients with esophageal cancer.

BACKGROUND: Several prognostic factors for patients who have undergone esophagectomy owing to esophageal squamous cell carcinoma have been suggested, including intraoperative blood loss. There are few data, however, suggesting such an association with the prognosis following radical esophagectomy. METHODS: Patients with esophageal squamous cell carcinoma who underwent radical esophagectomy were divided into two groups based on the median value of the intraoperative blood loss (510 g). A multivariate Cox proportional-hazard regression analysis was performed to determine if intraoperative blood loss could be an independent prognostic factor for long-term survival following radical esophagectomy. Kaplan-Meier survival analysis with a log-rank test was performed between the groups. RESULTS: From April 2005 to May 2009, a total of 37 patients underwent radical esophagectomy for the treatment of esophageal squamous cell carcinoma at the Juntendo Shizuoka Hospital and were assigned either to one of two groups: those with ≥510 g blood loss [bleeding group (BG), n = 19] or of those with <510 g blood loss [less bleeding group (LBG), n = 18]. The distribution of the stage of disease, the number of positive lymph nodes, and the presence of lymphatic and vascular invasion was comparable between the groups, but the Kaplan-Meier survival analysis demonstrated that survival was significantly worse in the BG group than in the LBG group (p = 0.00295). This was supported by the multivariate analysis, which indicated that intraoperative blood loss was independently associated with long-term survival after radical esophagectomy. CONCLUSIONS: Intraoperative blood loss could be a useful prognostic factor following radical esophagectomy in patients with esophageal squamous cell carcinoma.

Agenesis of the Left Hepatic Lobe Accompanied by Esophagogastric Cancer: A Case Report and Literature Review.

Agenesis of the left hepatic lobe is an exceedingly rare morphological anomaly. Moreover, agenesis of the left hepatic lobe accompanied by esophagogastric cancer is even rarer, with no reports to date. Agenesis of the hepatic lobe is commonly related to some anatomical variations of the gastrohepatic system. A 76-year-old man was referred to our hospital for surgery for esophagogastric cancer with short Barrett's esophagus. Multiple preoperative imaging modalities revealed agenesis of the left hepatic lobe accompanied by esophagogastric cancer. Robotic proximal gastrectomy and transhiatal lower esophagectomy were performed. Intraoperative findings showed agenesis of the left hepatic lobe. The patient's postoperative course was favorable. Today, 16 months after surgery, the patient is alive without recurrence of esophagogastric cancer. We report a case of agenesis of the left hepatic lobe in a patient undergoing robotic proximal gastrectomy and transhiatal lower esophagectomy for esophagogastric cancer. Preoperative comprehension of various visceral anomalies reduces the risk of surgical complications.

Clinicopathological and mutational analysis of esophageal basaloid squamous cell carcinoma.

Esophageal basaloid squamous cell carcinoma (EBSCC) is a poorly differentiated variant of esophageal squamous cell carcinoma (ESCC). We aimed to investigate the clinicopathological and molecular biological characteristics of EBSCC and enrolled 58 patients with EBSCCs. Clinicopathological factors including age, sex, tumor size and location, gross tumor type (superficial, protrusive, ulcerative, and unclassifiable), lymphovascular invasion, infiltrative growth, intramural invasion, TNM stage, and dominant histological type were examined. EBSCCs were classified into four types (solid, cribri, microcystic, and tubular) according to the dominant histology. Next-generation sequencing (NGS) of a cancer hotspot panel was performed in 19 cases. NGS identified TP53 as the most frequently mutated gene, and copy number variation analysis revealed the most frequent loss of heterozygosity (LOH) at the ataxia telangiectasia mutated (ATM) and retinoblastoma 1 (RB1) loci. Target sequencing for TP53 was performed for the remaining 39 cases. We also performed LOH analysis for TP53, ATM, and RB1 and immunohistochemical staining for p53, ATM, and Rb in all cases. The rates of TP53 mutations and LOH and p53 aberrant expression were high (79.3%, 63.2%, and 72.4%, respectively); however, the frequencies were similar to those reported for ESCC. LOH rates of the RB1 and ATM loci were also high (55.3% and 67.2%, respectively). Overall survival rate was 66.5%, and recurrence-free survival rate was 55.0%. Only conventional clinicopathological factors had a prognostic impact in EBSCC; the microcystic type had the poorest prognosis. Our findings could be useful in developing novel treatment strategies for EBSCC.

