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OBJECTIVE: To determine the interobserver variability for complications of pancreatoduodenectomy as defined by the International Study Group for Pancreatic Surgery (ISGPS) and others. SUMMARY BACKGROUND DATA: Good interobserver variability for the definitions of surgical complications is of major importance in comparing surgical outcomes between and within centers. However, data on interobserver variability for pancreatoduodenectomy-specific complications are lacking. METHODS: International cross-sectional multicenter study including 52 raters from 13 high-volume pancreatic centers in 8 countries on 3 continents. Per center, 4 experienced raters scored 30 randomly selected patients after pancreatoduodenectomy. In addition, all raters scored six standardized case vignettes. This variability and the 'within centers' variability were calculated for twofold scoring (no complication/grade A vs grade B/C) and threefold scoring (no complication/grade A vs grade B vs grade C) of postoperative pancreatic fistula (POPF), post-pancreatoduodenectomy hemorrhage (PPH), chyle leak (CL), bile leak (BL), and delayed gastric emptying (DGE). Interobserver variability is presented with Gwet's AC-1 measure for agreement. RESULTS: Overall, 390 patients after pancreatoduodenectomy were included. The overall agreement rate for the standardized cases vignettes for twofold scoring was 68% (95%-CI: 55%-81%, AC1 score: moderate agreement) and for threefold scoring 55% (49%-62%, AC1 score: fair agreement). The mean 'within centers' agreement for twofold scoring was 84% (80%-87%, AC1 score; substantial agreement). CONCLUSION: The interobserver variability for the ISGPS defined complications of pancreatoduodenectomy was too high even though the 'within centers' agreement was acceptable. Since these findings will decrease the quality and validity of clinical studies, ISGPS has started efforts aimed at reducing the interobserver variability.
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The objective of this study was to establish an evaluation technique for the feline pelvic cavity using computed tomography (CT). Client-owned cats with a normal pelvis (n = 50) or pelvic stenosis (n = 3) were included. We categorized pelvic CT images in the normal pelvis group into two types according to pelvic cavity shape, then calculated the sacral index (SI), pelvic canal area (PCA), and PCA/sacral width index (PSI). The reference intervals of these variables were determined based on the results in the normal pelvis group. In the normal pelvis group, the PSI, unlike the SI and PCA, was not affected by body weight. In addition to high intraobserver and interobserver reproducibilities, the PSI showed no significant differences according to pelvic cavity shape. However, the SI exhibited significant differences among pelvic cavity shapes. In the stenosis group, the postoperative PSI in all cats was within the reference interval. However, the postoperative SI in one case was lower than the reference interval. The PSI may become a new method for evaluation of the pelvic cavity, including the pelvic floor.
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In 2023, the Japan Pancreas Society (JPS) published the new eighth edition of the Japanese classification of pancreatic carcinoma. We present here an excerpted version in English, based on the latest edition. The major changes in this revision are as follows: In the eighth edition of the Union for International Cancer Control (UICC), the T category was changed to be based on tumor size; however, the eighth edition of the Japanese classification retains the previous T category based on local invasion factors. Lymph nodes have been renamed, and regional lymph nodes have been defined by location. Peritoneal cytology, which was not previously included in distant metastasis (M), has now been included in the M category. Moreover, significant additions have been made regarding the pathological diagnosis of endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) and criteria for histological assessment of the effects after chemotherapy and radiation therapy. Although this classification is aimed at carcinoma originating in the pancreas, not in the bile duct or duodenum, if the differentiation of the primary organ is difficult, this classification should be applied. It is also desirable to describe tumors other than carcinoma and metastatic tumors to the pancreas in accordance with this classification.
