The impact of neural invasion severity in gastrointestinal malignancies: a clinicopathological study.

OBJECTIVES: Because neural invasion (NI) is still inconsistently reported and not well characterized within gastrointestinal malignancies (GIMs), our aim was to determine the exact prevalence and severity of NI and to elucidate the true impact of NI on patient's prognosis. BACKGROUND: The union internationale contre le cancer (UICC) recently added NI as a novel parameter in the current TNM classification. However, there are only a few existing studies with specific focus on NI, so that the distinct role of NI in GIMs is still uncertain. MATERIALS AND METHODS: NI was characterized in approximately 16,000 hematoxylin and eosin tissue sections from 2050 patients with adenocarcinoma of the esophagogastric junction (AEG)-I-III, squamous cell carcinoma (SCC) of the esophagus, gastric cancer (GC), colon cancer (CC), rectal cancer (RC), cholangiocellular cancer (CCC), hepatocellular cancer (HCC), and pancreatic cancer (PC). NI prevalence and severity was determined and related to patient's prognosis and survival. RESULTS: NI prevalence largely varied between HCC/6%, CC/28%, RC/34%, AEG-I/36% and AEG-II/36%, SCC/37%, GC/38%, CCC/58%, and AEG-III/65% to PC/100%. NI severity score was uppermost in PC (24.9±1.9) and lowest in AEG-I (0.8±0.3). Multivariable analyses including age, sex, TNM stage, and grading revealed that the prevalence of NI was significantly associated with diminished survival in AEG-II/III, GC, and RC. However, increasing NI severity impaired survival in AEG-II/III and PC only. CONCLUSIONS: NI prevalence and NI severity strongly vary within GIMs. Determination of NI severity in GIMs is a more precise tool than solely recording the presence of NI and revealed dismal prognostic impact on patients with AEG-II/III and PC. Evidently, NI is not a concomitant side feature in GIMs and, therefore, deserves special attention for improved patient stratification and individualized therapy after surgery.

Impact of preoperative local water-filtered infrared A irradiation on postoperative wound healing: a randomized patient- and observer-blinded controlled clinical trial.

OBJECTIVE: In addition to a preoperative antibiotic single-shot prophylaxis, we tested the impact of a one-time preoperative water-filtered infrared A irradiation (wIRA) on postoperative wound healing of patients. BACKGROUND: wIRA improves wound healing in postoperative settings. METHODS: A total of 400 consecutive patients undergoing gastrointestinal surgery were randomly assigned to the treatment group (A) or placebo group (B). We applied wIRA for 20 minutes while patients were prepared for surgery. Patients and observer were blinded to group assignment. Primary endpoints were surgical site infections (SSIs), wound healing, and rate and level of pain within 30 days after surgery. Primary efficacy analysis was carried out on the basis of an intention-to-treat (ITT) population and a full-analysis set (FAS). Missing values of primary outcome variables were considered as SSIs and maximum pain levels in the ITT analysis, respectively. RESULTS FAS: The incidence of SSI was 9 of 178 patients (5.1%) within group A compared with 22 of 182 (12.1%) within group B [P = 0.018; relative risk (RR) = 0.42; 95% CI: 0.18-0.93]. ITT: 32 of 200 (16%) SSIs occurred within group A and 39 of 200 (20%) within group B (P = 0.248) with an RR of 0.74 (95% CI: 0.43-1.28). The wIRA group showed lower postoperative pain at both the ITT (P = 0.092) and the FAS analysis (P = 0.045). CONCLUSIONS: This trial indicates a clinically relevant benefit of one-time application of preoperative wIRA as a supportive addition to prophylactic antibiotics. wIRA contributes to both reduced SSI rates and postoperative pain but also effectively decreases morbidity and related expenses in the health care system.

The severity of neural invasion is associated with shortened survival in colon cancer.

