Prolonged Survival in Peritoneal Metastatic Appendiceal Carcinoma Patients Treated With Combined Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

INTRODUCTION: Primary treatment for peritoneal dissemination of appendiceal cancer is the combination of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. The endpoints were overall survival and evaluation of prognostic factors. METHODS: Clinicopathological and treatment-related factors were obtained from a prospective database. A total of 84 patients, 55 (65%) primary and 29 (35%) recurrent malignant appendiceal carcinomas with synchronous and metachronous peritoneal metastases, underwent multimodal treatment between 2011 and 2021. The endpoints of the study were overall survival and evaluation of prognostic factors. RESULTS: The median follow-up was 4.8 y; the mean age was 54.5 y (range 25-77), with a sex distribution of 69% female and 31% male. The mean peritoneal cancer index was 11.3. The proportion of mucinous, intestinal-type, signet ring cell, and goblet cell carcinoma was 56%, 23%, 11%, and 10%, respectively. The 5-y survival rate of the whole cohort was 56.7%. In primary and recurrent diseases, the overall median survival was 8.4 and 4.9 y. Significantly improved survival was detected after complete cytoreduction resection (hazard ratio [HR] for CCR-2 versus CCR-0: 9.388, 95% confidence interval [CI] 3.026-29.124, P = 0.001) and initial local operation with undelayed admission to the center (HR 0.262, 95% CI 0.089-0.773; P = 0.015). The five independent factors in Kaplan-Meier analysis and univariable Cox regression analysis associated with significant adverse survival were cancer antigen (CA) 19-9 over 37 IU/mL, signet ring cell and intestinal-type histology, positive nodal status, grading, and peritoneal cancer index >20. Neoadjuvant chemotherapy administration did not impact survival (HR 1.220, 95% CI 0.612-2.432, P = 0.571). CONCLUSIONS: With multimodal treatment, prolonged survival is attainable in stage IV primary and recurrent appendiceal carcinoma with peritoneal dissemination. Direct referral to specialized centers after confirmation of peritoneal metastasis is recommended because prompt definitive treatment may significantly improve survival.

Hyperthermic Intraperitoneal Chemotherapy With Cisplatin and Doxorubicin for 90 Minutes Versus 60 Minutes After Cytoreductive Surgery (CRS). Does the 30-Minute Difference Matter? A Comparative Study in a High Volume Centre.

BACKGROUND/AIM: This study compared the perioperative outcomes after the same combination of hyperthermic intraperitoneal chemotherapy (HIPEC) compounds when administered for 90 min vs. 60 min, while all other therapy variables remained constant. PATIENTS AND METHODS: A total of 120 patients were included with peritoneal surface malignancy who underwent cisplatin (75 mg/m2) and doxorubicin (15 mg/m2) closed HIPEC after cytoreductive surgery. RESULTS: Sixty-five patients (54.2%) in the 60 min and 55 patients (45.8%) in the 90 min HIPEC group were compared. Patients, tumor characteristics, and postoperative complications were comparable. The only significant difference was the rate of chest drain/pleural puncture with an incidence of 18.5% and 34.5% in the 60 min and 90 min group, respectively (p=0.045). After adjustment in a multi-variable regression analysis, the odds for patients with HIPEC 90 min of having chest drain or pleural puncture in comparison to patients with HIPEC 60 min was still higher, but not significant with an OR of 2.238 (95%CI=0.932-5.373; p=0.071). CONCLUSION: HIPEC administered for 90 min is safe and does not increase perioperative morbidity and mortality compared to the 60-min administration.

Stimulation of actin polymerization by vacuoles via Cdc42p-dependent signaling.

