Role of post-operative serum C-reactive protein levels as a predictor of complications in upper gastrointestinal surgery.

BACKGROUND: This study was undertaken to assess the value of C-reactive protein (CRP) in predicting infective complications after elective upper gastrointestinal surgery. METHODS: Demographic data, clinical outcomes and serial CRPs preoperatively to post-operative day (POD) 7 were collected for patients undergoing pancreatectomy, hepatectomy and oesophago-gastrectomy between 2005 and 2016. Areas under the curve (AUC) were used to evaluate diagnostic accuracy per day of measurement. RESULTS: Of the 249 patients, 63 (25.3%) developed infective complications and 25 (10%) developed severe infective complications (≥Clavien-Dindo Grade III). Patients with infective complications trended towards higher CRP levels on POD1-POD4 and had significantly higher CRP levels on POD5 (156 versus 114 mg/dL; P = 0.03), POD6 (146 versus 93 mg/dL; P < 0.01) and POD7 (135 versus 84.6 mg/dL; P < 0.01). CRP had the best diagnostic accuracy for severe infective complications on POD6 (AUC: 0.73) and POD7 (AUC: 0.63). A CRP cut-off of 120 mg/dL on POD6 had a negative predictive value of 96.1% and a CRP cut-off of 80 mg/dL on POD7 had a negative predictive value of 94.9%. CONCLUSION: CRP measurements can be used as a negative predictive marker of infective complications in the first post-operative week after major elective upper gastrointestinal surgery.

Contemporary strategies to improve the outcome in locally advanced pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with an overall 5-year survival rate of less than 7%. After many years of basic and clinical research efforts, pancreatic cancer patients presenting with locally advanced, unresectable tumors remain a therapeutic challenge. Despite the lack of high quality randomized controlled trials, perioperative/neoadjuvant treatment strategies seem to be beneficial in these patients. At present the FOLFIRINOX regimen, which was established in the palliative setting, is increasingly recognized as the backbone of neoadjuvant therapy for locally advanced PDAC. Surgical resection follows the same principles and guidelines as upfront surgery specifically regarding the extent of resection including lymphadenectomy, vascular resections and multivisceral resections. Because of the limited diagnostic accuracy of restaging after neoadjuvant treatment, an adjusted intraoperative strategy is necessary to minimize the risk of debulking procedures and maximize the chance of a potential curative resection. Locally advanced PDAC requires a multidisciplinary and individualized treatment approach, and further research efforts for novel and innovative therapies. This article provides an updated overview on strategies to improve the outcome in locally advanced PDAC.

Right Sided Colon Cancer as a Distinct Histopathological Subtype with Reduced Prognosis.

BACKGROUND/AIMS: Recent data suggest that tumors of the right and left colon should be distinguished as they differ in clinical and molecular characteristics. METHODS: A total of 1,319 patients who underwent surgical resection for colon cancer (CC) were investigated. Tumors between the ileocecal valve and the hepatic flexure were classified as right CC (RCC), tumors between the splenic flexure and the rectum as left CC (LCC). RESULTS: RCC revealed a higher cause-specific mortality risk (hazard ratio 1.36, 95% CI 1.10-1.68, p = 0.005) and lower 5-year cause-specific (RCC 64.9%, 95% CI 60.4-69.4, LCC 70.7%, 95% CI 67.2-74.2, p = 0.032) and disease-free (RCC 56.0%, 95% CI 51.5-60.5, LCC 59.9%, 95% CI 56.2-63.6, p = 0.025) survival rates. RCCs were more often microsatellite instable (RCC 37.2%, LCC 13.0%, p < 0.001) and more often showed KRAS (RCC 42.5%, LCC 18.9%, p = 0.001) and BRAF mutations (RCC 26.6%, LCC 3.2%, p < 0.001). CONCLUSION: RCC and LCC differ significantly regarding clinical, histopathological and molecular genetic features and can be considered as distinct entities. The reduced prognosis of RCC may be caused by higher rates of microsatellite instability, KRAS and BRAF mutations.

Outcome after surgery for acute right-sided colonic ischemia without feasible vascular intervention: a single center experience of 58 patients over 6 years.

