RESUMO
BACKGROUND: The ideal surveillance strategy after partial pancreatectomy for non-invasive IPMN remains undefined and existing guidelines provide conflicting recommendations. The present study was developed in anticipation of the joint meeting of the International Association of Pancreatology (IAP) and the Japan Pancreas Society (JPS) held in Kyoto in July 2022. METHODS: An international team of experts developed the four clinical questions (CQ) to operationalize issues pertaining to surveillance of patients in this context. A systematic review was designed following the PRISMA guidelines and registered in PROSPERO. The search strategy was executed in PubMed/Medline (Ovid), Embase, the Cochrane Library and Web of Science databases. Four investigators individually extracted data from the selected studies and drafted recommendations for each CQ. These were subsequently discussed and agreed upon that the IAP/JPS meeting. RESULTS: From a total of 1098 studies identified through the initial search, 41 studies were included in the review and informed the recommendations. No studies providing level one data were identified in this systematic review, all studies included were cohort or case-control studies. CONCLUSIONS: There is a lack of level 1 data addressing the issue of surveillance of patients following partial pancreatectomy for non-invasive IPMN. The definition of remnant pancreatic lesion in this setting is largely heterogeneous across all studies evaluated. Herein we propose an inclusive definition of remnant pancreatic lesions to guide future prospective efforts for reporting the natural history and long-term outcomes of these patients.
Assuntos
Carcinoma Ductal Pancreático , Neoplasias Císticas, Mucinosas e Serosas , Neoplasias Intraductais Pancreáticas , Neoplasias Pancreáticas , Humanos , Carcinoma Ductal Pancreático/patologia , Neoplasias Intraductais Pancreáticas/cirurgia , Neoplasias Intraductais Pancreáticas/patologia , Neoplasias Pancreáticas/patologia , Pancreatectomia/efeitos adversos , Estudos Retrospectivos , Neoplasias Císticas, Mucinosas e Serosas/cirurgiaRESUMO
PURPOSE: The current study summarized the clinical course and treatment outcomes of intestinal cancer in CD seen in our department and explored the steps to take in the future. METHODS: Subjects were patients who had been diagnosed with CD at our hospital and who underwent surgery in our department from 1985 to 2020. RESULTS: Thirty-one patients had CD and intestinal cancer, including 6 with cancer of the small intestine and 25 with cancer of the large intestine. In all six patients with cancer of the small intestine, the site where cancer or a tumor developed was at or near the site of the anastomosis made at a previous surgery. Of the 25 patients with cancer of the large intestine, 22 developed cancer in the rectum or anal region. CONCLUSION: Many of the patients with cancer of the small intestine had previously undergone surgery, and the cancer developed at or near the site of the anastomosis. In patients who have previously undergone resection of the small intestine, the small intestine needs to be examined regularly. Cancer of the large intestine often developed in the rectum or anal region of our patients, so a detailed examination of the same site needs to be performed.
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Neoplasias do Colo , Neoplasias Colorretais , Doença de Crohn , Cirurgiões , Humanos , Doença de Crohn/complicações , Doença de Crohn/cirurgia , Recidiva Local de Neoplasia , Reto/cirurgia , Neoplasias Colorretais/cirurgiaRESUMO
Gene variants that encode pancreatic enzymes with impaired secretion can induce pancreatic acinar endoplasmic reticulum (ER) stress, cellular injury and pancreatitis. The role of such variants in pancreatic cancer risk has received little attention. We compared the prevalence of ER stress-inducing variants in CPA1 and CPB1 in patients with pancreatic ductal adenocarcinoma (PDAC cases), enrolled in the National Familial Pancreas Tumor Registry, to their prevalence in noncancer controls in the Genome Aggregation Database (gnomAD). Variants of unknown significance were expressed and variants with reduced secretion assessed for ER stress induction. In vitro assessments were compared with software predictions of variant function. Protein variant software was used to assess variants found in only one gnomAD control ("n-of-one" variants). A meta-analysis of prior PDAC case/control studies was also performed. Of the 1385 patients with PDAC, 0.65% were found to harbor an ER stress-inducing variant in CPA1 or CPB1, compared to 0.17% of the 64 026 controls (odds ratio [OR]: 3.80 [1.92-7.51], P = .0001). ER stress-inducing variants in the CPA1 gene were identified in 4 of 1385 PDAC cases vs 77 of 64 026 gnomAD controls (OR: 2.4 [0.88-6.58], P = .087), and variants in CPB1 were detected in 5 of 1385 cases vs 33 of 64 026 controls (OR: 7.02 [2.74-18.01], P = .0001). Meta-analysis demonstrated strong associations for pancreatic cancer and ER-stress inducing variants for both CPA1 (OR: 3.65 [1.58-8.39], P < .023) and CPB1 (OR: 9.51 [3.46-26.15], P < .001). Rare variants in CPB1 and CPA1 that induce ER stress are associated with increased odds of developing pancreatic cancer.
