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OBJECTIVE: This study aimed to clarify the molecular mechanism of remnant pancreatic cancer (PC) development after primary PC resection. SUMMARY BACKGROUND DATA: Molecular mechanisms of the development of remnant PCs following primary PC resection are largely unknown. METHODS: Forty-three patients undergoing remnant PC resection after primary PC resection between 2001 and 2017 at 26 institutes were retrospectively analyzed. Clinicopathological features and molecular alterations detected by targeted amplicon sequencing of 36 PC-associated genes were evaluated. RESULTS: These patients showed significantly lower body mass indices and higher hemoglobin A1c values at remnant PC resection than at primary PC resection. A comparison of the molecular features between primary and remnant PCs indicated that remnant PCs were likely to develop via three different molecular pathways: successional, showing identical and accumulated alterations (n=14); phylogenic, showing identical and distinct alterations (n=26); and distinct, showing independent distinctive alterations (n=3). The similarity of gene alterations was associated with time to the remnant PC development (r=ï¼0.384, P=0.0173). Phylogenic pathways were significantly associated with the intraductal spread of carcinoma (P=0.007). Patient survival did not differ significantly depending on these molecular pathways. CONCLUSION: Molecular profiling uncovered three pathways for the development of remnant PCs, namely, successional, phylogenic, and distinct pathways. The vast majority of remnant PCs are likely to be molecularly associated with primary PCs either in the successional or phylogenic way. This information could impact the design of a strategy for monitoring and treating remnant PCs.
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BACKGROUND: /Objective: Preoperative treatment of resectable pancreatic ductal adenocarcinoma (PDAC) is gaining popularity worldwide. However, the characteristics of tumors located in the pancreatic head (Ph), or those in the body or tail (Pbt), after surgery following neoadjuvant chemoradiotherapy (NACRT) remain unclear. This study aimed to evaluate and compare the clinicopathological features, perioperative outcomes, and prognosis of patients with resectable PDAC who underwent NACRT followed by curative pancreatic resection, focusing on distinguishing between Ph and Pbt PDACs. METHODS: We included 107 patients with resectable PDAC who underwent curative resection following NACRT between 2009 and 2023. Clinicopathological features, perioperative and prognostic outcomes, recurrence patterns, and prognoses were compared between Ph and Pbt PDAC groups. RESULTS: Tumors were found in the Ph and Pbt in 64 and 43 patients, respectively. Albumin levels and lymphocyte-to-monocyte ratios after NACRT were significantly lower in the Ph group than in the Pbt group. The Pbt group showed significantly higher rates of positive peritoneal lavage cytology and serosal, arterial, and portal vein invasion than the Ph group did. Overall and recurrence-free survival were similar between the two groups. The most common site of initial postoperative recurrence was the lung only in both groups; however, the rate of peritoneal dissemination only was significantly higher in the Pbt group than in the Ph group. CONCLUSIONS: The prognoses based on tumor locations in the Ph and Pbt after surgery following NACRT are similar. Following the resection of resectable Pbt PDAC, the possibility of peritoneal dissemination recurrence should be considered.
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Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Prognóstico , Terapia Neoadjuvante , Estudos Retrospectivos , Quimiorradioterapia , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/patologia , Pancreatectomia , Adenocarcinoma/patologiaRESUMO
BACKGROUND: The intraoperative air leak test is commonly performed during rectal surgery to evaluate anastomotic integrity. However, its drawbacks include occasional difficulties in visualizing the exact point of the leak while maintaining the pelvis under saline, the need for repeat testing to identify the leak point, and a lack of continuous visualization of the leak point. OBJECTIVE: To evaluate the feasibility and clinical applicability of using aerosolized indocyanine green, a fluorescent tracer, for detecting rectal anastomotic leakage. DESIGN: Animal preclinical study. SETTING: Animal laboratory at Kagawa University. PATIENTS: Six healthy adult female beagles were included. INTERVENTIONS: An anastomotic leakage model with a single air leak point was created in each dog. Indocyanine green was aerosolized using a nebulizer kit with a stream of carbon dioxide flowing at 1.5 to 2.0 L/min. The aerosol was administered into the rectum transanally, and laparoscopic observations were performed. MAIN OUTCOME MEASURES: Air leak points were observed using a near-infrared fluorescence laparoscope, after which the presence of corresponding indocyanine green fluorescence was verified. RESULTS: Aerosolized indocyanine green was visualized laparoscopically at all anastomosis sites but not elsewhere. The median time from the administration of the aerosol to its visualization was 4.5 seconds. Pathological examinations were performed 4 weeks postsurgery in all dogs, and no histological abnormalities related to aerosolized indocyanine green administration were observed at the anastomosis sites. LIMITATIONS: The leak points were surgically created and did not occur naturally. CONCLUSIONS: Visualization of air leaks at the sites of rectal anastomosis was laparoscopically achievable by administering aerosolized indocyanine green transanally into the rectum in our canine model. This novel fluorescent leak test could be a valid alternative to established methods.
