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Acta Medica Okayama Oct 2023Gastric cancer with peritoneal metastases is typically a devastating diagnosis. Ligamentum teres hepatis (LTH) metastasis is an extremely rare presentation with only...
Gastric cancer with peritoneal metastases is typically a devastating diagnosis. Ligamentum teres hepatis (LTH) metastasis is an extremely rare presentation with only four known cases. Herein, we report salvage surgery of successive metastases to the abdominal wall and LTH in a patient originally presenting with advanced gastric cancer with peritoneal metastasis, leading to long-term survival. A 72-year-old man with advanced gastric cancer underwent curative-intent distal gastrectomy with D2 lymph node dissection for gastric outlet obstruction. During this procedure, three small peritoneal metastases were detected in the lesser omentum, the small mesentery, and the mesocolon; however, intraoperative abdominal lavage cytology was negative. We added cytoreductive surgery for peritoneal metastasis. The pathological diagnosis of the gastric cancer was tubular adenocarcinoma with pT4aN1pM1(PER/P1b)CY0 stage IV (Japanese classification of gastric carcinoma/JCGC 15th), or T4N1M1b stage IV (UICC 7th). Post-operative adjuvant chemotherapy with S-1 (TS-1)+cisplatin (CDDP) was administered for 8 months followed by S-1 monotherapy for 4 months. At 28 months after the initial surgery, a follow-up computed tomography (CT) detected a small mass beneath the upper abdominal wall. The ass showed mild avidity on 18F-fluorodeoxyglucose positron-emission (FDG-PET) CT. Salvage resection was performed for diagnosis and treatment, and pathological findings were consistent with primary gastric cancer metastasis. At 49 months after the initial gastrectomy, a new lesion was detected in the LTH with a similar level of avidity on FDG-PET CT as the abdominal wall metastatic lesion. We performed a second salvage surgery for the LTH tumor, which also showed pathology of gastric cancer metastasis. There has been no recurrence up to 1 year after the LTH surgery. With multidisciplinary treatment the patient has survived almost 5 years after the initial gastrectomy. Curative-intent gastrectomy with cytoreductive surgery followed by adjuvant chemotherapy for advanced gastric cancer with localized peritoneal metastasis might have had a survival benefit in our patient. Successive salvage surgeries for oligometastatic lesions in the abdominal wall and the LTH also yielded favorable outcomes.
Topics: Male; Humans; Aged; Stomach Neoplasms; Peritoneal Neoplasms; Fluorodeoxyglucose F18; Abdominal Wall; Round Ligament of Liver; Cisplatin; Gastrectomy; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37899267
DOI: 10.18926/AMO/65979 -
Journal of Clinical Medicine Oct 2023: In the treatment of post-cholecystectomy bile leaks, endoscopic naso-biliary drainage (ENBD) or biliary stenting using plastic stents is the standard of care. Fully...
: In the treatment of post-cholecystectomy bile leaks, endoscopic naso-biliary drainage (ENBD) or biliary stenting using plastic stents is the standard of care. Fully covered self-expandable metal stent (FCSEMS) placement across the sphincter of Oddi is considered a salvage therapy for refractory cases, but pancreatitis and migration are the major concerns. Intraductal placement of a dumbbell-shaped FCSEMS (D-SEMS) could avoid these drawbacks of FCMSESs. In this retrospective study, we investigated the usefulness of intraductal placement of the D-SEMS for post-cholecystectomy bile leaks. : Six patients who underwent intraductal placement of the D-SEMS for post-cholecystectomy bile leaks were enrolled. This method was performed as initial treatment in three patients and as salvage treatment in three ENBD refractory cases. : Technical and clinical successes were obtained in 6 (100%) patients and 5 (83%) patients, respectively. One clinically unsuccessful patient required laparoscopic peritoneal lavage. The early adverse event was one case of mild pancreatitis (17%). The median duration of the D-SEMS indwelling was 61 days (42-606 days) with no migration cases, all of which were successfully removed. The median follow-up after index ERCP was 761 (range: 161-1392) days with no cases of recurrent bile leaks. : Intraductal placement of the D-SEMS for post-cholecystectomy bile leaks might be safe and effective even in refractory cases.
