A network pharmacology-based investigation of emodin against pancreatic adenocarcinoma.

Pancreatic adenocarcinoma (PAAD) is one of the most common malignancies worldwide with an increasing incidence and poor outcome due to the lack of effective diagnostic and treatment methods. Emerging evidence implicates that emodin displays extensive spectrum anticancer properties. Differential expression genes in PAAD patients were analyzed by Gene Expression Profiling Interactive Analysis (GEPIA) website, and the targets of emodin were obtained via Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. Subsequently, enrichment analyses were performed using R software. A protein-protein interaction (PPI) network was constructed by STRING database and Cytoscape software was used to identify the hub genes. Prognostic value and immune infiltration landscapes were explored through Kaplan-Meier plotter (KM plotter) website and the Single-Sample Gene Set Enrichment Analysis package of R. Finally, molecular docking was used to computationally verify the interaction of ligand and receptor proteins. A total of 9191 genes were significantly differentially expressed in PAAD patients and 34 potential targets of emodin were obtained. Intersections of the 2 groups were considered as potential targets of emodin against PAAD. Functional enrichment analyses illustrated that these potential targets were linked to numerous pathological processes. Hub genes identified through PPI networks were correlated with poor prognosis and infiltration level of different immune cells in PAAD patients. Perhaps emodin interacted with the key molecules and regulate the activity of them. We revealed the inherent mechanism of emodin against PAAD with the aid of network pharmacology, which provided reliable evidence and a novel guideline for clinical treatment.

Factors Associated With Survival in Patients With End-of-Life Hematological Malignancies Who Received Chemotherapy: A Retrospective Single-Institution Study.

BACKGROUND: Clinicians can appropriately terminate treatment or reduce treatment intensity by determining prognostic factors of end-of-life chemotherapy. In particular, it provides important information for patients with hematological malignancies who receive chemotherapy until near-the-end of life compared with patients with solid tumors. This study aimed to clarify whether existing prognostic tools are associated with the survival in patients with end-of-life hematological malignancies who received chemotherapy. METHODS: We retrospectively reviewed the records of 247 patients diagnosed with hematological malignancies and died at our university hospital hematology ward between May 2015 and May 2021. We performed multivariate analysis in 82 (33.2%) patients who received end-of-life chemotherapy using the Palliative Prognostic Index (PPI) and inflammation-based prognostic models, such as the Glasgow Prognostic Score (GPS), Prognostic Nutritional Index (PNI), and Controlling Nutrition Status (CONUT). RESULTS: On comparing 82 patients who received end-of-life chemotherapy with 165 patients who did not, the proportion of patients with PPI group A, GPS score = 0, and CONUT normal/mild was significantly higher among patients who received chemotherapy. In multivariate analysis, we identified PPI groups B (2.0 < PPI ≤ 4.0) and C (PPI > 4.0) [hazard ratio (HR) 2.1290, 95% CI 1.1830-3.828, P = .01166, respectively] and age ≥ 65 years (HR 2.0170, 95% CI 1.1280-3.607, P = .01805) were associated with overall survival. CONCLUSION: PPI use and age were independent associating factors for patients with hematological malignancies receiving end-of-life chemotherapy. PPI, a popular prognostic tool may be helpful for patients and hematologists to make decisions about end-of-life care.

Prognostic Value of Palliative Prognostic Index for Hospitalized Patients With End-of-Life Hematologic Malignancies in a Japanese University Hospital.

PURPOSE: Uncertainty of prognosis is one reason patients with hematologic malignancies receive aggressive therapy near end of life more often than those with advanced solid tumors. It is unknown whether end-of-life prognosis prediction models are useful for patients with hematologic malignancies, especially hospitalized patients receiving chemotherapy, because most prognostic models were developed for patients with solid tumors. The purpose of this study was to evaluate the prognostic accuracy of the Palliative Prognostic Index (PPI) for end-of-life patients with advanced hematologic malignancies. METHODS: We retrospectively reviewed the records of 143 patients who became resistant to standard chemotherapy and died of disease progression in our university hospital hematology ward between May 2015 and November 2019. Patients were classified according to PPI scores (groups: A, PPI ≤ 2.0; B, 2.0 < PPI ≤ 4.0; and C, PPI > 4.0) based on their clinical charts at admission. The median overall survival for each patient (95% confidence interval) was calculated using the Kaplan-Meier method. Log-rank tests were used to determine significant differences between survival curves. RESULTS: Median patient age was 76 years (range: 39-92 years), and 59% were men. Median overall survival times in the PPI groups A, B, and C were 58 days, 36 days, and 10 days, respectively. Statistically significant differences in survival time were observed between the groups (P < .01); prediction accuracy was similar to that for patients with different diagnoses. CONCLUSION: The usefulness of PPI was validated for near-end-of-life hospitalized patients with hematologic malignancies.