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Carboxipeptidase B/genética , Carboxipeptidases A/genética , Carcinoma Ductal Pancreático/etiologia , Estresse do Retículo Endoplasmático/fisiologia , Neoplasias Pancreáticas/etiologia , Carboxipeptidase B/fisiologia , Carboxipeptidases A/fisiologia , Carcinoma Ductal Pancreático/genética , Estudos de Casos e Controles , Predisposição Genética para Doença , Variação Genética , Humanos , Neoplasias Pancreáticas/genética , RiscoRESUMO
BACKGROUND: Endoplasmic reticulum (ER) stress-inducing variants in several pancreatic secretory enzymes have been associated with pancreatic disease. Multiple variants in CEL, encoding carboxyl ester lipase, are known to cause maturity-onset diabetes of the young (MODY8) but have not been implicated in pancreatic cancer risk. METHODS: The prevalence of ER stress-inducing variants in the CEL gene was compared among pancreatic cancer cases vs. controls. Variants were identified by next-generation sequencing and confirmed by Sanger sequencing. Variants of uncertain significance (VUS) were assessed for their effect on the secretion of CEL protein and variants with reduced protein secretion were evaluated to determine if they induced endoplasmic reticulum stress. RESULTS: ER stress-inducing CEL variants were found in 34 of 986 cases with sporadic pancreatic ductal adenocarcinoma, and 21 of 1045 controls (P = 0.055). Most of the variants were either the CEL-HYB1 variant, the I488T variant, or the combined CEL-HYB1/I488T variant; one case had a MODY8 variant. CONCLUSION: This case/control analysis finds ER stress-inducing CEL variants are not associated with an increased likelihood of having pancreatic cancer.
Assuntos
Carboxilesterase , Neoplasias Pancreáticas , Humanos , Carboxilesterase/genética , Carboxilesterase/metabolismo , Ésteres , Lipase/genética , Lipase/metabolismo , Pâncreas/metabolismo , Hormônios Pancreáticos , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/genética , Estresse do Retículo Endoplasmático , Neoplasias PancreáticasRESUMO
An 83-year-old woman underwent laparoscopic distal gastrectomy and Billroth â ¡ reconstruction for gastric cancer. Since histopathological examination revealed that the lesion was Stage â ¢A, she had started taking S-1 as an adjuvant chemotherapy 7 weeks after gastrectomy. Seventeen days later after taking S-1 administration, she felt nauseous and self-interrupted. Nineteen days later, she was urgently hospitalized. Esophagogastroduodenoscopy(EGD)showed anastomotic lumen was open, but reconstructed small intestine mucosal damage was found, and reconstructed small intestine muscle layer was fused to anastomotic region. On 50th day of hospitalization, mucosa was regenerated and endoscopic balloon dilatation (EBD)was performed from 78th day. She was discharged on 151th day of hospitalization after 7 times of EBD. One year later, she does not need EBD and can be taken orally and has no recurrence.
