Endoscopic retrograde cholangiopancreatography as a single-modality 'gold-standard' treatment for common bile duct stones in the elderly.

BACKGROUND: There are more octogenarians presenting with gallstone disease each year. Many are not suitable for surgical intervention. An alternative treatment option for common bile duct stones in the elderly is endoscopic retrograde cholangiopancreatography (ERCP) with or without stent insertion. METHODS: We conducted a retrospective study using a prospectively collected database, analysing the outcomes of consecutive patients >80 years old who underwent an ERCP in a single centre for the treatment of common bile duct stones. RESULTS: In total, 156 patients, with a median age of 91 years, underwent an ERCP for choledocholithiasis over a 3-year period. ERCP was successful in 90% of patients but a proportion required repeat intervention. Forty-six (29%) patients had a concurrently inserted stent due to incomplete stone extraction. Six (4%) patients required a post-ERCP cholecystectomy due to ongoing symptoms. The overall ERCP complication rate was 7% (4% Clavien-Dindo 1 and 3% Clavien-Dindo 2), with no cases of post-ERCP pancreatitis or death. Patients were followed up over 5 years following index ERCP. There was a 60% 3-year survival and 30% 5-year survival rate following index ERCP. Importantly, of those who did not survive, only four patients (2.6%) had a death attributable to a biliary cause and none were fit for definitive surgery. CONCLUSIONS: ERCP can be considered as a possible definitive management option for treating common bile duct stones in the elderly, particularly in the comorbid population. Concurrent stenting is an effective temporizing strategy and mitigator of biliary-related readmission, but routine stent changes should be considered. Key messages What is already known on this topic Current guidelines advocate for laparoscopic cholecystectomy and common bile duct exploration in patients with choledocholithiasis. What this study adds Endoscopic retrograde cholangiopancreatography with or without stent insertion is a safe, alternative single-treatment modality for choledocholithiasis in the elderly comorbid population. How this study might affect research, practice, or policy Studies and guidelines evaluating treatment options for choledocholithiasis may be altered to accommodate patient-specific factors, including age and comorbid status, and the concurrent use of stenting as a either a temporizing or longer-term measure for complex stone disease.

Targeting Hyaluronic Acid and Peritoneal Dissemination in Colorectal Cancer.

Peritoneal metastasis (PM) from colorectal cancer (CRC) carries a significant mortality rate for patients and treatment is challenging. The development of PM is a multistep process involving detachment, adhesion, invasion and colonization of the peritoneal cavity. Cytoreductive surgery and HIPEC (hyperthermic intraperitoneal chemotherapy) for PM from CRC has some benefit but overall survival is poor and recurrence rates are high. Treatments to prevent the development of peritoneal metastasis could have the potential to improve CRC survival and disease-free outcomes. The ability of cancer cells to invade the peritoneum and become established as metastatic tumors is influenced by a multifactorial process. Hyaluronic acid (HA) has been shown to coat the mesothelial cells of the peritoneum and has been demonstrated to be utilized in various malignancies as part of the metastatic process in peritoneal dissemination. CD44, RHAMM (CD168) and ICAM-1 have all been shown to be binding partners for HA. Targeting HA-mediated binding may prevent adhesion to distant sites within the peritoneum through suppression of interaction of these molecules. Here we review the current literature and discuss key molecules involved with PM dissemination, with the potential to target these mechanisms in the delivery of future treatments.

Reduced kinase D­interacting substrate of 220 kDa (Kidins220) in pancreatic cancer promotes EGFR/ERK signalling and disease progression.