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An association between periodontal disease and the development of pancreatic cancer has been pointed out since before. Advances in genome analysis technology have revealed that a pancreatic cancer-specific microbiome is formed in the intestines and tumors of pancreatic cancer patients and modifies the progression of pancreatic cancer. Disturbance of microbiome( dysbiosis)suppresses anti-tumor immunity against pancreatic cancer, promoting cancer progression. Therefore, attempts are being made to correct dysbiosis by administration of probiotics or transplantation of microbiome, which is especially activating immune checkpoint inhibitors against cancer. In addition, specific intratumor bacteria has been identified that create an immunosuppressive microenvironment through crosstalk with pancreatic cancer cells. In the future, analysis of the microbiome distribution in pancreatic cancers may determine the following treatment strategy as an individualized treatment. We hope that innovations in omics technology will reveal more detailed functions of microbiome and lead to the development of effective treatments for pancreatic cancer.
Subject(s)
Microbiota , Pancreatic Neoplasms , Humans , Pancreatic Neoplasms/microbiology , Pancreatic Neoplasms/therapy , Pancreatic Neoplasms/immunology , Dysbiosis/microbiology , Dysbiosis/immunology , Dysbiosis/therapy , Tumor MicroenvironmentABSTRACT
Background: Distal pancreatectomy (DP) with lymph node (LN) dissection is the standard procedure for pancreatic ductal adenocarcinoma of the tail (Pt-PDAC). However, the optimal surgery including extent of LN dissection is still being debated. The present study investigated the incidence and prognostic impact of LN metastasis on patients suffering from Pt-PDAC. Patients and method: This multicenter, retrospective study involved 163 patients who underwent DP for resectable Pt-PDAC at 12 institutions between 2013 and 2017. The frequency of LN metastasis and the effect of LN dissection on Pt-PDAC prognosis were investigated. Results: There were high incidences of metastases to the LNs along the splenic artery in the patients with Pt-PDAC (39%). The rate of metastases in the LNs along the common hepatic, left gastric, and celiac arteries were low, and the therapeutic index for these LNs was zero. In pancreatic tail cancer located more distally, there were no metastases to the LNs along the common hepatic artery. Multivariate analysis revealed that tumor size was the only independent factor related to recurrence-free survival (HR = 2.01, 95% CI = 1.33-3.05, p = 0.001). The level of pancreas division and LN dissection along the common hepatic artery did not affect the site of tumor recurrence or recurrence-free survival. Conclusions: LN dissection along the hepatic artery for Pt-PDAC has little significance. Distal pancreatic transection may be acceptable in terms of oncological safety, but further examination of short-term outcomes and preservation of pancreatic function is required.
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PURPOSE: To establish if osteosarcopenia is related to postoperative complications, prognosis, and recurrence of colorectal cancer (CRC) after curative surgery. METHODS: The clinical data of 594 patients who underwent curative resection for CRC between January, 2013 and December, 2018 were analyzed retrospectively to examine the relationship between clinicopathological data and osteosarcopenia. The following definitions were used: sarcopenia, low skeletal muscle mass index; osteopenia, low bone mineral density on computed tomography at the level of the 11th thoracic vertebra; and osteosarcopenia, sarcopenia with osteopenia. RESULTS: Osteosarcopenia was identified in 98 patients (16.5%) and found to be a significant risk factor for postoperative complications (odds ratio 2.53; p = 0.011). The 5-year overall survival (OS) and recurrence-free survival (RFS) rates of the patients with osteosarcopenia were significantly lower than those of the patients without osteosarcopenia (OS: 72.5% and 93.9%, respectively, p < 0.0001; RFS: 70.8% and 92.4%, respectively, p < 0.0001). Multivariate analysis identified osteosarcopenia as an independent prognostic factor associated with OS (hazard ratio 3.31; p < 0.0001) and RFS (hazard ratio 3.67; p < 0.0001). CONCLUSION: Osteosarcopenia may serve as a predictor of postoperative complications and prognosis after curative surgery for CRC.