BACKGROUND: The predilection site of non-occlusive mesenteric ischemia is the right-sided colon. Surgical exploration followed by segmental bowel resection and primary anastomosis or ileostomy is recommended, if vascular interventions are not feasible and conservative treatment fails. We assessed the outcome of patients in this life-threatening condition. METHODS: From a prospective database 58 patients with urgent surgery for acute right-sided colonic ischemia without feasible vascular intervention (as a surrogate for non-occlusive mesenteric ischemia) were identified. Retrospectively the patients' characteristics, reason for ischemia, extent of resection, rate of ileostomy creation, 30 day and one year mortality, and rate of ileostomy-reversal at one year postoperative were assessed. RESULTS: Radiologically mesenteric arteriosclerotic disease was present in 54% of the patients. Vaso-occlusive mesenteric disease was suspected in 15% of the patients, but not confirmed intra-operatively. Ten patients underwent (extended) right-sided hemicolectomy with primary anastomosis (30-days mortality 20%, 1-year mortality 30%). Sixteen patients had (extended) right-sided hemicolectomy with creation of an ileostomy (30-days mortality 44%, 1-year mortality 86%, ostomy reversal in one patient). Twenty-five patients had (sub-) total colectomy with ileostomy creation (30-days mortality 60%, 1-year mortality 72%, ostomy reversal in two patients). Seven patients had exploration only (30-days mortality 86%, 1-year mortality 86%). Overall, the 30-days mortality-rate was 52% and the 1-year mortality-rate was 70%. Only 7% of the patients requiring an ostomy experienced ostomy-reversal. CONCLUSIONS: Patients with urgent surgery for acute right-sided colonic ischemia without feasible vascular intervention have a very high short and long-term mortality. The rate of ostomy-reversal is very low.

Distribution and quantification of irinotecan and its active metabolite SN-38 in colon cancer murine model systems using MALDI MSI.

Tissue distribution and quantitative analysis of small molecules is a key to assess the mechanism of drug action and evaluate treatment efficacy. The prodrug irinotecan (CPT-11) is widely used for chemotherapeutic treatment of colorectal cancer. CPT-11 requires conversion into its active metabolite SN-38 to exert the desired pharmacological effect. MALDI-Fourier transform ion cyclotron resonance (FT-ICR) and MALDI-time-of-flight (TOF) mass spectrometry imaging (MSI) were performed for detection of CPT-11 and SN-38 in tissue sections from mice post CPT-11 injection. In-depth information was gained about the distribution and quantity of drug compounds in normal and tumor tissue. The prodrug was metabolized, as proven by the detection of SN-38 in liver, kidney and digestive tract. In tumors from genetic mouse models for colorectal cancer (Apc (1638N/wt) x pvillin-Kras (V12G) ), CPT-11 was detected but not the active metabolite. In order to correlate drug distribution relative to vascularization, MALDI data were superimposed with CD31 (PECAM-1) immunohistochemistry. This analysis indicated that intratumoral access of CPT-11 mainly occurred by extravasation from microvessels. The present study exploits the power of MALDI MSI in drug analysis, and presents a novel approach to monitor drug distribution in relation to vessel functionality in preclinical and clinical research.

The evidence based dilemma of intraperitoneal drainage for pancreatic resection - a systematic review and meta-analysis.

BACKGROUND: Routine placement of intraperitoneal drains has been shown to be ineffective or potentially harmful in various abdominal surgical procedures. Studies assessing risks and benefits of abdominal drains for pancreatic resections have demonstrated inconsistent results. We thus performed a systematic review of the literature and meta-analyzed outcomes of pancreatic resections with and without intraoperative placement of drains. METHODS: A database search according to the PRISMA guidelines was performed for studies on pancreatic resection with and without intraperitoneal drainage. The subgroup 'pancreaticoduodenectomy' was analyzed separately. The quality of studies was assessed using the MINORS and STROBE criteria. Pooled estimates of morbidity, mortality and length of hospital stay were calculated using random effects models. RESULTS: Only two randomized trials were identified. Their results were contradictory. We thus included six further, retrospective studies in the meta-analysis. However, with I2 = 68% for any kind of complication, the estimate of inter-study heterogeneity was high. While overall morbidity after any kind of pancreatic resection was lower without drains (p = 0.04), there was no significant difference in mortality rates. In contrast, pooled estimates of outcomes after pancreaticoduodenectomy demonstrated no differences in morbidity (p = 0.40) but increased rates of intraabdominal abscesses (p = 0.04) and mortality (p = 0.04) without intraperitoneal drainage. CONCLUSION: Although drains are associated with slightly increased morbidity for pancreatic resections, routine omission of drains cannot be advocated, especially after pancreaticoduodenectomy. While selective drainage seems reasonable, further efforts to generate more reliable data are questionable because of the current studies and the presumed small differences in outcomes. TRIAL REGISTRATION: Systematic review registration number CRD42014007497.