Kidins220 is a transmembrane scaffold protein involved in several types of cancer. The aim of the present study was to examine the role of Kidins220 in tumorigenesis and disease progression of pancreatic cancer. The relevant signalling pathways including EGFR, EMT, and MMP were also investigated. The expression of Kidins220 was examined at the transcript and protein level. The Kidins220 knockdown cell model was established and its influence on cellular functions was determined. Involvement of Kidins220 in tumorigenesis and metastasis was examined in CD1 mice, respectively. The results showed that, reduced Kidin220 expression was associated with tumorigenesis, metastasis, and overall survival of pancreatic cancer. Knockdown of Kidins220 promoted proliferation, colony formation and tumorigenic capacity of pancreatic cancer cells in vitro and in vivo, respectively. Kidins220 regulated pancreatic cancer cell migration through the EGFR/AKT/ERK signalling pathway. Furthermore, enhanced EMT was observed in the pancreatic cancer cell lines with the knockdown of Kidins220, underlying EGFR regulation. Kidins220 also affected cell invasion via MMP1. A reduced expression of Kidins220 was observed in pancreatic cancer, which is associated with disease progression, distant metastasis and poor prognosis. The loss of Kidins220 in pancreatic cancer may contribute to disease progression through the upregulation of EGFR and downstream signalling.

The Evaluation of Durative Transfusion of Endostar Combined with Chemotherapy in Patients with Advanced Non-Small Cell Lung Cancer.

BACKGROUND: The overall survival (OS) in non-small cell lung cancer (NSCLC) is poor, with median OS of advanced NSCLC with standard systemic chemotherapy being reported at 13.6 months and the 5-year survival rate at less than 15%. Therefore, the aim of this study was to evaluate Endostar combined with chemotherapy in patients with advanced NSCLC. METHODS: Data on 116 cases of pathologically confirmed stage IIIB-IV NSCLC were retrospectively collected. The control group was treated with chemotherapy combined with intravenous infusion of Endostar while the test group received durative transfusion of Endostar. The short-term therapeutic effects including overall response rate (ORR), disease control rate (DCR), and safety were evaluated in both groups. In the follow-up, progression-free survival (PFS) and OS were also analysed. RESULTS: In the test group, the ORR was 53.4%, which was similar to that in the control group (44.8%) (p > 0.05). However, the DCR in the test group (86.2%) was significantly higher than that in the control group (70.7%) (p < 0.01). The median time to progression in the test group (6 months) was also significantly longer than that in the control group (4 months). Importantly, the median OS in the test group (17.5 months) was improved compared to the control group (13.5 months). The 1-year survival rate in the test and control groups was 9.7 and 15.8%, respectively. There was no significant difference in side effects (including thrombocytopenia, leucopenia, nausea, and vomiting) between the two groups. CONCLUSIONS: Endostar durative transfusion combined with chemotherapy showed a higher DCR, longer PFS and OS time, and was well tolerated in patients with advanced NSCLC.

Defunctioning Ileostomy Reversal Rates and Reasons for Delayed Reversal: Does Delay Impact on Complications of Ileostomy Reversal? A Study of 170 Defunctioning Ileostomies.

BACKGROUND: Temporary defunctioning ileostomy can reduce the consequences of anastomotic leak following low anterior resection. However, some patients never have their ileostomy reversed and in other cases the time to reversal of ileostomy can be delayed. The aim of this study was to identify the ileostomy closure rate following anterior resection, time to closure of ileostomy, reasons for delay in reversal and whether delay was associated with an increased complication rate. METHODS: Data were collected retrospectively on consecutive patients undergoing defunctioning ileostomy following anterior resection for rectal cancer, between January 2009 and August 2013. Data were collected on reversal of ileostomy rates, time to reversal, reasons for delayed reversal (defined as > 6 months) and complications following reversal. RESULTS: One hundred seventy patients were studied (median age 69 years, range 41 - 90 years), of whom 117 (69%) were male. One hundred twenty-seven (75%) patients had their ileostomies reversed. Median time to reversal was 6 months (range 1 - 42). In 63 patients who had delayed reversal, reasons were adjuvant chemotherapy (22, 35%), medical illness (14, 22%), anastomotic leak (9, 14%), and others (4, 7%). Postoperative complications occurred in 33 patients (26%). There was no postoperative mortality. Univariate analysis showed that delayed reversal was associated with an increased rate of complications and longer length of hospital stay following reversal (P < 0.05). CONCLUSIONS: One in four defunctioning ileostomies are not closed following anterior resection in our unit. Of those that are closed, approximately 50% have delayed closure beyond 6 months which is associated with increased risk of complications following their ileostomy reversal.