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This study aimed to confirm urinary protein fragments in relation to the presence of pancreatic ductal adenocarcinoma (PDAC) via a C-terminal proteomics strategy using exploratory and validation cohorts. Urinary fragments were examined by iTRAQ-labelling of tryptic peptides and concentrations of C-terminal fragments were evaluated. Only the urinary CD276 fragment showed a fold change (FC) of > 1.5 with a significant difference of P < 0.01 between healthy (H) and PDAC participants in both the exploratory (H, n = 42; PDAC, n = 39) and validation cohorts (H, n = 36; resectable PDAC, n = 28). The sensitivity and specificity of the CD276 fragment for diagnosing resectable PDAC were 75% and 89%, respectively, in the validation cohort. Postoperative urinary levels of the CD276 fragment were low as compared to those before surgery (n = 18, P < 0.01). Comprehensive C-terminus proteomics identified an increase in the urinary CD276 fragment level as a feature of patients with PDAC. The urinary CD276 fragment is a potential biomarker for detecting resectable PDAC.
Subject(s)
B7 Antigens , Biomarkers, Tumor , Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Proteomics , Humans , Pancreatic Neoplasms/urine , Pancreatic Neoplasms/surgery , Pancreatic Neoplasms/diagnosis , Proteomics/methods , Female , Male , Biomarkers, Tumor/urine , Aged , B7 Antigens/urine , B7 Antigens/metabolism , Middle Aged , Carcinoma, Pancreatic Ductal/urine , Carcinoma, Pancreatic Ductal/surgery , Carcinoma, Pancreatic Ductal/diagnosisABSTRACT
Pancreatic acinar cell carcinoma (PACC) is a very rare subtype of pancreatic cancer. Due to small number of patients, no standard chemotherapy protocol has been established. We experienced an extremely rare case of PACC with liver metastasis that showed a pathological complete response after modified FOLFIRINOX (mFFX) therapy. A 42-year-old man who underwent distal pancreatectomy for an 80 mm tumor at the pancreatic tail 3 years ago was referred to our hospital in September 2017 for the treatment of a recurrent liver tumor. Percutaneous biopsy revealed an acinar-neuroendocrine carcinoma, similar to the surgical specimen. He received eight cycles of irinotecan plus cisplatin chemotherapy. However, the tumor increased in size, and treatment was switched to mFFX therapy. The tumor in the liver shrank remarkably after nine cycles of mFFX therapy. Conversion surgery was selected, and the patient underwent hepatic left and caudate lobectomy 8 months after administration of mFFX. The resected specimen showed no viable tumor cells, indicating a pathological complete response. The histological diagnosis was reconsidered, and PACC was finally diagnosed via an additional immunohistological review. The patient has remained well with no recurrence for 6 years after surgery. This study is the first to report a case of pathological complete response with mFFX therapy for the recurrence of PACC.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Carcinoma, Acinar Cell , Fluorouracil , Irinotecan , Leucovorin , Liver Neoplasms , Neoplasm Recurrence, Local , Oxaliplatin , Pancreatic Neoplasms , Humans , Male , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/surgery , Irinotecan/therapeutic use , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Oxaliplatin/therapeutic use , Carcinoma, Acinar Cell/drug therapy , Carcinoma, Acinar Cell/pathology , Carcinoma, Acinar Cell/surgery , Fluorouracil/therapeutic use , Fluorouracil/administration & dosage , Leucovorin/therapeutic use , Liver Neoplasms/drug therapy , Liver Neoplasms/secondary , Liver Neoplasms/pathology , Liver Neoplasms/surgery , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/pathologyABSTRACT
BACKGROUND: Although immune checkpoint blockade (ICB) therapy has proven to be extremely effective at managing certain cancers, its efficacy in treating pancreatic ductal adenocarcinoma (PDAC) has been limited. Therefore, enhancing the effect of ICB could improve the prognosis of PDAC. In this study, we focused on the histamine receptor H1 (HRH1) and investigated its impact on ICB therapy for PDAC. METHODS: We assessed HRH1 expression in pancreatic cancer cell (PCC) specimens from PDAC patients through public data analysis and immunohistochemical (IHC) staining. The impact of HRH1 in PCCs was evaluated using HRH1 antagonists and small hairpin RNA (shRNA). Techniques including Western blot, flow cytometry, quantitative reverse transcription polymerase chain reaction (RT-PCR), and microarray analyses were performed to identify the relationships between HRH1 and major histocompatibility complex class I (MHC-I) expression in cancer cells. We combined HRH1 antagonism or knockdown with anti-programmed death receptor 1 (αPD-1) therapy in orthotopic models, employing IHC, immunofluorescence, and hematoxylin and eosin staining for assessment. RESULTS: HRH1 expression in cancer cells was negatively correlated with HLA-ABC expression, CD8+ T cells, and cytotoxic CD8+ T cells. Our findings indicate that HRH1 blockade upregulates MHC-I expression in PCCs via cholesterol biosynthesis signaling. In the orthotopic model, the combined inhibition of HRH1 and αPD-1 blockade enhanced cytotoxic CD8+ T cell penetration and efficacy, overcoming resistance to ICB therapy. CONCLUSIONS: HRH1 plays an immunosuppressive role in cancer cells. Consequently, HRH1 intervention may be a promising method to amplify the responsiveness of PDAC to immunotherapy.