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Verde de Indocianina , Reto , Humanos , Adulto , Animais , Feminino , Cães , Reto/cirurgia , Fístula Anastomótica/diagnóstico , Fluorescência , Anastomose Cirúrgica/métodos , Corantes , AerossóisRESUMO
BACKGROUND: Clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreatic resection can lead to severe postoperative complications. POPF is defined based on postoperative day (POD) 3 drainage fluid amylase level. POPF correlates with inflammatory parameters as well as drainage fluid bacterial infection. However, a standardized model based on these factors for predicting CR-POPF remains elusive. We aimed to identify inflammatory parameter- and drainage fluid culture-related risk factors for CR-POPF on POD 3 after pancreatoduodenectomy (PD) and distal pancreatectomy (DP). METHODS: Data from 351 patients who underwent PD or DP between 2013 and 2022 at a single institution were retrospectively analyzed. Risk factors for CR-POPF were investigated using multivariate analyses, and a prediction model combining the risk factors for CR-POPF was developed. RESULTS: Of the 351 patients, 254 and 97 underwent PD and DP, respectively. Multivariate analyses revealed that drainage fluid amylase level ≥722 IU/L, culture positivity, as well as neutrophil count ≥5473/mm3 on POD 3 were independent risk factors for CR-POPF in PD group. Similarly, drainage fluid, amylase level ≥500 IU/L, and culture positivity on POD 3 as well as pancreatic thickness ≥11.1 mm were independent risk factors in the DP group. The model for predicting CR-POPF achieved the maximum overall accuracy rate when the number of risk factors was ≥2 in both the PD and DP groups. CONCLUSIONS: Inflammatory parameters on POD 3 significantly influence the risk of CR-POPF onset after pancreatectomy. The combined models based on these values can accurately predict the risk of CR-POPF after pancreatectomy.
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Drenagem , Pancreatectomia , Fístula Pancreática , Pancreaticoduodenectomia , Complicações Pós-Operatórias , Humanos , Fístula Pancreática/etiologia , Fístula Pancreática/epidemiologia , Fístula Pancreática/diagnóstico , Feminino , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Pancreaticoduodenectomia/efeitos adversos , Pancreatectomia/efeitos adversos , Fatores de Risco , Amilases/análise , Amilases/metabolismo , Valor Preditivo dos Testes , AdultoRESUMO
OBJECTIVES: No protocol for esophagogastroduodenoscopic examination of the duodenum has been established. We examined the feasibility and ability to detect neoplasms of a novel duodenal examination protocol. METHODS: This was a two-facility, prospective, observational study. Our protocol, the Seven Pictures Rule (7PR), requires pictures of the following seven locations: anterior and posterior to the bulb, area of and contralateral to the superior duodenal angle, area of and contralateral to the ampulla, and the transverse duodenum. The primary outcome was rate of completion of 7PR. Secondary outcomes were overall rates of detecting neoplasms, rates of detecting neoplasms for each location, examination time, and completion rates for standard or ultrathin endoscopes. RESULTS: There were 1549 participants. The 7PR completion rate was 81.1% and the detection rates of overall neoplasms, adenomas, and carcinomas were 0.84%, 0.71%, and 0.06%, respectively. The area in which most neoplasms was detected was contralateral to the ampulla (69.2%), and the fewest the transverse duodenum (0%). Mean duration of duodenal examination was 53.1 s. Completion rates for standard vs. ultrathin were 84.4% (1077/1276) vs. 65.6% (179/273) (P < 0.01), respectively. CONCLUSIONS: Seven Pictures Rule is acceptable for duodenal examination and a potential quality indicator.
