Postoperative Adjuvant Chemotherapy Research Articles

Analysis of sequential chemotherapy efficacy in ovarian epithelial carcinoma, fallopian tube carcinoma and primary peritoneal carcinoma

Objective: To explore the sequential chemotherapy efficacy of different chemotherapeutic regimens in ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma. Methods: A retrospective analysis was conducted on clinical and pathological data of 100 patients with platinum-sensitive ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma treated at Peking University Peopel's Hospital from January 1992 to January 2019. All patients underwent staging surgery or cytoreductive surgery followed by adjuvant chemotherapy. Based on different postoperative adjuvant chemotherapy regimens, patients were divided into the sequential chemotherapy group (70 cases) and the conventional chemotherapy group (30 cases). Clinical and pathological characteristics, chemotherapy efficacy, adverse reactions, and prognosis were compared between the two groups. Results: (1) Clinical and pathological characteristics: the age, tumor types (including ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma), pathological types, International Federation of Gynecology and Obstetrics (FIGO) stage, postoperative residual disease size, presence of neoadjuvant chemotherapy, and total number of chemotherapy cycles were compared between the sequential chemotherapy group and the conventional chemotherapy group. There were no statistically significant differences observed in these characteristics between the two groups (all P>0.05). (2) Chemotherapy efficacy: the median sum of complete response (CR)+partial response (PR) duration in the sequential chemotherapy group was 80.0 months (range: 39 to 369 months), whereas in the conventional chemotherapy group, it was 28.0 months (range: 13 to 52 months). A statistically significant difference was observed between the two groups (Z=-7.82, P<0.001). (3) Chemotherapy adverse reactions: in the sequential chemotherapy group, 55 cases (79%, 55/70) experienced bone marrow suppression and 20 cases (29%, 20/70) had neurological symptoms. In the conventional chemotherapy group, these adverse reactions occurred in 11 cases (37%, 11/30) and 2 cases (7%, 2/30), respectively. Statistically significant differences were observed between the two groups for both bone marrow suppression and neurological symptoms (all P<0.05). For the other chemotherapy adverse reactions compared between the two groups, no statistically significant differences were observed (all P>0.05). (4) Prognosis: during the follow-up period, the recurrence rate in the sequential chemotherapy group was 73% (51/70) and in the conventional chemotherapy group was 100% (30/30). The median sum of recurrence-free interval was 70.5 months (range: 19 to 330 months) in the sequential chemotherapy group and 15.0 months (range: 6 to 40 months) in the conventional chemotherapy group. Statistically significant differences were observed between the two groups for both recurrence rate and median recurrence-free interval (all P<0.01).In the sequential chemotherapy group, the median progression-free survival (PFS) time was 84.0 months (range: 34 to 373 months), and the median overall survival (OS) time was 87.0 months (range: 45 to 377 months). In contrast, in the conventional chemotherapy group, the median PFS time was 30.5 months (range: 14 to 60 months), and the median OS time was 37.5 months (range: 18 to 67 months). Statistically significant differences were observed between the two groups for both PFS and OS (all P<0.001). In the sequential chemotherapy group, the 3-year, 5-year, and 10-year OS rates were 100% (70/70), 93% (65/70), and 21% (15/70), respectively. In contrast, in the conventional chemotherapy group, the OS rates were 50% (15/30) at 3 years, 3% (1/30) at 5 years, and 0 at 10 years, respectively. The two groups were compared respectively, and the differences were statistically significant (all P<0.05). Conclusions: Sequential chemotherapy significantly prolongs PFS and OS in patients with ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma. The efficacy is superior to that of the conventional chemotherapy, with manageable adverse reactions. The use of sequential chemotherapy as first-line treatment for patients with ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma is recommended.

Primary Ewing’s sarcoma of the uterine cervix: a case report and review of the literature

BackgroundEwing’s sarcoma (ES) is an aggressive cancer of bone and soft tissue, most of which tend to occur in the bone. Extraosseous Ewing’s sarcoma (EES) of the cervix is extremely rare.Case presentationIn the present work, we reported a 39-year-old cervical EES patient with a 2.5*2.1*1.8 cm tumor mass. According to previous literatures, our case is the smallest tumor found in primary cervical ES ever. The patient initially came to our hospital due to vaginal bleeding, and then the gynecological examination found a neoplasm between the cervical canal and partially in the external cervical orifice. The diagnosis of EES was confirmed below: Hematoxylin & Eosin staining (H&E) revealed small round blue malignant cells in biopsy specimens. Immunohistochemistry (IHC) showed the positive staining for CD99, NKX2.2, and FLI1. Disruption of EWSR1 gene was found by fluorescence in situ hybridization (FISH), and the EWSR1–FLI1 gene fusion was determined by next-generation sequencing (NGS). The patient received laparoscopic wide hysterectomy, bilateral adnexectomy, pelvic lymphadenectomy, and postoperative adjuvant chemotherapy and remained disease free with regular follow-up for 1 year.ConclusionsThrough a systematic review of previously reported cervical ES and this case, we highlighted the importance of FISH and NGS for the accuracy of ESS diagnosis, which could assist on the optimal treatment strategy. However, due to the rarity of the disease, there is no standard treatment schemes. Investigation on molecular pathological diagnosis and standardization of treatment regimens for cervical ES are critical to patients’ prognosis.

