RESUMO
Objective: To examine the impact of varied surgical treatment strategies on the prognosis of patients with initial resectable gastric cancer liver metastases (IR-GCLM). Methods: This is a retrospective cohort study. Employing a retrospective cohort design, the study selected clinicopathological data from the national multi-center retrospective cohort study database, focusing on 282 patients with IR-GCLM who underwent surgical intervention between January 2010 and December 2019. There were 231 males and 51 males, aging (M(IQR)) 61 (14) years (range: 27 to 80 years). These patients were stratified into radical and palliative treatment groups based on treatment decisions. Survival curves were generated using the Kaplan-Meier method and distinctions in survival rates were assessed using the Log-rank test. The Cox risk regression model evaluated HR for various factors, controlling for confounders through multivariate analysis to comprehensively evaluate the influence of surgery on the prognosis of IR-GCLM patients. A restricted cubic spline Cox proportional hazard model assessed and delineated intricate associations between measured variables and prognosis. At the same time, the X-tile served as an auxiliary tool to identify critical thresholds in the survival analysis for IR-GCLM patients. Subgroup analysis was then conducted to identify potential beneficiary populations in different surgical treatments. Results: (1) The radical group comprised 118 patients, all undergoing R0 resection or local physical therapy of primary and metastatic lesions. The palliative group comprised 164 patients, with 52 cases undergoing palliative resections for gastric primary tumors and liver metastases, 56 cases undergoing radical resections for gastric primary tumors only, 45 cases undergoing palliative resections for gastric primary tumors, and 11 cases receiving palliative treatments for liver metastases. A statistically significant distinction was observed between the groups regarding the site and the number of liver metastases (both P<0.05). (2) The median overall survival (OS) of the 282 patients was 22.7 months (95%CI: 17.8 to 27.6 months), with 1-year and 3-year OS rates were 65.4% and 35.6%, respectively. The 1-year OS rates for patients in the radical surgical group and palliative surgical group were 68.3% and 63.1%, while the corresponding 3-year OS rates were 42.2% and 29.9%, respectively. A comparison of OS between the two groups showed no statistically significant difference (P=0.254). Further analysis indicated that patients undergoing palliative gastric cancer resection alone had a significantly worse prognosis compared to other surgical options (HR=1.98, 95%CI: 1.21 to 3.24, P=0.006). (3) The size of the primary gastric tumor significantly influenced the patients' prognosis (HR=2.01, 95%CI: 1.45 to 2.79, P<0.01), with HR showing a progressively increasing trend as tumor size increased. (4) Subgroup analysis indicates that radical treatment may be more effective compared to palliative treatment in the following specific cases: well/moderately differentiated tumors (HR=2.84, 95%CI 1.49 to 5.41, P=0.001), and patients with liver metastases located in the left lobe of the liver (HR=2.06, 95%CI 1.19 to 3.57, P=0.010). Conclusions: In patients with IR-GCLM, radical surgery did not produce a significant improvement in the overall prognosis compared to palliative surgery. However, within specific patient subgroups (well/moderately differentiated tumors, and patients with liver metastases located in the left lobe of the liver), radical treatment can significantly improve prognosis compared to palliative approaches.
