Validation of a Nomogram to Predict Recurrence in Patients with Mucinous Neoplasms of the Appendix with Peritoneal Dissemination After Cytoreductive Surgery and HIPEC.

BACKGROUND: Survival of patients affected by mucinous appendiceal neoplasms with peritoneal dissemination (PD) is mainly related to histopathological features. However, prognostic stratification is still a concern, as the clinical course of the disease is often unpredictable. The aim of this study is to construct and externally validate a nomogram predicting disease-free survival (DFS) in mucinous appendiceal neoplasms with PD treated by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). PATIENTS AND METHODS: Patients treated in two referral centers were included: Hospital General Universitario Gregorio Marañón, Madrid, Spain (derivation cohort) and Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy (validation cohort). Cox regression analysis identified factors associated with shorter DFS in the derivation cohort. The nomogram performance was externally evaluated in the validation cohort using concordance index and calibration plots. Histology was classified according to the Peritoneal Surface Oncology Group International (PSOGI). RESULTS: The derivation cohort included 95 patients, and the validation cohort 348. Five-year DFS rates were 51.5 and 62%, respectively. Cox regression analysis (derivation cohort) identified PSOGI histology of the peritoneal components, number of preoperative elevated tumor marker, and peritoneal disease extent, as assessed by peritoneal carcinomatosis index, to be predictors of DFS. The model's predictive capacity was higher than that of PSOGI classification alone, with respective concordance indexes of 0.702 ± 0.023 and 0.610 ± 0.018 (validation cohort). The nomogram approximated the perfect model in the calibration plots at 3- and 5-year DFS. CONCLUSIONS: An easy-to-use model that provides better prognostic stratification than histopathological features has been constructed. This nomogram may help clinicians in individualized survival predictions and informed clinical decision-making.

Defining stage in mucinous tumours of the appendix with peritoneal dissemination: the importance of grading terminology: systematic review.

BACKGROUND: Mucinous appendiceal neoplasms with peritoneal dissemination (PD) show a wide spectrum of clinical behaviour. Histological grade has been correlated with prognosis, but no universally accepted histological grading has been established. The aim of this systematic review was to provide historical insight to understand current grading classifications, basic histopathological features of each category, and to define which classification correlates best with prognosis. METHODS: MEDLINE and the Cochrane Library were searched for studies that reported survival across different pathological grades in patients with mucinous neoplasm of the appendix with PD treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. PRISMA guidelines were followed. RESULTS: Thirty-eight studies were included. Ronnett's classification was the most common (9 studies). Classifications proposed by the Peritoneal Surface Oncology Group International (PSOGI) (6 studies) and the seventh or eighth edition of the AJCC (7 studies) are gaining in popularity. Nine studies supported a two-tier, 12 a three-tier, and two a four-tier classification system. Three studies demonstrated that acellular mucin had a better prognosis than low-grade pseudomyxoma peritonei in the PSOGI classification or M1bG1 in the eighth edition of the AJCC classification. Four studies demonstrated that the presence of signet ring cells was associated with a worse outcome than high-grade pseudomyxoma peritonei in the PSOGI classification and M1bG2 in the eighth edition of the AJCC. CONCLUSION: There is a great need for a common language in describing mucinous neoplasms of the appendix with PD. Evolution in terminology as a result of pathological insight turns the four-tiered PSOGI classification system into a coherent classification option.

On the mechanism underlying tellurite reduction by Aeromonas caviae ST dihydrolipoamide dehydrogenase.

The dihydrolipoamide dehydrogenase (LpdA) from the tellurite-resistant bacterium Aeromonas caviae ST reduces tellurite to elemental tellurium. To characterize this NADH-dependent activity, the A. caviae lpdA gene was subjected to site-directed mutagenesis and genes containing C45A, H322Y and E354K substitutions were individually transformed into Escherichia coli Δlpd. Cells expressing the modified genes exhibited decreased pyruvate dehydrogenase, dihydrolipoamide dehydrogenase and TR activity regarding that observed with the wild type A. caviae lpdA gene. In addition, cells expressing the altered lpdA genes showed increased oxidative stress levels and tellurite sensitivity than those carrying the wild type counterpart. The involvement of Cys residues in LpdA's TR activity was analyzed using specific inhibitors that interact with catalytic cysteines and/or disulfide bridges such as aurothiomalate, zinc or nickel. TR activity of purified LpdA was drastically affected by these compounds. Since LpdA belongs to the flavoprotein family, the involvement of the FAD/NAD(P)(+)-binding domain in TR activity was determined. FAD removal from purified LpdA results in loss of TR activity, which was restored with exogenously added FAD. Substitutions in E354, involved in FAD/NADH binding, resulted in low TR activity because of flavin loss. Finally, changing H322 (involved in NAD(+)/NADH binding) by tyrosine also resulted in altered TR activity.