Subject(s)
Immune Checkpoint Inhibitors , Pancreatic Neoplasms , Humans , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/genetics , Immune Checkpoint Inhibitors/pharmacology , Immune Checkpoint Inhibitors/therapeutic use , Mice , Animals , Receptors, Histamine H1/metabolism , Receptors, Histamine H1/genetics , Histocompatibility Antigens Class I/metabolism , Histocompatibility Antigens Class I/genetics , Cell Line, Tumor , Female , Histamine H1 Antagonists/pharmacology , Histamine H1 Antagonists/therapeutic use , MaleABSTRACT
A 5-year-old intact male mixed-breed cat weighing 4.5 kg was referred to our hospital with a left testicular mass. CT revealed mild heterogeneous contrast enhancement and calcification in the testicular mass. A well-defined, contrast-enhancing, multiloculated mass with fluid-filled areas was extended from the testicular mass in the scrotum to the caudal aspect of the left kidney. The abdominal mass extended to the right crus of the diaphragm, and the gastrointestinal tract was compressed dorsally. Histopathology was consistent with teratoma. Characteristic CT findings in a feline testicular teratoma may include calcification and cystic areas.
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BACKGROUND: Recently, two molecular subtypes of pancreatic ductal adenocarcinoma (PDAC) have been proposed: the "Classical" and "Basal-like" subtypes, with the former showing better clinical outcomes than the latter. However, the "molecular" classification has not been applied in real-world clinical practice. This study aimed to establish patient-derived organoids (PDOs) for PDAC and evaluate their application in subtype classification and clinical outcome prediction. METHODS: We utilized tumor samples acquired through endoscopic ultrasound-guided fine-needle biopsy and established a PDO library for subsequent use in morphological assessments, RNA-seq analyses, and in vitro drug response assays. We also conducted a prospective clinical study to evaluate whether analysis using PDOs can predict treatment response and prognosis. RESULTS: PDOs of PDAC were established at a high efficiency (> 70%) with at least 100,000 live cells. Morphologically, PDOs were classified as gland-like structures (GL type) and densely proliferating inside (DP type) less than 2 weeks after tissue sampling. RNA-seq analysis revealed that the "morphological" subtype (GL vs. DP) corresponded to the "molecular" subtype ("Classical" vs. "Basal-like"). The "morphological" classification predicted the clinical treatment response and prognosis; the median overall survival of patients with GL type was significantly longer than that with DP type (P < 0.005). The GL type showed a better response to gemcitabine than the DP type in vitro, whereas the drug response of the DP type was improved by the combination of ERK inhibitor and chloroquine. CONCLUSIONS: PDAC PDOs help in subtype determination and clinical outcome prediction, thereby facilitating the bench-to-bedside precision medicine for PDAC.