PURPOSE: Neural invasion (NI) is a histopathologic feature of colon cancer that receives little consideration. Therefore, we conducted a morphologic and functional characterization of NI in colon cancer. EXPERIMENTAL DESIGN: NI was investigated in 673 patients with colon cancer. Localization and severity of NI was determined and related to patient's prognosis and survival. The neuro-affinity of colon cancer cells (HT29, HCT-116, SW620, and DLD-1) was compared with pancreatic cancer (T3M4 and SU86.86) and rectal cancer cells (CMT-93) in the in vitro three-dimensional (3D)-neural-migration assay and analyzed via live-cell imaging. Immunoreactivity of the neuroplasticity marker GAP-43, and the neurotrophic-chemoattractant factors Artemin and nerve growth factor (NGF), was quantified in colon cancer and pancreatic cancer nerves. Dorsal root ganglia of newborn rats were exposed to supernatants of colon cancer, rectal cancer, and pancreatic cancer cells and neurite density was determined. RESULTS: NI was detected in 210 of 673 patients (31.2%). Although increasing NI severity scores were associated with a significantly poorer survival, presence of NI was not an independent prognostic factor in colon cancer. In the 3D migration assay, colon cancer and rectal cancer cells showed much less neurite-targeted migration when compared with pancreatic cancer cells. Supernatants of pancreatic cancer and rectal cancer cells induced a much higher neurite density than those of colon cancer cells. Accordingly, NGF, Artemin, and GAP-43 were much more pronounced in nerves in pancreatic cancer than in colon cancer. CONCLUSION: NI is not an independent prognostic factor in colon cancer. The lack of a considerable biologic affinity between colon cancer cells and neurons, the low expression profile of colonic nerves for chemoattractant molecules, and the absence of a major neuroplasticity in colon cancer may explain the low prevalence and impact of NI in colon cancer.

The severity of neural invasion is a crucial prognostic factor in rectal cancer independent of neoadjuvant radiochemotherapy.

OBJECTIVE: To provide a comprehensive characterization of neural invasion (NI) in rectal adenocarcinoma (RC), to establish a novel NI-severity scoring system, and to assess the prognostic value of NI with emphasis on its localization and severity. BACKGROUND: The literature merely contains small-scale studies with limited histopathological characterization of NI in RC. METHODS: Neural invasion was thoroughly characterized in 296 patients with locally advanced uT3-RC (139 with primary resection and 157 with neoadjuvant radiochemotherapy [nRCTx]). To identify the precise localization of NI, we investigated the main tumor, peritumoral area, adjacent normal tissue, and all lymph nodes. To classify the clinical impact of NI, an NI severity score was established and related to patient prognosis. RESULTS: Neural invasion was detected in 32% of patients with primary resection and in 19% (P = 0.010) receiving nRCTx. The major location of NI was found in the peritumoral area. The prevalence of NI in the main tumor within the primary resection group was 6%, whereas it was absent in the nRCTx group (P = 0.002). Increasing NI severity, but not NI localization, was associated with a significantly poorer survival and increased local recurrence rate in both groups. Multivariate analysis (including TNM-stage, grading, and Carcinoembryonic antigen (CEA)) revealed NI prevalence and severity as independent prognostic factors. CONCLUSIONS: Neural invasion in RC has a heterogeneous appearance in regard to its localization and its severity. nRCTx seems to have a suppressive effect on NI. Neural invasion severity might be applied as a novel tool to estimate accurately patient's prognosis and thus should be considered in pathology reports.

Neural invasion in pancreatic cancer: the past, present and future.

In the past 15 years, invasion of nerves by cancer cells has escaped from its role as a mere bystander in cancer biology and turned into an attractive niche to study the heterotypic interaction between cancer cells and neurons. Today, neural invasion (NI) in pancreatic cancer (PCa) stands out due to the recent demonstration of its association with tumor progression, local recurrence and neuropathic pain. Accordingly, recent research on NI in PCa revealed the critical involvement of numerous nerve- or cancer cell-derived molecules in several novel in vitro and in vivo models of NI, which, however, still need further major improvement.