Optimizing tumor-associated antigen-stimulated autologous dendritic cell and cytokine-induced killer cell coculture to enhance cytotoxicity for cancer immunotherapy in manufacturing.

BACKGROUND: Dendritic Cell Cytokine-induced killer cell (DC-CIK) coculture treatment in cancer immunotherapy has been shown to be effective. However, the cost of DC- CIK therapy is prohibitive for many patients, and the lack of standard manufacturing processes and treatment strategies are major limitations. Our study used tumor lysate as a tumor-associated antigen source and DCs and CIK cells in coculture. We developed an efficient method to obtain autologous DCs- and CIK cells from peripheral blood. We used flow cytometry to assess DC activation and the cytometric bead array assay to quantify cytokines secreted by CIK cells. RESULTS: We evaluated the antitumor activity of DC- CIK coculture in vitro with the K562 cell line. We demonstrated that a manufacturing process employing frozen immature DCs can yield the lowest loss with the highest economic benefits. DC-CIK coculture can effectively upgrade CIK cells' immunological specificity to tumors in the presence of tumor-associated antigens. CONCLUSION: In vitro experiments revealed that when the DC- CIK cell ratio was 1: 20 in the coculture, CIK cells secreted the highest number of cytokines on the 14th day and the antitumor immune effect showed the highest potency. CIK cells' cytotoxicity to K562 cells was highest when the CIK: K562 cell ratio was 25: 1. We developed an efficient manufacturing process for DC- CIK coculture, while also establishing the optimal DC- CIK cell ratio for immunological activity and the best cytotoxic CIK: K562 cell ratio.

The efficacy of adjuvant chemotherapy for older adults with stage II/III gastric cancer: a retrospective cohort study.

BACKGROUND: Adjuvant chemotherapy is recommended as the standard treatment for patients with stage II/III resected gastric cancer. However, it is unclear whether older patients also benefit from an adjuvant chemotherapy strategy. This study aimed to investigate the clinical impact of adjuvant chemotherapy in older patients with stage II/III gastric cancer. METHODS: This retrospective, real-world study analyzed 404 patients with stage II/III gastric cancer visited at our institute between January 2009 and December 2019. The clinical characteristics and outcomes of patients aged 70 years or older who received adjuvant chemotherapy were compared with those who did not receive this type of treatment. Propensity score analysis was performed to mitigate selection bias. RESULTS: Of the 404 patients analyzed, 179 were aged 70 years or older. Fewer older patients received adjuvant chemotherapy than did younger patients (60.9% vs. 94.7%, respectively; P < 0.001). Among patients aged 70 years or older, those who received adjuvant chemotherapy had improved disease-free survival (DFS) (5-year DFS rate, 53.1% vs. 30.4%; P < 0.001) and overall survival (OS) (5-year OS rate, 68.7% vs. 52.1%; P = 0.002) compared to those who did not receive adjuvant chemotherapy. A similar survival benefit was observed in the propensity-matched cohort. Multivariate analysis showed that more advanced stage was associated with poorer OS. Receipt of adjuvant chemotherapy was independently associated with a decreased hazard of death (hazard ratio (HR), 0.37; 95% confidence intervals (CI), 0.20-0.68; P = 0.002). CONCLUSIONS: Adjuvant chemotherapy may benefit older stage II/III gastric cancer patients aged ≥ 70 years. Further prospective studies are needed to confirm these findings.

Liver resection for hepatocellular carcinoma in oldest old patients.

BACKGROUND: For hepatocellular carcinoma (HCC), liver resection is a classical curative modality, despite its technical complexity. The incidence of HCC in the oldest old people (aged ≥ 85 years) is rising along with the global increase in life expectancy. Currently, no report has addressed liver resection for HCC in this aged population. PATIENTS AND METHODS: We conducted a retrospective review of 1889 patients receiving curative liver resection for newly diagnosed HCC from 1992 to 2016. At the time of operation, 1858 of them were aged < 85 years (group A), and 31 were aged ≥ 85 years (group B). Another 18 oldest old patients, whose HCC was considered resectable but were not operated on due to the patient's refusal, served as the control group (group C). The clinicopathological characteristics and early and long-term outcomes were compared between groups A and B. All associated co-morbidities of the patients were well-treated before liver resection. The overall survival (OS) rates were also compared between groups B and C. RESULT: Group B had a significantly higher incidence of associated co-morbidities and hepatitis C infection. Postoperative complication rates and 90-day mortality rates after liver resection did not differ between groups A and B (p = 0.834 and p = 1.000, respectively), though group B had a longer postoperative stay (p = 0.001). In groups A and B, the 5-year disease-free survival rates were 29.7% and 22.6% (p = 0.163), respectively, and their overall survival rates were 43.5% and 35.5% (p = 0.086). The overall survival rate of group B was significantly different from group C (35.5% vs. 0%, p = 0.001). CONCLUSION: Despite a longer postoperative recovery period, liver resection for HCC in the oldest old patients may be justified if co-morbidities are well controlled.