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Laparoscopia , Neoplasias Gástricas , Idoso de 80 Anos ou mais , Constrição Patológica , Feminino , Gastrectomia/efeitos adversos , Gastroenterostomia , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgiaRESUMO
We previously reported that protein tyrosine phosphatase non-receptor type 3 (PTPN3), which is upregulated in activated lymphocytes, acts as an immune checkpoint. However, the mechanism by which PTPN3 expression is enhanced in activated lymphocytes is unknown. In this study, we analyzed the mechanism of PTPN3 expression in activated lymphocytes with a view for developing a novel immune checkpoint inhibitor that suppresses PTPN3. Through the activation process, lymphocytes showed enhanced NFκB activation as well as increased PTPN3 expression. NFκB enhanced proliferation, migration, and cytotoxicity of lymphocytes. Furthermore, NFκB enhanced PTPN3 expression and tyrosine kinase activation. TGFß reduced PTPN3 expression and NFκB activation in the cancer microenvironment, and suppressed the biological activity of lymphocytes. The results of this study are expected to provide significant implications for improving existing immunotherapy and developing novel immunotherapy.
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NF-kappa B/metabolismo , Proteína Tirosina Fosfatase não Receptora Tipo 3/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Humanos , Ativação Linfocitária/imunologia , Linfócitos/metabolismo , NF-kappa B/fisiologia , Fosforilação/imunologia , Proteína Tirosina Fosfatase não Receptora Tipo 3/genética , Transdução de Sinais/imunologia , Fator de Crescimento Transformador beta/fisiologiaRESUMO
It has been shown that protein tyrosine phosphatase non-receptor type (PTPN) 3 inhibits T-cell activation. However, there is no definitive conclusion about how the inhibition of PTPN3 in lymphocytes affects immune functions in human lymphocytes. In the present study, we showed that PTPN3 inhibition significantly contributes to the enhanced activation of activated human lymphocytes. The PTPN3 expression of lymphocytes was significantly increased through the activation process using IL-2 and anti-CD3 mAb. Interestingly, inhibiting the PTPN3 expression in activated lymphocytes significantly augmented the proliferation, migration, and cytotoxicity through the phosphorylation of zeta-chain-associated protein kinase 70 (ZAP-70), lymphocyte-specific protein tyrosine kinase (LCK), and extracellular signal-regulated kinases (ERK). Lymphocyte activation by PTPN3 inhibition was observed only in activated CD3+ T cells and not in NK cells or resting T cells. In therapy experiments using autologous tumors and lymphocytes, PTPN3 inhibition significantly augmented the number of tumor-infiltrated lymphocytes and the cytotoxicity of activated lymphocytes. Our results strongly imply that PTPN3 acts as an immune checkpoint in activated lymphocytes and that PTPN3 inhibitor may be a new non-antibody-type immune checkpoint inhibitor for cancer therapy.
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Pontos de Checagem do Ciclo Celular , Ativação Linfocitária , Neoplasias Ovarianas/prevenção & controle , Proteína Tirosina Fosfatase não Receptora Tipo 3/antagonistas & inibidores , Linfócitos T/imunologia , Animais , Apoptose , Movimento Celular , Proliferação de Células , Feminino , Humanos , Proteína Tirosina Quinase p56(lck) Linfócito-Específica/metabolismo , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Fosforilação , Receptores de Antígenos de Linfócitos T/metabolismo , Transdução de Sinais , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto , Proteína-Tirosina Quinase ZAP-70/metabolismoRESUMO
BACKGROUND: The effects of subcutaneous closed-suction Blake drain for preventing incisional surgical site infections (SSIs) after colorectal surgery have never been evaluated in a randomized controlled trial (RCT). Thus, we performed a RCT to evaluate the clinical benefits of using a subcutaneous closed-suction Blake drain in patients undergoing colorectal surgery. METHOD: Consecutive patients who underwent colorectal surgery were enrolled in this study. Patients were randomly assigned to the subcutaneous closed-suction drainage arm or the control (no subcutaneous drainage) arm. The primary endpoint was incidence rate of incisional SSIs. And, we performed logistic regression analysis to detect predictive factors for incisional SSIs after colorectal surgery. RESULTS: From November 2012 to September 2014, a total of 240 patients were enrolled in this study. One-hundred-seventeen patients who were treated by the control arm and 112 patients by the subcutaneous drainage arm were judged to be eligible for analysis. The incidence of incisional SSIs rate was 8.7 % in the overall patients. The incidence of incisional SSIs rate was 12.8 % in the control arm and 4.5 % in the subcutaneous drainage arm. There was significantly reduction of the incidence in the subcutaneous drainage arm than in the control arm (p = 0.025). Logistic regression analysis demonstrated that thickness of subcutaneous fat >3.0 cm, forced expiratory volume in 1 s as percent of forced vital capacity (FEV1.0 %) >70 %, and subcutaneous drain were independent predictors of postoperative incisional SSIs (p = 0.008, p = 0.004, and p = 0.017, respectively). CONCLUSION: The results of our RCT suggest that a subcutaneous Blake drain is beneficial for preventing incisional SSIs in patients undergoing colorectal surgery.
