Prognostic impact of concomitant pH-regulating drugs in patients with non-small cell lung cancer receiving epidermal growth factor receptor tyrosine kinase inhibitors: the Tokushukai REAl-world Data project 01-S1.

PURPOSE: This study aimed to examine the prognostic impact of concomitant pH-regulating drug use in patients with epidermal growth factor receptor (EGFR)-mutation-positive non-small-cell lung cancer (NSCLC) receiving EGFR-tyrosine kinase inhibitors (TKIs). METHODS: We conducted a nationwide retrospective cohort study and reviewed clinical data of consecutive patients with NSCLC treated with the first-line EGFR-TKIs in 46 hospitals between April 2010 and March 2020. Cox regression analyses were conducted to examine the differences in overall survival (OS) between patients treated with and without concomitant pH-regulating drugs, including potassium-competitive acid blockers (P-CABs), proton pump inhibitors (PPIs), and H2-receptor antagonists (H2RAs). RESULTS: A total of 758 patients were included in the final dataset, of which 307 (40%) were administered concomitant pH-regulating drugs while receiving frontline EGFR-TKIs. After adjusting for basic patient characteristics, patients administered gefitinib, erlotinib, afatinib, and osimertinib with concomitant pH-regulating drugs had lower OS than those without concomitant pH-regulating drugs, with hazard ratios of 1.74 (with a 95% confidence interval of 1.34-2.27), 1.33 (0.80-2.22), 1.73 (0.89-3.36), and 5.04 (1.38-18.44), respectively. The 2-year OS rates of patients receiving gefitinib with or without concomitant pH-regulating drugs were 65.4 and 77.5%, those for erlotinib were 55.8 and 66.6%, and those for afatinib were 63.2 and 76.9%, respectively. The 1-year OS rates of patients receiving osimertinib with or without concomitant pH-regulating drugs were 88.1% and 96.9%, respectively. CONCLUSION: In addition to the first-generation EGFR-TKIs, the second- and third-generation EGFR-TKIs also resulted in OS deterioration in patients with EGFR mutation-positive NSCLC when used concurrently with pH-regulating drugs.

Inflammation­based prognostic markers of metastatic pancreatic cancer using real­world data in Japan: The Tokushukai REAl­world Data (TREAD) project.

Inflammation-based prognostic markers based on a combination of blood-based parameters, including the modified Glasgow prognostic score (mGPS), have been associated with clinical outcomes in patients with various types of cancer. The present study aimed to evaluate and compare the accuracy of these previously reported markers in patients with metastatic pancreatic cancer receiving first-line chemotherapy. A total of 846 patients were identified between April 2010 and March 2020 as part of a nationwide real-world study from 46 Tokushukai medical group hospitals in Japan. Blood laboratory data collected within 14 days of starting first-line chemotherapy assessed 17 inflammation-based prognostic markers. Information from patients with no missing data was used to compare the accuracy and performance of the inflammation-based prognostic markers. A total of 487 patients were eligible for this supplemental analysis. The 17 inflammation-based markers demonstrated significant prognostic value. Among them, the concordance rate with overall survival (OS) was highest for mGPS. The median OS time of patients with mGPS 0, 1 and 2 was 8.2, 6.0 and 2.9 months, respectively. Compared with mGPS 0, mGPS 1 and 2 showed hazard ratios of 1.39 (95% confidence interval, 1.07-1.81) and 2.63 (2.00-3.45), respectively. The present real-world data analysis showed that various previously reported inflammation-based markers had significant prognostic value in patients with metastatic pancreatic cancer. Among these markers, the mGPS demonstrated the highest level of accuracy. This trial has been registered in the University Hospital Medical Information Network Clinical Trials Registry as UMIN000050590 on April 1, 2023.

Real-world treatment outcomes of metastatic biliary tract cancer patients in Japan: the Tokushukai REAl-world data project 04 (TREAD 04).