PubMed: 37892668
DOI: 10.3390/jcm12206530 -
Current Rheumatology Reviews 2024Malignancy-associated vasculitis usually presents in the form of polyarteritis nodosa or leukocytoclastic vasculitis. However, ANCA vasculitis associated with malignancy...
BACKGROUND
Malignancy-associated vasculitis usually presents in the form of polyarteritis nodosa or leukocytoclastic vasculitis. However, ANCA vasculitis associated with malignancy is rare. Here, we present a case of MPO+ ANCA vasculitis with pauci-immune GN associated with invasive ductal carcinoma of the breast.
CASE PRESENTATION
A 66-year-old female with a history of rheumatoid arthritis, Hashimoto's thyroiditis, and psoriasis presented with multiple joint pain, body aches, petechial rash, paresthesia and numbness, and deranged renal function a month after diagnosis of localized left breast invasive ductal carcinoma. Renal biopsy showed crescentic pauci-immune glomerulonephritis, and serology was positive for Perinuclear Antineutrophil Cytoplasmic Antibody (P-ANCA) and myeloperoxidase (MPO). The disease course was complicated by diverticulitis with peritonitis and intraperitoneal abscess collection, which required laparoscopic peritoneal lavage and additional interventional radiology-guided drainage of the abscess. We treated the patient successfully with steroids, rituximab, and mastectomy for left breast malignant lesions, resulting in the resolution of symptoms, normalization of inflammatory markers, and ANCA seroconversion.
CONCLUSION
Treating ANCA-associated Vasculitis (AAV) in surgical emergencies like bowel perforation can be challenging. Individualized treatment strategy tailored to patients' acute needs is crucial. In this case, we considered malignancy-associated vasculitis and pursued treatment that fit the patient's clinical situation in a multidisciplinary approach.
Topics: Female; Humans; Aged; Antibodies, Antineutrophil Cytoplasmic; Glomerulonephritis; Abscess; Breast Neoplasms; Mastectomy; Vasculitis; Peroxidase; Carcinoma, Ductal
PubMed: 37855288
DOI: 10.2174/0115733971246438230924163114 -
Frontiers in Oncology 2023Currently, gastric cancer with positive lavage cytology without gross peritoneal dissemination (GC-CY1) is a special type of metastatic form with poor prognosis....
Study protocol of a phase II clinical trial evaluating the efficacy of neoadjuvant intraperitoneal and systemic albumin-bound paclitaxel combined with camrelizumab and S-1 in the treatment of patients with exfoliative cell-positive gastric cancer.
BACKGROUND
Currently, gastric cancer with positive lavage cytology without gross peritoneal dissemination (GC-CY1) is a special type of metastatic form with poor prognosis. Consensus guidelines on treatment strategies for patients with GC-CY1 have not been established. This study involves a single-arm, prospective, phase II clinical trial to examine the efficacy and safety of neoadjuvant intraperitoneal and systemic (NIPS) albumin-bound paclitaxel combined with Camrelizumab and S-1 in the treatment of GC-CY1 patients.
METHODS/DESIGN
This is a prospective single-center exploratory study, and the primary endpoints of the trial are R0 resection rate and conversion rate of abdominal free cancer cells (FCCs), with secondary endpoints of 3-year progression-free survival (PFS); 3-year overall survival (OS); objective remission rate (ORR); disease control rate (DCR); safety and TRG classification.
DISCUSSION
This study is the first to apply NIPS albumin-bound paclitaxel combined with Camrelizumab and S-1 to the conversion therapy of GC-CY1 patients. It is speculated that this combination of regimens will increase the negative conversion rate of FCCs by 20%, which will provide innovative insights into conversion treatment ideas for GC-CY1 patients to be managed in a more comprehensive and optimized manner.
CLINICAL TRIAL REGISTRATION
http://clinicaltrials.gov/, identifier NCT05410847.
PubMed: 37841441
DOI: 10.3389/fonc.2023.1201928 -
World Journal of Surgical Oncology Oct 2023To investigate the risk factors associated with the development of occult peritoneal metastasis in advanced gastric cancer, and establish and externally validate a...
BACKGROUND
To investigate the risk factors associated with the development of occult peritoneal metastasis in advanced gastric cancer, and establish and externally validate a nomogram for predicting the occurrence of occult peritoneal metastasis in patients with advanced gastric cancer.