Long-term survival after conversion surgery for an esophageal neuroendocrine carcinoma: a case report

BackgroundEsophageal neuroendocrine carcinomas (NECs) are extremely rare. Published information on their clinical features, pathological findings, and prognosis is lacking. The optimal treatment for esophageal NECs has not yet been determined because they appear extremely malignant histologically and have a poor prognosis. We here report on a patient with an esophageal NEC who was successfully treated with multidisciplinary therapies.Case presentationThe patient, a 47-year-old man, was admitted to our hospital with dysphagia and weight loss and an ECOG performance status of 3–4. Upper endoscopy showed a large circumferential neoplasm at the esophagogastric junction. Computed tomography showed lymph node metastases around the left gastric artery. Echocardiography raised a suspicion of invasion of the left atrium. Histopathological examination of biopsy tissue revealed diffuse proliferation of small atypical cells resembling naked nuclei with extensive necrosis and degeneration. The cells showed positive staining for CD56, chromogranin A, and synaptophysin on immunohistochemical analysis. Ki67 was positive in over 90% of cells. He was diagnosed with an esophageal NEC that had infiltrated the left atrium; his cancer was therefore inoperable. Because of his poor overall condition, palliative radiotherapy (30 Gy in 15 fractions) was administered, accompanied by nutritional management. This was followed by four courses of chemotherapy with carboplatin plus etoposide, after which the primary tumor and locoregional lymph node metastases were found to have shrunk. Thoracoscopic- and laparoscopic-assisted McKeown esophagectomy were performed. The postoperative pathological diagnosis was NEC pT3pN0M0 Stage II. The patient had a good postoperative course and received two courses of postoperative adjuvant chemotherapy (carboplatin plus etoposide). Currently, 3 years after commencing treatment, there is no evidence of recurrence.ConclusionsAs mentioned above, there is no established treatment regime for esophageal NEC, and the benefits of conversion surgery are unknown. Our patient achieved long-term recurrence-free survival after radiation therapy, chemotherapy, and surgery for an esophageal NEC with left atrial invasion and multiple lymph node metastases. Conversion surgery for esophageal NECs that respond to chemotherapy may contribute to long-term survival.

Circ-0075305 hinders gastric cancer stem cells by indirectly disrupting TCF4–β-catenin complex and downregulation of SOX9

CircRNAs are covalently closed, single-stranded RNA that form continuous loops and play a crucial role in the initiation and progression of tumors. Cancer stem cells (CSCs) are indispensable for cancer development; however, the regulation of cancer stem cell-like properties in gastric cancer (GC) and its specific mechanism remain poorly understood. We elucidate the specific role of Circ-0075305 in GC stem cell properties. Circ-0075305 associated with chemotherapy resistance was identified by sequencing GC cells. Subsequent confirmation in both GC tissues and cell lines revealed that patients with high expression of Circ-0075305 had significantly better overall survival (OS) rates than those with low expression, particularly when treated with postoperative adjuvant chemotherapy for GC. In vitro and in vivo experiments confirmed that overexpression of Circ-0075305 can effectively reduce stem cell-like properties and enhance the sensitivity of GC cells to Oxaliplatin compared with the control group. Circ-0075305 promotes RPRD1A expression by acting as a sponge for corresponding miRNAs. The addition of LF3 (a β-catenin/TCF4 interaction antagonist) confirmed that RPRD1A inhibited the formation of the TCF4–β-catenin transcription complex through competitive to β-catenin and suppressed the transcriptional activity of stem cell markers such as SOX9 via the Wnt/β-catenin signaling pathway. This leads to the downregulation of stem cell-like property-related markers in GC. This study revealed the underlying mechanisms that regulate Circ-0075305 in GCSCs and suggests that its role in reducing β-catenin signaling may serve as a potential therapeutic candidate.

Analysis of chemoresistance characteristics and prognostic relevance of postoperative gemcitabine adjuvant chemotherapy in pancreatic cancer.