Lower gastrointestinal bleeding in a male with jejunal Dieulafoy's lesion after successful surgical resection: A case report and literature review.

INTRODUCTION: Dieulafoy's lesion (DL) presented with small bowel bleeding constitutes a group of rare and potentially life-threatening prognosis. Several case series have described this condition, yet it remains unclear as to what is the optimal treatment and predicted outcome for patients who have been diagnosed. PATIENT CONCERNS: We present a 21-year-old male experiencing bloody stool for 1 day. DIAGNOSIS: Computed tomography of the abdomen exhibited active contrast extravasations and segmental wall thickening in the jejunum, and enteroscopy showed one 15-millimeter sized subepithelial tumor at the proximal jejunum. INTERVENTIONS: Due to unstable vital signs he received an emergent transcatheter arterial embolization, and surgeon performed a laparoscopic surgical resection thereafter under the impression of potential malignancy. The pathologist confirmed jejunal DL with organizing thrombus. OUTCOMES: He was discharged on the 8th day of hospitalization without recurrent bleeding. CONCLUSION: A systematic literature review of 98 published cases taken from PubMed dating back to 1978 was undertaken, and the patients with DL and small bowel bleeding involved mainly the jejunum, followed by the duodenum and ileum. Meanwhile, DL-related duodenal bleeding was diagnosed mostly by an enteroscopy, as well as endoscopic interventions. Jejunal and ileal bleeding due to DL was surveyed through endoscopy and surgery, while surgical resection remained the choice for bleeding cessation. Only anticoagulant use (OR = 18.16; P = .08) was associated with a higher risk of overall mortality, although it was non-significant in univariate analysis. We emphasize that individualized treatment as well as prompt measurement should be implemented accordingly.

Surgical Indications for Huge Hepatocellular Carcinoma.

BACKGROUND/AIM: This study aimed to retrospectively analyse adverse predictors to identify patients with huge hepatocellular carcinoma who were not appropriate candidates for hepatic resection. PATIENTS AND METHODS: From 551 patients with hepatocellular carcinoma who underwent hepatectomy between 1992 and 2019, 92 were diagnosed with huge hepatocellular carcinoma (diameter >10 cm) and 115 were diagnosed with large hepatocellular carcinoma (diameter=5-10 cm). Clinical features and overall and disease-free survival rates were compared between the two groups. RESULTS: Cumulative overall survival was significantly worse in the huge group than in the large group (p=0.035). In the huge group, multivariate analyses revealed that liver cirrhosis, multiple intrahepatic metastases (≥4), poor histological grade, and macroscopic portal vein invasion were significantly associated with poor prognosis. CONCLUSION: We identified four adverse predictors of survival and determined that patients with two or more predictors are not appropriate candidates for straightforward hepatic resection.

Concomitant Hepatectomy and Atrial Thrombectomy under Cardiopulmonary Bypass versus Staged Hepatectomy in the Treatment for Hepatocellular Carcinoma with Large Right Atrial Tumor Thrombi.

(1) Background: Hepatocellular carcinoma (HCC) with a large right atrium tumor thrombus (RATT) is a rare and critical presentation. Emergency hepatectomy and thrombectomy under cardiopulmonary bypass (CPB) is life-saving and potentially curative. The aim of this study is to propose an appropriate approach for this condition. (2) Methods: In period A (1998 to 2010, n = 7), hepatectomy and thrombectomy were concomitantly performed, and staged hepatectomy was performed in period B (2011 to 2018, n = 17). (3) Results: The median overall survival time (MOST) in the published studies was 14 months. Moreover, the blood loss, blood transfusion rate, length of ICU stays, and hospital costs were significantly reduced in period B. The MOSTs of patients in period A (n = 6) and period B (n = 17) were 14 vs. 18 months (p = 0.099). The median disease-free survival times (MDFTs) in period A (n = 6) and period B (n = 15) were 8 vs. 14 months (p = 0.073), while the MOSTs in period A and period B were 14 vs. 24 months (p = 0.040). (4) Conclusions: Emergency thrombectomy under CPB and staged hepatectomy 4-6 weeks later may be an appropriate approach for HCC with large RATT. However, the optimal waiting interval requires further investigation.

Colo-pancreaticoduodenectomy for locally advanced colon carcinoma-feasibility in patients presenting with acute abdomen.