Long-term outcomes of postgastrectomy syndrome after total laparoscopic distal gastrectomy using the augmented rectangle technique.

BACKGROUND: For total laparoscopic distal gastrectomies for gastric cancer, the reconstruction method is critical to the clinical outcome of the procedure. However, which reconstruction technique is optimal remains controversial. We originally reported the augmented rectangle technique (ART) as a reconstruction option for total laparoscopic Billroth I reconstructions. Still, little is known about its effect on long-term outcomes, specifically the incidence of postgastrectomy syndrome and its impact on quality of life. AIM: To analyze postgastrectomy syndrome and quality of life after ART using the Postgastrectomy Syndrome Assessment Scale-37 (PGSAS-37) questionnaire. METHODS: At Juntendo University, a total of 94 patients who underwent ART for Billroth I reconstruction with total laparoscopic distal gastrectomies for gastric cancer between July 2016 and March 2020 completed the PGSAS-37 questionnaire. Multidimensional analysis was performed, comparing those 94 ART cases from our institution (ART group) to 909 distal gastrectomy cases with a Billroth I reconstruction from other Japanese institutions who also completed the PGSAS-37 as part of a larger national database (PGSAS group). RESULTS: Patients in the ART group had significantly better total symptom scores in all the symptom subscales (i.e., esophageal reflux, abdominal pain, meal-related distress, indigestion, diarrhea, constipation, and dumping). The loss of body weight was marginally greater for those in the ART group than in the PGSAS group (-9.3% vs -7.9%, P = 0.054). The ART group scored significantly lower in their dissatisfaction of ongoing symptoms, during meals, and with daily life. CONCLUSION: ART for Billroth I reconstruction provided beneficial long-term results for postgastrectomy syndrome and quality of life in patients undergoing total laparoscopic distal gastrectomies for gastric cancer.

Pfetin as a prognostic biomarker for gastrointestinal stromal tumor: validation study in multiple clinical facilities.

OBJECTIVE: The aim of this study is to confirm the prognostic value of pfetin in gastrointestinal stromal tumor patients. We recently reported the utility of pfetin, a novel prognostic biomarker in gastrointestinal stromal tumor. Gastrointestinal stromal tumor spans a wide spectrum from cases with curable disease to those with fatal tumors due to metastasis and recurrence. There is no biomarker predicting metastasis and/or recurrence of gastrointestinal stromal tumor though imatinib mesylate can improve recurrence-free survival. METHODS: Pfetin expression was examined in 40 gastrointestinal stromal tumor patients from the Juntendo University Shizuoka Hospital using immunohistochemistry. Correlations between immunohistochemical findings and clinicopathologic parameters were examined. The pfetin expression results were integrated with the clinicopathologic data in a total of 299 cases including our 40 new gastrointestinal stromal tumor cases and 259 others with previously reported data. RESULTS: Immunohistochemical study demonstrated the disease-free survival rate to be 93.75% for pfetin-positive and 25.0% for pfetin-negative patients among the 40 cases from the Juntendo University Shizuoka Hospital (P= 0.0006). When all 299 cases were included, the disease-free survival rate was 92.44% for pfetin-positive and 60.81% for pfetin-negative patients (P< 0.0001). Both uni- and multivariate analyses revealed that, among the clinicopathologic parameters examined, only pfetin expression was an independent prognostic factor (P< 0.05). CONCLUSIONS: These results confirm the possible clinical utility of pfetin as a prognostic biomarker for gastrointestinal stromal tumor. Pfetin appears to be a novel clinically applicable prognostic factor, which may be useful for deciding whether to administer imatinib mesylate or not.