Effects of once-yearly zoledronic acid on bone density and incident vertebral fractures in nonmetastatic castration-sensitive prostate cancer patients with osteoporosis.

BACKGROUND: Androgen deprivation therapy (ADT) is the effective treating prostate cancer but is often accompanied by cancer treatment-induced bone loss (CTIBL), which impairs the patient's quality of life. In patients with nonmetastatic castration-sensitive prostate cancer (M0CSPC) who already have osteoporosis before starting ADT, appropriate bone-modifying agent intervention must be performed in parallel, as the patient has a high risk of future fracture. However, little is known about therapeutic interventions aimed at preventing the progression of CTIBL and new fractures. The present study explored the effect of once-yearly zoledronic acid 5 mg (ZOL 5 mg) on bone mineral density (BMD) and new vertebral fractures (VFs) in M0CSPC patients with coexisting osteoporosis before starting ADT. METHODS: We conducted a retrospective, multi-institutional, cohort study involving 42 M0CSPC patients with osteoporosis who had undergone ADT with/without a single intravenous infusion of ZOL 5 mg at the start of ADT (ZOL 5 mg group, n = 26; control group, n = 16). The association of the ZOL 5 mg with changes in the BMD from baseline to 12 months and the incidence of VFs were evaluated. RESULTS: Prevalent VFs were found in 47.6% of all patients at baseline. ZOL 5 mg significantly increased the lumbar spine BMD (LS-BMD) (mean rate of change: + 4.02%, p < 0.0001) and significantly decreased the TRACP-5b (mean rate of change: - 52.1%, p < 0.0001) at 12 months after starting ADT. Incident VFs were identified in 19.0% of all patients at 12 months after starting ADT. After adjusting for the age, BMI, and changes in the LS-BMD, ZOL 5 mg was not significantly associated with incident VFs (odds ratio 0.66, 95% confidence interval 0.04-11.3, p = 0.7774). CONCLUSION: ZOL 5 mg significantly increased the LS-BMD 12 months after starting ADT, and our short-term results showed that ZOL 5 mg was not significantly correlated with the suppression of incident vertebral fractures.

The Current Status of Screening for Essential Thrombocythemia and Polycythemia Vera in Clinical Practice-Report from a Single Institution.

OBJECTIVE: We investigate the current status of screening for essential thrombocythemia(ET)and polycythemia vera(PV), at our hospital. METHODS: According to the World Health Organization(WHO)diagnostic criteria. PATIENTS: All patients who visited Juntendo University Urayasu Hospital between May 1984(when the hospital opened)and January 2019. RESULT: More than 90% of patients with elevated platelet counts(PLT)(n=25,062)and more than 90% of patients with elevated hemoglobin( Hb)or hematocrit(Ht)levels(n=16,422)did not visit the department of hematology, suggesting that there could be a high percentage of patients with potentially latent ET and PV visiting the hospital. In addition, a large number of patients fulfilling the laboratory criteria for ET/PV visited various departments of the hospital other than the department of hematology. CONCLUSION: Because ET/PV manifests with diverse symptoms, including non-specific symptoms and symptoms pertaining to other organ systems. Based on the findings, we consider that it is essential to disseminate information about the WHO diagnostic criteria/clinical symptoms and possibility of latent ET/PV to all departments of the hospital, and to establish cooperation between the department of hematology and other departments.

A Comparison of the Predictive Role of the Geriatric Nutritional Risk Index and Immunonutritional Parameters for Postoperative Complications in Elderly Patients with Renal Cell Carcinoma.

BACKGROUND: The geriatric nutritional risk index (GNRI) is reportedly a useful factor for predicting postoperative complications in elderly patients with several cancers. The aim of this study was to investigate the relationship between postoperative complications and the GNRI in elderly patients with renal cell carcinoma (RCC). MATERIALS AND METHODS: The clinical data of 62 patients who were ≥65 years old and underwent open surgery for RCC were analyzed retrospectively. The American Society of Anesthesiologists physical status, Charlson comorbidity index, surgical procedure, body mass index, GNRI, platelet-lymphocyte ratio (PLR), neutrophil-lymphocyte ratio (NLR), psoas muscle index (PMI), visceral fat area, and subcutaneous fat area were examined. The association of the GNRI and immunonutritional parameters with postoperative complications was analyzed by the univariate and multivariate analyses. RESULTS: Grade ≥ II postoperative complications evaluated by the Clavien-Dindo classification were seen in 11 out of 62 cases. In the Spearman's correlation test, the GNRI showed a significant negative correlation with the PLR and NLR and a significant positive correlation with the PMI. The group with postoperative complications showed a significantly lower GNRI, higher PLR, and higher NLR than those without complications. In the multivariate analysis, a GNRI ≤92 was independently associated with postoperative complications. CONCLUSION: The GNRI might play an important role in evaluation of the risk of postoperative complications in open surgery for elderly RCC patients.