To investigate the relationship between chemoresistance in pancreatic cancer patients receiving postoperative gemcitabine adjuvant therapy and specific clinical/pathological characteristics, as well as its impact on patient prognosis. From June 2018 to June 2021, clinical and pathological data of 148 pancreatic cancer patients were collected, and 101 patients were followed up for tumor recurrence/metastasis and survival status. The correlation between chemoresistance and specific clinical/pathological characteristics or patient prognosis was retrospectively analyzed. Of the 148 patients, 78 were in the chemoresistance group and 70 in the non-chemoresistance group. Univariate analysis showed that the development of chemoresistance may be related to patient age, combined diabetes, preoperative CA19-9 level, tumor size, AJCC stage, vascular invasion, and positive lymph node ratio. Furthermore, subsequent multivariate analysis incorporating these variables indicated that tumor size may be a key factor influencing chemoresistance (p < 0.001, OR = 1.584). Log-rank test showed patients in the chemoresistance group had worse overall survival (OS) (HR = 2.102, p = 0.018) and progression free survival (PFS) (HR = 3.208, p = 0.002) than patients in the non-chemoresistance group; and patients with smaller size tumors (diameter ≤3 cm) had significantly better OS (HR = 2.923, p < 0.001) and PFS (HR = 2.930, p = 0.003) than those with larger size tumors (diameter >3 cm). Patients with pancreatic cancer receiving postoperative gemcitabine adjuvant therapy are more likely to develop chemoresistance when their tumor sizes are larger (diameter >3 cm). Development of chemoresistance exacerbates the prognosis of patients with pancreatic cancer, and larger tumor size is also a risk factor for poor prognosis in these patients.

Prognostic factors and significance of postoperative adjuvant chemotherapy in patients with advanced gastric cancer undergoing neoadjuvant chemotherapy followed by gastrectomy.

In Japan, gastrectomy with D2 lymph node dissection and postoperative adjuvant chemotherapy are the standard treatments for locally advanced gastric cancer. Neoadjuvant chemotherapy (NAC) is not affected by postgastrectomy syndromes or postoperative complications. This multicenter retrospective study investigated the prognostic factors and significance of postoperative adjuvant chemotherapy in patients with advanced gastric cancer who underwent NAC followed by gastrectomy. Consecutive patients (n = 221) with advanced gastric cancer who underwent NAC followed by curative surgery were enrolled in this study. Prognostic factors including postoperative adjuvant chemotherapy were investigated using univariate and multivariate analyses. A multivariate analysis revealed that pathological lymph node metastasis (ypN) status and postoperative adjuvant chemotherapy were independent prognostic factors for the overall and relapse-free survival. Forty-five patients (20.4%) did not receive postoperative adjuvant chemotherapy. There were no significant differences between patients with and without adjuvant chemotherapy for all factors, except age. The most common reason for not undergoing postoperative adjuvant chemotherapy was a poor condition (n = 23). ypN status and postoperative adjuvant chemotherapy were independent prognostic factors in gastric cancer patients who underwent NAC followed by curative gastrectomy. It is important to maintain the patient's condition during NAC and the perioperative period so that they can receive postoperative adjuvant chemotherapy.

The Clinical Impact of the Prognostic Immune and Nutritional Index in Gastric Cancer Patients Who Received Curative Treatment.

The prognostic immune and nutritional index (PINI) was developed and reported as a promising prognostic factor. This study aimed to clarify the clinical impact of the PINI in gastric cancer (GC) patients who received curative treatment. Patients who underwent curative resection for GC at Yokohama City University between 2005 and 2020 were selected based on their medical records. The PINI was calculated by dividing the serum albumin concentration (g/dl) by the serum monocyte concentration. Both measurements were performed prior to surgery. A total of 262 patients were included in this study. Based on the 3- and 5-year overall survival (OS), we set the cutoff value of the PINI at 3.4 in the present study. The 3- and 5-year OS rates were 69.0% and 66.1%, respectively, in the PINI-low group and 90.5% and 82.8% in the PINI-high group. There were significant differences between the two groups (p<0.001). A multivariate analysis of factors associated with OS identified PINI as an independent prognostic factor (hazard ratio=1.996; 95% confidence interval=1.096-3.636, p=0.024). Similar results were observed for RFS. In addition, the PINI status affected the recurrence pattern, postoperative anastomotic leakage, and the introduction of postoperative adjuvant chemotherapy. The PINI is a promising nutritional and inflammatory marker for patients with GC and might be a useful marker for the treatment and management of patients with GC.

Effects of tumor marker regression load score on long-term prognosis of gastric cancer patients undergoing radical surgery after neoadjuvant chemotherapy