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Adenoma , Neoplasias Duodenais , Humanos , Adenoma/diagnóstico , Adenoma/patologia , Neoplasias Duodenais/diagnóstico , Neoplasias Duodenais/patologia , Duodeno/patologia , Endoscopia do Sistema Digestório , Estudos ProspectivosRESUMO
BACKGROUND: Identifying malignant transformation in pancreatic branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) remains challenging, but the standardized uptake value (SUV) obtained from 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET)/CT has the potential to become a valuable parameter for differentiation. This study aimed to assess the effectiveness of SUV of FDG-PET/CT in distinguishing low-grade dysplasia (LGD), high-grade dysplasia (HGD), and intraductal papillary mucinous carcinoma (IPMC) within BD-IPMNs. METHODS: We assessed 58 patients with confirmed BD-IPMN undergoing surgery between 2008 and 2022. Receiver operating characteristic curves were plotted using the tumor-to-blood pool ratio (TBR) of FDG-PET/CT in two scenarios: one considering HGD + IPMC as positive and the other considering only IPMC as positive. RESULTS: In the cohort of 58 cases, there were 39 females, and the median age was 71 years. The median TBR value was 1.45 (range, 0.35-25.44). The TBRs exhibited a significant correlation with each histopathology (p < 0.001). Furthermore, in the multivariate analysis, TBR was independently significant in both scenarios, with HGD + IPMC defined as malignant (p = 0.001) and with only IPMC defined as malignant (p = 0.024). CONCLUSIONS: TBR might have the potential to serve as a valuable parameter for indicating malignant transformation in pancreatic BD-IPMNs.
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Adenocarcinoma Mucinoso , Carcinoma Ductal Pancreático , Neoplasias Intraductais Pancreáticas , Neoplasias Pancreáticas , Feminino , Humanos , Idoso , Fluordesoxiglucose F18 , Neoplasias Intraductais Pancreáticas/diagnóstico por imagem , Neoplasias Intraductais Pancreáticas/cirurgia , Neoplasias Intraductais Pancreáticas/patologia , Carcinoma Ductal Pancreático/diagnóstico por imagem , Carcinoma Ductal Pancreático/cirurgia , Carcinoma Ductal Pancreático/patologia , Tomografia Computadorizada por Raios X , Estudos Retrospectivos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Sensibilidade e Especificidade , Adenocarcinoma Mucinoso/patologia , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/patologia , Tomografia por Emissão de PósitronsRESUMO
Subsequent to a medical examination, a 61-year-old male was referred to our hospital with jaundice. He was diagnosed with intrahepatic cholangiocarcinoma involving the hepatic hilum and was referred to our department to undergo a left trisectionectomy of the liver, extrahepatic bile duct resection, and regional lymphadenectomy. He was discharged on postoperative day 39 without liver failure. Two months postoperatively, positron-emission tomography/computed tomography(PET/ CT)indicated recurrences in the bone, and paraaortic lymph node. Gemcitabine and cisplatin combination first-line therapy was administered. Disease progression occurred after 4 courses of therapy. Gene panel testing was performed and the patient was switched to pembrolizumab owing to high microsatellite instability. After 2 courses of pembrolizumab, notable shrinkage of the paraaortic lymph node recurrence was confirmed on computed tomography as well as a partial response. PET-CT revealed disappearance of abnormal accumulation in all lesions at 20 months postoperatively. This has been sustained for 24 months following surgery without remarkable immune-related side-effects.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias dos Ductos Biliares , Colangiocarcinoma , Recidiva , Humanos , Masculino , Colangiocarcinoma/cirurgia , Colangiocarcinoma/genética , Colangiocarcinoma/tratamento farmacológico , Pessoa de Meia-Idade , Neoplasias dos Ductos Biliares/cirurgia , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , HepatectomiaRESUMO
OBJECTIVE: The aim of this study was to investigate the safety and survival benefits of portal vein and/or superior mesenteric vein (PV/SMV) resection with jejunal vein resection (JVR) for pancreatic ductal adenocarcinoma (PDAC). SUMMARY BACKGROUND DATA: Few studies have shown the surgical outcome and survival of pancreatic resection with JVR, and treatment strategies for patients with PDAC suspected of jejunal vein (JV) infiltration remain unclear. METHODS: In total, 1260 patients who underwent pancreatectomy with PV/ SMV resection between 2013 and 2016 at 50 facilities were included; treatment outcomes were compared between the PV/SMV group (PV/ SMV resection without JVR; n = 824), PV/SMV-J1 V group (PV/SMV resection with first jejunal vein resection; n = 394), and PV/SMV-J2,3 V group (PV/SMV resection with second jejunal vein or later branch resection; n = 42). RESULTS: Postoperative complications and mortality did not differ between the three groups. The postoperative complication rate