Assuntos
Neoplasias Hepáticas , Neoplasias Gástricas , Humanos , Masculino , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Adulto , Prognóstico , Taxa de Sobrevida , Idoso de 80 Anos ou mais , Modelos de Riscos Proporcionais , Cuidados Paliativos , Estimativa de Kaplan-Meier , Hepatectomia/métodos , Resultado do TratamentoRESUMO
The incidence of adenocarcinoma of esophagogastric junction (AEG) is increasing in recent years. Its diagnosis, lymph node metastasis and digestive tract reconstruction are all different from those of upper gastric cancer. With the development of the concept of function preserving surgery for gastric cancer, the clinical application of laparoscopic proximal gastrectomy in AEG is increasing. In this kind of operation, in addition to ensuring sufficient radical cure of tumor, the short-term smooth recovery and long-term quality of life of patients are also important. The reconstruction of digestive tract after proximal stomach operation is of great significance. According to the author's own practical experience, in clinical work, the author selects different surgical resection scope and digestive tract reconstruction methods according to Siewert classification of AEG. For Siewert â ¡ AEG, laparoscopic PG is mostly used, and laparoscopic esophageal tubular gastric side-to-side anastomosis or double channel anastomosis is mostly used for digestive tract reconstruction. It is believed that with the emergence of long-term follow-up results and the development of multicenter randomized controlled research, some controversial questions will be better answered. We should pay attention to the individual differences of patients. For different individuals, combined with the operator's experience, on the basis of ensuring the radical cure of tumor, we should adopt appropriate surgical resection scope and digestive tract reconstruction, so as to bring better long-term quality of life for patients.
Assuntos
Adenocarcinoma , Neoplasias Esofágicas , Laparoscopia , Neoplasias Gástricas , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Junção Esofagogástrica/patologia , Junção Esofagogástrica/cirurgia , Gastrectomia/métodos , Humanos , Qualidade de Vida , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgiaRESUMO
Objective: To investigate the clinicopathological features of gastrointestinal stromal tumor (GIST) with KIT/PDGFRA "homozygous mutation", the efficacy of targeted therapy and the prognosis. Methods: A retrospective cohort study and propensity score matching were used. "Homozygous mutation" was defined as the detection of KIT/PDGFRA gene status of GIST by Sanger sequencing, which showed that there was only mutant gene sequence in the sequencing map, lack of wild-type sequence or the peak height of mutant gene sequence was much higher than that of wild-type gene sequence (> 3 times). "Heterozygous mutation" was defined as the mutant gene sequences coexisted with wild type gene sequences, and the peak height was similar (3 times or less). The clinicopathological data and follow-up information of 92 GIST patients with KIT/PDGFRA "homozygous mutation" were collected from 4 hospitals in Shanghai from January 2008 to May 2021 (Renji Hospital, Shanghai Jiaotong University School of Medicine: 70 cases; Zhongshan Hospital, Fudan University: 14 cases; Changhai Hospital, Naval Military Medical University: 6 cases and Ruijin Hospital, Shanghai Jiaotong University School of Medicine: 2 cases). Patients with perioperative death, other malignancies, and incomplete clinicopathological information were excluded. The clinicopathological features of the patients and the efficacy of targeted drug therapy were observed and analyzed. The efficacy was evaluated using Choi criteria, which were divided into complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). In addition, a total of 230 patients with high-risk GIST with "heterozygous mutation" in exon 11 of KIT gene and 117 patients with recurrent or metastatic GIST with "heterozygous mutation" in exon 11 of KIT gene were included. The propensity score matching method was used to match GIST patients with "heterozygous" and "homozygous" mutations in exon 11 of KIT gene (1â¶1) for survival analysis. The disease-free survival (DFS) between two groups of high-risk GIST patients who underwent complete surgical resection were compared. And progression-free survival (PFS) in patients with recurrent or metastatic GIST were compared. Results: Of the 92 GIST cases with KIT/PDGFRA "homozygous mutation", 58 were males and 34 were females, with a median onset age of 62 (31-91) years. Primary GIST 83 cases. Primary high-risk GIST (53 cases), metastatic GIST (21 cases) and recurrent GIST (9 cases) accounted for 90.2% (83/92). There