Home-Based Trimodal Prehabilitation in Patients with Peritoneal Carcinomatosis Undergoing Cytoreductive Surgery: Effect on Functional Walking Capacity and Skeletal Muscle Mass.

BACKGROUND: Patients with peritoneal carcinomatosis often suffer from loss of skeletal muscle mass and require extensive surgery. Multimodal prehabilitation may improve physical status but its benefits for these specific patients remain unknown. This study aimed to evaluate the effect of prehabilitation on functional walking capacity and skeletal muscle mass, as well as its association with postoperative complications. PATIENTS AND METHODS: A prospective study of patients with peritoneal carcinomatosis following a home-based trimodal prehabilitation program was carried out. Functional walking capacity was assessed with the 6-min walk test (T6MWT), and by the appendicular skeletal muscle index (ASMI) estimated by bioelectrical impedance analysis. Data were collected at the first medical appointment and on the day before surgery. A 90-day postoperative morbidity was registered according to the Clavien-Dindo classification. RESULTS: A total of 62 patients were included in the analysis. Women were more prevalent (77.4%) and peritoneal metastasis from ovarian origin accounted for 48.4%. Clavien II-V grades occurred in 30 (57.7%) patients. After prehabilitation, functional walking capacity improved by 42.2 m (39.62-44.72 m) compared with baseline data (p < 0.001), but no improvement was observed in the ASMI (p = 0.301). Patients able to walk at least 360 m after prehabilitation suffered fewer Clavien-Dindo II-V postoperative complications (p = 0.016). A T6MWT of less than 360 m was identified as an independent risk factor in the multivariable analysis (OR 3.99; 1.01-15.79 p = 0.048). CONCLUSIONS: This home-based trimodal prehabilitation program improved functional walking capacity but not ASMI scores in patients with peritoneal metastasis before surgery. A T6MWT of less than 360 m was found to be a risk factor for postoperative complications.

Population pharmacokinetics of oxaliplatin after intraperitoneal administration with hyperthermia in Wistar rats.

BACKGROUND: The evaluation of the efficacy and toxicity of hyperthermic intraoperative peritoneal chemotherapy presents some difficulties, due in part to the lack of information about the pharmacokinetic behavior of the drugs administered in this procedure. The aim of this study was to characterize the population pharmacokinetics of hyperthermic intraoperative peritoneal oxaliplatin in Wistar rats and to evaluate the effect of treatment-related covariates dose, instillation time and temperature on the pharmacokinetic parameters. METHODS: Oxaliplatin peritoneal and plasma concentrations from 37 rats treated by either intravenous or intraperitoneal oxaliplatin administrations under different instillation times, temperatures and doses were analyzed according to a population pharmacokinetic approach using the software NONMEM V7.3®. RESULTS: Intraperitoneal (n = 115) and plasma (n = 263) concentrations were successfully described according to a two-compartment model with first order absorption. No significant effect of dose, temperature and instillation time on pharmacokinetic parameters was found. However, an abrupt decrease in the elimination process was observed, reflected in the structural pharmacokinetic model through a modification in clearance. The typical parameters values and the interindividual variability (CV %) in clearance, central and peripheral volume of distribution were 3.25 mL/min (39.1%), 53.6 mL (37.8%) and 54.1 mL (77.3%), respectively. Clearance decreased to 0.151 mL/min (39.1%) when the instillation was still ongoing, at 31.4 min. One of the possible reasons behind the clearance decrease would be an alteration of renal function due to surgery and/or hyperthermia. CONCLUSIONS: This study described the deterioration of the drug elimination process due to the procedure, and estimated the time at which this deterioration is most likely to occur. In addition, dose, instillation time and temperature had no influence in the PK parameters.

Usefulness of the log odds of positive lymph nodes to predict and discriminate prognosis in gastric carcinomas.