BackgroundThe effects of the dynamics of serum tumor markers (CA72-4, CEA, CA19-9, CA125 and AFP) before and after neoadjuvant chemotherapy (NACT) on the prognosis of gastric cancer(GC) patients remain unclear. MethodsThe training set contained 334 GC patients from Fujian Medical University Union Hospital (FJMUUH) and 113 GC patients in Qinghai University Affiliated Hospital (QhUAH) were used as an external validation set. Tumor marker regression load (ΔTMRL) indicator, including ΔCA72-4, ΔCEA, ΔCA19-9, ΔCA125, and ΔAFP, is defined as [(postNACT marker– preNACT marker)/preNACT marker]. Tumor marker regression load score (TMRLS) consists of ΔCA72-4, ΔCEA and ΔCA125. The predictive performance of the nomogram-TMRLS was evaluated using the area under the receiver operating characteristic(ROC) curve(AUC), decision curve analysis(DCA), and C-index. ResultsPatients from FJMUUH were divided into two groups, TMRLS-low and TMRLS-high, determined by R package maxstat. Survival analysis revealed a higher 3-year overall survival(OS) in the TMRLS-low than in the TMRLS-high group. The TMRLS-high group who received postoperative adjuvant chemotherapy(AC) showed a significantly higher 3-year OS rate than those who did not. Multivariate COX regression analysis indicated that TMRLS was an independent prognostic factor for OS. A nomogram for predicting OS based on TMRLS showed a significantly higher C-index and AUC than the ypTNM stage. The above results were also found in the QhUAH external validation cohort. ConclusionTMRLS is a novel independent prognostic factor for GC who underwent NACT and a radical gastrectomy. Furthermore, the TMRLS-high group, who received postoperative AC, may achieve better survival outcomes. Notably, the predictive performance of the nomogram-TMRLS significantly outperformed that of the ypTNM stage.

Poorly differentiated mucinous carcinoma of the ascending colon complicated by bilateral ovarian mature cystic teratomas in a 17-year-old female patient: a case report

BackgroundColorectal cancer (CRC) is one of the most common cancers worldwide, and screening colonoscopy has led to a decreasing incidence rate. However, the incidence of CRC is increasing among young people, especially adolescents and young adults (AYAs) who are not routinely screened. Although CRC is the fourth most common cancer among AYAs, it is extremely rare. In younger patients, CRC is often diagnosed later, and the proportion of patients with advanced CRC is higher than that in older patients. We herein present a case of poorly differentiated mucinous carcinoma of the ascending colon complicated by bilateral ovarian mature cystic teratomas (MCTs) in an AYA.Case presentationA 17-year-old female patient presented with a chief complaint of abdominal pain and diarrhea that had persisted for more than 3 years. Colonoscopy revealed circumferential wall thickening of the ascending colon, and colonic biopsy revealed a mucous mass and findings of adenocarcinoma, predominantly signet ring cell carcinoma. Abdominal computed tomography (CT) and pelvic magnetic resonance imaging (MRI) showed bilateral ovarian tumors. Laparoscopic right hemicolectomy and enucleation of bilateral ovarian tumors were performed. Although the ascending colon cancer formed a large mass, there were no signs of peritoneal dissemination or direct invasion to the surrounding organs. Microscopically, the ascending colon was a poorly differentiated mucinous carcinoma with signet ring cell carcinoma and lymph node metastasis (9/42). The ovarian tumors were diagnosed as MCTs without any malignant components. The pathological diagnosis was ascending colon cancer (pT4aN2bM0, pStage IIIC) and bilateral ovarian MCTs. Microsatellite instability (MSI) testing was negative, and there were no gene mutations in either RAS or BRAF. Postoperative adjuvant chemotherapy with oxaliplatin and 5-FU was started.ConclusionsWe presented a case of locally advanced ascending colon cancer in a 17-year-old female patient. CRC rarely occurs in AYAs. However, the incidence has gradually increased in recent years. It should be considered as a differential diagnosis for young patients with long-term abdominal symptoms of unknown cause.

Prognostic factors for resected cases with gallbladder carcinoma: A systematic review and meta-analysis.

Current meta-analysis was performed to systematically evaluate the potential prognostic factors for overall survival (OS) among resected cases with gallbladder carcinoma (GBC). PubMed, EMBASE, and the Cochrane Library were systematically retrieved and hazard ratio (HR) and its 95% confidence interval (CI) were directly extracted from the original study or roughly estimated via Tierney's method. Standard Parmar modifications were used to determine pooled HRs. A total of 36 studies with 11502 cases were identified. Pooled results of univariate analyses indicated that advanced age (HR=1.02, P=0.00020), concurrent gallstone disease (HR=1.22, P=0.00200), elevated preoperative CA199 level (HR=1.93, P<0.00001), advanced T stage (HR=3.09, P<0.00001), lymph node metastasis (HR=2.78, P<0.00001), peri-neural invasion (HR=2.20, P<0.00001), lymph-vascular invasion (HR=2.37, P<0.00001), vascular invasion (HR=2.28, P<0.00001), poorly differentiated tumor (HR=3.22, P<0.00001), hepatic side tumor (HR=1.85, P<0.00001), proximal tumor (neck/cystic duct) (HR=1.78, P<0.00001), combined bile duct resection (HR=1.45, P<0.00001), and positive surgical margin (HR=2.90, P<0.00001) were well-established prognostic factors. Pathological subtypes (P=0.53000) and postoperative adjuvant chemotherapy (P=0.70000) were not prognostic factors. Pooled results of multi-variate analyses indicated that age, gallstone disease, preoperative CA199, T stage, lymph node metastasis, peri-neural invasion, lymph-vascular invasion, tumor differentiation status, tumor location (peritoneal side vs hepatic side), surgical margin, combined bile duct resection, and postoperative adjuvant chemotherapy were independent prognostic factors. Various prognostic factors have been identified beyond the 8th AJCC staging system. By incorporating these factors into a prognostic model, a more individualized prognostication and treatment regime would be developed. Upcoming multinational studies are required for the further refine and validation.