OBJECTIVES: To investigate temporal trends in treatment patterns and prognostic factors for overall survival in patients with metastatic biliary tract cancer. METHODS: From the Tokushukai REAl-world Data project, we identified 945 patients with metastatic biliary tract cancer treated with gemcitabine, tegafur/gimeracil/oteracil, gemcitabine plus cisplatin, gemcitabine plus tegafur/gimeracil/oteracil or gemcitabine plus cisplatin and tegafur/gimeracil/oteracil between April 2010 and March 2022. Stratified/conventional Cox regression analyses were conducted to examine the association between overall survival and patient- and tumour-related factors, study period, hospital volume, hospital type and first-line chemotherapy regimen. Using inverse probability of treatment weighting with propensity scores, overall survival was also compared between monotherapy and combination therapy groups. RESULTS: We enrolled 366 patients (199 men; median age, 72 years). Over a median follow-up of 5.2 months, the median overall survival was 7.0 months (95% confidence interval 6.2-9.0), and the median time to treatment failure was 3.5 months (95% confidence interval 3.1-4.5). Median overall survival and time to treatment failure for gemcitabine/tegafur-gimeracil-oteracil/gemcitabine plus cisplatin/gemcitabine plus tegafur-gimeracil-oteracil/gemcitabine plus cisplatin and tegafur-gimeracil-oteracil regimen were 6.2/6.6/7.9/16.2/15.1 and 2.8/3.4/4.1/15.3/7.4 months, respectively. Primary disease site, previous surgery, previous endoscopic procedures and hospital type were identified as significant prognostic factors. Inverse probability of treatment weighting analysis demonstrated that combination therapy had a significantly better prognosis than monotherapy (hazard ratio 0.61, 95% confidence interval 0.43-0.88, P = 0.006). CONCLUSIONS: Our real-world data analysis showed that standard care for metastatic biliary tract cancer is widely used in hospitals throughout Japan and verified the survival benefits of combination therapy over monotherapy observed in prior clinical trials. CLINICAL TRIAL NUMBER: UMIN000050590 (http://www.umin.ac.jp/ctr/index.htm).

Stepwise prolongation of overall survival from first to third generation EGFR-TKIs for EGFR mutation-positive non-small-cell lung cancer: the Tokushukai REAl-world Data project (TREAD 01).

OBJECTIVE: The introduction of new-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has afforded promising overall survival outcomes in clinical trials for non-small-cell lung cancer. We aim to investigate the current adoption rate of these agents and the real-world impact on overall survival among institutions. METHODS: In a nationwide retrospective cohort study of 46 Tokushukai Medical Group hospitals in Japan, we analyzed clinical data of consecutive patients with non-small-cell lung cancer receiving EGFR-TKIs between April 2010 and March 2020. Univariate and multivariate Cox regression analyses examined the associations between overall survival and patient/tumor-related factors and first-line EGFR-TKIs. RESULTS: A total of 758 patients (58.5% females; median age, 73 years) were included. Of 40 patients diagnosed in 2010, 72.5% received gefitinib, whereas 81.3% of 107 patients diagnosed in 2019 received osimertinib as the first-line EGFR-TKI. With a median follow-up of 15.8 months, the median overall survival was 28.4 months (95% confidence interval, 15.3-31.0). In a multivariate Cox regression analysis, age, body mass index, disease status, EGFR mutational status and first-line epidermal growth factor receptor tyrosine kinase inhibitor were identified as significant prognostic factors after adjusting for background factors including study period, hospital volume and hospital type. The estimated 2-year overall survival rates for gefitinib, erlotinib, afatinib and osimertinib were 70.1% (95% confidence interval 59.7-82.4), 67.8% (95% confidence interval 55.3-83.2), 75.5% (95% confidence interval 64.7-88.0) and 90.8% (95% confidence interval 84.8-97.3), respectively. The median time to treatment failure of gefitinib, erlotinib, afatinib and osimertinib were 12.8, 8.8, 12.0 and 16.9 months or more, respectively. CONCLUSIONS: Our real-world data revealed that the swift and widespread utilization of newer-generation EGFR-TKIs in patients with EGFR mutation-positive non-small-cell lung cancer, and that these newer-generation EGFR-TKIs can prolong overall survival regardless of hospital volume or type. Therefore, osimertinib could be a reasonable first choice treatment for these patients across various clinical practice settings.

Real­world treatment outcomes among patients with metastatic pancreatic cancer in Japan: The Tokushukai real­world data project.