BACKGROUND: The lymph node ratio (LNR) and log odds of positive lymph nodes (LODDS) have been proposed to minimize the stage migration phenomenon. The value of the LODDS and LNR staging systems to predict and discriminate prognosis was assessed and compared to the International Union Against Cancer (UICC) TNM classification (pN). METHODS: Three hundred and twenty-six patients with gastric carcinoma were retrospectively studied. Disease-specific survival rates were calculated for every pN, LNR, and LODDS category. RESULTS: Four LNR categories (0, 1-25, 26-75, and >76 %) and four LODDS categories (-5 to -3, > -3 to -1, > -1 to 3, and >3 to 5) were established. In the multivariate analysis, only the stage pT3-4 versus pT1-2 (HR 1.88, 95 % CI 1.11-3.20, p=0.02) and LODDS as continuous variable (HR 1.40, 95 % CI 1.21-1.61, p<0.001) remained as independent prognostic factors. In patients with <16 lymph nodes retrieved, only the LODDS system could discriminate different disease-specific survival curves for every category. LODDS categories were able to discriminate subgroups with different prognoses in pN stages and LNR categories. CONCLUSIONS: The LODDS staging system was superior to the pN classification and LNR system to discriminate risk prognosis especially in patients with an insufficient number of retrieved lymph nodes.

Prognosis for gastric carcinomas with an insufficient number of examined negative lymph nodes.

BACKGROUND: The optimal system for lymph node (LN) staging in gastric cancer is still a subject of debate. The aim of our study was to analyse the probability of error in negative LN (pN0) gastric carcinomas when a low number of LNs were harvested using a probabilistic model. METHODS: Patients with gastric carcinoma who underwent R0 resection at three university hospitals between 2004 and 2009 were retrospectively included. A Bayesian model was used to analyse the probability of error for negative LNs (pN0) gastric carcinomas. Kaplan-Meier survival curves and the log-rank test were used to compare the overall and specific mortality of prognosis groups. RESULTS: Of the 291 patients included, 123 were classified as pN0 (42%). A significant correlation was found between the extent of the LN dissection performed and the number of the LNs retrieved. According to the Bayesian model the carcinomas with 9 or fewer negative lymph nodes were considered to have a high risk (HR) of misclassification, whereas patients with 10-25 LNs analysed and those with more than 26 negative lymph nodes were considered to have a moderate risk (MR) and low risk (LR), respectively. The log-rank test showed a significant improvement in the disease-specific survival for the MR pN0 (p < 0.001) and LR pN0 (p < 0.04) but not for the HR pN0 patients compared to pN1 patients. CONCLUSIONS: The proposed probabilistic model is clinically useful for differentiating the prognosis in pN0 gastric carcinomas when an insufficient number of negative lymph nodes are retrieved.

Randomized clinical trial comparing simple drainage of anorectal abscess with and without fistula track treatment.

BACKGROUND AND AIMS: Anal abscess is a frequent acute proctological disorder and whether the underlying fistula should be treated at the same time when the abscess is drained remains controversial. We examined indications for drainage alone versus drainage plus fistulotomy in terms of recurrence and continence. PATIENTS AND METHODS: We carried out a randomized prospective study of 200 consecutive patients with anal abscess. One group received drainage alone, while in the other group drainage plus fistulotomy was performed when a subcutaneous-mucosa, low transsphincteral, or intersphincteral fistula was found. Delayed progressive fistulotomy with suture threads was performed in cases of high transsphincteric or suprasphincteric fistula. RESULTS: The internal opening of the fistula track was found in 83% of the patients. The recurrence rate was related to the surgical technique employed: 29% in the group with drainage alone and 5% in the group for which treatment of the fistula track was attempted. The incontinence rate was also related to the surgical option. In those receiving drainage and treatment of the fistula track incontinence was restricted mostly to patients with delayed fistulotomy (36.7%), compared to 2.8% of patients when simple fistulotomy was performed. There was no incontinence in the drainage alone group. CONCLUSION: Drainage of anal abscess with fistulotomy can be safely performed in cases of subcutaneous, intersphincteral, or low transsphincteral fistulae with a minimal recurrence rate. However, drainage alone and posterior treatment of the fistula track is recommended for high transsphincteral or suprasphincteral fistulae.

Changes in P-glycoprotein expression in gastric carcinoma with respect to distant gastric mucosa may be influenced by p53.