were 90 cases of KIT gene"homozygous mutation" (exon 11 for 88 cases, exon 13 for 1 case, exon 17 for 1 case), and 2 cases of PDGFRA gene "homozygous mutation" (exon 12 for 1 case, exon 18 for 1 case). The median follow-up time was 49 (8-181) months. Among the 61 cases of primary localized GIST undergoing complete surgical resection, 2 cases were intermediate-risk GIST, 5 cases were low-risk GIST, and 1 case was very low-risk GIST, of whom 1 case of intermediate-risk GIST received 1-year adjuvant imatinib mesylate (IM) therapy after operation, and no tumor recurrence developed during the follow-up period. The remaining 53 cases were high-risk GIST, and follow-up data were obtained from 50 cases, of whom 22 developed tumor recurrence during follow-up. Of 9 patients directly receiving neoadjuvant targeted therapy (IM or avapritinib), 5 had complete imaging follow-up data, and the evaluation of efficacy achieved PR. Of all the 92 GIST cases with KIT/PDGFRA "homozygous mutation", 50 (54.4%) had tumor metastasis or tumor recurrence or progression during follow-up, and 12 (13.0%) died of the tumor. Survival analysis combined with propensity score showed that in 100 cases of high-risk GISTs with complete resection, GISTs with "homozygous mutation" in exon 11 of KIT gene had shorter disease-free survival (DFS) than GISTs with "heterozygous mutation" in exon 11 of KIT gene (median DFS: 72 months vs. 148 months, P=0.015). In 60 cases of recurrent or metastatic GISTs with KIT gene exon 11 mutation, IM was used as the first-line treatment, and the progression-free survival (PFS) of GISTs with "homozygous mutation" was shorter compared to GISTs with "heterozygous mutation" (median PFS: 38 months vs. 69 months, P=0.044). The differences were statistically significant. Conclusions: "Homozygous mutation" in KIT/PDGFRA gene is associated with the progression of GIST. The corresponding targeted therapeutic drugs are still effective for GIST with KIT/PDGFRA gene "homozygous mutation". Compared with GIST patients with "heterozygous mutation" in KIT exon 11, GIST patients with "homozygous mutation" in KIT exon 11 are more likely to relapse after surgery and to develop resistance to IM. Therefore, it is still necessary to seek more effective treatment methods for this subset of cases.
Assuntos
Antineoplásicos , Tumores do Estroma Gastrointestinal , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , China , Feminino , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/genética , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia , Prognóstico , Proteínas Proto-Oncogênicas c-kit/genética , Pirazóis , Pirróis , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Estudos Retrospectivos , TriazinasRESUMO
In the past, surgeons thought that severe presacral hemorrhage during proctectomy was caused by damage of the presacral venous plexus. By studying the anatomy and clinical data, we found that injury of the sacral basivertebral vein also caused this serious complication. Presacral hemorrhage is seen as massive bleeding from the distal pelvic surface of sacrum or from one to several large-caliber foramina of sacral basivertebral veins in that area. This type of presacral hemorrhage is more dangerous than that from simple injury of presacral venous plexus and sometimes it is fatal. We describe the anatomic features of the vertebral venous system and its close relationship with severe presacral hemorrhage. We also propose some new concepts about cause, hemostatic measures, and principles of prevention.
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Hemorragia Gastrointestinal/terapia , Doenças Retais/terapia , Reto/cirurgia , Adulto , Idoso , Feminino , Hemorragia Gastrointestinal/prevenção & controle , Técnicas Hemostáticas , Humanos , Ligadura , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Doenças Retais/prevenção & controle , Sacro/irrigação sanguínea , Veias/anatomia & histologia , Veias/lesões , Veias/cirurgiaRESUMO
Waterbloom samples of the colonial cyanobacterium Microcystis aeruginosa, collected in fish ponds at the Hydrobiological Institute, Wuhan, People's Republic of China, were hepatotoxic to mice. Lyophilized cells had an LD50 (i.p. mouse; 40 mg/kg) and signs of poisoning similar to that reported for other cyanobacterial hepatotoxic peptides. Two toxins, with an LD50 (i.p. mouse) of 40 and 150 micrograms/kg, were isolated using gel filtration and high performance liquid chromatography. The amino acid composition and mol. wt (994) of the 40 micrograms/kg toxin was the same as that for microcystin-LR, while the 150 micrograms/kg toxin had an amino acid composition and mol. wt (1048) different from any of the reported cyanobacteria heptapeptide toxins reported to date.