The present study aimed to investigate temporal trends in treatment patterns and prognostic factors for overall survival (OS) among patients with metastatic pancreatic cancer. From the Tokushukai REAl-world Data project, 1,093 patients with metastatic pancreatic cancer treated with gemcitabine, tegafur/gimeracil/oteracil (S-1), gemcitabine plus S-1, gemcitabine plus nab-paclitaxel, or fluorouracil, folic acid, oxaliplatin and irinotecan (FOLFIRINOX) between April 2010 and March 2020 were identified. Stratified/conventional Cox regression analyses were conducted to examine associations between patient- and tumor-related factors, study period, hospital volume, hospital type and first-line chemotherapy regimens. Overall, 846 patients were selected (503 male patients; median age, 70 years) after excluding ineligible patients. Over a median follow-up of 5.4 months, the median OS was 6.8 months (95% confidence interval, 6.3-7.4). The median OS for gemcitabine, S-1, gemcitabine plus S-1, gemcitabine plus nab-paclitaxel and FOLFIRINOX regimens was 5.9, 5.3, 7.7, 9.0 and 9.5 months, respectively. The median OS for 2010-2013, 2014-2017 and 2017-2020 was 6.2, 7.1 and 7.8 months, respectively. Performance status, body mass index and first-line chemotherapy regimens were identified to be significant prognostic factors. In summary, the real-world data indicated that standard care, including chemotherapy, for metastatic pancreatic cancer was widely used in hospitals throughout Japan and verified the survival benefits of gemcitabine plus nab-paclitaxel and FOLFIRINOX observed in prior clinical trials. This trial has been registered in the University Hospital Medical Information Network Clinical Trials Registry as UMIN000050590 on April 1, 2023.

Preoperative prognostic predictors and treatment strategies for surgical procedure focused on the sequential organ failure assessment score in nonocclusive mesenteric ischemia: a multicenter retrospective cohort study.

BACKGROUND: Several large-scale studies have assessed endovascular and surgical treatment methods for nonocclusive mesenteric ischemia (NOMI); however, the prognostic factors for NOMI remain unclear. Therefore, this study aimed to evaluate risk factors for in-hospital mortality among patients with NOMI who underwent laparotomy and to examine therapeutic strategies that may improve the prognosis. MATERIALS AND METHODS: In this multicenter retrospective study, the authors reviewed the electronic medical records retrieved from the inpatient database of patients with NOMI at eight district general hospitals between January 2011 and January 2021. A total of 88 patients who underwent laparotomies were divided into survivor and nonsurvivor groups, and statistical analysis was performed to determine clinical and physiological factors. RESULTS: Exploratory laparotomy based on second-look surgery was the first treatment choice. The overall mortality rate was 48.8%, with a male-to-female ratio of 1.1:1. The median Sequential Organ Failure Assessment (SOFA) score was 8 [interquartile range: 3.75-14.2], and the median SOFA scores were 5 [3-7] in the survivor group and 13 [9-17.5] in the nonsurvivor group. Univariate analysis revealed a significant difference in BMI ( P <0.001), hypoglycemia ( P =0.0012), previous cardiovascular surgery ( P =0.0019), catecholamine use ( P <0.001), SOFA score ( P <0.001), platelet count ( P =0.0023), and lactate level ( P <0.001). Logistic regression analysis using the factors with significant differences revealed that SOFA score ≥10 (odds ratio 23.3; 95% CI: 1.94-280.00; P =0.013) was an independent prognostic factor. In addition, catecholamine use was suggested as a factor with a SOFA score greater than or equal to 10. CONCLUSION: This study confirmed that a SOFA score of greater than or equal to 10 may be associated with increased mortality. While closely monitoring low blood pressure and renal dysfunction, survival rates may be improved if surgical intervention is performed before the SOFA score reaches greater than or equal to 10.

Real-World Outcomes of Systemic Therapy in Japanese Patients with Cancer (Tokushukai REAl-World Data Project: TREAD): Study Protocol for a Nationwide Cohort Study.