The impact of modified T3 sub-staging on the prognosis of gallbladder cancer patients

Objective: To explore the value of a new modified T3 sub-staging for the prognosis evaluation in gallbladder cancer patients. Methods: This is a retrospective case-series study. The clinical data of patients with pathologically confirmed stage T3 gallbladder cancer who were admitted to the Department of Hepatobiliary Surgery,the First Affiliated Hospital of Xi'an Jiaotong University from January 2011 to December 2021 were retrospectively analyzed. A total of 190 patients were enrolled in this study, 67 males and 123 females, with an age (M(IQR)) of 63(14) years (range:17 to 88 years). The stage T3 was divided into four sub-stages according to the site of tumor invasion: (1) T3a:tumor perforates the serosa,but not invading the liver and one other adjacent structure; (2) T3b:tumor perforates the serosa and invades one other adjacent structure,but not the liver; (3) T3c:tumor perforates the serosa and invades the liver,but not one other adjacent structure; (4) T3d:tumor perforates the serosa,invades the liver and one other adjacent structure. To evaluate the application value of this modified sub-staging,the Kaplan-Meier method was used to draw the survival curve,univariate analysis and multivariate analysis were done using the Log-rank test and Cox proportional hazard model respectively. Results: According to the modified T3 sub-staging method,34 patients (17.9%) were in stage T3a,24 cases(12.6%) were in stage T3b, 97 cases (51.1%) were in stage T3c, and 35 cases (18.4%) were in stage T3d. The median survival time of patients in stages T3a,T3b,T3c and T3d after radical resection was 72.0 months, 32.0 months, 12.0 months and 10.0 months, respectively. The 1-, 3-, and 5-year survival rates of patients in stage T3a, T3b, T3c and T3d were 79.4%, 53.3%, and 53.3%; 79.2%, 44.6%, and 26.0%;49.5%,27.5%,and 18.1%;42.9%,15.9%, and 15.9% (χ2=18.349,P<0.01),respectively. Univariate analysis showed that gallbladder stones,pathological differentiation,perineural invasion, N stage,postoperative adjuvant therapy and modified T3 substage were factors affecting patient prognosis(all P<0.05). Cox multivariate analysis showed that modified sub-stages with T3c (HR=2.043, 95%CI:1.176 to 3.549) and T3d(HR=2.419, 95%CI:1.284 to 4.555), accompanied by gallbladder stones (HR=1.661,95%CI:1.150 to 2.398),pathological differentiation with poorly differentiated(HR=1.709,95%CI:1.198 to 2.438), and the N stage with N1 and N2(HR=1.602, 95%CI:1.090 to 2.355, 2.714, 95%CI: 1.621 to 4.544) were independent prognostic risk factors for patients in stage T3,while postoperative adjuvant chemotherapy(HR=0.351) was a protective factor for prognosis. There was no statistically significant difference in survival between patients with stage T3a and T3b who underwent hepatic wedge resection and liver segment or major resection (P=0.402). For patients with stage T3c and T3d with liver invasion,the survival difference after hepatic wedge resection and segmental or major resection was statistically significant (P=0.008). Conclusion: The modified T3 sub-staging system based on the depth and direction of tumor invasion maybe helpful to further stratify the prognosis of patients with gallbladder cancer.

Machine Learning-Based Prediction of Pathological Responses and Prognosis After Neoadjuvant Chemotherapy for Non–Small-Cell Lung Cancer: A Retrospective Study

BackgroundNeoadjuvant chemotherapy has variable efficacy in patients with non–small-cell lung cancer (NSCLC), yet reliable noninvasive predictive markers are lacking. This study aimed to develop a radiomics model predicting pathological complete response and postneoadjuvant chemotherapy survival in NSCLC. Materials and MethodsRetrospective data collection involved 130 patients with NSCLC who underwent neoadjuvant chemotherapy and surgery. Patients were randomly divided into training and independent testing sets. Nine radiomics features from prechemotherapy computed tomography (CT) images were extracted from intratumoral and peritumoral regions. An auto-encoder model was constructed, and its performance was evaluated. X-tile software classified patients into high and low-risk groups based on their predicted probabilities. survival of patients in different risk groups and the role of postoperative adjuvant chemotherapy were examined. ResultsThe model demonstrated area under the receiver operating characteristic (ROC) curve of 0.874 (training set) and 0.876 (testing set). The larger the area under curve (AUC), the better the model performance. Calibration curve and decision curve analysis indicated excellent model calibration (Hosmer–Lemeshow test, P = .763, the higher the P-value, the better the model fit) and potential clinical applicability. Survival analysis revealed significant differences in overall survival (P = .011) and disease-free survival (P = .017) between different risk groups. Adjuvant chemotherapy significantly improved survival in the low-risk group (P = .041) but not high-risk group (P = 0.56). ConclusionThis study represents the first successful prediction of pathological complete response achievement after neoadjuvant chemotherapy for NSCLC, as well as the patients’ survival, utilizing intratumoral and peritumoral radiomics features.