BACKGROUND: En bloc right hemicolectomy plus pancreaticoduodenectomy (PD) is administered for locally advanced colon carcinoma that invades the duodenum and/or pancreatic head. This procedure may also be called colo-pancreaticoduodenectomy (cPD). Patients with such carcinomas may present with acute abdomen. Emergency PD often leads to high postoperative morbidity and mortality. Here, we aimed to evaluate the feasibility and outcomes of emergency cPD for patients with advanced colon carcinoma manifesting as acute abdomen. METHODS: We retrospectively reviewed 4898 patients with colorectal cancer who underwent curative colectomy during the period from 1994 to 2018. Among them, 30 had locally advanced right colon cancer and had received cPD. Among them, surgery was performed in 11 patients in emergency conditions (bowel obstruction: 6, perforation: 3, tumor bleeding: 2). Selection criteria for emergency cPD were the following: (1) age ≤ 60 years, (2) body mass index < 35 kg/m2, (3) no poorly controlled comorbidities, and (4) perforation time ≤ 6 h. Three patients did not meet the above criteria and received non-emergency cPD after a life-saving diverting ileostomy, followed by cPD performed 3 months later. We analyzed these patients in terms of their clinicopathological characteristics, the early and long-term postoperative outcomes, and compared findings between emergency cPD group (e-group, n = 11) and non-emergency cPD group (non-e-group, n = 19). After cPD, staged pancreaticojejunostomy was performed in all e-group patients, and on 15 of 19 patients in the non-e-group. RESULTS: The non-e-group was older and had a higher incidence of associated comorbidities, while other clinicopathological characteristics were similar between the two groups. None of the patients in the two groups succumbed from cPD. The postoperative complication rate was 63.6% in the e-group and 42.1% in the non-e-group (p = 0.449). The 5-year overall survival rate were 15.9% in the e-group and 52.6% in the non-e-group (p = 0.192). CONCLUSIONS: Emergency cPD is feasible in highly selected patients if performed by experienced surgeons. The early and long-term positive outcomes of emergency cPD are similar to those after non-emergency cPD in patients with acute abdominal conditions.

Clinical practice guidelines for the management of liver metastases from extrahepatic primary cancers 2021.

BACKGROUND: Hepatectomy is standard treatment for colorectal liver metastases; however, it is unclear whether liver metastases from other primary cancers should be resected or not. The Japanese Society of Hepato-Biliary-Pancreatic Surgery therefore created clinical practice guidelines for the management of metastatic liver tumors. METHODS: Eight primary diseases were selected based on the number of hepatectomies performed for each malignancy per year. Clinical questions were structured in the population, intervention, comparison, and outcomes (PICO) format. Systematic reviews were performed, and the strength of recommendations and the level of quality of evidence for each clinical question were discussed and determined. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess evidence and make recommendations. RESULTS: The eight primary sites were grouped into five categories based on suggested indications for hepatectomy and consensus of the guidelines committee. Fourteen clinical questions were devised, covering five topics: (1) diagnosis, (2) operative treatment, (3) ablation therapy, (4) the eight primary diseases, and (5) systemic therapies. The grade of recommendation was strong for one clinical question and weak for the other 13 clinical questions. The quality of the evidence was moderate for two questions, low for 10, and very low for two. A flowchart was made to summarize the outcomes of the guidelines for the indications of hepatectomy and systemic therapy. CONCLUSIONS: These guidelines were developed to provide useful information based on evidence in the published literature for the clinical management of liver metastases, and they could be helpful for conducting future clinical trials to provide higher-quality evidence.

Embedding fistulojejunostomy: An easy and secure technique for refractory external pancreatic fistula.

BACKGROUND: Refractory external pancreatic fistula (REPF) is a rare but troublesome event. Fistulojejunostomy with direct suture of the fistula wall to jejunal wall has been demonstrated as a solution. However, it is sometimes technically difficult and some cases of failure were reported. METHODS: An embedding fistulojejunostomy (EFJ) was designed. The fistula tract was detached from the abdominal wall and impactedly inserted into a Roux-en-Y jejunal lumen without direct suture of the fistula wall to the jejunal wall. Five patients with REPF for > 3 months underwent this procedure in the past 10 years. The preoperatively-placed drainage tubes temporarily exteriorized the pancreatic fluid for 30 days. RESULTS: All fistulojejunostomy procedures were accomplished within 15 minutes. Four patients had uneventful recovery with a postoperative hospital stay ≤ 10 days. One patient had wound infection and needed hospitalization for 23 days. Except for one patient who required pancreatic enzyme supplements for 8 months, no other patient had pancreatic exocrine insufficiency. After follow up for 12-124 months, no patient required pancreatic enzyme supplements, and no patient had recurrent fistula or diabetes mellitus. CONCLUSION: EFJ makes fistulojejunostomy easier and more secure with a satisfactory early and long-term outcome. It may be a desirable technique for REPF.