Cohort studies using large-scale databases have become increasingly important in recent years. The Tokushukai Medical Group is a leading medical group in Japan that includes 71 general hospitals nationwide from Hokkaido to Okinawa, with a total of 18,000 beds, and a unified electronic medical record system. This retrospective cohort study aims to evaluate the real-world outcomes of systemic therapy for Japanese patients with cancer using this merit of scale. All adult patients with cancer who received systemic therapy using a centrally registered chemotherapy protocol system at 46 hospitals from April 2010 to March 2020 will be identified (~48,850 patients). Key exclusion criteria include active double cancer and inadequate data extraction. Data will be obtained through electronic medical records, diagnosis procedure combination data, medical prescription data, and the national cancer registration system that includes sociodemographic variables, diagnostic and laboratory tests, concomitant drug prescriptions, cost, and overall survival. Kaplan-Meier estimates will be calculated for time-to-event analyses. Stratified/conventional Cox proportional hazards regression analyses will be conducted to examine the relationships between overall survival and related factors. Our findings provide important insights for future research directions, policy initiatives, medical guidelines, and clinical decision-making.

Clinical impact of laparoscopic surgery and adhesion prevention material for prevention of small bowel obstruction.

Aim: Adhesive small bowel obstructions (SBO) are one of the most common complications following abdominal surgery, and they decrease patient quality of life. Since 2000, laparoscopic surgery has been employed with increasing frequency, as has adhesion prevention material (APM). In this study we tried to evaluate whether laparoscopic surgery and APM reduce the incidence of SBO. Methods: In Cohort 1, we included patients who developed SBO and received inpatient treatment between 2015 and 2018. We evaluated the elapsed time between precedent surgery and the onset of SBO, and what kind of surgery most often causes SBO. In Cohort 2, we included patients who underwent digestive surgery between 2012 and 2014 and evaluated SBO incidence within 5 y after the precedent surgery. Results: In all, 2058 patients were included in Cohort 1. Of these, 164 had experienced no precedent surgery. Among patients with a history of abdominal surgery, 29.7% experienced SBO within 1 y after the precedent surgery and 48.1% within 3 y. Altogether, 18798 patients were analyzed in Cohort 2. The incidence of SBO after laparoscopic colorectal surgery was lower than that of open colorectal surgery (P < .001), and laparoscopic gastroduodenal surgery was also lower (P = .02). However, there were no differences between laparoscopic and open surgery for other types of surgery. The use of APM had no effect on SBO incidence in any type of abdominal surgery. Conclusions: Laparoscopic surgery helps to reduce SBO incidence only in colorectal surgery, and possibly in gastroduodenal surgery. APM does not reduce SBO after abdominal surgery.

A Surgical Case of Bronchial Artery Aneurysm Connecting to a Pulmonary Artery and Vein Complicated by Racemose Hemangioma.

We report a surgical case of bronchial artery aneurysm (BAA) that directly connected to a pulmonary artery and a pulmonary vein through an abnormal vessel. It was complicated by racemose hemangioma. This is a rare vascular malformation. An 82-year-old female had a large BAA that was found incidentally. First, we consider treating the BAA with embolization by interventional radiology (IVR). However, because of strong meandering of the bronchial artery, we could not advance a microcatheter into the BAA. Therefore, a surgical operation was performed through a standard posterior lateral thoracotomy. The BAA was located between the upper and lower lobes and directly connected to the pulmonary artery. Some bronchial artery branches that provided inflow to the aneurysm were ligated, and the abnormal vessel that connected the BAA to the upper pulmonary vein was ligated easily. A fistula between the BAA and pulmonary artery was sutured by the cardiovascular surgeon using an artificial cardiopulmonary device, with permissive stenosis of A2b (ascending A2).

Multimodal treatment for acute empyema based on the patient's condition, including patients who are bedridden: A single center retrospective study.

BACKGROUND: The incidence of acute empyema has increased in various countries; some elderly patients with acute empyema have contraindications for surgery under general anesthesia. Therefore, suitable management based on a patient's clinical condition is required. METHODS: We evaluated the different surgical and nonsurgical therapeutic approaches available for patients with acute empyema. This was a retrospective study of 57 patients with acute empyema who received treatment in our department between May 2015 and February 2019. For patients who did not initially improve with drainage or drainage combined with fibrinolytic therapy, surgery, or additional percutaneous drainage was performed based on their general condition. We compared several clinical factors pertaining to the patients who underwent surgical versus nonsurgical treatment. RESULTS: Our study showed that the patients with a performance status of 0-2 and an American Society of Anesthesiologists physical status classification of class II or lower underwent surgery safely without major operative complications. The combination of repeated drainage of the pleural cavity and fibrinolytic therapy appeared to be a reasonable nonsurgical management option for patients in poor overall condition. CONCLUSION: For an aging population, we think that the combination of repeated pleural cavity drainage procedures and fibrinolytic therapy is a reasonable nonsurgical strategy for the management of patients with acute empyema.

