Expression of ZKSCAN3 protein suppresses proliferation, migration, and invasion of pancreatic cancer through autophagy.

Elevated autophagy activity enhances the malignancy of pancreatic cancer (PaCa), and autophagy is recognized as a novel therapeutic target. Zinc finger protein with KRAB and SCAN domains 3 (ZKSCAN3) is a transcription factor that suppresses autophagy, but its association with PaCa is unknown. We analyzed the function of ZKSCAN3 in PaCa and investigated whether autophagy regulation through ZKSCAN3 could become a new therapeutic target for PaCa. Using reverse transcription-quantitative polymerase chain reaction and western blotting, we observed that ZKSCAN3 expression was upregulated in several PaCa cell lines compared with normal pancreatic ductal epithelial cells. Additionally, comparing ZKSCAN3 expression with the prognosis of PaCa patients using web databases, we found that higher ZKSCAN3 expression in PaCa was associated with extended overall survival. Knocking down ZKSCAN3 promoted the proliferation of PaCa cells. Moreover, following ZKSCAN3 knockdown, PaCa cells exhibited significantly enhanced migratory and invasive properties. Conversely, overexpression of ZKSCAN3 significantly suppressed the proliferation, migration and invasion of PaCa cells. Additionally, the knockdown of ZKSCAN3 increased the expression of LC3-II, a marker of autophagy, whereas ZKSCAN3 overexpression decreased LC3-II expression. In a xenograft mouse model, tumors formed by MIA PaCa-2 cells in which ZKSCAN3 was knocked down significantly increased in size compared with the control group. In conclusion, ZKSCAN3 expression was upregulated in several pancreatic cancer cells. Additionally, it was revealed that ZKSCAN3 is negatively correlated with the malignancy of PaCa through autophagy. These results suggest that autophagy regulation via ZKSCAN3 may be a new therapeutic target for PaCa.

The Natural Product Parthenolide Inhibits Both Angiogenesis and Invasiveness and Improves Gemcitabine Resistance by Suppressing Nuclear Factor κB Activation in Pancreatic Cancer Cell Lines.

We previously established pancreatic cancer (PaCa) cell lines resistant to gemcitabine and found that the activity of nuclear factor κB (NF-κB) was enhanced upon the acquisition of gemcitabine resistance. Parthenolide, the main active ingredient in feverfew, has been reported to exhibit antitumor activity by suppressing the NF-κB signaling pathway in several types of cancers. However, the antitumor effect of parthenolide on gemcitabine-resistant PaCa has not been elucidated. Here, we confirmed that parthenolide significantly inhibits the proliferation of both gemcitabine-resistant and normal PaCa cells at concentrations of 10 µM and higher, and that the NF-κB activity is significantly inhibited, even by 1 µM parthenolide. In Matrigel invasion assays and angiogenesis assays, the invasive and angiogenic potentials were higher in gemcitabine-resistant than normal PaCa cells and were inhibited by a low concentration of parthenolide. Furthermore, Western blotting showed suppressed MRP1 expression in gemcitabine-resistant PaCa treated with a low parthenolide concentration. In a colony formation assay, the addition of 1 µM parthenolide improved the sensitivity of gemcitabine-resistant PaCa cell lines to gemcitabine. These results suggest that parthenolide may be used as a novel therapeutic agent for the treatment of gemcitabine-resistant PaCa.

Survival Prediction of Patients Who Were Terminally Ill Using the EORTC QLQ-C15-PAL Scores and Laboratory Test Values.

Background: Prognostics for patients with cancer is especially important for the supportive care of those who are terminally ill. We previously found that symptom scores as patient-reported outcomes (PROs)-such as dyspnea and fatigue scores-some biochemical parameters, the palliative performance scale (PPS) scores, and symptom clusters were useful prognostic factors; however, the predictability of a prognosis based on these factors remains unclear. Objective: To identify appropriate three-week survival predictive factor(s), in terms of performance, in patients who were terminally ill. Design: We collected symptom scores as PROs using the Japanese version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 Palliative Care (EORTC QLQ-C15-PAL). Setting/Subjects: We used data from terminally ill patients with cancer who were hospitalized at the palliative care unit of the Higashisumiyoshi-Morimoto Hospital (Osaka, Japan) from June 2018 to December 2019 (n = 130), as well as additional data obtained from the same clinical study from January to March 2020 (n = 31). Measurements: To evaluate predictive performance, indices such as sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy were calculated. Results: We found that the presence of a symptom cluster showed high sensitivity but low specificity and that a higher PPS value (>30) showed high specificity but low sensitivity, suggesting that these factors could provide relevant information for survival prognosis (less than or equal to three weeks). Conclusion: Symptom clusters obtained from patients is important for effective supportive care of those who are terminally ill.

