Lobaplatin hyperthermic intraperitoneal chemotherapy plus cytoreduction and rechallenge using cetuximab for wild-type RAS peritoneal metastatic colon cancer: a case report and literature review.

BACKGROUND: Synchronous peritoneal metastasis of colorectal cancer usually predicts a bleak prognosis. Hyperthermic intraperitoneal chemotherapy (HIPEC) and cytoreductive surgery (CRS) have brought a glimmer of hope to the treatment of peritoneal cancer. Few cases treated with lobaplatin have been reported in the literature and the regimen is controversial. In this case, the comprehensive treatment scheme of lobaplatin-based HIPEC plus CRS and rechallenge using cetuximab plus systemic chemotherapy is effective, especially for the patients with left colon cancer (wild-type RAS). CASE PRESENTATION: A 49 year-old man with signet ring cell carcinoma of sigmoid colon with extensive abdominal metastasis (wild-type RAS) was hospitalized with prolonged abdominal pain, distention and abdominal mass. After receiving HIPEC with lobaplatin and XELOX regimen combined with cetuximab for eight cycles, the patient had been treated with the FOLFIRI regimen and cetuximab for 24 cycles, which discontinued due to myelosuppression. Because the disease recurred unfortunately 4 months later, the FOLFIRI + cetuximab regimen was initiated again and stopped after two cycles. Intestinal obstruction occurred 1 month later, so open total colectomy, CRS + HIPEC and ileorectal anastomosis were performed. Capecitabine adjuvant chemotherapy was administered, followed by the maintenance therapy with FOLFIRI + cetuximab regimen. After that, the patient has been in relatively stable condition. By August 2021, the overall survival is more than 45 months, which displays significant curative effect. CONCLUSION: For peritoneal metastasis from left colon cancer, the management with CRS + lobaplatin HIPEC and rechallenge of systemic chemotherapy plus targeted medicine based on gene detection can dramatically improve prognosis and extend the overall survival.

Adjuvant chemotherapy benefits on patients with elevated carcinoembryonic antigen in stage IIA colon cancer: a SEER-based analysis.

OBJECTIVE: Indications for adjuvant chemotherapy in stage IIA (T3N0M0) colon cancer are still controversial. The purpose of this study was to evaluate the prognostic value of elevated carcinoembryonic antigen (CEA) levels for cancer-specific survival (CSS) and overall survival (OS) in patients with stage IIA colon cancer. We aimed to examine the impact of adjuvant chemotherapy on OS in stage IIA colon cancer patients with elevated CEA levels. METHODS: Patients with stage IIA colon cancer (N = 3477) diagnosed between 2010 and 2015 were identified using the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier and Cox proportional hazards regression models were used to assess the prognostic effect of CEA on CSS and OS. RESULTS: Cox regression analysis demonstrated that CEA was an independent risk factor for CSS and OS in patients with stage IIA colon cancer (CSS: HR = 2.001, 95% CI 1.603-2.499, P < 0.001; OS: HR = 1.530, 95% CI 1.335-1.752, P < 0.001). In the subgroup with elevated CEA, patients received adjuvant chemotherapy had a better OS compared with those did not (χ2 = 10.585, p = 0.001). CONCLUSION: CEA was an independent risk factor for CSS and OS in patients with stage IIA colon cancer. Patients with stage IIA colon cancer with an elevated CEA level might benefit from adjuvant chemotherapy.

CRISPR-based detection of Helicobacter pylori in stool samples.

BACKGROUND: Noninvasive detection of Helicobacter pylori plays an important role in clinical practice. However, few noninvasive methods have been applied in epidemiological studies due to the requirement for expensive equipment and complicated processes. The aim of this study was to establish a reliable, fast, and inexpensive noninvasive method based on CRISPR-Cas12a technology for the detection of Helicobacter pylori in stool specimens. METHOD: A novel detection method based on CRISPR-Cas12a technology was established and validated with 41 stool specimens collected from Zhujiang Hospital and compared with reliable Helicobacter pylori detection assays, such as the rapid urease test and urea breath test. RESULT: A CRISPR-Cas12a system-based method was established, and its sensitivity and specificity were evaluated. Utilizing a lateral flow biosensor, the limit of detection was 5 copies/µl, and our method could successfully distinguish Helicobacter pylori from other pathogens, suggesting no cross-reactivity with other pathogens. Furthermore, lateral flow biosensor strips were utilized to test stool specimens, which could display the detection results in an accessible way. CONCLUSION: Our CRISPR-Cas12a system-based method successfully detected Helicobacter pylori in stool specimens. It is a rapid, simple, and inexpensive method for the detection and screening of Helicobacter pylori, which makes it a very promising supplemental test. However, its sensitivity and specificity compared with those of the gold standard test still need to be examined.

Complete remission in a patient with metastatic gastric cancer receiving tislelizumab combined with chemotherapy: a case report.