Sigmoid colon strangulation caused by bilateral fallopian tubes: A case report.

INTRODUCTION: There are no reports regarding sigmoid colon strangulation caused by bilateral fallopian tubes, which is a rare type of large bowel obstruction. Herein, we report a case of successful laparoscopic treatment of sigmoid colon strangulation. PRESENTATION OF CASE: A 54-year-old woman presented to our hospital with intermittent abdominal pain. Her medical history was significant for endometriosis; however, there was no surgical history. The physical examination revealed tenderness over the lower abdomen. CT scan shows closed loop obstruction of sigmoid colon. Exploratory laparoscopy was performed, and a sigmoid colon strangulated by bilateral fallopian tubes was detected. The adhesions consisting of bilateral fallopian tubes were dissected laparoscopically. The patient's postoperative course was uneventful, with no complications. DISCUSSION: The most common cause of large bowel obstruction (LBO) is colorectal cancer, including volvulus and diverticulitis. In this case, the adhesion of both the right and left fallopian tubes caused LBO, and it is conceivable that the etiology involved is endometriosis. Few cases have reported bowel obstruction associated with a fallopian tube, and the laparoscopic approach is very rare. In our case, we immediately performed laparoscopic exploration before colon strangulation led to necrosis or perforation. Therefore, we succeeded in releasing the strangulation laparoscopically. CONCLUSION: We report a case of sigmoid colon strangulation that was treated laparoscopically. This approach can be the treatment of choice for sigmoid colon strangulation.

Endovascular aortic repair for abdominal aortic injury complicated with bowel injury due to blunt abdominal trauma: A case report.

INTRODUCTION AND IMPORTANCE: Blunt abdominal aortic injury (BAAI) resulting from blunt abdominal trauma is rare; therefore, there are no standard guidelines for its treatment. Herein, we report the successful treatment of BAAI via endovascular aortic repair (EVAR) performed immediately after emergency laparotomy to repair a bowel injury. CASE PRESENTATION: A 78-year-old man was injured after being caught between a shovel car and the bumper of his own car for approximately 15 s. Upon arrival at the hospital, the patient was conscious and had stable vital signs, abdominal and low back pain, and numbness in the right lower limb. Computed tomography revealed contrast medium leakage into the mesentery, as well as aortic dissection and rupture. Hemostasis and intestinal resection were completed, and EVAR was performed immediately after abdominal closure. The patient was discharged from the hospital at 35 days after surgery. CLINICAL DISCUSSION: In this case, there existed a risk of artificial blood vessel infection if reconstruction was simultaneously performed with intestinal resection. Symptoms of lower limb ischemia that were observed prior to surgery resolved. After open surgery, bleeding was controlled, and the patient's vital signs were stable. EVAR was performed as treatment for aortic injury, thereby reducing the risk of direct implant infection and enabling minimally invasive treatment. CONCLUSION: EVAR may be useful for the treatment of BAAI in the presence of intestinal injuries, reduce the risk of implant infection, and allow for a one-time, minimally invasive treatment.

Resolution of fibrosis by siRNA HSP47 in vitamin A-coupled liposomes induces regeneration of chronically injured livers.