associated with PV/ SMV reconstruction was 11.9% in PV/SMV group, 8.6% in PV/SMV-J1 V group, and 7.1% in PV/SMV-J2,3V group; there were no significant differences among the three groups. Overall survival did not differ between PV/SMV and PV/SMV-J1 V groups (median survival; 29.2 vs 30.9 months, P = 0.60). Although PV/SMV-J2,3 V group had significantly shorter survival than PV/SMV group who underwent upfront surgery ( P = 0.05), no significant differences in overall survival of patients who received preoperative therapy. Multivariate survival analysis revealed that adjuvant therapy and R0 resection were independent prognostic factors in all groups. CONCLUSION: PV/SMV resection with JVR can be safely performed and may provide satisfactory overall survival with the pre-and postoperative adjuvant therapy.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Pancreatectomia , Veia Porta/cirurgia , Veia Porta/patologia , Veias Mesentéricas/cirurgia , Pancreaticoduodenectomia , Resultado do Tratamento , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos , Neoplasias PancreáticasRESUMO
BACKGROUND: Optimal management of non-functioning pancreatic neuroendocrine tumors (PanNETs) ≤20 mm is controversial. The biological heterogeneity of these tumors poses challenges when deciding between resection and observation. METHODS: In this multicenter, retrospective cohort study, we analyzed all patients (n = 78) who underwent resection of non-functioning PanNETs ≤20 mm at three tertiary medical centers from 2004 to 2020 to assess the utility of preoperatively available radiological features and serological biomarkers of non-functioning PanNETs in choosing an optimal surgical indication. The radiological features included non-hyper-attenuation pattern on enhancement computed tomography (CT; hetero/hypo-attenuation) and main pancreatic duct (MPD) involvement, and serological biomarkers included elevation of serum elastase 1 and plasma chromogranin A (CgA) levels. RESULTS: Of all small non-functioning PanNETs, 5/78 (6%) had lymph node metastasis, 11/76 (14%) were WHO grade II, and 9/66 (14%) had microvascular invasion; 20/78 (26%) had at least one of these high-risk pathological factors. In the preoperative assessment, hetero/hypo-attenuation and MPD involvement were observed in 25/69 (36%) and 8/76 (11%), respectively. Elevated serum elastase 1 and plasma CgA levels were observed in 1/33 (3%) and 0/11 (0%) patients, respectively. On multivariate logistic regression analysis, hetero/hypo-attenuation (odds ratio [OR] 6.1, 95% confidence interval [CI] 1.7-22.2) and MPD involvement (OR 16.8, 95% CI 1.6-174.3) were significantly associated with the high-risk pathological factors. The combination of the two radiological worrisome features correctly predicted non-functioning PanNETs with high-risk pathological factors, with about 75% sensitivity, 79% specificity, and 78% accuracy. CONCLUSIONS: This combination of radiological worrisome features can accurately predict non-functioning PanNETs that may require resection.
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Tumores Neuroendócrinos , Neoplasias Pancreáticas , Humanos , Tumores Neuroendócrinos/patologia , Estudos Retrospectivos , Neoplasias Pancreáticas/patologia , Medição de Risco , Elastase PancreáticaRESUMO
Locally advanced pancreatic cancer (LAPC), which progresses locally and surrounds major vessels, has historically been deemed unresectable. Surgery alone failed to provide curative resection and improve overall survival. With the advancements in treatment, reports have shown favorable results in LAPC after undergoing successful chemotherapy therapy or chemoradiation therapy followed by surgical resection, so-called "conversion surgery", at experienced high-volume centers. However, recognizing significant regional and institutional disparities in the management of LAPC, an international consensus meeting on conversion surgery for LAPC was held during the Joint Congress of the 26th Meeting of the International Association of Pancreatology (IAP) and the 53rd Annual Meeting of Japan Pancreas Society (JPS) in Kyoto in July 2022. During the meeting, presenters reported the current best multidisciplinary practices for LAPC, including preoperative modalities, best systemic treatment regimens and durations, procedures of conversion surgery with or without vascular resections, biomarkers, and genetic studies. It was unanimously agreed among the experts in this meeting that "cancer biology is surpassing locoregional anatomical resectability" in the era of effective multiagent treatment. The biology of pancreatic cancer has yet to be further elucidated, and we believe it is essential to improve the treatment outcomes of LAPC patients through continued efforts from each institution and more international collaboration. This article summarizes the agreement during the discussion amongst the experts in the meeting. We hope that this will serve as a foundation for future international collaboration and recommendations for future guidelines.