Subject(s)
Carcinoma, Pancreatic Ductal , Organoids , Pancreatic Neoplasms , Humans , Carcinoma, Pancreatic Ductal/pathology , Carcinoma, Pancreatic Ductal/genetics , Carcinoma, Pancreatic Ductal/drug therapy , Organoids/pathology , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/drug therapy , Male , Prognosis , Female , Aged , Middle Aged , Prospective Studies , Endoscopic Ultrasound-Guided Fine Needle Aspiration/methods , Treatment OutcomeABSTRACT
Background: Pancreatic ductal adenocarcinoma (PDAC) has a high mortality rate owing to its late diagnosis and aggression. In addition, there are relatively few minimally invasive screening methods for the early detection of PDAC, making the identification of biomarkers for this disease a critical priority. Recent studies have reported that microRNAs in extracellular vesicles (EV-miRs) from bodily fluids can be useful for the diagnosis of PDACs. Given this, we designed this study to evaluate the utility of cancer EVs extracted from duodenal fluid (DF) and their resident EV-miRs as potential biomarkers for the detection of PDAC. Methods: EV-miRs were evaluated and identified in the supernatants of various pancreatic cancer cell lines (Panc-1, SUIT2, and MIAPaca2), human pancreatic duct epithelial cells, and the DF from patients with PDAC and healthy controls. EVs were extracted using ultracentrifugation and the relative expression of EV-miR-20a was quantified. Results: We collected a total of 34 DF samples (27 PDAC patients and seven controls) for evaluation and our data suggest that the relative expression levels of EV-miR-20a were significantly higher in patients with PDAC than in controls (p = 0.0025). In addition, EV-miR-20a expression could discriminate PDAC from control patients regardless of the location of the tumor with an area under the curve values of 0.88 and 0.88, respectively. Conclusions: We confirmed the presence of EVs in the DF and suggest that the expression of EV-miR-20a in these samples may act as a potential diagnostic biomarker for PDAC.
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PURPOSE: This study explored the difficulty factors in robot-assisted low and ultra-low anterior resection, focusing on simple measurements of the pelvic anatomy. METHODS: This was a retrospective analysis of the clinical data of 61 patients who underwent robot-assisted low and ultra-low anterior resection for rectal cancer between October 2018 and April 2023. The relationship between the operative time in the pelvic phase and clinicopathological data, especially pelvic anatomical parameters measured on X-ray and computed tomography (CT), was evaluated. The operative time in the pelvic phase was defined as the time between mobilization from the sacral promontory and rectal resection. RESULTS: Robot-assisted low and ultra-low anterior resections were performed in 32 and 29 patients, respectively. The median operative time in the pelvic phase was 126 (range, 31-332) min. A multiple linear regression analysis showed that a short distance from the anal verge to the lower edge of the cancer, a narrow area comprising the iliopectineal line, short anteroposterior and transverse pelvic diameters, and a small angle of the pelvic mesorectum were associated with a prolonged operative time in the pelvic phase. CONCLUSION: Simple pelvic anatomical measurements using abdominal radiography and CT may predict the pelvic manipulation time in robot-assisted surgery for rectal cancer.
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Familial adenomatous polyposis (FAP) is a heritable disease that increases the risk of colorectal cancer (CRC) development because of heterozygous mutations in APC. Little is known about the microenvironment of FAP. Here, single-cell RNA sequencing was performed on matched normal tissues, adenomas, and carcinomas from four patients with FAP. We analyzed the transcriptomes of 56,225 unsorted single cells, revealing the heterogeneity of each cell type, and compared gene expression among tissues. Then we compared the gene expression with that of sporadic CRC. Furthermore, we analyzed specimens of 26 FAP patients and 40 sporadic CRC patients by immunohistochemistry. Immunosuppressiveness of myeloid cells, fibroblasts, and regulatory T cells was upregulated even in the early stages of carcinogenesis. CD8+ T cells became exhausted only in carcinoma, although the cytotoxicity of CD8+ T cells was gradually increased according to the carcinogenic step. When compared with those in the sporadic CRC microenvironment, the composition and function of each cell type in the FAP-derived CRC microenvironment had differences. Our findings indicate that an immunosuppressive microenvironment is constructed from a precancerous stage in FAP.