BACKGROUND AND AIM: In chronic hepatic diseases where treatment strategies are not available, deposited fibrotic tissues deteriorate the intrinsic regeneration capacity of the liver by creating special restrictions. Thus, if the anti-fibrosis modality is efficiently applied, the regeneration capacity of the liver should be reactivated even in such refractory hepatic diseases. METHODS: Rat liver fibrosis was induced by dimethyl-nitrosamine (DMN). Another liver fibrosis model was established in CCl4 treated Sox9CreERT2ROSA26: YFP mice. To resolve hepatic fibrosis, vitamin A-coupled liposomes containing siRNA HSP47 (VA-liposome siHSP47) were employed. EpCAM + hepatic progenitor cells from GFP rats were transplanted to DMN rat liver to examine their trans-differentiation into hepatic cells after resolution of liver fibrosis. RESULTS: Even under continuous exposure to such strong hepatotoxin as DMN, rats undergoing VA-liposome siHSP47 treatment showed an increment of DNA synthesis of hepatocytes with the concomitant restoration of impaired liver weight and normalization of albumin levels. These results were consistent with the observation that GFP + EpCAM hepatic progenitor cells transplanted to DMN rat liver, trans-differentiated into GFP + mature hepatic cells after VA-liposome siHSP47 treatment. Another rodent model also proved regeneration potential of the fibrotic liver in CCl4 administered Sox9CreERT2ROSA26: YFP mice, VA-liposome siHSP47 treatment-induced restoration of liver weight and trans-differentiation of YEP + Sox9 + cells into YFP + hepatic cells, although because of relatively mild hepatotoxicity of CCl4, undamaged hepatocytes also proliferated. CONCLUSIONS: These results demonstrated that regeneration of chronically damaged liver indeed occurs after anti-fibrosis treatment even under continuous exposure to hepatotoxin, which promises a significant benefit of the anti-fibrosis therapy for refractory liver diseases.

Chemoprevention of pancreatic cancer by inhibition of glutathione-S transferase P1.

Pancreatic cancer is among the most refractory malignancies with poor prognosis. Thus, preventive approaches, in addition to the development of novel therapeutic strategies are essential for this type of cancer. KRAS mutations occur very early in the development of pancreatic cancers and could be targeted for its prevention, yet specific inhibitors for mutated KRAS are lacking. Accordingly, Glutathione-S Transferase p1 (GSTP1), which we recently found to be an autocrine stimulator of mutated KRAS signaling, is predicted to be an alternative target for chemoprevention of pancreatic cancer. In this study, chemopreventive effects of O-Hexadecyl-γ-glutamyl-S-benzyl-cysteinyl-D-phenyl glycine-Ethylester (HGBPE), which we previously synthesized to inhibit GSTP1 activity, was analyzed for its effect on the prevention of a rat pancreatic carcinogenesis model induced by 7,12-dimethyl-benzanthracene (DMBA). Rats administered with DMBA were grouped into five cohorts. In the treated group I, which was treated neither with HGBPE nor vehicle, sequential appearance of precancerous lesions, ductal complexes, and adenocarcinoma was confirmed as previously reported. We also confirmed in this group that mutations of KRAS and expression of GSTP1 simultaneously occurred in the ductal complex. To rats of groups II and IV, HGBPE was administered, and vehicle to those of group III and V. In groups of II and IV, the incidence of both ductal complex and adenocarcinoma were significantly lower than those in groups III and V. These data clearly suggest the efficacy of HGBP as a potential chemopreventive agent for pancreatic cancer.

Laparoscopic treatment for renal paratransplant hernia: A case report.

INTRODUCTION: There are limited reports regarding renal paratransplant hernia (RPH), which is a rare type of internal hernia. Herein, we report a case of successful laparoscopic treatment of RPH. PRESENTATION OF CASE: A kidney transplant recipient presented to our emergency department with a 6-h history of abdominal pain and vomiting. The patient had received a living-related donor kidney transplantation and native nephrectomy in our hospital last year. Computed tomography (CT) confirmed a diagnosis of RPH. We performed laparoscopic exploration, and the findings showed an incarcerated small bowel in the retroperitoneal space through a peritoneal defect. Short laparotomy was performed to resect the non-viable bowel. The peritoneal defect was opened adequately. The patient's postoperative course was uneventful, with no complications. DISCUSSION: RPH is an uncommon variant of internal hernia, which is a rare surgical complication after kidney transplantation. Early diagnosis and treatment are important once RPH develops. Due to immunosuppression in kidney transplant recipients, typical signs of peritonitis were not observed. This event can be critical to the patient. Laparoscopic surgery has recently become a treatment option for small bowel obstructions. We believe that this surgical procedure is useful for patients with RPH. CONCLUSION: We report a case of RPH treated laparoscopically. This approach can be a treatment of choice for RPH.

Monitoring the Sequential Organ Failure Assessment score in nonocclusive mesenteric ischemia increases the survival rate: A single-center observational study.

