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Background/Aim: Diagnosing primary splenic malignant lymphoma (PSML) is challenging due to the non-specific nature of splenomegaly, necessitating splenic biopsy for confirmation. However, performing partial splenic resection for diagnostic purposes is an elective procedure due to the risk of major hemorrhage. Despite the longstanding practice of splenectomy over the past few decades, it remains invasive and may result in severe early or late complications. Hence, we present laparoscopic partial splenectomy (LPS) in a patient suspicious of PSML for diagnostic purposes in this study. Case Report: An 81-year-old woman presented to our hospital with a one-month history of fever and dry cough. Atypical cells had been detected in her peripheral blood nine months ago. However, at that time, a bone marrow examination did not reveal any atypical cells. The laboratory tests revealed a soluble interleukin receptor-2 levels of 4,667 U/dl and atypical cells were also found in peripheral blood. Abdominal computed tomography showed splenomegaly without any other relevant findings. These findings are suspicious of PSML and LPS without vessel ligation was performed and a small fraction of the spleen from the inferior pole measuring 1.8×1.0 cm was resected. The operation lasted for 63 min with minimal estimated blood loss. Histopathological findings were compatible with the diagnosis of diffuse B-cell lymphoma. The postoperative clinical course was uneventful, and splenomegaly demonstrated improvement six months after the operation. Conclusion: LPS without vessel ligation for biopsy may be valuable for the diagnosis of malignant lymphoma, particularly when there are no swollen lymph nodes, as it offers a less invasive approach.

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BACKGROUND: Gastric wall abscess (GWA) itself is a rare clinicopathological condition, and there has been no report of primary gastric cancer complicated by GWA. Herein, we present a case of advanced gastric cancer with intramural abscess, which was successfully treated with curative gastrectomy. CASE REPORT: A 77-year-old woman was admitted to the hospital for dull epigastric pain with inflammatory findings and diagnosed with advanced gastric cancer (cT4aN1M0 Stage III) with intramural abscess. Since an endoscopic ultrasonography-guided abscess drainage was not effective, after conservative therapy with antibiotics, she underwent distal gastrectomy with D2 lymphadenectomy and fortunately the tumor with abscess was safely and curatively removed without perforation. Microscopically, the 82×65 mm tumor invaded the subserosa and contained tubular adenocarcinoma with neuroendocrine cell carcinoma (pT3N0M0 Stage IIB), and the abscess formed from the ulcerative lesion of the cancer extended to the subserosa. The postoperative clinical course was uneventful, and she remained disease-free during the 22 months follow-up. CONCLUSION: Given the nature of the disease and the difficulty in endoscopic treatment, gastrectomy should be performed immediately for advanced gastric cancer with GWA to ensure control of both gastric cancer and infection.

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We present a case of 72-year-old man who was diagnosed with gastric cancer that occurred after coronary artery bypass grafting(CABG)with the right gastroepiploic artery(RGEA). Gastrointestinal endoscopy revealed a 0-Ⅱc lesion at the posterior wall of gastric angle, and diagnosis was cStage Ⅰ(T2N0M0). Cardiac computed-tomography showed an occlusion of the RGEA graft, suggesting that the RGEA graft could be ligated and dissected. Coronary angiography showed no severe stenosis of the right coronary artery, suggesting that coronary revascularization was not necessary. He underwent laparoscopic distal gastrectomy with D2 lymph node dissection. During the operation, the RGEA graft was dissected after clamp test for 20 minutes to confirm no cardiac event. In such cases, it is crucial to consider whether it is possible or not to dissect the RGEA graft and whether to restore the coronary flow with preoperative meticulous examination.

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BACKGROUND: Foreign body granuloma (FBG) is a well-known type of granulomatous formation, and intraabdominal FBG (IFBG) is primarily caused by surgical residues. Multifocal IFBGs caused by gastrointestinal perforation is an extremely rare and interesting clinicopathological condition that resembles peritoneal dissemination. Here, we present a case of IFBGs mimicking peritoneal dissemination caused by bowel perforation and describe the value of intraoperative pathological examinations for rapid IFBG diagnosis. CASE SUMMARY: An 86-year-old woman with an incarcerated femoral hernia was admitted to the hospital and underwent operation. During the operation, the incarcerated ileum was perforated during repair due to hemorrhage necrosis, and a small volume of enteric fluid leaked from the perforation. The incarcerated ileum was resected, and the femoral hernia was repaired without mesh. Four months later, a second operation was performed for an umbilical incisional hernia. During the second operation, multiple small, white nodules were observed throughout the abdominal cavity, resembling peritoneal dissemination. The results of peritoneal washing cytology in Douglas' pouch and the examination of frozen nodule sections were compatible with IFBG diagnosis, and incisional hernia repair was performed. CONCLUSION: IFBGs can mimic malignancy. Intraoperative pathological examinations and operation history are valuable for the rapid diagnosis to avoid excessive treatments.