Subject(s)
Adenoma , Adenomatous Polyposis Coli , Colorectal Neoplasms , Humans , CD8-Positive T-Lymphocytes/pathology , Adenomatous Polyposis Coli/complications , Adenomatous Polyposis Coli/genetics , Adenomatous Polyposis Coli/pathology , Adenomatous Polyposis Coli Protein/genetics , Carcinogenesis , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Tumor MicroenvironmentABSTRACT
PURPOSE: Cholelithiasis occurs often after gastrectomy. However, no consensus has been established regarding the difference in the incidence of postgastrectomy cholelithiasis with different reconstruction methods. In this study, we examined the frequency of cholelithiasis after two major reconstruction methods, namely Billroth-I (B-I) and Roux-en-Y (R-Y) following laparoscopic distal gastrectomy (LDG) for gastric cancer. METHODS: Among 696 gastric cancer patients who underwent LDG between April 2000 and March 2017, after applying the exclusion criteria, 284 patients who underwent B-I and 310 who underwent R-Y were examined retrospectively. The estimated incidence of cholelithiasis was compared between the methods, and factors associated with the development of cholelithiasis in the gallbladder and/or common bile duct were investigated. RESULTS: During the median follow-up of 61.2 months, 52 patients (8.8%) developed cholelithiasis postgastrectomy; 12 patients (4.2%) after B-I and 40 (12.9%) after R-Y (p = 0.0002). Among them, choledocholithiasis was more frequent in patients who underwent R-Y (n = 11, 27.5%) vs. B-I (n = 1, 8.3%) (p = 0.0056). Univariate and multivariate analyses revealed that male sex, body mass index > 22.5 kg/m2, and R-Y reconstruction were significant predictors of the development of postLDG cholelithiasis. CONCLUSION: Regarding cholelithiasis development, B-I reconstruction should be preferred whenever possible during distal gastrectomy.
Subject(s)
Choledocholithiasis , Laparoscopy , Stomach Neoplasms , Humans , Male , Stomach Neoplasms/epidemiology , Stomach Neoplasms/surgery , Stomach Neoplasms/complications , Retrospective Studies , Incidence , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/surgery , Anastomosis, Roux-en-Y/adverse effects , Anastomosis, Roux-en-Y/methods , Gastrectomy/adverse effects , Gastrectomy/methods , Laparoscopy/adverse effects , Laparoscopy/methods , Choledocholithiasis/surgery , Treatment OutcomeABSTRACT
BACKGROUND: Minimally invasive distal pancreatectomy (MIDP), including laparoscopic and robotic distal pancreatectomy, has gained widespread acceptance over the last decade owing to its favorable short-term outcomes. However, evidence regarding its oncologic safety is insufficient. In March 2023, a randomized phase III study was launched in Japan to confirm the non-inferiority of overall survival in patients with resectable pancreatic cancer undergoing MIDP compared with that of patients undergoing open distal pancreatectomy (ODP). METHODS: This is a multi-institutional, randomized, phase III study. A total of 370 patients will be enrolled from 40 institutions within 4 years. The primary endpoint of this study is overall survival, and the secondary endpoints include relapse-free survival, proportion of patients undergoing radical resection, proportion of patients undergoing complete laparoscopic surgery, incidence of adverse surgical events, and length of postoperative hospital stay. Only a credentialed surgeon is eligible to perform both ODP and MIDP. All ODP and MIDP procedures will undergo centralized review using intraoperative photographs. The non-inferiority of MIDP to ODP in terms of overall survival will be statistically analyzed. Only if non-inferiority is confirmed will the analysis assess the superiority of MIDP over ODP. DISCUSSION: If our study demonstrates the non-inferiority of MIDP in terms of overall survival, it would validate its short-term advantages and establish its long-term clinical efficacy. TRIAL REGISTRATION: This trial is registered with the Japan Registry of Clinical Trials as jRCT 1,031,220,705 [ https://jrct.niph.go.jp/en-latest-detail/jRCT1031220705 ].