BACKGROUND: The effectiveness of some chemotherapeutic agents used to treat gastric carcinoma patients may be impaired by the presence of P-glycoprotein (P-gp) and the status of p53. A modulation of P-gp expression by p53 or other alterations during tumorigenesis have been reported. The authors analyzed P-gp expression in relation to p53 and histopathologic features in gastric carcinoma. METHODS: Forty-one resected gastric carcinomas and mucosa distant from the tumor were assessed for P-gp expression by immunohistochemistry with C494 and JSB-1 antibodies. p53 expression was also immunohistochemically assessed by DO7 antibody in tumor samples. P-gp and p53 expression were semiquantitatively analyzed according to the percentage of stained cells. Histologic type, grade, vessel invasion, and stage were also studied. RESULTS: Moderate or high P-gp expression was detected in gastric carcinoma in 29 cases (71%) and in gastric mucosa remote from the tumor in 36 cases (88%). This reduction in P-gp expression was observed in 22% of the carcinomas, all but 1 being p53 immunonegative tumors. Thus, 8 (42%) of the p53 immunonegative carcinomas showed a loss of P-gp expression compared with their distant gastric mucosa. All p53 immunopositive carcinomas coexpressed P-gp. No correlation between P-gp expression and histologic type, grade, vessel invasion, or stage was found. CONCLUSIONS: P-gp expression in gastric carcinomas is frequent and coexpression with p53 is found. The analysis of P-gp expression in carcinomas and distant mucosa show that it is not regulated by p53, but a loss of P-gp detected in some of these carcinomas is mainly associated with a lack of p53 protein accumulation.

Detection of P-glycoprotein in frozen and paraffin-embedded gastric adenocarcinoma tissues using a panel of monoclonal antibodies.

AIMS: Most chemotherapeutic regimens used against gastric carcinoma include anthracyclines whose effectiveness can be impaired by the presence of P-glycoprotein. In order to obtain a reliable pattern of P-glycoprotein expression in these tumours an immunohistochemical study using a panel of anti-P-glycoprotein antibodies was performed in frozen and paraffinized tissues. METHODS AND RESULTS: Frozen and paraffinized samples from 25 gastric carcinomas were immunohistochemically analysed using a panel of four anti-P-glycoprotein monoclonal antibodies including C219, MRK16, JSB-1 and C494. Semiquantitative analysis indicated that moderate or high P-glycoprotein levels were detected in 40% to 76% of gastric adenocarcinomas, depending on the anti-P-glycoprotein antibody used. The antibody C494 was the most sensitive in detecting P-glycoprotein in both frozen and paraffinized gastric carcinoma samples. Moreover, C494 showed a pattern of staining exclusively associated with the plasma membrane, in contrast to the cytoplasmic with reinforcement of plasma membrane pattern displayed by the other three antibodies. Significant differences in P-glycoprotein levels were obtained when C494 and MRK16 were used in frozen tissues. Finally, detection of P-glycoprotein in frozen samples did not improve when compared to paraffinized ones. CONCLUSIONS: It appears that P-glycoprotein is frequently expressed in gastric adenocarcinomas, and the use of C494 complemented by JSB-1 is recommended for reliable detection of P-glycoprotein in this neoplasm.

Failure to detect early recurrence of gastric cancer.

Early gastric cancer recurrence is sometimes difficult to diagnose even by protocols using imaging techniques and tumor markers. We report a gastric cancer recurrence diagnosed by the appearance of a Sister Mary Joseph's nodule that illustrates the lack of sensitivity of these methods. We also discuss the protocol we currently follow for these patients.

Follow-up of patients resected for gastric cancer.

In this study we used a cost-outcome analysis to evaluate our follow-up protocol for patients who had been resected for gastric cancer. We designed a descriptive cross-sectional trial through consecutive sampling of patients who had undergone resection of gastric carcinoma and were followed in our outpatient department during 1991. Serological (CEA) and or imaging procedures were pathologic at least two months prior to the onset of symptoms in 33% of recurrences. No significant correlation was found between serum CEA levels and CEA tumor tissue staining in patients who recurred. Only 17% of patients who relapsed underwent further treatment (surgery and chemotherapy) with no improvement found in terms of survival. The overall cost per year has been estimated at US$ 6118. Our results show that serological levels of CEA and available imaging techniques for routine follow-up provide little advantage in diagnosing gastric cancer recurrence over clinical surveillance alone.