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A 77-year-old man was admitted to our hospital with symptoms of epigastralgia and vomiting. Detailed investigation revealed unresectable advanced gastric cancer accompanied by multiple lymph node metastases and invasion of the pancreas(UM, type 3, cT4b, N3, M0, Stage ⅢC). The patient received nivolumab immunotherapy after first-line S-1 plus oxaliplatin(SOX)chemotherapy and second-line nab-paclitaxel(PTX)plus ramucirumab(RAM)chemotherapy. Remarkable tumor reduction was observed after 3 courses of nivolumab immunotherapy, and the patient subsequently underwent radical total gastrectomy with splenectomy and D2 lymphadenectomy. Histopathological examination of the resected stomach showed a near complete response, and only small metastatic foci remained in No. 2 lymph nodes, resulting in R0 resection. The patient was followed up without adjuvant therapy, and he is alive 6 months after the treatment without any symptoms of recurrence. The mechanism of action of immune checkpoint inhibitors is fundamentally different from that of conventional cytotoxic chemotherapeutic agents. Recently, several reports have described good responses to immune checkpoint inhibitors in cases where conventional chemotherapy has been unsuccessful. When predictive biomarkers of response to immune checkpoint inhibitors are identified, a combination therapy of preceding immunotherapy and subsequent surgery might provide an efficient radical therapeutic effect even in cases of unresectable advanced gastric cancer.

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BACKGROUND: High-mobility group box-1 (HMGB1) is involved in a broad range of inflammatory responses and the progression of various types of malignancy. However, the roles of HMGB1 in the progression of esophageal squamous cell carcinoma (ESCC) are unclear. The aim of this study was to investigate the significance of intracellular and extracellular HMGB1 in ESCC. METHODS: HMGB1 levels were measured in the tissue and plasma of patients with ESCC, or in ESCC cell lines and their conditioned medium. The effects of downregulation of intracellular HMGB1 or upregulation of extracellular HMGB1 on proliferation, cell migration, and invasion were evaluated using proliferation, transwell, and wound healing assays. RESULTS: Downregulation of HMGB1 expression inhibited cell proliferation, migration, and invasion. On the other hand, upregulation of extracellular HMGB1 level by addition of recombinant HMGB1 promoted the migratory and invasive abilities of ESCC cells through increases of phosphorylation of the signal-regulated kinase 1/2 and NF-κBp65 proteins. These effects of extracellular HMGB1 were attenuated by treatment with recombinant soluble thrombomodulin, which adsorbs HMGB1. The expression of HMGB1 was significantly higher in tumor tissue (p = 0.008), and the concentration of HMGB1 in the plasma was significantly higher in patients with ESCC than in healthy volunteers (p = 0.04). Cancer-specific survival was worse in patients with high concentration of plasma HMGB1 (p = 0.01). CONCLUSION: Increase of HMGB1 levels in tumor cells or plasma plays a crucial role in the malignant potential of ESCC. Intracellular and extracellular HMGB1 may be a therapeutic target in ESCC.

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A 71-year-old male with a past history of Stage Ⅱb transverse colon cancer was pointed out a mass lesion penetrating into the stomach on abdominal computed tomography 1 year after surgery. The mass lesion was pathologically diagnosed as local recurrence of the previous colon cancer by upper gastrointestinal endoscopy. As he presented progressive anemia due to persistent tumor bleeding and no other recurrent lesion was recognized, surgical treatment was performed. Since intraoperative inspection suspected direct invasion to the pancreas, the patient underwent tumor resection in combination with distal pancreatectomy and partial resection of the stomach. Histopathological examination revealed negative surgical margins, resulting in R0 resection. Loco-regional therapies such as surgery and radiotherapy are considered appropriate for the treatment of local recurrence since pathogenesis of local recurrence is different from that of distant metastasis. As local recurrence may show various symptoms, we should aggressively consider surgical resection. Especially, complete resection of recurrent lesion is the only therapeutic strategy which can achieve radical cure. Although worsening of QOL might be a matter of concern depending on the site of recurrence, extended surgery with secure surgical margins is encouraged in cases of solitary recurrence.