A case of omental herniation through the esophageal hiatus successfully treated by laparoscopic surgery.

Case: We report a rare case of omental herniation through the esophageal hiatus. A 46-year-old man visited our emergency department complaining of epigastralgia. Abdominal examination revealed muscular defense and rebound tenderness in his upper abdomen. A computed tomography scan showed a fat density mass in the posterior mediastinum. A laparoscopic operation was carried out under the diagnosis of omental herniation through the esophageal hiatus. Outcome: Abdominal pain disappeared dramatically after the operation. The postoperative course was uneventful. Conclusion: Although a fat density mass in the posterior mediastinum is likely to be diagnosed as a lipomatous tumor, omental herniation through the esophageal hiatus should be taken into consideration as a possible diagnosis for acute abdominal pain in the emergency department.

Natural orifice specimen extraction using prolapsing technique in single-incision laparoscopic colorectal resections for colorectal cancers.

INTRODUCTION: It is often technically difficult to cut the lower rectum with an endoscopic linear stapler in single-incision laparoscopic colorectal resections (SILC) because some surgical devices are inserted through the same access platform. If the rectum is cut incorrectly, it may cause anastomotic leakage. We recently applied natural orifice specimen extraction (NOSE) using the prolapsing technique to overcome this technical difficulty in SILC procedures in selected patients. MATERIALS AND SURGICAL TECHNIQUE: The access platform is placed in the small umbilical incision area. SILC is performed using a surgical technique similar to the conventional laparoscopic medial-to-lateral approach. The proximal part of the tumor site is transected with laparoscopic staplers. Then, the tumor lesion and bowel are pulled out of the body through the anus by means of inversion. Next, the distal side of the bowel is cut with a stapler and the rectal stump is reinforced with sutures under direct vision. The distal side of the bowel is then pushed back into the body. NOSE with prolapsing technique is then complete. After that, the anvil is attached to the proximal part of the bowel at the umbilical incision site, and intracorporeal anastomosis is performed. DISCUSSION: NOSE with prolapsing technique was applied in 14 SILC procedures for colorectal cancer patients. All procedures were successful, and there were no anastomotic leakages in the series. This technique enabled us to perform pure SILC safely without affecting cosmesis, even in cases where we needed to cut the lower rectum.

Laparoscopic one-stage resection of right and left colon complicated diverticulitis equivalent to Hinchey stage I-II.

PURPOSE: The safety and effectiveness of laparoscopic surgery is well established for recurrent, uncomplicated diverticular disease, but not for complicated diverticular disease. Using the Hinchey classification, we compared laparoscopic colon resection (LAPH) with conventional open colon resection (OPH) for the treatment of complicated diverticulitis equivalent to Hinchey stage I-II. METHODS: In this study, the Hinchey classification (I-IV) was also adopted for right-sided diverticulitis (I'-IV'). We reviewed the clinical records of 58 patients who underwent colon resection for complicated colon diverticulitis (Hinchey stage I-IV or I'-IV') between May 1994 and December 2008. Fifty-two patients underwent colon resection for Hinchey I-II or I'-II' disease; as LAPH in 36 and as OPH in 16. Only one patient required conversion to the open procedure after laparoscopy. RESULTS: The overall complication rate was significantly higher in the OPH group (43.8%) than in the LAPH group (16.7%; P < 0.05). Wound infection was significantly more common in the OPH group (37.5%) than in the LAPH group (11.1%; P < 0.05). Hospital stay was significantly shorter in the LAPH group (P < 0.05). Hartmann procedure was performed in one patient from each group. No anastomotic leakage occurred in either group. CONCLUSION: Our findings indicate that laparoscopic surgery can be performed safely and effectively even for patients with Hinchey I-II, I'-II' colonic diverticulitis.

Laparoscopic appendectomy for complicated appendicitis: a comparison with open appendectomy.