METHODS
A total of 111 patients with advanced gastric cancer who underwent laparoscopic exploration or peritoneal lavage cytology examination at the Affiliated Drum Tower Hospital of Nanjing University Medical School from August 2014 to December 2021 were retrospectively analyzed. The patients diagnosed between 2019 and 2021 were assigned to the training set (n = 64), while those diagnosed between 2014 and 2016 constituted the external validation set (n = 47). In the training set, patients were classified into two groups based on preoperative imaging and postoperative pathological data: the occult peritoneal metastasis group (OPMG) and the peritoneal metastasis negative group (PMNG). In the validation set, patients were classified into the occult peritoneal metastasis group (CY1P0, OPMG) and the peritoneal metastasis negative group (CY0P0, PMNG) based on peritoneal lavage cytology results. A nomogram was constructed using univariate and multivariate analyses. The performance of the nomogram was evaluated using Harrell's C-index, the area under the receiver operating characteristic curve (AUC), decision curve analysis (DCA), and calibration plots.
RESULTS
This study analyzed 22 potential variables of OPM in 111 gastric cancer patients who underwent laparoscopic exploration or peritoneal lavage cytology examination. Logistic regression analysis results showed that Lauren classification, CLDN18.2 score and CA125 were independent risk factors for OPM in patients with gastric cancer. We developed a simple and easy-to-use prediction nomogram of occult peritoneal metastasis in advanced gastric cancer. This nomogram had an excellent diagnostic performance. The AUC of the bootstrap model in the training set was 0.771 and in the validation set was 0.711. This model showed a good fitting and calibration and positive net benefits in decision curve analysis.
CONCLUSION
We have developed a prediction nomogram of OPM for gastric cancer. This novel nomogram has the potential to enhance diagnostic accuracy for occult peritoneal metastasis in gastric cancer patients.
Topics: Humans; Retrospective Studies; Peritoneal Neoplasms; Stomach Neoplasms; Nomograms; Peritoneum; Claudins
PubMed: 37833730
DOI: 10.1186/s12957-023-03188-2 -
Cellular & Molecular Immunology Dec 2023Primary immune thrombocytopenia (ITP) is an autoimmune hemorrhagic disorder in which macrophages play a critical role. Mammalian sterile-20-like kinase 4 (MST4), a...
Primary immune thrombocytopenia (ITP) is an autoimmune hemorrhagic disorder in which macrophages play a critical role. Mammalian sterile-20-like kinase 4 (MST4), a member of the germinal-center kinase STE20 family, has been demonstrated to be a regulator of inflammation. Whether MST4 participates in the macrophage-dependent inflammation of ITP remains elusive. The expression and function of MST4 in macrophages of ITP patients and THP-1 cells, and of a macrophage-specific Mst4 (Mst4) ITP mouse model were determined. Macrophage phagocytic assays, RNA sequencing (RNA-seq) analysis, immunofluorescence analysis, coimmunoprecipitation (co-IP), mass spectrometry (MS), bioinformatics analysis, and phosphoproteomics analysis were performed to reveal the underlying mechanisms. The expression levels of the MST4 gene were elevated in the expanded M1-like macrophages of ITP patients, and this elevated expression of MST4 was restored to basal levels in patients with remission after high-dose dexamethasone treatment. The expression of the MST4 gene was significantly elevated in THP-1-derived M1 macrophages. Silencing of MST4 decreased the expression of M1 macrophage markers and cytokines, and impaired phagocytosis, which could be increased by overexpression of MST4. In a passive ITP mouse model, macrophage-specific depletion of Mst4 reduced the numbers of M1 macrophages in the spleen and peritoneal lavage fluid, attenuated the expression of M1 cytokines, and promoted the predominance of FcγRIIb in splenic macrophages, which resulted in amelioration of thrombocytopenia. Downregulation of MST4 directly inhibited STAT1 phosphorylation, which is essential for M1 polarization of macrophages. Our study elucidates a critical role for MST4 kinase in the pathology of ITP and identifies MST4 kinase as a potential therapeutic target for refractory ITP.
Topics: Animals; Mice; Humans; Purpura, Thrombocytopenic, Idiopathic; Macrophages; Thrombocytopenia; Inflammation; Cytokines; Mammals; STAT1 Transcription Factor
PubMed: 37833401
DOI: 10.1038/s41423-023-01089-8 -
Journal of Inflammation Research 2023Intra-abdominal infection is a complex pathophysiological process involving multiple systems and organs of the body. Abdominal infections complicated by severe sepsis or...