Subject(s)
Laparoscopy , Pancreatic Neoplasms , Robotic Surgical Procedures , Humans , Pancreatectomy/adverse effects , Pancreatectomy/methods , Japan/epidemiology , Robotic Surgical Procedures/adverse effects , Robotic Surgical Procedures/methods , Neoplasm Recurrence, Local/surgery , Treatment Outcome , Laparoscopy/adverse effects , Laparoscopy/methods , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Retrospective StudiesABSTRACT
BACKGROUND: Gastric cancer (GC) is characterized by an immunosuppressive and treatment-resistant tumor immune microenvironment (TIME). Here, we investigated the roles of different immunosuppressive cell types in the development of the GC TIME. METHODS: Single-cell RNA sequencing (scRNA-seq) and multiplex immunostaining of samples from untreated or immune checkpoint inhibitor (ICI)-resistant GC patients were used to examine the correlation between certain immunosuppressive cells and the prognosis of GC patients. RESULTS: The results of the scRNA-seq analysis revealed that tumor-infiltrating monocytic myeloid-derived suppressor cells (TI-M-MDSCs) expressed higher levels of genes with immunosuppressive functions than other immunosuppressive cell types. Additionally, M-MDSCs in GC tissues expressed significantly higher levels of these markers than adjacent normal tissues. The M-MDSCs were most enriched in GC tissues relative to adjacent normal tissues. Among the immunosuppressive cell types assessed, the M-MDSCs were most enriched in GC tissues relative to adjacent normal tissues; moreover, their presence was most strongly associated with a poor prognosis. Immediate early response 3 (IER3), which we identified as a differentially expressed gene between M-MDSCs of GC and adjacent normal tissues, was an independent poor prognostic factor in GC patients (P = 0.0003). IER3+ M-MDSCs expressed higher levels of genes with immunosuppressive functions than IER3- M-MDSCs and were abundant in treatment-resistant GC patients. CONCLUSIONS: The present study suggests that TI-M-MDSCs, especially IER3+ ones, may play a predominant role in the development of the immunosuppressive and ICI-resistant GC TIME.
Subject(s)
Myeloid-Derived Suppressor Cells , Stomach Neoplasms , Humans , Myeloid-Derived Suppressor Cells/metabolism , Myeloid-Derived Suppressor Cells/pathology , Stomach Neoplasms/pathology , Tumor Microenvironment , Gene Expression , PrognosisABSTRACT
Preoperative treatment is commonly carried out for borderline resectable pancreatic ductal adenocarcinoma (PDAC). However, the relationship between the combination of immune cells in the tumor microenvironment and their intratumoral heterogeneity along with their association with histological findings remains unclear, especially in patients receiving preoperative chemotherapy. We aimed to explore the therapeutic strategies for patients with PDAC with poor prognosis after receiving chemotherapy based on histological and immunological microenvironmental classifications. We investigated the correlation between the prognosis and histological immune microenvironmental factors of patients who initially underwent surgery (n = 100) and were receiving gemcitabine plus nab-paclitaxel (GEM + nabPTX) as preoperative chemotherapy (n = 103). Immune profiles were generated based on immune cell infiltration into the tumor, and their correlation with patient outcomes and histological features was analyzed. Tumor-infiltrating neutrophils (TINs) were identified as independent poor prognostic factors using multivariate analysis in both surgery-first and preoperative chemotherapy groups. The patients were further classified into four groups based on immune cell infiltration into the tumor. Patients with high CD15 infiltration into the tumor and immature stroma at the cancer margins showed the worst prognosis in the preoperative chemotherapy group. The analysis of mRNA expression and immunohistochemical features revealed that CXCR2, the receptor for CXCL8, was correlated with disease-free and overall survival. We inferred that patients with immature stroma at the margins and high infiltration of CD15+ neutrophils within the tumor showed the worst prognosis and they could particularly benefit from treatment with inhibitors targeting CXCR2 or CXCL8.