We have previously shown that actin ligands inhibit the fusion of yeast vacuoles in vitro, which suggests that actin remodeling is a subreaction of membrane fusion. Here, we demonstrate the presence of vacuole-associated actin polymerization activity, and its dependence on Cdc42p and Vrp1p. Using a sensitive in vitro pyrene-actin polymerization assay, we found that vacuole membranes stimulated polymerization, and this activity increased when vacuoles were preincubated under conditions that support membrane fusion. Vacuoles purified from a VRP1-gene deletion strain showed reduced polymerization activity, which could be recovered when reconstituted with excess Vrp1p. Cdc42p regulates this activity because overexpression of dominant-negative Cdc42p significantly reduced vacuole-associated polymerization activity, while dominant-active Cdc42p increased activity. We also used size-exclusion chromatography to directly examine changes in yeast actin induced by vacuole fusion. This assay confirmed that actin undergoes polymerization in a process requiring ATP. To further confirm the need for actin polymerization during vacuole fusion, an actin polymerization-deficient mutant strain was examined. This strain showed in vivo defects in vacuole fusion, and actin purified from this strain inhibited in vitro vacuole fusion. Affinity isolation of vacuole-associated actin and in vitro binding assays revealed a polymerization-dependent interaction between actin and the SNARE Ykt6p. Our results suggest that actin polymerization is a subreaction of vacuole membrane fusion governed by Cdc42p signal transduction.

Functional differences of photosystem II from Synechococcus elongatus and spinach characterized by flash induced oxygen evolution patterns.

Detailed comparative studies of flash induced oxygen evolution patterns in thylakoids from the thermophilic cyanobacterium Synechococcus elongatus (S. elongatus; also referred to as Thermosynechococcus elongatus) and from spinach led to the following results: (i) the miss parameter alpha of S. elongatus thylakoids exhibits a pronounced temperature dependence with a minimum of 7% at 25 degrees C and values of 17 and 10% at 3 and 35 degrees C, respectively, while for spinach thylakoids alpha decreases continuously from 18% at 35 degrees C down to 8% at 3 degrees C; (ii) at all temperatures, the double hit probability beta exceeds in S. elongatus the corresponding values of spinach by an increment Delta beta of about 3%; (iii) at 20 degrees C the slow relaxation of the oxidation states S(2) and S(3) is about 15 and 30 times, respectively, slower in S. elongatus than in spinach, while the reduction of these S states by tyrosine Y(D) is 2-3 times faster; (iv) the reaction S(0)Y(D)(ox) --> S(1)Y(D) is slower by a factor of 4 in S. elongatus as compared to spinach; and (v) the activation energies of S state dark relaxations in S. elongatus are all within a factor of 1.5 as compared to the previously reported values from spinach thylakoids [Vass, I., Deak, Z., and Hideg, E. (1990) Biochim. Biophys. Acta 1017, 63-69; Messinger, J., Schröder, W. P., and Renger, G. (1993) Biochemistry 32, 7658-7668], but the difference between the activation energies of the slow S(2) and S(3) decays is significantly larger in S. elongatus than in spinach. These results are discussed in terms of differences between cyanobacteria and higher plants on the acceptor side of PSII and a shift of the redox potential of the couple Y(D)/Y(D)(ox). The obtained data are also suitable to address questions about effects of the redox state of Y(D) on the miss probability and the possibility of an S state dependent miss parameter.

Nitric oxide-induced formation of the S-2 state in the oxygen-evolving complex of photosystem II from Synechococcus elongatus.

In spinach photosystem II (PSII) membranes, the tetranuclear manganese cluster of the oxygen-evolving complex (OEC) can be reduced by incubation with nitric oxide at -30 degrees C to a state which is characterized by an Mn(2)(II, III) EPR multiline signal [Sarrou, J., Ioannidis, N., Deligiannakis, Y., and Petrouleas, V. (1998) Biochemistry 37, 3581-3587]. This state was recently assigned to the S(-)(2) state of the OEC [Schansker, G., Goussias, C., Petrouleas, V., and Rutherford, A. W. (2002) Biochemistry 41, 3057-3064]. On the basis of EPR spectroscopy and flash-induced oxygen evolution patterns, we show that a similar reduction process takes place in PSII samples of the thermophilic cyanobacterium Synechococcus elongatus at both -30 and 0 degrees C. An EPR multiline signal, very similar but not identical to that of the S(-)(2) state in spinach, was obtained with monomeric and dimeric PSII core complexes from S. elongatus only after incubation at -30 degrees C. The assignment of this EPR multiline signal to the S(-)(2) state is corroborated by measurements of flash-induced oxygen evolution patterns and detailed fits using extended Kok models. The small reproducible shifts of several low-field peak positions of the S(-)(2) EPR multiline signal in S. elongatus compared to spinach suggest that slight differences in the coordination geometry and/or the ligands of the manganese cluster exist between thermophilic cyanobacteria and higher plants.