Assuntos
Cirurgia Colorretal/efeitos adversos , Tela Subcutânea/patologia , Infecção da Ferida Cirúrgica/etiologia , Infecção da Ferida Cirúrgica/prevenção & controle , Idoso , Feminino , Humanos , Incidência , Masculino , Prognóstico , Sucção , Infecção da Ferida Cirúrgica/epidemiologia , Resultado do TratamentoRESUMO
We investigated whether hypoxia-induced activation of Hh signaling contributes to PDL-1 expression in cancer and whether it affects the anti-tumor function of activated lymphocytes. Hypoxia augmented PDL-1 expression and inhibition of Hh signaling reduced PDL-1 expression under hypoxia. When activated lymphocytes were cocultured with cancers treated with a Hh inhibitor, activated lymphocyte cell numbers increased under hypoxia. In contrast, this increase was abrogated when cancer cells were treated with a PDL-1 neutralizing antibody. These results suggest that Hh signaling is one of regulatory pathways of PDL-1 expression under hypoxia and that inhibiting Hh signaling may induce lymphocyte anti-tumor activity.
Assuntos
Antígeno B7-H1/metabolismo , Proteínas Hedgehog/antagonistas & inibidores , Hipóxia/imunologia , Linfócitos/imunologia , Neoplasias/imunologia , Antígenos de Neoplasias/imunologia , Antígeno B7-H1/genética , Linhagem Celular Tumoral , Técnicas de Cocultura , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Hipóxia/terapia , Ativação Linfocitária , Terapia de Alvo Molecular , Neoplasias/terapia , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , RNA Interferente Pequeno/genética , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Receptor Smoothened/genética , Receptor Smoothened/metabolismo , Transativadores , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Alcaloides de Veratrum/farmacologia , Proteína GLI1 em Dedos de Zinco/genética , Proteína GLI1 em Dedos de Zinco/metabolismoRESUMO
Nonocclusive mesenteric ischemia (NOMI) is a life-threatening disorder. Early diagnosis is challenging because NOMI lacks specific symptoms. A 52-year-old man who received extended cholecystectomy with Roux-en-Y hepaticojejunostomy for gallbladder cancer (GBC) presented to our hospital with nausea and vomiting. Neither tender nor peritoneal irritation sign was present on abdominal examination. Blood test exhibited marked leukocytosis (WBC:19,800/mm3). A contrast-enhanced abdominal computed tomography (CT) scan revealed remarkable wall thickening and lower contrast enhancement effect localized to Roux limb. On hospital day 2, abdominal arterial angiography revealed angio-spasm at marginal artery and arterial recta between 2nd jejunal artery and 3rd jejunal artery, leading us to the diagnosis of NOMI. We then administered continuous catheter-directed infusion of papaverine hydrochloride until hospital day 7. Furthermore, the patient was anticoagulated with intravenous unfractionated heparin and antithrombin agents for increasing D-dimer level and decreasing antithrombin III level. On hospital day 8, diluted oral nutrition diet was initiated and gradually advanced as tolerated. On hospital day 21, the patient was confirmed of improved laboratory test data and discharged with eating a regular diet. We experienced a rare case of NOMI on Roux limb after 2 years of extended cholecystectomy with hepaticojejunostomy for GBC, promptly diagnosed and successfully treated by interventional radiology (IVR).