PURPOSE
Intra-abdominal infection is a complex pathophysiological process involving multiple systems and organs of the body. Abdominal infections complicated by severe sepsis or septic shock have a high mortality rate of 30-50%. Therefore, novel strategies to treat sepsis are urgently needed.
METHODS
Andrographolide (AD), the main active ingredient of , reportedly exerts beneficial effects on mice with sepsis. However, its exact mechanism of action in attenuating inflammation due to intra-abdominal sepsis remains unclear to date. Hence, this study aimed to examine the therapeutic effects of AD on cecal ligation and puncture (CLP)-induced sepsis and elucidate the underlying mechanisms.
RESULTS
Results showed that AD therapy could significantly improve the 7-day survival rate and alleviate pathological organ injury in mice with CLP. In addition, AD treatment decreased the levels of proinflammatory factors, such as tumor necrosis factor-α and interleukin (IL)-6 in the peritoneal cavity fluid and blood and increased the level of anti-inflammatory factor IL-10 in the peritoneal cavity fluid of mice with CLP. Moreover, bacterial counts in the blood and peritoneal lavage fluid were lower in the mice treated with AD than in those untreated. Mechanistically, AD treatment increased the percentage and phagocytic activity of macrophages in the peritoneal cavity.
CONCLUSION
These data showed that AD can improve the survival of mice with intra-abdominal sepsis by enhancing bacterial clearance, as evidenced by the increased percentages and phagocytic activity of macrophages in the peritoneal cavity. This study is the first to demonstrate the protective effects of AD against intra-abdominal sepsis.
PubMed: 37822531
DOI: 10.2147/JIR.S422342 -
Nan Fang Yi Ke Da Xue Xue Bao = Journal... Sep 2023To investigate the effect of Isodopharicin C (Iso C), a traditional Chinese herbal medicine extract, on NLRP3 inflammasome activation and lipopolysaccharide...
OBJECTIVE
To investigate the effect of Isodopharicin C (Iso C), a traditional Chinese herbal medicine extract, on NLRP3 inflammasome activation and lipopolysaccharide (LPS)-induced septic shock in mice.
METHODS
Murine bone marrow-derived macrophages (BMDM) and human monocytic THP-1 cells were stimulated with LPS before treatment with different NLRP3 inflammasome agonists to activate canonical NLRP3 inflammasomes. The non-canonical NLRP3 inflammasomes were activated by intracellular LPS transfection, and AIM2 inflammasomes were activated with poly A: T. The cleavage of caspase-1 induced by NLRP3 activation was measured using Western blotting. The levels of NLRP3-dependent and -independent pro-inflammatory cytokines in the cell culture supernatant were detected using ELISA, and the intracellular potassium ion concentration was measured using ICP-OES. In the animal experiment, C57BL/6J mouse models of septic shock (induced by intraperitoneal LPS injection) were treated with Iso C, and the levels of IL-1β, TNF-α and IL-6 in the serum and peritoneal lavage fluid were detected using ELISA. The survival time of the mice was observed within 48 h after LPS injection and a survival curve was plotted.
RESULTS
In BMDM cells, Iso C dose-dependently inhibited the activation of canonical NLRP3 inflammasomes and non-canonical NLRP3 inflammasomes (<0.05) without obviously affecting the secretion levels of TNF-α and IL-6 (>0.05), the activation of AIM2 inflammasomes (>0.05), or K + efflux, the upstream signaling of NLRP3 activation (>0.05). Iso C inhibited the activation of canonical NLRP3 inflammasomes in human THP-1 cells. In septic C57BL/6J mice, Iso C treatment significantly reduced IL-1β levels in the serum and peritoneal lavage fluid, and prolonged the survival time of the mice (<0.05).
CONCLUSION
Iso C specifically inhibits NLRP3 inflammasome activation and alleviates septic shock in mice, and can serve as a potential small molecule compound for treatment of inflammatory diseases.