ABSTRACT: Several large-scale studies have assessed the endovascular and surgical treatments for nonocclusive mesenteric ischemia (NOMI); nonetheless, the prognostic factors for NOMI remain unclear.In this single-center study, we retrospectively reviewed the electronic medical records of 197, 149 patients were retrieved from the inpatient database of our hospital from January 2011 to January 2020; 79 patients with NOMI were observed. A total of 44 patients who underwent laparotomy were statistically analyzed and divided into the survivor and non-survivor groups. Prognostic factors were compared between the 2 groups. Exploratory laparotomy based on a second-look surgery was the first treatment choice.The overall mortality rate was 61.3%, with a male-to-female ratio of 1.6:1. The median Sequential Organ Failure Assessment (SOFA) score was 11.06 [5.75-17.25]. The median SOFA score was 5 [interquartile range: 3-8] in the survivor group and 14.8 [interquartile range: 10.5-19] in the non-survivor group. The log-rank test showed a significant difference in the presence of diabetes mellitus (P = .025), hypoglycemia (P = .001), SOFA score ≥10 (P < .001), hemoglobin levels ≥11 g/dL (P = .003), platelet count ≥12.9 × 104/µL (P = .01), lactate levels ≥2.6 mmol/L (P = .005), and base excess <-3.0 (P < .023). Multivariate analysis using the factors with significant differences revealed that SOFA score ≥10 (hazard ratio for death, 1.199; 95% confidence interval, 1.101-1.305; P < .001) was an independent prognostic factor.The SOFA score can be used to assess disease severity. A SOFA score of ≥10 may be associated with increased mortality.

Intraoperative angiography with indocyanine green injection for precise localization and resection of small bowel bleeding.

AIM: Bleeding in the small bowel rarely occurs, and its treatment is challenging. Surgery is sometimes required in unstable patients; however, intraoperative identification of the bleeding site is extremely difficult. Many methods have been reported, but no standard strategy has been established yet. Here, we aimed to assess the safety and feasibility of intraoperative angiography with indocyanine green staining to accurately identify small bowel bleeding sites. METHODS: This retrospective study analyzed contrast-enhanced computed tomography images of patients (n = 8) with small bowel extravasation who underwent surgery. If extravasation or other vessel abnormalities that were potential bleeding sites were detected on intraoperative angiography, a microcatheter was placed as close as possible to the extravasation site. Laparotomy was carried out, and 3-5 mL indocyanine green was injected through the microcatheter. The green-stained segment of the small bowel was resected. RESULTS: Seven of the eight patients had positive angiographic findings and underwent bowel resection. The eighth patient had no abnormalities and hence did not undergo laparotomy. The rate of hemostatic success among the resected cases was 85.7% (six of seven cases). The resected specimens showed pathologic features in six of the seven patients (85.7%), all of whom achieved hemostasis. One patient had pneumonia and congestive heart failure that required longer hospital stay, but no mortality occurred. CONCLUSIONS: Intraoperative angiography with indocyanine green injection, followed by resection for massive small bowel bleeding is effective. This can be a therapeutic option for hemodynamically unstable patients.

A CRAF/glutathione-S-transferase P1 complex sustains autocrine growth of cancers with KRAS and BRAF mutations.

The Ras/RAF/MEK/ERK pathway is an essential signaling cascade for various refractory cancers, such as those with mutant KRAS (mKRAS) and BRAF (mBRAF). However, there are unsolved ambiguities underlying mechanisms for this growth signaling thereby creating therapeutic complications. This study shows that a vital component of the pathway CRAF is directly impacted by an end product of the cascade, glutathione transferases (GST) P1 (GSTP1), driving a previously unrecognized autocrine cycle that sustains proliferation of mKRAS and mBRAF cancer cells, independent of oncogenic stimuli. The CRAF interaction with GSTP1 occurs at its N-terminal regulatory domain, CR1 motif, resulting in its stabilization, enhanced dimerization, and augmented catalytic activity. Consistent with the autocrine cycle scheme, silencing GSTP1 brought about significant suppression of proliferation of mKRAS and mBRAF cells in vitro and suppressed tumorigenesis of the xenografted mKRAS tumor in vivo. GSTP1 knockout mice showed significantly impaired carcinogenesis of mKRAS colon cancer. Consequently, hindering the autocrine loop by targeting CRAF/GSTP1 interactions should provide innovative therapeutic modalities for these cancers.

Association of pre-operative chronic kidney disease and acute kidney injury with in-hospital outcomes of emergency colorectal surgery: a cohort study.

