The prognostic significance of CXCR4 and SDF-1 in differentiated thyroid cancer depends on CD8+ density.

BACKGROUND: Tumor infiltration with cytotoxic CD8+ T-cells is associated with a favorable outcome in several neoplasms, including thyroid cancer. The chemokine axis CXCR4/SDF-1 correlates with more aggressive tumors, but little is known concerning the prognostic relevance in relation to the tumor immune microenvironment of differentiated thyroid cancer (DTC). METHODS: A tissue microarray (TMA) of 37 tumor specimens of primary DTC was analyzed by immunohistochemistry (IHC) for the expression of CD8+, CXCR4, phosphorylated CXCR4 and SDF-1. A survival analysis was performed on a larger collective (n = 456) at RNA level using data from The Cancer Genome Atlas (TCGA) papillary thyroid cancer cohort. RESULTS: Among the 37 patients in the TMA-cohort, the density of CD8+ was higher in patients with less advanced primary tumors (median cells/TMA-punch: 12.5 (IQR: 6.5, 12.5) in T1-2 tumors vs. 5 (IQR: 3, 8) in T3-4 tumors, p = 0.05). In the TCGA-cohort, CXCR4 expression was higher in patients with cervical lymph node metastasis compared to N0 or Nx stage (CXCR4high/low 116/78 vs. 97/116 vs. 14/35, respectively, p = 0.001). Spearman's correlation analysis of the TMA-cohort demonstrated that SDF-1 was significantly correlated with CXCR4 (r = 0.4, p = 0.01) and pCXCR4 (r = 0.5, p = 0.002). In the TCGA-cohort, density of CD8+ correlated with CXCR4 and SDF-1 expression (r = 0.58, p < 0.001; r = 0.4, p < 0.001). The combined marker analysis of the TCGA cohort demonstrated that high expression of both, CXCR4 and SDF-1 was associated with reduced overall survival in the CD8 negative TCGA cohort (p = 0.004). CONCLUSION: These findings suggest that the prognostic significance of CXCR4 and SDF-1 in differentiated thyroid cancer depends on the density of CD8 positive T-lymphocytes. Further studies with larger sample sizes are needed to support our findings and inform future investigations of new treatment and diagnostic options for a more personalized approach for patients with differentiated thyroid cancer.

Long-term urogenital assessment after elective laparoscopic sigmoid resection for diverticulitis: a comparison between central and peripheral vascular resection.

AIM: Increasing attention has been given to postoperative gastrointestinal functional outcome and quality of life after sigmoid resection for diverticulitis. Conversely, very little has been described about postoperative urogenital functional outcome and even less about its potential relationship to the type of vascular approach. The aim of this study was to evaluate whether central ligation of the inferior mesenteric artery (IMA) compared with peripheral dissection could impair urinary and sexual function in the long term. METHOD: Patients undergoing elective laparoscopic sigmoid resection for diverticulitis from 2004 to 2017 were retrospectively analysed. They were asked to complete the American Urological Association Symptom Index (AUASI) questionnaire. Men received the five-item version of the International Index of Erectile Function (IIEF-5) questionnaire. Patients were then divided according to the type of vascular resection. RESULTS: A response rate of the 36.4% to the AUASI and 43.8% to the IIEF-5 questionnaires was achieved. Three hundred and twenty four patients with a mean age of 62 ± 9.85 years were analysed for their urinary function (IMA preserved n = 217; IMA resected n = 107) in a median follow-up of 87 months. Furthermore, 115 men with a mean age of 60 ± 8.97 years were investigated for their sexual function (IMA preserved n = 80; IMA resected n = 35) in a median follow-up of 89 months. No difference (AUASI: 8 ± 6.32 IMA preserved vs. 7 ± 6.26 IMA resected, P = 0.204; IIEF-5: 15 ± 7.67 IMA preserved vs. 15 ± 8.61 IMA resected, P = 0.674) was found regarding the type of vascular approach during sigmoid resection. CONCLUSIONS: No association was found between the type of vascular approach and the long-term urogenital functional outcome in patients undergoing sigmoid resection for diverticulitis.

Predictive model estimating the decrease of postoperative gastrointestinal quality of life index (GIQLI) in patients after elective laparoscopic sigmoid resection for diverticular disease.

BACKGROUND: Growing consideration in quality of life (QoL) has changed the therapeutic strategy in patients suffering from diverticular disease. Patients' well-being plays a crucial role in the decision-making process. However, there is a paucity of studies investigating patients' or surgery-related factors influencing the postoperative gastrointestinal function. The aim of this study was to investigate in a predictive model patients or surgical variables that allow better estimation of the postoperative gastrointestinal QoL. METHODS: This observational study retrospectively analyzed patients undergoing elective laparoscopic sigmoidectomy for diverticulitis between 2004 and 2017. The one-time postoperative QoL was assessed with the gastrointestinal quality of life index (GIQLI) in 2019. A linear regression model with stepwise selection has been applied to all patients and surgery-related variables. RESULTS: Two hundred seventy-two patients with a mean age of 62.30 ± 9.74 years showed a mean GIQLI of 116.39±18.25 at a mean follow-up time of 90.4±33.65 months. Women (n=168) reported a lower GIQLI compared to male (n=104; 112.85±18.79 vs 122.11±15.81, p<0.001). Patients with pre-operative cardiovascular disease (n=17) had a worse GIQLI (106.65 ±22.58 vs 117.08±17.66, p=0.010). Finally, patients operated less than 5 years ago (n=63) showed a worse GIQLI compared to patients operated more than 5 years ago (n=209; 111.98±19.65 vs 117.71±17.63, p=0.014). CONCLUSIONS: Female gender and the presence of pre-operative cardiovascular disease are predictive for a decreased postoperative gastrointestinal QoL. Furthermore, patients' estimation of gastrointestinal functioning seems to improve up to 5 years after surgery.