Topics: Animals; Humans; Mice; Inflammasomes; Interleukin-1beta; Interleukin-6; Lipopolysaccharides; Mice, Inbred C57BL; NLR Family, Pyrin Domain-Containing 3 Protein; Shock, Septic; Tumor Necrosis Factor-alpha
PubMed: 37814861
DOI: 10.12122/j.issn.1673-4254.2023.09.04 -
Journal of Hepato-biliary-pancreatic... Nov 2023Staging laparoscopy (SL) has been advocated for pancreatic cancer, mainly to evaluate the peritoneal washing cytology (CY) status, which seems to impact the prognosis of...
BACKGROUND
Staging laparoscopy (SL) has been advocated for pancreatic cancer, mainly to evaluate the peritoneal washing cytology (CY) status, which seems to impact the prognosis of pancreatic cancer. To establish an optimal treatment strategy for CY positive (CY+) pancreatic cancer cases, real-world clinical data about CY status-depending surgical outcomes should be accumulated.
METHODS
Peritoneal washing samples were collected from 183 consecutive patients who could be classified as either resectable or borderline resectable (BR) pancreatic cancer between January 2012 and December 2020. Correlations between the CY status and other clinicopathological parameters with the recurrence patterns and survival outcomes were examined. In addition, we analyzed several risk factors for the CY+ status and attempted to identify the patient population that may benefit most from SL.
RESULTS
A total of 24 of the 183 patients were CY+. Peritoneal recurrence occurred more frequently in CY+ cases than in CY- cases (29% vs. 6%, p < .001) and median survival time after surgery was significantly shorter in CY+ cases than in CY- cases (28.5 months vs. 67.5 months; p < .001). In detail, almost all CY+ patients among curative resection-intended cases had either elevated preoperative serum CA19-9 levels (≥250 U/mL) or DUPAN-2 levels (≥150 U/mL). Significant predictive factors of CY positivity were BR status (p = .028) and serum CA19-9 level exceeding 250 U/mL (p = .008).
CONCLUSION
CY status was identified as an independent prognostic factor, and SL examination should be recommended, especially for patients with risk factors for CY positivity, such as BR cancer and elevated serum CA19-9 levels.
Topics: Humans; CA-19-9 Antigen; Peritoneal Neoplasms; Peritoneal Lavage; Pancreatic Neoplasms; Laparoscopy; Prognosis; Neoplasm Staging; Retrospective Studies
PubMed: 37799038
DOI: 10.1002/jhbp.1373 -
Journal of Gastrointestinal Cancer Mar 2024Extensive intraperitoneal lavage (EIPL) is a novel therapeutic intervention that aims to limit the chance of peritoneal metastasis during gastrectomy. Clinical... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Extensive intraperitoneal lavage (EIPL) is a novel therapeutic intervention that aims to limit the chance of peritoneal metastasis during gastrectomy. Clinical trials on using EIPL after gastrectomy show controversial results. We aimed to summarize the evidence of efficacy and safety for using EIPL after gastrectomy to limit the possibility of peritoneal metastasis and improve survival.
METHODS
A literature search on PubMed, Scopus, Embase, and Web of Sciences was conducted till June 2023 to identify eligible RCTs that assess the efficacy and safety of EIPL after gastrectomy. The hazard ratio with 95% CI was used to determine the survival probability, the risk ratio with 95% CI was used to assess the surgical outcomes, and ROB-2 and GRADE guidelines were used to assess the risk of bias and the certainty of evidence respectively.
RESULTS
Six eligible studies with a total of 1993 patients were included in the meta-analysis. Regarding survival benefits, the survival of the EIPL group did not differ significantly from the non-EIPL group, and the pooled HR of overall survival was 0.86 (95% CI 0.58-1.26) P = 0.44, the disease-free survival was 0.81 (0.58-1.13) P = 0.21, and peritoneal recurrence-free survival was 0.97 (0.79-1.2) P = 0.25. There is no significant association between EIPL and short-term postoperative outcomes. The use of EIPL does not appear to affect postoperative mortality, infection, anastomotic leakage, bleeding, ileus, or hospital stay.
CONCLUSION
Our study yielded insufficient evidence about the survival benefits and surgical outcomes of EIPL in patients with gastric cancer after gastrectomy. Therefore, it is not recommended for treating gastric cancer patients.
Topics: Stomach Neoplasms; Humans; Peritoneal Lavage; Gastrectomy; Peritoneal Neoplasms; Treatment Outcome
PubMed: 37750984
DOI: 10.1007/s12029-023-00971-y