The prognosis for patients with advanced gastric cancer (AGC) is poor, with limited treatment options available due to the difficulty of resection. In recent years, chemotherapy and immunotherapy for AGC have shown promising efficacy. However, there is a controversy regarding the surgery of primary tumors and/or metastases in patients with stage IV gastric cancer after systematic therapy. Here, we present a 63-year-old retired female of AGC with supraclavicular metastasis with positive PD-L1 and tumor mutational burden-high (TMB-H). After receiving 8 cycles of capecitabine and oxaliplatin (XELOX) in combination with tislelizumab, the patient achieved complete remission (CR). No evidence of recurrence was identified during follow-up. To the best of our knowledge, this is the first case of AGC with supraclavicular metastasis who achieved CR after treatment with tislelizumab. The mechanism of CR was discussed by genomic and recent clinical studies. The results indicated that programmed death ligand-1 (PD-L1) combined positive score (CPS) ≥5 may serve as a clinical indication and standard for chemo-immune combination therapy. In combination with other similar reports, patients with microsatellite instability-high/defective mismatch repair (MSI-H/dMMR), (TMB-H), and positive PD-L1 had better sensitivity to tislelizumab. The patient recovered successfully except for symptoms of gastrointestinal hemorrhage during treatment, which may be associated with the treatment cycle and age. Immunotherapy with tislelizumab has been well-established in the treatment of malignant melanoma, lung cancer, and clear-cell kidney cancer, but its efficacy and safety for esophageal and gastric cancers remain to be validated. The CR of our patient suggested the prospects of tislelizumab in the immunotherapy of gastric cancer. Additionally, a watch-and-wait (WW) method maybe offered for patients with AGC who achieved complete clinical remission (CCR) after immune combination therapy if the patient was older or in poor physical condition.

Case Report: Complete Remission of a Patient With Metastatic Gastric Cancer Treated With Nivolumab Combined With Chemotherapy After Palliative Surgery.

Metastatic advanced gastric cancer, for which treatment strategies are extremely limited, has a poor prognosis. Complete remission is rare. Patients usually lose the opportunity of therapeutic surgery because the lesions cannot be completely removed, although it can greatly prolong their survival time. Palliative surgery usually suggests bad outcomes. In recent years, the immune checkpoint inhibitor (ICI) nivolumab has shown significant efficacy in the treatment of advanced gastric cancer. However, its applicable conditions and optimal withdrawal time remain controversial owing to its low response rate and high incidence of immune-related adverse events. Herein, we introduce a 66-year-old male patient with advanced gastric cancer with multiple liver metastases who underwent laparoscopic total gastrectomy for acute gastric bleeding. The patient received eight cycles of S-1 plus oxaliplatin (SOX) and switched to eight cycles of SOX plus nivolumab combined regimen in a stable state, later achieving complete remission. There was no recurrence for 32 months after the surgery. This is the first reported case of gastric cancer with multiple liver metastases with long-term complete remission with nivolumab treatment after palliative surgery. The potential mechanism of complete remission was discussed through clinical, genomic, and immune characteristics. The patient had a history of psoriasis and was positive for programmed death ligand 1 (PD-L1), and the interaction of TP53 mutation and HER-2 (-) gene may be associated with complete remission.

Patient-Derived Organoid Facilitating Personalized Medicine in Gastrointestinal Stromal Tumor With Liver Metastasis: A Case Report.

The gastrointestinal stromal tumors (GIST) are a rare gastrointestinal tract malignancy. The two primary mutation sites are found in KIT and platelet-derived growth factor receptor-α (PDGFR-α) genes. The current study reports on a point mutation within the exon 11 of KIT, named KIT p.V560E. Patient-derived organoids (PDOs) are potential 3D in vitro models of tissues that can be used to identify sensitivity toward specific targets in patients with tumors and allow for personalized medicine when drugs specific for newly identified genetic locus mutations are not yet available. This study describes a 68-year-old patient who complained of diffused abdominal pain and intermittent melena lasting more than 10 days. He has no other gastrointestinal abnormalities, prior abdominal surgery, or related family history. Surgery was conducted first to remove the lesions and ascertain the disease through histology and immunohistochemical stains of the mass. Immunohistochemistry revealed that the tumor was positive for CD117 and Dog-1. Based on the above findings, he was diagnosed with GISTs. Gene detection analysis and organoid culture were then performed to verify clinical decisions. KIT p.V560E and the reduced number of RB1 copies were identified as two obvious mutations, so the patient was administrated first-line treatment of imatinib 400 mg/d. However, progressive disease prompted us to switch to sunitinib, and his condition gradually improved. Meanwhile, organoid culture showed sensitivity to sunitinib and tolerance to imatinib with half-maximal inhibitory concentration (IC50) values of 0.89 and >20, respectively. In summary, to the best of our knowledge, this is the first time that the established organoid culture indicated that the GISTs organoid could identify the sensitivity to target therapies and facilitate individual-based treatment.