BACKGROUND: Pre-operative kidney function is known to be associated with surgical outcomes. However, in emergency surgery, the pre-operative kidney function may reflect chronic kidney disease (CKD) or acute kidney injury (AKI). We examined the association of pre-operative CKD and/or AKI with in-hospital outcomes of emergency colorectal surgery. METHODS: We conducted a retrospective cohort study including adult patients undergoing emergency colorectal surgery in 38 Japanese hospitals between 2010 and 2017. We classified patients into five groups according to the pre-operative status of CKD (defined as baseline estimated glomerular filtration rate < 60 mL/min/1.73 m2 or recorded diagnosis of CKD), AKI (defined as admission serum creatinine value/baseline serum creatinine value ≥ 1.5), and end-stage renal disease (ESRD): (i) CKD(-)AKI(-), (ii) CKD(-)AKI(+), (iii) CKD(+)AKI(-), (iv) CKD(+)AKI(+), and (v) ESRD groups. The primary outcome was in-hospital mortality, while secondary outcomes included use of vasoactive drugs, mechanical ventilation, blood transfusion, post-operative renal replacement therapy, and length of hospital stay. We compared these outcomes among the five groups, followed by a multivariable logistic regression analysis for in-hospital mortality. RESULTS: We identified 3002 patients with emergency colorectal surgery (mean age 70.3 ± 15.4 years, male 54.5%). The in-hospital mortality was 8.6% (169/1963), 23.8% (129/541), 15.3% (52/340), 28.8% (17/59), and 32.3% (32/99) for CKD(-)AKI(-), CKD(-)AKI(+), CKD(+)AKI(-), CKD(+)AKI(+), and ESRD, respectively. Other outcomes such as blood transfusion and post-operative renal replacement therapy showed similar trends. Compared to the CKD(-)AKI(-) group, the adjusted odds ratio (95% confidence interval) for in-hospital mortality was 2.54 (1.90-3.40), 1.29 (0.90-1.85), 2.86 (1.54-5.32), and 2.76 (1.55-4.93) for CKD(-)AKI(+), CKD(+)AKI(-), CKD(+)AKI(+), and ESRD groups, respectively. Stratified by baseline eGFR (> 90, 60-89, 30-59, and < 30 mL/min/1.73 m2) and AKI status, the crude in-hospital mortality and adjusted odds ratio increased in patients with baseline eGFR < 30 mL/min/1.73 m2 among patients without AKI, while these were constantly high regardless of baseline eGFR among patients with AKI. Additional analysis restricting to 2162 patients receiving the surgery on the day of hospital admission showed similar results. CONCLUSIONS: The differentiation of pre-operative CKD and AKI, especially the identification of AKI, is useful for risk stratification in patients undergoing emergency colorectal surgery.

Successful treatment of hepatic gas gangrene by open drainage: A case report and review of the Japanese literature.

INTRODUCTION: Liver gas gangrene is rare and has a low prognosis. This case, reports a successful treatment of hepatic gas gangrene using an open drainage technique, followed by antibiotics and hyperbaric oxygen therapy (HBO). PRESENTATION OF THE CASE: An 82-year-old male with a history of left hepatectomy and bile duct resection for hilar cholangiocarcinoma presented with chilling, lethargy and dyspnea. He had a history of diabetes mellitus, hypertension, atrial fibrillation, and angina pectoris. Physical examination revealed scleric icterus, right hypochondrium tenderness and percussion tenderness of the liver, with warm extremities. Laboratory findings revealed leukocytosis and increased levels of hepatobiliary enzymes. A computed tomography (CT) scan showed gas accumulation in an S8 lesion with portal vein gas. Percutaneous drainage was performed immediately, and broad-spectrum antibiotics were started, but the drainage was insufficient. Consequently, laparotomy drainage was carried out, followed by HBO. No abscess was detected at one-year of follow-up. DISCUSSION: Hepatic gas gangrene progresses rapidly and has a high mortality rate. Malignant disease and diabetes mellitus may be predisposing factors. While half of non-clostridial cases survive, most cases of hepatic gas gangrene are associated with clostridial infection and have a fatal outcome. CONCLUSION: All survival cases of hepatic gas gangrene were treated by laparotomy drainage, thus immediate laparotomy seems essential to prevent a fatal outcome.