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Gastroenterologia , Neoplasias Pancreáticas , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Japão , Terapia Neoadjuvante/métodos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/cirurgiaRESUMO
Recent evidence indicates that RNA-dependent RNA polymerase (RdRP) activity of human telomerase reverse transcriptase (hTERT) regulates expression of target genes and is directly involved in tumor formation in a telomere-independent manner. Non-canonical function of hTERT has been considered as a therapeutic target for cancer therapy. We have previously shown that hTERT phosphorylation at threonine 249 (p-hTERT), which promotes RdRP activity, is an indicator of an aggressive phenotype and poor prognosis in liver and pancreatic cancers, using two cohorts with small sample sizes with polyclonal p-hTERT antibody. To clarify the clinical relevance of p-hTERT, we developed a specific monoclonal antibody and determined the diagnostic and prognostic value of p-hTERT in cancer specimens using a large cohort. A monoclonal antibody for phosphorylated hTERT (p-hTERT) at threonine 249 was developed and validated. The antibody was used for the immunohistochemical staining of formalin-fixed, paraffin-embedded specimens from 1523 cases of lung, colon, stomach, pancreatic, liver, breast, and kidney cancers. We detected elevated p-hTERT expression levels in cases with a high mitotic activity, high pathological grade, and high nuclear pleomorphism. Elevated p-hTERT expression was an independent prognostic factor for lung, pancreatic, and liver cancers. Furthermore, p-hTERT expression was associated with immature and aggressive features, such as adenosquamous carcinoma (lung and pancreas), invasive type of cancer (lung), high serum alpha-fetoprotein level (liver), and triple-negative status (breast). In conclusion, RdRP activity indicated by p-hTERT expression predicts aggressive cancer phenotypes in various types of cancer. Thus, p-hTERT is a novel biomarker for the diagnosis of aggressive cancers with a poor prognosis. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
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Neoplasias , Telomerase , Anticorpos Monoclonais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Humanos , Neoplasias/genética , Neoplasias/patologia , Fosforilação , Prognóstico , RNA Polimerase Dependente de RNA , Telomerase/genética , Treonina/metabolismoRESUMO
BACKGROUND: The recently developed endoscopic full-thickness resection technique requires reliable closure. The main closure methods are the purse-string suture (PSS) technique and over-the-scope clip (OTSC) technique; however, basic data on the closure strength of each technique are lacking. This study was performed to compare the closure strengths of these two methods in an ex vivo porcine model. METHODS: In the traction test, a virtual 5-cm full-thickness closure line was closed by the following six methods three times each: conventional hemoclips, mucosal PSS, seromuscular PSS, mucosal OTSC, seromuscular OTSC, and surgical suture. The primary endpoint was the tension at the starting point of dehiscence, measured in Newtons (N) by an automatic traction machine. In the leak test, a 15-mm gastric full-thickness defect was closed by PSS or OTSC six times each, and the closed stomach was then pressurized in a water container. The primary endpoint was the leak pressure when air bubbles appeared. The secondary endpoints were the procedure time and presence of complete inverted closure. RESULTS: The mean tension was 2.16, 3.68, 5.15, 18.30, 19.30, and 62.40 N for conventional hemoclips, mucosal PSS, seromuscular PSS, mucosal OTSC, seromuscular OTSC, and surgical suture, respectively. Complete inverted closure was observed for seromuscular PSS, seromuscular OTSC, and surgical suture. The mean leak pressure was 13.7 and 24.8 mmHg in the PSS and OTSC group, respectively (P < 0.01). The mean procedure time was 541 and 169 s in the PSS and OTSC group, respectively (P < 0.01). Complete inverted closure was observed in OTSC alone. CONCLUSION: The OTSC, which allows complete inverted closure, showed greater closure strength than PSS. Considering the size limitation suitable for single OTSC, a therapeutic strategy for closing the larger size is further warranted.