Short- and long-term outcomes for primary anastomosis versus Hartmann's procedure in Hinchey III and IV diverticulitis: a multivariate logistic regression analysis of risk factors.

PURPOSE: The management of perforated diverticulitis with generalized peritonitis is still controversial and no preferred standardized therapeutic approach has been determined. We compared surgical outcomes between Hartmann's procedure (HP) and primary anastomosis (PA) in patients with Hinchey III and IV perforated diverticulitis. METHODS: Multicenter retrospective analysis of 131 consecutive patients with Hinchey III and IV diverticulitis operated either with HP or PA from 2015 to 2018. Postoperative morbidity was compared after adjustment for known risk factors in a multivariate logistic regression. RESULTS: Sixty-six patients underwent HP, while PA was carried out in 65 patients, 35.8% of those were defunctioned. HP was more performed in older patients (74.6 vs. 61.2 years, p < .001), with Hinchey IV diverticulitis (37% vs. 7%, p < .001) and in patients with worse prognostic scores (P-POSSUM Physiology Score, p < .001, Charlson Comorbidity Index p < .001). Major morbidity and mortality were higher in HP compared to PA (30.3% vs. 9.2%, p = .002 and 10.6% vs. 0%, p = .007, respectively) with lower stoma reversal rate (43.9% vs. 86.9%, p < .001). In a multivariate logistic regression, PA was independently associated with lower postoperative morbidity and mortality (OR 0.24, 95% CI 0.06-0.96, p = .044). CONCLUSIONS: In comparison to PA, HP is associated with a higher morbidity, higher mortality, and a lower stoma reversal rate. Although a higher prevalence of risk factors in HP patients may explain these outcomes, a significant increase in morbidity and mortality persisted in a multivariate logistic regression analysis that was stratified for the identified risk factors.

IL-22-mediates Cross-talk between Tumor Cells and Immune Cells Associated with Favorable Prognosis in Human Colorectal Cancer.

The positive prognostic role of the immune environment in colorectal cancer is widely accepted. However, there are few data about the prognostic significance of interleukin-22 in human colorectal cancer which is still debated. In our study we could demonstrate for the first time a positive prognostic role of interleukin-22 in human colorectal cancer relying on its capacity to induce in tumor cells the production of chemokines recruiting into the tumor microenvironment neutrophils associated with a favorable clinical outcome.

Malignant melanoma metastasis in the gallbladder. A case report of an unusual metastatic site.

INTRODUCTION: Malignant melanoma is a neoplasia with the ability to metastasize to all organs. Most frequently, metastases derives from a skin primary. A solitary metastasis in the gallbladder is rarely mentioned in current literature. PRESENTATION OF CASE: We present the case of a 62-year-old female patient with the unusual metastatic spread of malignant melanoma into the gallbladder. The lesion was detected during routine follow up appointment six years after the initial surgical and radio-chemotherapeutic treatment of a malignant melanoma on the back. Following multidisciplinary team meeting, it was decided to perform a laparoscopic cholecystectomy to remove the gallbladder metastasis. DISCUSSION: New occurrence of a melanoma metastasis in the gallbladder is extremely rare, especially in stable disease. The therapeutical concept must be discussed extensively in the present of this metastasized tumor. CONCLUSION: In otherwise stable disease, palliative surgery for metastasis in the gallbladder is a possible option to prevent biliary complications. In a palliative setting always weigh up the risks and benefits while maintaining the quality of life.

Infiltration by IL22-Producing T Cells Promotes Neutrophil Recruitment and Predicts Favorable Clinical Outcome in Human Colorectal Cancer.

Immune cell infiltration in colorectal cancer effectively predicts clinical outcome. IL22, produced by immune cells, plays an important role in inflammatory bowel disease, but its relevance in colorectal cancer remains unclear. Here, we addressed the prognostic significance of IL22+ cell infiltration in colorectal cancer and its effects on the composition of tumor microenvironment. Tissue microarrays (TMA) were stained with an IL22-specific mAb, and positive immune cells were counted by expert pathologists. Results were correlated with clinicopathologic data and overall survival (OS). Phenotypes of IL22-producing cells were assessed by flow cytometry on cell suspensions from digested specimens. Chemokine production was evaluated in vitro upon colorectal cancer cell exposure to IL22, and culture supernatants were used to assess neutrophil migration in vitro Evaluation of a testing (n = 425) and a validation TMA (n = 89) revealed that high numbers of IL22 tumor-infiltrating immune cells were associated with improved OS in colorectal cancer. Ex vivo analysis indicated that IL22 was produced by CD4+ and CD8+ polyfunctional T cells, which also produced IL17 and IFNγ. Exposure of colorectal cancer cells to IL22 promoted the release of the neutrophil-recruiting chemokines CXCL1, CXCL2, and CXCL3 and enhanced neutrophil migration in vitro Combined survival analysis revealed that the favorable prognostic significance of IL22 in colorectal cancer relied on the presence of neutrophils and was enhanced by T-cell infiltration. Altogether, colorectal cancer-infiltrating IL22-producing T cells promoted a favorable clinical outcome by recruiting beneficial neutrophils capable of enhancing T-cell responses.