A Path to High-Value Gastric Cancer Surgery Care Delivery

Objective: To evaluate the feasibility, safety, and effectiveness of a comprehensive regional program, including the Minimally Invasive Recovery and Empowerment Care (MIREC) pathway, that can significantly reduce hospital stays after laparoscopic gastrectomy without increasing adverse events. Background: Cost-effectiveness and improving patient outcomes are crucial in providing quality gastric cancer care worldwide. Methods: To compare the outcomes of gastric cancer surgery using 2 different models of care within an integrated healthcare system from February 2012 to March 2023. The primary endpoint was the length of hospital stay. The secondary endpoints were the need for intensive care unit care, emergency room (ER) visits, readmission, reoperation, and death within 30 days after surgery. Results: There were 553 patients, 167 in the pre-(February 2012–April 2016) and 386 in the post-MIREC period (May 2016–March 2023). Perioperative chemotherapy utilization increased from 31.7% to 76.4% (P &lt; 0.0001). Laparoscopic gastrectomy increased from 17.4% to 97.7% (P &lt; 0.0001). Length of hospitalization decreased from 7 to 2 days (P &lt; 0.0001), with 32.1% and 88% of patients discharged home on postoperative day 1 and postoperative day 2, respectively. When comparing pre- and post-MIREC, intensive care unit utilization (10.8% vs. 2.9%, P &lt; 0.0001), ER visits (34.7% vs. 19.7%, P = 0.0002), and readmission (18.6% vs. 11.1%, P = 0.019) at 30 days were also considerably lower. In addition, more patients received postoperative adjuvant chemotherapy (31.4% to 63.5%, P &lt; 0.0001), and the time between gastrectomy and starting adjuvant chemotherapy was also less (49–41 days; P = 0.002). Conclusion: This comprehensive regional program, which encompasses regionalization care, laparoscopic approach, modern oncologic care, surgical subspecialization, and the MIREC pathway, can potentially improve gastric cancer surgery outcomes. These benefits include reduced hospital stays and lower complication rates. As such, this program can revolutionize how gastric cancer surgery is delivered, leading to a higher quality of care and increased value to patients.

The CRP-albumin-lymphocyte (CALLY) Index Is an Independent Prognostic Factor for Gastric Cancer Patients who Receive Curative Treatment.

The CRP-albumin-lymphocyte (CALLY) index is a promising biomarker. We clarified the clinical impact of the CALLY index in gastric cancer patients who received curative treatment. Consecutive patients who underwent curative resection for gastric cancer at Yokohama City University from 2005 to 2020 were selected based on medical records. The CALYY index was calculated as follows: serum ALB level (g/dl) × lymphocyte count (cells/μl)/C-reactive protein (mg/dl) ×104 Results: Two hundred fifty-nine patients were included in the present study. The three- and five-year overall survival (OS) rates were 64.8% and 57.0%, respectively, in the CALLY index-low group, and 86.2% and 78.2%, respectively, in the CALLY index-high group. There were significant differences between the two groups. A multivariate analysis demonstrated that the CALLY index was an independent prognostic factor for overall survival (hazard ratio=1.791; 95% confidence interval=1.067-3.009; p=0.028). When comparing the perioperative clinical course between the CALLY index-low and CALLY index-high groups, there were significant differences in postoperative surgical complications and adjuvant chemotherapy. The CALLY score was an independent prognostic factor for patients with gastric cancer. Our results suggest that the CALLY index is a promising tool for assessing inflammation and nutritional status in patients undergoing gastric cancer treatment and management.

Clinical Impact of Preoperative Prognostic Nutritional Index in Surgical Patients With Pancreatic Cancer Treated With Perioperative Adjuvant Chemotherapy.