Solo surgery in robot-assisted gastrectomy versus laparoscopic gastrectomy for gastric cancer: a propensity score-matched analysis.

BACKGROUND: Robot-assisted gastrectomy (RG) for gastric cancer is still not well standardized. This study aimed to explore the feasibility and effectiveness of solo surgery in robot-assisted gastrectomy (SRG) for gastric cancer compared to laparoscopic gastrectomy (LG). METHODS: This was a single-center retrospective comparative study between SRG and conventional LG. Between April 2015 and December 2022, 510 patients underwent gastrectomy, and data from a prospectively collected database were analyzed. We identified 372 patients who underwent LG (n = 267) and SRG (n = 105) and the remaining 138 patients were excluded because of remnant gastric cancer, esophagogastric junction cancer, open gastrectomy, concurrent surgery for concomitant malignancies, RG before starting SRG, or cases in which the author was unable to perform or supervise gastrectomy. Propensity score matching was performed at a ratio of 1:1 to reduce bias from confounding patient-related variables, and short-term outcomes were compared between the groups. RESULTS: After propensity score matching, 90 pairs of patients who underwent LG and SRG were selected. In the propensity-matched cohort, the operation time was significantly shorter in the SRG group than that in the LG group (SRG = 305.7 ± 74.0 min vs. LG = 340.3 ± 91.65 min, p < 0.0058), less estimated blood loss was observed in the SRG group than that in the LG group (SRG = 25.6 ± 50.6 mL vs. LG = 76.1 ± 104.2 mL, p < 0.0001) and postoperative hospital stay was shorter in the SRG group than that in the LG group (SRG = 7.1 ± 0.8 days vs. LG = 9.1 ± 7.7 days, p = 0.015). CONCLUSION: We found that SRG for gastric cancer was technically feasible and effective with favorable short-term outcomes, including shorter operative time, less estimated blood loss, shorter hospital stays, and lower postoperative morbidity than those in LG.

Pathologic method for extracting good prognosis group in triple-negative breast cancer after neoadjuvant chemotherapy.

The area of residual tumor (ART) is a prognostic factor in patients treated with neoadjuvant chemotherapy (NAC) for lung, pancreatic, and rectal cancers. This study aimed to evaluate the usefulness of ART as a method for predicting the prognosis of triple-negative breast cancer (TNBC) patients after NAC. We included 143 patients with TNBC treated with NAC. The ART at the maximum cut surface of the residual tumor was measured. We divided the patients into three groups: ART-0 (ART = 0 mm2 ), ART-low (0 mm2  < ART ≤ 136mm2 ), and ART-high (ART > 136 mm2 ), and compared their clinicopathologic factors and prognosis. There were no significant differences in either recurrence-free survival (RFS) or overall survival (OS) between ART-0 and ART-low; however, the ART-high group had significantly shorter RFS and OS than the ART-0 and ART-low groups. Multivariate analysis showed that ART-0 and -low and ypN(-) were independent favorable prognostic factors for RFS. Groups with both ART-low and ypN(-) as well as those with ART-0 and ypN(-) showed significantly longer OS and RFS than the other groups (P < .05). Moreover, there was no significant difference in the RFS and OS between the ART-0 and ypN(-) groups and the ART-low and ypN(-) groups (P = .249 and P = .554, respectively). We concluded that ART is a candidate histopathological evaluation method for predicting the prognosis of TNBC patients treated with NAC. Furthermore, postoperative chemotherapy could be omitted in patients with ART-0 and ypN(-) (pathological complete response) and those with ART-low and ypN(-).

Symptom clusters and their influence on prognosis using EORTC QLQ-C15-PAL scores in terminally ill patients with cancer.