Assuntos
Anastomose em-Y de Roux , Isquemia Mesentérica , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Mesentérica/diagnóstico por imagem , Isquemia Mesentérica/etiologia , Isquemia Mesentérica/cirurgia , Isquemia Mesentérica/terapia , Neoplasias da Vesícula Biliar/diagnóstico por imagem , Neoplasias da Vesícula Biliar/cirurgia , Neoplasias da Vesícula Biliar/complicações , Colecistectomia , Tomografia Computadorizada por Raios X , Complicações Pós-Operatórias/terapia , Complicações Pós-Operatórias/cirurgia , Complicações Pós-Operatórias/diagnóstico por imagem , Radiologia Intervencionista/métodos , JejunostomiaRESUMO
BACKGROUND/AIM: Self-expandable metallic stent (SEMS) placement is becoming the standard bridge-to-surgery (BTS) strategy for potentially curable left-sided obstructive colorectal cancer (OCRC). The study objective was to evaluate the effectiveness of SEMS placement as a BTS strategy for both right- and left-sided OCRC. PATIENTS AND METHODS: We retrospectively compared the short- and long-term outcomes of patients with OCRC who underwent placement of a SEMS versus a trans-nasal/anal decompression tube (DCT). The cohort comprised 57 patients with stage II/III right-sided OCRC (DCT, n=20; SEMS, n=8) or left-sided OCRC (DCT, n=9; SEMS, n=20). The short-term outcomes were the incidence of postoperative complications, rate of laparoscopic surgery, rate of stoma construction, and postoperative hospital stay; long-term outcomes were the 3-year overall survival (OS) and relapse-free survival (RFS). RESULTS: The SEMS group had a higher rate of laparoscopic surgery (85.7% vs. 6.9%, p<0.001), lower rate of stoma construction (10.7% vs. 34.5%, p=0.03), and shorter postoperative hospital stay (14 vs. 17 days, p=0.04) than the DCT group. Both groups had a similar incidence of postoperative complications. The 3-year OS and RFS were also similar in the DCT and SEMS groups for both right-sided OCRC (OS, 75.0% vs. 87.5%, HR=1.51, 95% CI=0.22-10.25, p=0.7; RFS, 65.0% vs. 50.0%, HR=0.97, 95% CI=0.28-3.36, p=0.9) and left-sided OCRC (OS, 88.8% vs. 90.0%, HR=1.19, 95% CI=0.10-14.29, p=0.9; RFS, 77.8% vs. 85.0%, HR=1.03, 95% CI=0.16-6.5, p=0.9). CONCLUSION: SEMS placement is a reasonable BTS strategy for left- and right-sided OCRC that achieves comparable short- and long-term outcomes to DCT insertion.
Assuntos
Neoplasias Colorretais , Obstrução Intestinal , Stents Metálicos Autoexpansíveis , Humanos , Masculino , Feminino , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/complicações , Neoplasias Colorretais/patologia , Stents Metálicos Autoexpansíveis/efeitos adversos , Idoso , Pessoa de Meia-Idade , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Complicações Pós-Operatórias/etiologia , Idoso de 80 Anos ou mais , Descompressão Cirúrgica/métodos , LaparoscopiaRESUMO
We report a case of consciousness disorder following the fourth course of chemotherapy with cisplatin (CDDP) and 5- fluorouracil (5-FU) in a patient with esophageal cancer. A 74-year-old man was admitted to our hospital to receive chemotherapy for esophageal cancer. Six days after chemotherapy, the patient showed impaired consciousness and his serum sodium concentration was found to be 125 mEq/L, but no edema or dehydration was noted. This hyponatremic state was diagnosed as CDDP-induced syndrome of inappropriate secretion of antidiuretic hormone (SIADH) on the basis of serum and urine hypo-osmolality. Accordingly, fluid intake was restricted and sodium supplements were administered, resulting in an appropriate increase in the serum sodium concentration to 132 mEq/L in 4 days.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Transtornos da Consciência/etiologia , Neoplasias Esofágicas/tratamento farmacológico , Síndrome de Secreção Inadequada de HAD/induzido quimicamente , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Transtornos da Consciência/tratamento farmacológico , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Síndrome de Secreção Inadequada de HAD/diagnóstico , Síndrome de Secreção Inadequada de HAD/tratamento farmacológico , Masculino , Sódio/uso terapêuticoRESUMO