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Estômago , Tração , Suínos , Animais , Estômago/cirurgia , Endoscopia , Suturas , Técnicas de SuturaRESUMO
BACKGROUND: The benefit of preoperative treatment followed by pancreatic resection in older patients with pancreatic ductal adenocarcinoma (PDAC) remains unclear. In this retrospective analysis of prospectively collected data, we evaluated the significance and safety of preoperative treatment followed by curative resection for older PDAC patients. METHODS: We evaluated 122 patients with resectable and borderline resectable PDAC who received neoadjuvant chemoradiotherapy (NACRT) followed by curative resection between 2009 and 2019. Changes in the prognostic nutritional indices during NACRT, surgical outcomes, and prognosis were compared between older (≥75 years, n = 44) and younger patients (<75 years, n = 78). RESULTS: The completion rate, adverse event rate, changes in prognostic nutritional indices during NACRT, and prognosis were similar between the groups. In multivariate analysis, an elevated C-reactive protein/albumin ratio (CRP/Alb) ≥ 33.1% during NACRT (p = 0.035) and no postoperative adjuvant chemotherapy (p = 0.041) were identified as significant predictors of overall survival. CONCLUSIONS: NACRT followed by pancreatic resection could be safely performed in older patients, with a similar prognosis as that of younger patients, despite an increased frequency of postoperative complications. Elevated CRP/Alb during NACRT and no postoperative adjuvant chemotherapy were poor prognostic factors for older patients.
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Adenocarcinoma , Carcinoma Ductal Pancreático , Quimiorradioterapia , Terapia Neoadjuvante , Idoso , Humanos , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/cirurgia , Quimiorradioterapia/métodos , Terapia Neoadjuvante/métodos , Pancreatectomia/efeitos adversos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Estudos Retrospectivos , Neoplasias PancreáticasRESUMO
INTRODUCTION: Advances in metabolomics have significantly improved cancer detection, diagnosis, treatment, and prognosis. OBJECTIVES: To investigate the relationship between metabolic tumor volume (MTV) using 2-deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography (PET)/ computed tomography (CT) and metabolomics data in patients with colorectal cancer (CRC). METHODS: The metabolome in tumor tissues was analyzed using capillary electrophoresis time-of-flight mass spectrometry in 33 patients with newly diagnosed CRC who underwent FDG PET/CT before treatment and had tumor tissue post-surgery. Based on the FDG PET data, MTV was calculated and was dichotomized according to the median value, and tumors were divided into low-MTV and high-MTV tumors. Metabolomics data were compared between the low-MTV and high-MTV tumors. RESULTS: The levels of most glycolysis-related metabolites were not different between low-MTV and high-MTV tumors. The level of component of the initial part of the tricarboxylic acid (TCA) cycle, citrate, was significantly lower in the high-MTV tumor than in the low-MTV tumor. The TCA intermediate succinate level was significantly higher in the high-MTV tumor than in the low-MTV tumor. In contrast, the TCA intermediate fumarate level was significantly lower in the high-MTV tumor than in the low-MTV tumor. The levels of many amino acids were significantly higher in the high-MTV tumor than in the low-MTV tumor. CONCLUSIONS: Although preliminary, these results suggest that tumors with high FDG metabolism in CRC may obtain more energy by using a reverse reaction of the TCA cycle and amino-acid metabolism. However, further research is required to clarify this relationship.
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Neoplasias Colorretais , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Fluordesoxiglucose F18/metabolismo , Glucose , Metabolômica , Neoplasias Colorretais/diagnóstico por imagemRESUMO
BACKGROUND AND OBJECTIVES: There is little data on the correlation between the reduction in fluorodeoxyglucose positron emission tomography (FDG-PET) radioactive accumulation and carbohydrate antigen 19-9 (CA19-9) levels with pathological tumor responses (PTRs) and prognosis after neoadjuvant chemoradiotherapy (NACRT) for patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: This study was a retrospective analysis of prospectively collected data from 102 patients with resectable (R-) and borderline resectable (BR-) PDAC who received NACRT, followed by curative resection. Data were prospectively collected and compared between the responders and nonresponders to NACRT. RESULTS: Patients with 60% or