PURPOSE: The aims of the present study were to investigate the symptom clusters in terminally ill patients with cancer using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 Palliative Care (EORTC QLQ-C15-PAL), and to examine whether these symptom clusters influenced prognosis. METHODS: We analyzed data from 130 cancer patients hospitalized in the palliative care unit from June 2018 to December 2019 in an observational study. Principal component analysis was used to detect symptom clusters using the scored date of 14 items in the QLQ-C15-PAL, except for overall QOL, at the time of hospitalization. The influence of the existence of these symptom clusters and Palliative Performance Scale (PPS) on survival was analyzed by Cox proportional hazards regression analysis, and survival curves were compared between the groups with or without existing corresponding symptom clusters using the log-rank test. RESULTS: The following symptom clusters were identified: cluster 1 (pain, insomnia, emotional functioning), cluster 2 (dyspnea, appetite loss, fatigue, and nausea), and cluster 3 (physical functioning). Cronbach's alpha values for the symptom clusters ranged from 0.72 to 0.82. An increased risk of death was significantly associated with the existence of cluster 2 and poor PPS (log-rank test, p = 0.016 and p < 0.001, respectively). CONCLUSION: In terminally ill patients with cancer, three symptom clusters were detected based on QLQ-C15-PAL scores. Poor PPS and the presence of symptom cluster that includes dyspnea, appetite loss, fatigue, and nausea indicated poor prognosis.

The role of EORTC QLQ-C15-PAL scores and inflammatory biomarkers in predicting survival in terminally ill patients with cancer.

BACKGROUND: The clinical use of patient-reported outcomes as compared to inflammatory biomarkers for predicting cancer survival remains a challenge in palliative care settings. We evaluated the role of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 Palliative scores (EORTC QLQ-C15-PAL) and the inflammatory biomarkers C-reactive protein (CRP), albumin (Alb), and neutrophil-lymphocyte ratio (NLR) for survival prediction in patients with advanced cancer. METHODS: This was an observational study in terminally ill patients with cancer hospitalized in a palliative care unit between June 2018 and December 2019. Patients' data collected at the time of hospitalization were analyzed. Cox regression was performed to examine significant factors influencing survival. A receiver operating characteristic (ROC) analysis was performed to estimate cut-off values for predicting survival within 3 weeks, and a log-rank test was performed to compare survival curves between groups divided by the cut-off values. RESULTS: Totally, 130 patients participated in the study. Cox regression suggested that the QLQ-C15-PAL dyspnea and fatigue scores and levels of CRP, Alb, and NLR were significantly associated with survival time, and cut-off values were 66.67, 66.67, 3.0 mg/dL, 2.5 g/dL, and 8.2, respectively. The areas under ROC curves of these variables were 0.6-0.7. There were statistically significant differences in the survival curves between groups categorized using each of these cut-off values (p < .05 for all cases). CONCLUSION: Our findings suggest that the assessment of not only objective indicators for the systemic inflammatory response but also patient-reported outcomes using EORTC QLQ-C15-PAL is beneficial for the prediction of short-term survival in terminally ill patients with cancer.

A simple and reliable procedure for laparoscopic port-site closure.

PURPOSE: One of the complications in laparoscopic surgery is port-site hernia. It is a rare but potentially dangerous complication. Especially when using ports with a size 10 mm or more, it is required to securely close the port site. However, this procedure is often difficult especially for obese patients. METHODS: We herein devised a new closure method by using a device developed for port site. These techniques are methods that can close the port site by a combination of putting in and out of thread and port rotation without removing a port. The port-site closure with these techniques was done for 53 port sites of 41 patients. RESULTS: The port site was closed horizontally or vertically, depending on the shape of the port site for two patients. Modified Z-suture was done for other 37 patients. To date, we have not noted any complications from this new method, including port-site hernia. CONCLUSION: With our technique, we could save operation time and reduce stress of us especially for obese patients. We would like to increase the number of patients and verify the safety and usefulness in further study.

Comparison of Patient Self-Reported Quality of Life and Health Care Professional-Assessed Symptoms in Terminally ill Patients With Cancer.