BACKGROUND: Although laparoscopic appendectomy (LA) is widely performed in many countries, LA for complicated appendicitis, which includes perforated or gangrenous appendicitis with or without localized or disseminated peritonitis, has not become a common practice yet. METHODS: We retrospectively analyzed the clinical records of 230 patients who had undergone appendectomy for complicated appendicitis: 141 had undergone LA, 84 had conventional open appendectomy (OA), and 5 patients had conversion to the open procedure after laparoscopy. The LA group (total LA) was subdivided into "early experience (early LA: cases 1-56)" and "late experience (late LA: case 57 and higher)." We defined the early LA group as the comparison group to minimize selection bias. RESULTS: Patient demographics were similar in the early LA and OA groups (P > 0.05). Wound infection was significantly more frequent in the OA group (P < 0.05). Intra-abdominal infection was equally common in these two groups. The overall rate of postoperative complications was significantly higher in the OA group (32.1%) than in the early LA group (18%; P < 0.05). This incidence was 12.8% in the total LA group. Hospital stay was significantly shorter in the early LA group (10.6 +/- 3.9 days; P < 0.05), and 8.9 +/- 3.7 days in the total LA group. CONCLUSIONS: Our findings indicate that LA is safe and useful even for the treatment of complicated appendicitis if performed by an experienced surgeon.

Pretreatment of sivelestat sodium hydrate improves the lung microcirculation and alveolar damage in lipopolysaccharide-induced acute lung inflammation in hamsters.

Damage to the lung microcirculation and alveoli caused by activated leukocytes is known to play an important role in the development of acute lung injury (ALI). The aim of this study is to evaluate the difference in the effect of pretreatment and posttreatment of a synthetic neutrophil elastase inhibitor sivelestat on ALI. Hamsters were instilled with 10.0 mg/kg of lipopolysaccharide (LPS) intratracheally for 1 h to simulate ALI. Two milligrams per kilogram of sivelestat was injected intraperitoneally either previously or after LPS infusion. One and 24 hours after the infusion of LPS, pulmonary microcirculation was observed under the intravital microscopy. In another series, the blood cell counts were evaluated. The adhesive leukocyte count on the endothelium was significantly lower in pretreatment group compared with control group (P < 0.01), whereas the difference was not significant in the posttreatment group. Similarly, the number of obstructed capillary was significantly lower in the pretreatment group (P < 0.01). The width of interstitium was significantly lower in the pretreatment and posttreatment group (P < 0.01 and 0.05, respectively). A comparison of white blood cell counts showed a better maintenance in pretreatment group (P < 0.05). Pretreatment of sivelestat demonstrated a protective effect on both intravascular and extravascular damage in the lung, whereas posttreatment only suppressed the latter damage.

Antithrombin ameliorates endotoxin-induced organ dysfunction more efficiently when combined with danaparoid sodium than with unfractionated heparin.

OBJECTIVE: This study investigated the potential benefits of combination therapy using antithrombin (AT) with danaparoid sodium (DA) compared with the use of AT with unfractionated heparin (UFH) in the treatment of sepsis. METHODS: Rats infused with lipopolysaccharide were treated with either DA alone, AT alone, AT plus DA, AT plus UFH, or human serum albumin as controls. AT (125 U/kg) was injected into the AT group immediately after lipopolysaccharide infusion. The AT/DA and AT/UFH groups received the same dose of AT in conjunction with either DA (400 U/kg) or UFH (400 U/kg). The status of the mesenteric microcirculation was examined by intra-vital microscopy and the laboratory indices of coagulation, inflammation, and organ dysfunction were measured. RESULTS: The coagulation markers were improved following the administration of DA or UFH. The decreases in the WBC counts were significantly suppressed in the AT/DA group. The elevation of IL-6 decreased in the AT, DA, and AT/DA groups (all p<0.01) but not in the AT/UFH group. The prostaglandin I2 levels were significantly elevated only in the AT/DA group (p<0.05). The WBC adhesion was significantly suppressed in the DA, AT/UFH, and AT/DA groups (p<0.05), and the RBC velocity was best maintained in the AT/DA group with no associated increase in capillary hemorrhage. The elevation of ALT and BUN significantly improved only in the AT/DA group. ONCLUSION: Organ dysfunction can thus be alleviated by even moderate doses of AT replacement when co-administered with DA.

Laparoscopy-assisted low anterior resection with a prolapsing technique for low rectal cancer.

Laparoscopy-assisted low anterior resection (LAR) for low rectal cancer is a difficult procedure, presenting problems with rectal washout, selecting the appropriate distal transection line, and achieving safe anastomosis. To resolve these problems, we used a prolapsing technique to perform laparoscopy-assisted LAR. Total mesorectal excision (TME) is performed laparoscopically. The proximal colon is transected laparoscopically with the aid of an endoscopic stapler, and the distal rectum, including the lesion, are everted and pulled transanally to outside the body. Only washout of and wiping off the distal rectum and intestinal resection are performed extracorporeally. The distal rectum is pushed back through the anus into the pelvis, and intracorporeal anastomosis is completed laparoscopically with a double-stapling technique. Our limited experience suggests that the prolapsing technique helps to prevent problems with laparoscopy-assisted LAR in selected patients with low rectal cancer.