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A 63-year-old man underwent proximal gastrectomy for gastrointestinal stromal tumor(GIST)of the stomach 19 years ago. Local recurrence of GIST of the stomach occurred 13 years later, and the tumor was resected. Since then, he had adjuvant chemotherapy. Six years later, computed tomography revealed a soft-tissue shadow at the left lateral side of the stomach, and positron emission tomography also revealed fluorodeoxyglucose uptake at the same site. The recurrence of GIST was suspected, and therefore laparoscopic resection was performed. The operative time was 70 minutes. Blood loss was 10 g. Immunohistochemical examination showed positivity for c-kit and CD34, leading to a diagnosis of recurrence of GIST. The postoperative course was uneventful, and the patient was discharged on the fifth postoperative day. At present, the patient is alive without adjuvant chemotherapy 13 months since surgery. GIST may recur 10 years or more after surgery. Therefore, long-term surveillance seems to be mandatory.

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Esophageal squamous cell carcinoma (ESCC) is a lethal malignancy. However, there are few useful markers for diagnosis and treatment. Glutathione S-transferase Pi 1 (GSTP1) has been reported as a predictor of malignancy or anticancer drug resistance in some cancers. We investigated the association of GSTP1 expression with the malignancy or drug resistance in ESCC cell lines and clinical tissue samples. Proliferation and apoptosis assays regarding GSTP1 expression were examined in ESCC cell lines. Proliferation of GSTP1 knockdown cells was significantly decreased (P < .01), and the frequency of early apoptosis was increased (P < .05). Invasion capacity of GSTP1 knockdown cells was slightly decreased in transwell assay. These results suggest that GSTP1 plays an important role in malignant potential. To examine the effects of GSTP1 on drug resistance, chemosensitivity assay and apoptosis assay under cisplatin exposure were carried out. Viability of GSTP1 knockdown cells treated with cisplatin was lower than that of control cells (P < .01). Moreover, the frequency of early and late apoptosis in GSTP1 knockdown cells was markedly increased over that of control cells by cisplatin exposure (P < .01). In immunohistochemistry assay of resected tissue samples, GSTP1 expression was significantly associated with clinical downstaging (P = .04) in 72 ESCC patients with neoadjuvant chemotherapy. Furthermore, there was a significant association between GSTP1 expression in resected tissue and biopsy samples in 34 ESCC patients without neoadjuvant chemotherapy (P = .02). In summary, GSTP1 was related to malignant potential and may be a predictive marker of drug resistance in ESCC patients.

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Synovial sarcoma (SS) is genetically characterized by chromosomal translocation, which generates SYT-SSX fusion transcripts. Although SS can occur in any body part, primary gastric SS is substantially rare. Here we describe a detection of the fusion gene sequence of gastric SS in plasma cell-free DNA (cfDNA). A gastric submucosal tumor was detected in the stomach of a 27-year-old woman and diagnosed as SS. Candidate intronic primers were designed to detect the intronic fusion breakpoint and this fusion sequence was confirmed in intron 10 of SYT and intron 5 of SSX2 by genomic polymerase chain reaction (PCR) and direct sequencing. A locked nucleic acid (LNA) probe specific to the fusion sequence was designed for detecting the fusion sequence in plasma and the fusion sequence was detected in preoperative plasma cfDNA, while not detected in postoperative plasma cfDNA. This technique will be useful for monitoring translocation-derived diseases such as SS.

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BACKGROUND: Peritoneal metastasis consists of a highly complex series of steps, and the details of the underlying molecular mechanism remain largely unclear. In this study, the effects of tumor-derived exosomes (TEX) on the progression of gastric cancers were investigated in peritoneal metastasis. RESULTS: TEX were internalized in both mesothelial and gastric cancer cells in a cellular origin non-specific manner. Internalization of TEX into mesothelial cells promoted significant adhesion between mesothelial and gastric cancer cells, and TEX internalization into gastric cancer cells significantly promoted migratory ability, while internalization of mesothelial cell-derived exosomes did not. Expression of adhesion-related molecules, such as fibronectin 1 (FN1) and laminin gamma 1 (LAMC1), were increased in mesothelial cells after internalization of TEX from gastric cancer cell line and malignant pleural effusion. METHODS: TEX were extracted from cell-conditioned medium by ultracentrifugation. The effects of TEX on the malignant potential of gastric cancer were investigated in adhesion, invasion, and proliferation assays. PCR array as well as western blotting were performed to determine the underlying molecular mechanisms. The molecular changes in mesothelial cell after internalization of TEX derived from malignant pleural effusion were also confirmed. CONCLUSIONS: TEX may play a critical role in the development of peritoneal metastasis of gastric cancer, which may be partially due to inducing increased expression of adhesion molecules in mesothelial cells.