In our comprehensive analysis of pancreatic cancer pathology, we found that the C4orf47 molecule was upregulated in hypoxic environments. C4orf47 is reported to be a centrosome-associated protein, but its biological significance in cancer is completely unknown; therefore, we assessed its role in pancreatic cancer. We found that C4orf47 was a direct target of HIF-1α and is upregulated in hypoxic conditions, in which it suppressed the cell cycle and inhibits cell proliferation through up-regulation of the cell cycle repressors Fbxw-7, P27, and p57; and the down-regulation of the cell cycle promoters c-myc, cyclinD1, and cyclinC. Furthermore, C4orf47 induced epithelial-mesenchymal transition and enhanced their cell plasticity and invasiveness. In addition, the p-Erk/p-p38 ratio was significantly enhanced and down-regulated CD44 expression by C4orf47 suppression, suggesting that C4orf47 is involved in pancreatic cancer dormancy under hypoxic conditions. Furthermore, the potential of C4orf47 expression was a good prognostic biomarker for pancreatic cancer. These results contribute to the elucidation of the pathology of refractory pancreatic cancer and the development of novel therapeutic strategies.
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A 77-year-old woman who had undergone laparoscopic pylorus-preserving gastrectomy for gastric cancer showed dilatation of the main pancreatic duct in the distal pancreas on ultrasonography during postoperative surveillance. Detailed examination revealed that she had a main-duct type intraductal papillary mucinous neoplasm with high-risk stigmata. As invasive malignancy was not suggested, laparoscopic splenic vessel-preserving distal pancreatectomy was performed to preserve the remnant stomach. Although adhesions around the gastroduodenostomy and splenic artery were severe, the magnified laparoscopic view facilitated the identification of appropriate dissection layers, resulting in limited blood loss. The distal pancreas was successfully resected without sacrificing blood flow to the remnant stomach. The postoperative course was uneventful. The pathological diagnosis was low-grade intraductal papillary mucinous neoplasm. Laparoscopic splenic vessel-preserving distal pancreatectomy for benign or low-grade malignant disease of the distal pancreas can be useful for preserving the remnant stomach in patients with a history of gastrectomy.
Assuntos
Laparoscopia , Neoplasias Pancreáticas , Idoso , Feminino , Gastrectomia , Humanos , Laparoscopia/métodos , Pancreatectomia/métodos , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/cirurgia , Piloro/cirurgia , Artéria Esplênica/patologiaRESUMO
INTRODUCTION AND IMPORTANCE: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is often found incidentally during examination for other diseases. In addition to the risk of malignant transformation, patients with IPMN are at risk of developing pancreatic cancer. We report a case of pancreatic tail cancer that developed separately from a preexisting IPMN after minimally invasive esophagectomy for cancer of the esophagogastric junction and was resected successfully by laparoscopic distal pancreatectomy. CASE PRESENTATION: A 72-year-old man underwent thoracoscopic and laparoscopic esophagectomy for esophagogastric junction cancer. He had undergone surgery for ascending colon cancer 20 years ago. At that time, IPMN was confirmed in the pancreatic body by a preoperative examination. Computed tomography was regularly performed for postoperative work-up and follow-up of the IPMN, and a solid lesion with cystic components was detected in the pancreatic tail 9 months after the operation. On detailed examination, pancreatic ductal adenocarcinoma concomitant with IPMN, accompanied by a retention cyst, was considered. Laparoscopic distal pancreatectomy was successfully performed after neoadjuvant chemotherapy. Pathological diagnosis of the lesion in the pancreatic tail was of an invasive intraductal papillary mucinous carcinoma (ypT3ypN0yM0 ypStageIIA). CLINICAL DISCUSSION: If an IPMN is detected during preoperative examination for malignancies of other organs, careful follow-up is necessary due to the high risk of pancreatic cancer development. Furthermore, initial operation with minimally invasive surgery may reduce adhesion and facilitate subsequent surgeries. CONCLUSION: We have provided evidence that supports the importance of a careful follow-up of IPMNs, even if they are low risk.