Methods for detection of Helicobacter pylori from stool sample: current options and developments.

Accurate detection of Helicobacter pylori infection and determination of antibiotics have significant meaning in clinical practice. The detection methods can be categorized into two types, invasive and non-invasive, but nowadays we use the urease breath test most frequently which is non-invasive. However, many developing countries cannot meet the requirements for having specialized equipment and they lack trained personnel. Also, for the children, it is difficult to make them cooperate for the test. Methods that detect Helicobacter pylori from stool sample can be a promising alternative for detection used in children and mass screening. Stool antigen tests have several advantages such as rapidity, simplicity, and cheapness, though their results may be influenced by the heterogenicity of antigens, the nature of biochemical techniques, and the amount of antigen presented in the stool. PCR-based methods can specifically detect Helicobacter pylori infection and antibiotic resistance by targeting specific gene sequence, but they also are limited by the requirements of facilities and experts, the existence of inhibitory substance, and interference from the dead bacteria. Some novel methods also deserve our attention. Here we summarized the results of researches about methods using stool sample and we hope our work can help clinicians choose the appropriate test in clinical practice.

Metagenomic NGS optimizes the use of antibiotics in appendicitis patients: bacterial culture is not suitable as the only guidance.

BACKGROUND: Previous treatment guidelines have suggested that bacteria are associated with the severity of appendicitis, and the use of postoperative antibiotics should be guided according to the bacteria culture results derived from intraoperative samples. However, this approach has many limitations. Patients were commonly administrated antibiotics during the perioperative period, which can lead to inaccurate culture result. AIM: To assess the relationship between pathogenic bacteria and appendicitis and optimize the process of antibiotic selection. METHODS: A nonconsecutive case series analysis was conducted from January to July 2017. Nineteen patients were divided into two groups according to their postoperative histological results (Non-perforated: phlegmonous/Perforated: gangrenous, n = 9/10) and postoperative bacterial culture results (Negative/Positive, n = 8/11). Patients were administrated same antibiotics during the perioperative period. During appendectomy, the diseased appendixes were collected, and whole metagenomic sequencing was used to identify the pathogenic bacteria in the specimens. Conventional technology was used to culture bacteria from appendix samples. RESULTS: We identified 361 species in the appendix samples. Six species in the appendix samples had relative abundances > 5%. No significant differences were observed in the bacterial composition of the two assayed groups. In particular, according to the grouping of culture results, the sequencing analysis results were completely different from those of the culture-based method. CONCLUSION: In clinical practice, because patients are regularly administrated antibiotics during the perioperative period, these antibiotics inevitably affect the results of bacterial culture. Therefore, bacterial culture results are not suitable for exclusively guiding the use of antimicrobial agents after appendicitis. Next-generation sequencing has numerous advantages, such as precisely characterizing the profiles of microbiota and their antibiotic resistance in appendicitis patients. Based on the above results, we propose that a combination of bacterial culture and next-generation sequencing should be used to improve the efficacy of antibiotic therapy.

PCB52 induces hepatotoxicity in male offspring through aggravating loss of clearance capacity and activating the apoptosis: Sex-biased effects on rats.

Polychlorinated biphenyls (PCBs), a kind of persistent organic pollutant, can induce hepatotoxicity in mammals. However, PCB-induced hepatotoxicity in offspring and the underlying mechanisms have been rarely studied. In the present study, Wistar rats were administered with corn oil or PCB52 (1 mg/kg body weight/day, by gavage) from gestational day 7 to postnatal day 21. In the PCB52-treated group, birth body lengths and weights were significantly decreased compared with the control group, suggesting developmental toxicity. Cytoplasmic injury in hepatocytes was observed in PCB52-treated male offspring, while no pathologic change was observed in female offspring, suggesting sex-biased hepatotoxicity. Furthermore, using an RNA-Seq method, coincided with the sexual bias, 454 differential expression genes (DEGs) were screened out in liver tissues of PCB52-treated male offspring, while 10 DEGs were screened out in female offspring. By KEGG annotation analysis, 4 in 12 significant pathways in male offspring were metabolism-related. In the present study, together with cytoplasmic injury of hepatocytes, decreased metabolic enzymes both at RNA and protein levels might aggravate loss of clearance capacity of hepatocytes and induce hepatotoxicity. Moreover, over-expressed peroxisome proliferator-activated receptor delta and mitogen-activated protein kinase 9 might activate apoptosis, which was verified by the augments of cleaved poly ADP-ribose polymerase 1 and caspase 3 in PCB52-treated male offspring. Taken together, PCB52 had developmental toxicity and induced sex-biased hepatotoxicity. The hepatotoxicity in male offspring might be attributed to the aggravated loss of clearance capacity and activation of apoptosis.