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UNLABELLED: BACK GROUND/AIM: The purpose of the present study was to clarify the clinicopathological features of non-hepatitis B and -C (NBNC) hepatocellular carcinoma (HCC), the incidence of which has been increasing. PATIENTS AND METHODS: Two hundred and eighty-four patients with HCC were classified into three groups according to viral hepatitis status, namely NBNC, hepatitis B, and hepatitis C. We compared the three groups and studied related risk factors. RESULTS: Patients without cirrhosis who had increased number of platelets and diabetes mellitus, and a serum alpha-feto-protein (AFP) level <100 ng/dl were more common in the NBNC group. The cumulative survival and disease-free survival were better in the NBNC group than in the other groups. The tumor size and hepatitis B or C viral status were found to be independent risk factors of disease-free survival and the presence of multiple lesions was the only independent risk factor of survival. CONCLUSION: Close follow-up of NBNC liver cirrhosis and early detection of NBNC-HCC can improve the prognosis after surgery.

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BACKGROUND: Mesohepatectomy with total resection of the caudate lobe and extrahepatic bile duct is sometimes performed for hilar cholangiocarcinoma or gallbladder carcinoma; however, only a few reports on mesohepatectomy with total caudate lobectomy of the liver for hepatocellular carcinoma are available. METHODS: A 71-year-old woman was preoperatively diagnosed with hepatocellular carcinoma in the central bisections (Couinaud's segments 4, 5, and 8) and the paracaval portion of the caudate lobe. Mesohepatectomy with total caudate lobectomy of the liver permitted the removal of tumors to provide a cancer-free raw surface of the liver. Mobilization of the caudate lobe is an important procedure in this surgery. Before the liver parenchyma was dissected, all short hepatic veins were ligated and divided from the left to the right side as the left lateral section was retracted to the right, and the caudate lobe branches of the portal vein and hepatic artery were ligated and divided. After the liver parenchymal dissection, both between the left lateral and medial sections and between the right anterior and posterior sections, the Glissonean branches of the caudate lobe were ligated and divided as the central bisections were anteriorly retracted. Finally, liver parenchymal dissection was performed between the caudate lobe and the right posterior section, which was along the right side of the inferior vena cava. RESULTS: The surgery time was 538 minutes and blood loss was 1,207 mL. No blood transfusions were required during or after surgery. The postoperative course was uncomplicated. The patient is still alive 25 months after hepatectomy. CONCLUSION: Although mesohepatectomy with total caudate lobectomy of the liver is technically more difficult than mesohepatectomy of the liver because the caudate lobe must be completely detached from the inferior vena cava and the hilar plate, it is a safe and effective treatment method in selected patients with hepatocellular carcinoma located at both the central bisections and the paracaval portion of the caudate lobe.

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In contrast to the definitive role of the transcription factor, CCAAT/Enhancer binding protein α (C/EBPα), in steady-state granulopoiesis, previous findings have suggested that granulopoiesis during emergency situations, such as infection, is dependent on C/EBPß. In this study, a novel lentivirus-based reporter system was developed to elucidate the molecular switch required for C/EBPß-dependency. The results demonstrated that two cyclic AMP responsive elements (CREs) in the proximal promoter region of C/EBPß were involved in the positive regulation of C/EBPß transcription during granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced differentiation of bone marrow cells. In addition, the transcripts of CRE binding (CREB) family proteins were readily detected in hematopoietic stem/progenitor cells. CREB was upregulated, phosphorylated and bound to the CREs in response to GM-CSF stimulation. Retroviral transduction of a dominant negative CREB mutant reduced C/EBPß mRNA levels and significantly impaired the proliferation/differentiation of granulocyte precursors, while a constitutively active form of CREB facilitated C/EBPß transcription. These data suggest that CREB proteins are involved in the regulation of granulopoiesis via C/EBPß upregulation.

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