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BACKGROUND: Primary gastric synovial sarcoma is extremely rare, only 44 cases have been reported so far, and there have been no reports of laparoscopic endoscopic cooperative surgery for this condition. CASE PRESENTATION: A 45-year-old male patient presented with gastric pain. Esophagogastroduodenoscopy was performed that led to the identification of an 8-mm submucosal tumor in the anterior wall of the antrum, and a kit-negative gastrointestinal stromal tumor was suspected following biopsy. On endoscopic ultrasonography, the boundary of the tumor, mainly composed of the second layer, was depicted as a slightly unclear low-echo region, and a pointless no echo region was scattered inside. A boring biopsy revealed synovial sarcoma. Positron emission tomography did not reveal fluorodeoxyglucose (18F-FDG) accumulation in the stomach or other organs. Thus, the patient was diagnosed with a primary gastric synovial sarcoma, and laparoscopic endoscopic cooperative surgery was performed. The tumor of the antrum could not be confirmed laparoscopically from the serosa, and under intraoperative endoscopy, it had delle on the mucosal surface, which was removed by a method that does not involve releasing the gastric wall. Immunohistochemistry showed that the spindle cells were positive for EMA, BCL-2 protein, TLE-1, and SS18-SSX fusion-specific antibodies but negative for KIT and DOG-1. The final pathological diagnosis was synovial sarcoma of the stomach. The postoperative course was good, and the patient was discharged from the hospital on the 11th postoperative day. CONCLUSION: Resection with laparoscopic endoscopic cooperative surgery (LECS), which has not been reported before, was effective for small synovial sarcomas that could not be confirmed laparoscopically. With the combination of laparoscopic and endoscopic approaches to neoplasia with a non-exposure technique (CLEAN-NET) procedure, it was possible to excise the tumor with the minimum excision range of the gastric serosa without opening the stomach.
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Hypoxia is a characteristic feature of the tumor microenvironment in pancreatic ductal adenocarcinoma (PDAC). We have recently explored new targeting molecules and pathways in PDAC cells under hypoxic conditions. In this study, we performed a microarray experiment to analyze the genes up-regulated in PDAC cell lines under hypoxia compared to normoxia, and identified human family with sequence similarity 115, member C (FAM115C) as a candidate gene for further study. Our data showed that FAM115C was overexpressed in PDAC cell lines under hypoxia, and FAM115C inhibition promoted PDAC cell migration and invasion in vitro. FAM115C inhibition did not affect tumor cell proliferation in PDAC. Immunohistochemically, FAM115C expression was observed ubiquitously in normal pancreas, pancreatic intraepithelial neoplasia (PanIN) and PDAC tissue, and it was located mainly in the nucleus but also in the cytoplasm of cells. In qPCR analysis, high expression of FAM115C was correlated with better prognosis in patients with PDAC. Our findings suggest that FAM115C could be a novel tumor suppressor associated with prolonged survival in patients with PDAC.
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Pancreatic ductal adenocarcinoma (PDAC) is resistant to immunotherapy. As a factor of resistance, the dense fibrosis of this cancer acts as a barrier to inhibit immune cell infiltration into a tumor. We examined the influence of a Hedgehog signal inhibitor, Patched 1-interacting peptide, on fibrosis, infiltration of immune cells, and immunotherapeutic effects on PDAC. We found that this peptide inhibited proliferation and migration of cancer-associated fibroblasts and cancer cells. Furthermore, this peptide reduced the production of extracellular matrix and transforming growth factor ß1 in cancer-associated fibroblasts and induced expression of HLA-ABC in PDAC cells and interferon-γ in lymphocytes. In vivo, the peptide suppressed fibrosis of PDAC and increased immune cell infiltration into tumors. The combination of this peptide and an anti-programmed death-1 antibody augmented the antitumor effect, and this combination showed the same effect in experiments using cancer cells and autologous lymphocytes. These results indicate that, in addition to the direct effect of tumor suppression, the Patched 1-interacting peptide increases the infiltration of immune cells by reducing fibrosis of PDAC and consequently enhances the effect of immunotherapy. Therefore, treatment with this peptide may be a novel therapy with 2 different mechanisms: direct tumor suppression and enhancing the immune response against PDAC.