BACKGROUND: Few studies evaluated whether health care professionals accurately assess several symptoms for patients with cancer in palliative care units. We determined the agreement level for several symptoms related to quality of life (QOL) between patient-reported QOL assessment and health care professional-assessed symptoms based on the Support Team Assessment Schedule (STAS). METHOD: An observational study was performed with terminally ill patients with cancer hospitalized in the palliative care unit between June 2018 and December 2019. Patients and health care professionals independently assessed 7 symptoms at the time of hospitalization and after 1 week. Patients completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C15-PAL). In examining the proportions of exact agreement, "exact agreement" referred to the pairs of the scores (QLQ-C15-PAL vs STAS) being (1 vs 0), (2 vs 1), (3 vs 2 or 3), or (4 vs 4). The relationships of physical functioning between QLQ-C15-PAL and Palliative Performance Scale (PPS) were examined. RESULTS: Of 130 patients, approximately 60% had PPS scores from 40 to 60. The highest mean score on QLQ-C15-PAL was for fatigue (63.8). The exact agreement on symptoms between patients and health care professionals ranged from 15.4% (fatigue) to 57.7% (nausea and vomiting). The mean of the transformed QLQ-C15-PAL and proportions of exact agreement were negatively correlated (R 2 = 0.949, P < .05). The physical function scores in QLQ-C15-PAL for each PPS group showed no differences. CONCLUSION: We expect patient-reported outcomes including QLQ-C15-PAL to be added to health care professionals' assessment of serious symptoms such as fatigue in terminally ill patients with cancer.

Port site hernia repair using the VersaOne™ Fascial Closure System: a case report.

The use of laparoscopic surgery has become widespread in recent years. One of its complications is port site hernia (PHS). It can be difficult to close the fascia at the time of laparoscopy, especially in obese patients, and there is a risk of herniation through a fascial defect with incomplete closure. It is important to ascertain closure of the defect when repairing PHS to prevent recurrence. We report a 47-year-old woman who developed a PHS at the superior aspect of the umbilicus. We repaired the defect using the VersaOneTM Fascial Closure System with laparoscopic guidance. This system allows the port site to be reliably closed while observing the suture from the abdominal cavity. The incision is the same size as a port site. If the abdominal wall is thick and the PHS has a diameter of ~10 mm, this method is considered to be indicated, regardless of the site.

Eversion stripping of the esophagus with intraesophageal insufflation-A case report.

INTRODUCTION: Patients with esophageal cancer frequently cannot tolerate thoracotomy due to their overall debilitated condition. Moreover, some patients have severe adhesions in the thoracic cavity. Eversion stripping of the esophagus is an option for resection in these patients. PRESENTATION OF CASE: A 64-year-old man was admitted to our institution with the chief complaint of epigastric pain. Endoscopic examination showed a protruding lesion 22cm from the incisors, with a superficial and circumferential mucosal irregularity on the distal side of the lesion. Biopsy revealed squamous cell carcinoma. Clinical stage was T1b(sm)N0M0, cStage I. In addition to the poor pulmonary status of the patient, adhesions in the intrathoracic cavity were predicted. The decision was made to perform esophageal resection without a thoracotomy. In order to ensure complete invagination of the esophagus, the esophagus was insufflated prior to stripping. The stripping process was observed with a gastroscope. During the stripping, the esophagus did not bunch up, and stripping was smooth and with minimal resistance. DISCUSSION: The stripping resection of the esophagus is an important option for the esophageal surgeon. In this case report, we describe a new eversion stripping method of the esophagus. This easy and reliable stripping method incorporates intraesophageal insufflation. CONCLUSION: The indications for blunt esophageal dissection without thoracotomy have been decreasing. On the other hand, our method seems to be useful in optimal case of stripping of esophagus.

Resection of the Gastric Tube Reconstructed through the Retrosternal Route without Sternotomy.

With advances of combined modality therapy, prognoses in esophageal cancer have been improving. After resection of esophageal cancer, the development of gastric tube cancer is a risk. While such cancer in an early stage can be cured endoscopically, total gastric tube resection is indicated in advanced stages. A 68-year-old man underwent subtotal esophagectomy reconstructed with a gastric tube through the retrosternal route. Gastric cancer was found one and a half years postoperatively. The gastric tube was resected without sternotomy. This is the first report of a patient undergoing resection of the gastric tube reconstructed through the retrosternal route without sternotomy.