more reduction in maximum standardized uptake value (SUVmax) on FDG-PET, with 75% or more reduction in CA19-9 levels, or with 50%-100% of tumor cells destroyed due to NACRT had significantly better recurrence-free survival (RFS) than each of the nonresponders (p = 0.028, <0.001, and 0.022, respectively). The reduction rates of SUVmax and CA19-9 levels were correlated with PTR. The combined evaluation of these biomarkers reflected RFS. CONCLUSIONS: Reduction rates of FDG uptake and CA19-9 levels were preoperative predictors of pathological response to NACRT. These biomarkers of local response had prognostic value in R-PDAC and BR-PDAC. The combined evaluation of these biomarkers allowed for reliable prediction of RFS after surgery.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Antígeno CA-19-9 , Carcinoma Ductal Pancreático/cirurgia , Quimiorradioterapia , Fluordesoxiglucose F18 , Humanos , Terapia Neoadjuvante , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/terapia , Prognóstico , Estudos Retrospectivos , Neoplasias PancreáticasRESUMO
OBJECTIVE: We investigated the metabolic changes in pancreatic ductal adenocarcinoma to identify the mechanisms of treatment response of neoadjuvant chemoradiation therapy. METHODS: Frozen tumor and non-neoplastic pancreas tissues were prospectively obtained from 88 patients with pancreatic ductal adenocarcinoma who underwent curative-intent surgery. Sixty-two patients received neoadjuvant chemoradiation therapy and 26 patients did not receive neoadjuvant therapy (control group). Comprehensive analysis of metabolites in tumor and non-neoplastic pancreatic tissue was performed by capillary electrophoresis-mass spectrometry. RESULTS: Capillary electrophoresis-mass spectrometry detected 90 metabolites for analysis among more than 500 ionic metabolites quantified. There were significant differences in 27 tumor metabolites between the neoadjuvant chemoradiation therapy and control groups. There were significant differences in eight metabolites [1-MethylnNicotinamide, Carnitine, Glucose, Glutathione (red), N-acetylglucosamine 6-phosphate, N-acetylglucosamine 1-phosphate, UMP, Phosphocholine] between good responder and poor responder for neoadjuvant chemoradiation therapy. Among these metabolites, phosphocholine, Carnitine and Glutathione were associated with recurrence-free survival only in the neoadjuvant chemoradiation therapy group. Microarray confirmed marked gene suppression of choline transporters [CTL1-4 (SLC44A1-44A4)] in pancreatic ductal adenocarcinoma tissue of neoadjuvant chemoradiation therapy group. CONCLUSION: The present study identifies several important metabolic consequences and potential neoadjuvant chemoradiation therapy targets in pancreatic ductal adenocarcinoma. Choline metabolism is one of the key pathways involved in recurrence of the patients with pancreatic ductal adenocarcinoma who received neoadjuvant chemoradiation therapy.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Antígenos CD , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/terapia , Carnitina , Quimiorradioterapia , Glutationa , Humanos , Terapia Neoadjuvante , Recidiva Local de Neoplasia/diagnóstico , Proteínas de Transporte de Cátions Orgânicos , Pancreatectomia , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/terapia , Fosforilcolina , Neoplasias PancreáticasRESUMO
INTRODUCTION: This multi-institutional retrospective study aimed to evaluate the efficacy of preoperative self-expandable metallic stent (SEMS) placement for patients with left-sided obstructive colorectal cancer (OCRC). METHODS: Overall, 520 consecutive patients who received treatment for OCRC were enrolled. Of these, the data of 253 patients who underwent primary tumour resection for left-sided OCRC were reviewed. The short- and long-term outcomes were compared between the SEMS group and other three groups: transanal decompression tube (TaDT), decompressing stoma (DS), and emergency resection (ER). RESULTS: The SEMS group had a higher frequency of laparoscopic surgery (p < 0.001), lesser frequency of postoperative stoma (p < 0.001), and more dissected lymph nodes (p < 0.001) than the other groups. Moreover, the SEMS group had shorter postoperative hospital stays than the TaDT, DS, and ER groups (p = 0.005, p = 0.037, and p < 0.001, respectively). The Kaplan-Meier survival curves of recurrence-free survival and overall survival did not differ significantly between the SEMS group and the other three groups in patients with stage II and III diseases. DISCUSSION/CONCLUSION: Elective surgery after SEMS placement may improve short-term outcomes compared to other treatment strategies, with similar long-term outcomes.