Assuntos
Neoplasias Pancreáticas/etiologia , Neoplasias Pancreáticas/patologia , Receptor Patched-1/metabolismo , Peptídeos/metabolismo , Domínios e Motivos de Interação entre Proteínas , Animais , Antineoplásicos Imunológicos/farmacologia , Carcinoma Ductal Pancreático/etiologia , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/terapia , Comunicação Celular , Linhagem Celular Tumoral , Modelos Animais de Doenças , Suscetibilidade a Doenças , Fibrose , Humanos , Imunoterapia , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/genética , Ativação Linfocitária/imunologia , Linfócitos/efeitos dos fármacos , Linfócitos/imunologia , Linfócitos/metabolismo , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Linfócitos do Interstício Tumoral/patologia , Camundongos , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/terapia , Receptor Patched-1/química , Receptor Patched-1/genética , Peptídeos/farmacologia , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
We previously reported that brain-derived neurotrophic factor (BDNF)/neurotrophic receptor tyrosine kinase 2 (NTRK2/TRKB) signaling contributes to induction of malignant phenotype of gallbladder cancer (GBC). Recently, pan-TRK inhibitors have been evaluated and their dramatic clinical activity is being shown for a variety of cancer types harboring an NTRK rearrangement in phase I trials. ONO-7579 is an oral pan-TRK inhibitor currently under investigation in phase I/II clinical trial for TRK-rearranged solid tumors. In this study, we evaluated the anticancer effect of ONO-7579 using GBC cells with or without KRAS mutant, NOZ, TYGBK-1. Our study showed that ONO-7579 had a suppressive effect on GBC proliferation in TYGBK-1, and on invasive potential and vascular endothelial growth factor expression in TYGBK-1 and NOZ. Our data indicated that ONO-7579 could be a promising treatment option for patients with GBC.
Assuntos
Neoplasias da Vesícula Biliar/tratamento farmacológico , Glicoproteínas de Membrana/antagonistas & inibidores , Compostos Orgânicos/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Receptor trkB/antagonistas & inibidores , Fator Neurotrófico Derivado do Encéfalo/antagonistas & inibidores , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Neoplasias da Vesícula Biliar/enzimologia , Neoplasias da Vesícula Biliar/metabolismo , Neoplasias da Vesícula Biliar/patologia , Humanos , Glicoproteínas de Membrana/biossíntese , Invasividade Neoplásica , Compostos Orgânicos/química , Receptor trkB/biossíntese , Fator A de Crescimento do Endotélio Vascular/biossínteseRESUMO
BACKGROUND/AIM: Metronidazole (MNZ) is a common antibiotic that exerts disulfiram-like effects when taken together with alcohol. However, the relationship between MNZ and aldehyde dehydrogenase (ALDH) activity remains unclear. This study investigated whether MNZ reduces cancer stemness by suppressing ALDH activity and accordingly reducing the malignancy of cholangiocarcinoma (CCA). MATERIALS AND METHODS: We developed gemcitabine (GEM)-resistant TFK-1 cells and originally established CCA cell line from a patient with GEM-resistant CCA. Using these cell lines, we analyzed the impacts of MNZ for cancer stem cell markers, invasiveness, and chemosensitivity. RESULTS: MNZ reduced ALDH activity in GEM-resistant CCA cells, leading to decreased invasiveness and enhanced chemosensitivity. MNZ diminished the invasiveness by inducing mesenchymal-epithelial transition and enhancing chemosensitivity by increasing ENT1 (equilibrative nucleoside transporter 1) and reducing RRM1 (ribonucleotide reductase M1). CONCLUSION: MNZ reduced cancer stemness in GEM-resistant CCA cells. Combined GEM and MNZ would be a promising therapeutic strategy for cancer stem-like CAA.