The prognostic nutritional index (PNI) is used as a marker to evaluate the nutritional and immunological status of patients with various cancers. This study aimed to investigate whether preoperative PNI is a prognostic factor in patients with pancreatic cancer who underwent perioperative adjuvant chemotherapy and surgical resection. We retrospectively enrolled 232 pancreatic cancer patients who underwent surgical resection with perioperative adjuvant chemotherapy between January 2013 and December 2022. Overall survival (OS) and relapse-free survival (RFS) rates were calculated using the Kaplan-Meier method. Univariate and multivariate analyses were performed using the Cox proportional hazards regression models. The optimal cutoff value for the preoperative PNI was 44.3 in the present study. PNI <44.3 was associated with older age (p<0.001) and affected the clinical course of postoperative adjuvant chemotherapy. The PNI <44.3 had an important influence on the decreased OS (25.1 vs. 39.0 months) and RFS (13.1 vs. 22.8 months). In univariate and multivariate analyses, the preoperative PNI was an independent prognostic factor for OS [hazard ratio (HR)=1.682, 95% confidence interval (CI)=1.059-2.673, p=0.028] and RFS (HR=1.559, 95% CI=1.037-2.344, p=0.033). Preoperative PNI is a prognostic factor for both OS and RFS in patients with pancreatic cancer who underwent perioperative adjuvant chemotherapy and surgical resection. This study suggests that a low PNI may cause a lack of full-dose adjuvant chemotherapy, leading to recurrence and resulting in a poor prognosis for surgical pancreatic cancer patients treated with perioperative adjuvant chemotherapy.

Fulminant myocarditis during postoperative adjuvant chemotherapy for lung cancer with atezolizumab: a case report

BackgroundPostoperative adjuvant systemic therapy with atezolizumab for lung cancer has been reported to be effective. Although myocarditis is a rare immune adverse event associated with atezolizumab, it can have a serious course and should be treated with caution. We herein report a case of fulminant myocarditis during adjuvant systemic therapy with atezolizumab.Case presentationThe patient was a 49-year-old Asian woman. She was diagnosed with pT2aN1M0 stage IIB (Programmed Death Ligand 1(PD-L1), 50%) after surgery for right upper lobe lung adenocarcinoma. Atezolizumab was administered following platinum-based adjuvant chemotherapy. On day 14, the patient was hospitalized because of deterioration in her general condition caused by fever. On day 16, she developed dyspnea, which worsened, and on day 17, she experienced shock. Blood tests, echocardiography, and cardiac catheterization were performed, and the patient was diagnosed with cardiogenic shock due to myocarditis. Initial measures did not improve the patient’s shock state. The patient was transferred to hospital for the use of an assistive circulatory system. Pulse steroid therapy was administered, and myocarditis showed a tendency toward improvement. A retrospective review of the patient’s history revealed a decreased lymphocyte count and an increase in the neutrophil/lymphocyte ratio, which may be useful for detecting severe immune-related adverse events. The troponin levels were elevated, but creatine phosphokinase level remained within the normal range.ConclusionMyocarditis can be fatal due to the rapid progression of symptoms. Close follow-up, a prompt diagnosis, and therapeutic intervention are important. Decreased lymphocyte counts, increased neutrophil/lymphocyte ratios, and the measurement of multiple myocardial biomarkers are considered useful for the early diagnosis of myocarditis.

Desulfovibrio desulfuricans and its derived metabolites confer resistance to FOLFOX through METTL3

Chemoresistance is a critical factor contributing to poor prognosis in clinical patients with cancer undergoing postoperative adjuvant chemotherapy. The role of gut microbiota in mediating resistance to tumour chemotherapy remains to be investigated. Patients with CRC were categorised into clinical benefit responders (CBR) and no clinical benefit responders (NCB) based on chemotherapy efficacy. Differential bacterial analysis using 16S rRNA sequencing revealed Desulfovibrio as a distinct microbe between the two groups. Employing a syngeneic transplantation model, we assessed the effect of Desulfovibrio on chemotherapy by measuring tumour burden, weight, and Ki-67 expression. We further explored the mechanisms underlying the compromised chemotherapeutic efficacy of Desulfovibrio using metabolomics, western blotting, colony formation, and cell apoptosis assays. In comparison, Desulfovibrio was more abundant in the NCB group. Invivo experiments revealed that Desulfovibrio colonisation in the gut weakened the efficacy of FOLFOX. Treatment with Desulfovibrio desulfuricans elevates serum S-adenosylmethionine (SAM) levels. Interestingly, SAM reduced the sensitivity of CRC cells to FOLFOX, thereby promoting the growth of CRC tumours. These experiments suggest that SAM promotes the growth and metastasis of CRC by driving the expression of methyltransferase-like 3 (METTL3). A high abundance of Desulfovibrio in the intestines indicates poor therapeutic outcomes for postoperative neoadjuvant FOLFOX chemotherapy in CRC. Desulfovibrio drives the manifestation of METTL3 in CRC, promoting resistance to FOLFOX chemotherapy by increasing the concentration of SAM. This study is supported by Wuxi City Social Development Science and Technology Demonstration Project (N20201005).

Predictive role of the prognostic nutritional index in patients with pancreatic ductal adenocarcinoma who underwent neoadjuvant chemoradiotherapy followed by curative pancreatic resection: A retrospective study using prospectively collected data.