Colorectal cancer surgery remains effective with rising patient age.

BACKGROUND: The incidence of colorectal cancer rises disproportionally in aging persons. With a shift towards higher population age in general, an increasing number of older patients require adequate treatment. This study aims to investigate differences between young and elderly patients who undergo resection for colorectal cancer, regarding clinical characteristics, morbidity, and prognosis. METHODS: By retrospective analysis of 6 years (2007 to 2012) of a prospectively documented database, a total of 636 patients were identified who underwent oncological resection for colorectal cancer at our institution. Of this total, all 569 patients with primary colorectal adenocarcinoma were included. Four hundred ten patients were 74 years or younger and 159 were 75 years or older. The median follow-up was 22 months. RESULTS: Older patients had significantly more comorbidities (85 % vs. 56 %, p < 0.001) and a higher ASA score (p < 0.001). The mean length of stay in the hospital was longer (24 vs. 20 days, p = 0.002), as was the length of postoperative intensive care stay (4 vs. 2 days, p = 0.003). However, elderly patients did not have significantly higher rates of intraoperative complications or surgical morbidity. Tumor-specific 2-year survival was 83 ± 4 % for the elderly and 87 ± 2 % for the younger patients, which was not significantly different (p = 0.90). CONCLUSIONS: Long-term outcome after oncologic resection for colorectal cancer does not differ between elderly and younger patients. Age in general should not be considered as a limiting factor for colorectal cancer surgery or tumor-specific prognosis.

Mucinous and signet-ring cell colorectal cancers differ from classical adenocarcinomas in tumor biology and prognosis.

OBJECTIVES: To define the prognostic value of different histological subtypes of colorectal cancer. BACKGROUND: Most colorectal cancers are classical adenocarcinomas (AC). Less frequent subtypes include mucinous adenocarcinomas (MAC) and signet-ring cell carcinomas (SC). In contrast to established prognostic factors such as TNM and grading, the histological subtype has no therapeutical consequences so far, although it may reflect different biological behavior. METHODS: Between 1982 and 2012, a total of 3479 consecutive patients underwent surgery for primary colorectal cancer (AC, MAC, or SC). Clinical, histopathological, and survival data were analyzed. RESULTS: Of all 3479 patients, histological subtype was AC in 3074 cases (88%), MAC in 375 cases (11%), and SC in 30 cases (0.9%). MAC (51%, P < 0.001) and SC (50%, P = 0.029) occurred more frequently in right-sided tumors than AC (28%). Compared with AC, tumor stages and histological grading were higher in MAC and SC (P < 0.001 for each). Rates of angioinvasion were lower in MAC than in AC (5% vs 9%, P = 0.011). Rates of lymphatic invasion were higher in SC than in AC (67% vs 25%, P < 0.001). Five-year cause-specific survival was 67 ± 1% for AC, 61 ± 3% for MAC, and 21 ± 8% for SC (P < 0.001 for difference between the groups). In multivariable analysis, survival did not differ significantly between AC and MAC after correction for tumor stage. However, SC remained an independent prognostic factor associated with worse survival (hazard ratio = 2.5, 95% confidence interval = 1.6-3.8, P < 0.001). CONCLUSIONS: MAC and SC are histological subtypes of colorectal cancer with different characteristics than classical AC. Both are diagnosed in more advanced tumor stages, but the dismal prognosis of SC seems to be caused by its intrinsic tumor biology.