Assuntos
Neoplasias Colorretais , Obstrução Intestinal , Stents Metálicos Autoexpansíveis , Neoplasias Colorretais/complicações , Neoplasias Colorretais/cirurgia , Humanos , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia , Estudos Retrospectivos , Stents , Resultado do TratamentoRESUMO
BACKGROUND: There is insufficient evidence on whether indocyanine green (ICG) fluorescence angiography can reduce the incidence of anastomotic leakage (AL). This retrospective cohort study aimed to evaluate the effect of ICG fluorescence angiography on AL rates in laparoscopic rectal cancer surgery at a single institution. METHODS: Patients who underwent laparoscopic low anterior resection or intersphincteric resection with ICG fluorescence angiography (ICG group; n = 73) and patients who underwent a similar surgical procedure for rectal cancer without ICG fluorescence (non-ICG group; n = 114) were enrolled consecutively in this study. ICG fluorescence angiography was performed prior to transection of the proximal colon, and anastomosis was performed with sufficient perfusion using ICG fluorescence imaging. AL incidence was compared between both groups, and the risk factors for AL were analyzed. RESULTS: AL occurred in 3 (4.1%) and 14 (12.3%) patients in the ICG and non-ICG groups, respectively. In the ICG group, the median perfusion time from ICG injection was 34 s, and 5 patients (6.8%) required revision of the proximal transection line. None of the patients requiring revision of the proximal transection line developed AL. In univariate analysis, longer operating time (odds ratio: 2.758; 95% confidence interval: 1.023-7.624) and no implementation of ICG fluorescence angiography (odds ratio: 3.266; 95% confidence interval: 1.038-11.793) were significant factors associated with AL incidence, although the creation of a diverting stoma or insertion of a transanal tube was insignificant. CONCLUSION: ICG fluorescence angiography was associated with a significant reduction in AL during laparoscopic rectal cancer surgery. Changes in the surgical plan due to ICG fluorescence visibility may help improve the short-term outcomes of patients with rectal cancer.
Assuntos
Laparoscopia , Neoplasias Retais , Humanos , Fístula Anastomótica/diagnóstico por imagem , Fístula Anastomótica/epidemiologia , Fístula Anastomótica/etiologia , Verde de Indocianina , Estudos Retrospectivos , Incidência , Neoplasias Retais/cirurgia , Neoplasias Retais/complicações , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Anastomose Cirúrgica/métodos , Imagem Óptica/métodosRESUMO
Ampullary carcinomas of the duodenum are uncommon. Moreover, the diversity in the clinical outcomes of these patients makes it difficult to interpret previous studies and clinical trial results. The difficulty in proper staging of ampullary carcinomas, especially with regard to the T category of the tumor in the TNM system, reflects the anatomic complexity and non-uniform histopathologic subtypes. One major reason for this difficulty in interpretation is that the tumors may arise from any of the three epithelia (duodenal, biliary, or pancreatic) that converge at this location. Generally, ampullary carcinomas are classified into intestinal and pancreaticobiliary types based on morphology and immunohistochemical features. While many studies have described their specific characteristics and clinical impact, the prognostic value of these subtypes is controversial. In recent years, whole-exome sequencing analyses have advanced our understanding of the genomic overview of ampullary carcinoma. Gene mutations serve as prognostic and predictive biomarkers for this disease. Therefore, basic knowledge of the genomic profile of ampullary carcinomas is required for surgeons to understand how best to apply precision medicine as well as surgery and adjuvant therapies. This review provides an overview of the current basic and clinical issues of ampullary carcinoma.
Assuntos
Adenocarcinoma , Ampola Hepatopancreática , Neoplasias Duodenais , Adenocarcinoma/genética , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Neoplasias Duodenais/genética , Neoplasias Duodenais/mortalidade , Neoplasias Duodenais/patologia , Neoplasias Duodenais/terapia , Genes Neoplásicos/genética , Humanos , Excisão de Linfonodo/métodos , Mutação , Terapia Neoadjuvante , Estadiamento de Neoplasias , Pancreaticoduodenectomia/métodos , Medicina de Precisão , Prognóstico , Taxa de Sobrevida , Sequenciamento do ExomaRESUMO
BACKGROUND: The management of postoperative bleeding, after gastric endoscopic submucosal dissection (ESD), has become particularly important because of the recent increase in antithrombotic use. Endoscopic shielding with polyglycolic acid (PGA) sheets has been shown to be effective. However, shrinkage and early displacement of the sheet remain challenges. This study aimed to determine the efficacy and safety of our developed method, named wafer paper and ring-mounted PGA sheet (WaRP). MATERIAL AND METHODS: Twenty-four patients with antithrombotic uptake who underwent the WaRP method following gastric ESD were retrospectively examined. This involved the delivery of a PGA sheet wrapped in wafer paper with ring-thread, and its fixation on the gastric floor using hemoclips. The primary outcome was the technical success rate of the WaRP, and several secondary outcomes were evaluated. RESULTS: The technical success rate of WaRP was 100%. The procedure lasted a mean of 10.5 min (SD 6.7 min). The prevalence of complete retention at follow-up endoscopy was 83.3% (20/24). There were no WaRP-associated complications, but post-ESD hemorrhage occurred in two patients undergoing hemodialysis (8.3%). CONCLUSIONS: The WaRP method is a simple and reliable means of PGA sheet delivery and placement that reduces the incidence of post-ESD hemorrhage.