Despite a strong association between nutritional indices and disease prognosis, evidence regarding the evaluation of nutritional indices after preoperative treatment for pancreatic ductal adenocarcinoma (PDAC) is insufficient. We evaluated the clinical significance of the prognostic nutritional index (PNI) in patients with resectable (R-) and borderline resectable (BR-) PDAC who received neoadjuvant chemoradiotherapy (NACRT) followed by pancreatic resection. We assessed 153 patients with R- and BR-PDAC who underwent NACRT followed by curative resection between 2009 and 2022. We evaluated the association between preoperative PNI after NACRT and short- and long-term outcomes. The median preoperative PNI value after NACRT was 42.1, and the optimal cutoff value from the time-dependent receiver operating characteristic curve was 38.6. The low PNI group (PNI < 38.6, n = 44) exhibited significantly worse inflammatory parameters, surgical outcomes, and prognoses than the high PNI group (PNI ≥ 38.6, n = 109). Multivariate analysis identified preoperative PNI ≤ 38.6 (hazard ratio [HR]: 2.32, 95% confidence interval [CI]: 1.00-5.38, p = .049), blood loss ≥1642 mL (HR: 3.05, 95% CI: 1.65-5.64, p < .001), node positive pathology (HR: 2.10, 95% CI: 1.32-3.34, p = .002), and lack of postoperative adjuvant chemotherapy (HR: 3.55, 95% CI: 2.05-6.15, p < .001) as significant predictors of overall survival. For patients with R- and BR-PDAC receiving preoperative treatment, it is imperative to closely monitor their nutritional status when determining the optimal surgical procedure timing.

Clinical characteristics and prognostic impact of direct distant organ metastasis in colorectal cancer

BackgroundColorectal cancer (CRC) is the third most common type of cancer worldwide, and distant metastasis is frequently noted at diagnosis or follow-up. Notably, some patients with CRC can present with distant organ metastasis without any nodal involvement, which was defined as direct distant organ metastasis (DDOM). In this study, we evaluated the prognostic significance of DDOM for patients with CRC. MethodsThis study included 325 patients who had undergone primary colorectal cancer resection between August 2008 and December 2021. The patients with and without DDOM were compared (Kaplan–Meier analysis) in terms of overall survival (OS) and time to recurrence. Furthermore, the patients’ clinicopathological risk factors and protective factors were analyzed (multivariate Cox proportional hazards model). ResultsOf the 325 patients, 65 (20%) had DDOM (Direct+ group) and 260 (80%) did not (Direct− group). The Kaplan–Meier analysis revealed that OS was significantly better in the Direct+ group than in the Direct− group (p < 0.01). A subgroup analysis by CRC stage was performed; for the patients with non-stage-IV CRC, the rate of OS was significantly higher in the Direct+ group than in the Direct− group (p = 0.02). However, DDOM did not affect the OS of the patients with stage IV CRC. The multivariate analysis indicated DDOM, left colon tumor location, and postoperative adjuvant chemotherapy were significant protective factors for disease-related mortality in the patients with non-stage-IV CRC; by contrast, body mass index, curative resection, and postoperative adjuvant chemotherapy were identified to be significant protective factors in the patients with stage IV CRC. ConclusionsDDOM appears to be significantly associated with improved OS in patients with non-stage-IV CRC but not in those with stage IV CRC. Furthermore, the time to cancer recurrence may not vary significantly between patients with DDOM and those without it.

Impact of the neutrophil-to-lymphocyte ratio on patients with locally advanced non-small cell lung cancer who suffer radiation pneumonitis during the course of induction chemoradiotherapy followed by surgery.

Radiation pneumonitis (RP) is an obstacle for patients after surgery following induction chemoradiotherapy for locally advanced non-small cell lung cancer (LA-NSCLC). We performed a comparative analysis of the association between clinicopathological factors, including the neutrophil-to-lymphocyte ratio (NLR) and prognosis, in LA-NSCLC patients with or without RP during induction chemoradiotherapy followed by surgery. The subjects of this analysis were 168 patients undergoing trimodality therapy for LA-NSCLC between January, 1999 and May, 2019. Patients were divided into two groups: the RP group (n = 41) and the non-RP group (n = 127). We compared the clinicopathological factors including the NLR between the groups and analyzed the association between the NLR and prognosis. The RP group had more patients with tumors located in the lower lobe, more bilobar resections, shorter operative times, no implementation of postoperative adjuvant chemotherapy, and a higher postoperative NLR than the non-RP group. There were no significant differences in serious postoperative complications and the prognosis. Patients with a low postoperative NLR had a significantly better prognosis in the non-RP group, and a trend toward a better prognosis even in the RP group. Postoperative NLR may be a useful prognostic factor, even for patients who suffer RP after trimodality therapy for LA-NSCLC.