Subject(s)
Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Humans , Pancreatic Neoplasms/pathology , Neutrophils/metabolism , Prognosis , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Tumor MicroenvironmentABSTRACT
BACKGROUND/AIM: Family history of colorectal cancer (CRC) is a known risk factor for CRC. However, its prognostic value in patients with CRC remains controversial. This study aimed to clarify the prognostic impact of a family history of CRC. PATIENTS AND METHODS: We retrospectively reviewed the database from 1978 to 2018 and enrolled 3,655 consecutive patients with CRC. We investigated the clinicopathological factors of patients with CRC with and without a family history. After propensity score matching, we performed a survival analysis of patients with CRC with and without a family history. RESULTS: Patients with CRC with a family history of CRC had a young onset (63.2 and 65.9; p<0.001), were more likely to be female (54.3% and 49.7%; p=0.042), had less symptomatic disease (76.9% and 80.8%; p=0.008), were more likely to have right-sided colon cancer (27.5% and 26.1%), and had less distant metastases (11.3% and 14.9%; p=0.023) and multiple CRCs (10.2% and 7.8%) compared with those without a family history of CRC. Prior to propensity score matching, CRC-specific survival analysis showed that a family history of CRC was a good prognostic factor (p=0.022). After propensity score matching, survival curves overlapped between the two groups. CONCLUSION: Patients with CRC with a family history of CRC had specific clinicopathological features including younger onset, female sex, proximal colon location, fewer symptoms, smaller number of distant metastases, likelihood of multiple diseases, and earlier cancer stage. Family history of CRC in patients with CRC was not a prognostic factor.
Subject(s)
Colorectal Neoplasms , Humans , Female , Male , Propensity Score , Prognosis , Retrospective Studies , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/geneticsABSTRACT
BACKGROUND: Left-sided portal hypertension including gastric venous congestion may be caused by ligating the splenic vein during pancreaticoduodenectomy with portal vein resection or total pancreatectomy. The usefulness of reconstruction with the splenic vein has been reported in such cases. However, depending on the site of the tumor and other factors, it may be impossible to leave sufficient length of the splenic vein, making anastomosis difficult. We report two patterns of reconstruction with the right gastroepiploic vein during pancreaticoduodenectomy and total pancreatectomy to prevent left-sided portal hypertension. CASE PRESENTATION: The first patient was a 79-year-old man who underwent pancreaticoduodenectomy for pancreatic cancer. The root of the splenic vein was infiltrated by the tumor, and we resected this vein at the confluence of the portal vein. Closure of the portal vein was performed without reconstruction of the splenic vein. To prevent left-sided portal hypertension, we anastomosed the right gastroepiploic vein to the middle colic vein. Postoperatively, there was no suggestion of left-sided portal hypertension, such as splenomegaly, varices, and thrombocytosis. The second case was a 63-year-old woman who underwent total pancreatectomy for pancreatic cancer. The splenic vein-superior mesenteric vein confluence was infiltrated by the tumor, and we resected the portal vein, including the confluence. End-to-end anastomosis was performed without reconstruction of the splenic vein. We also divided the left gastric vein, left gastroepiploic vein, right gastroepiploic vein, and right gastric vein, which resulted in a lack of drainage veins from the stomach and severe gastric vein congestion. We anastomosed the right gastroepiploic vein to the left renal vein, which improved the gastric vein congestion. Postoperatively, imaging confirmed short-term patency of the anastomosis site. Although the patient died because of tumor progression 8 months after the surgery, no findings suggested left-sided portal hypertension, such as varices. Reconstruction with the right gastroepiploic vein during pancreaticoduodenectomy and total pancreatectomy is useful to prevent left-sided portal hypertension.