Relationship between skeletal muscle function, body composition, and weight loss in patients with advanced pancreatic and gastrointestinal cancers.

BACKGROUND: Muscle function and its correlation with body composition and weight loss have not been studied deeply in pancreas and gastrointestinal cancers. This research aims to determine the skeletal muscle function and its relationship with body compartments, significant weight loss, and performance status (ECOG) 0-2 in a population with advanced digestive cancers. METHODS: A cross-sectional study was designed to determine the relationship between muscular function, weight loss, and body composition. Patients with advanced digestive adenocarcinomas were evaluated. Muscle strength was examined by hand grip technique and body composition by bioimpedance analysis. Values of hemoglobin and albumin were measured in plasma. RESULTS: A sample of 81 patients was included. They had adenocarcinoma of stomach (n = 9), pancreas (n = 28), or colorectum (n = 44). With regard to skeletal muscle function, sub-maximal strength increased when percentage of weight loss decreased (p = 0.002) or when any of the following variables increased: skeletal muscle (p < 0.001), waist-hip ratio (p < 0.001), body surface area (p < 0.001), and body mass index (p = 0.001). According to multivariate analysis of these variables, only percentage of weight loss and skeletal muscle remained statistically significant. Endurance had no correlation with any of the variables. Higher weight loss was found in tumors of the upper tract (stomach and pancreas) in comparison with those of the lower tract (colorectal) (p = 0.005). CONCLUSIONS: In advanced digestive cancer, sub-maximal strength correlated inversely with weight loss and directly with skeletal muscle such as in lung and head and neck cancers. On the other hand, endurance had no correlation with any of the variables considered.

Relationship between weight loss and parameters of skeletal muscle function in patients with advanced cancer and fatigue.

PURPOSE: This study aims to determine the influence of significant weight loss on parameters of skeletal muscle function in a population of advanced cancer patients with fatigue. METHODS: A cross-sectional and comparative study was designed between two arms of advanced cancer patients with fatigue (fatigue numeral scale (FNS) ≥4). A arm (n = 27) with ≥5 % weight loss in the last 6 months, and B arm (n = 22) without weight loss. Muscle strength was examined by hand grip technique and measurements of body composition by bioimpedance analysis (BIA), values of hemoglobin, albumin, lactic dehydrogenase (LDH), c-reactive protein (CRP), urine creatinine, and FNS. These variables were compared between both groups and correlated within each group. RESULTS: here were no differences concerning parameters of muscle strength between both arms. A arm had values of CRP ≥10 ug/dl in 77 % compared with 38.5 % of B arm (p = 0.004). A arm showed a higher percentage of body cell mass (%BCM) than B arm (p = 0.005). The A arm also showed a lower percentage of fat mass (%FM) (p = 0.014) when compared to the B arm. FNS was higher in A arm (median 7 vs 5; p = 0.047). All the variables of muscle strength had a significant positive correlation. In A arm, BCM had a negative significant correlation with CRP (p = 0.021). CONCLUSIONS: In this study, significant weight loss and high CRP did not have influence on parameters of skeletal muscular function. We consider that further studies should be necessary, preferably with longitudinal designs to evaluate these findings.

Relationship between weakness and phase angle in advanced cancer patients with fatigue.

OBJECTIVE: This study aims to determine the relationship between weakness and bioimpedance analysis (BIA)-derived phase angle in a population of untreated cancer patients with fatigue. METHODS: We prospectively evaluated 41 treatment-naive cancer patients of several origins that presented with performance status 1-2, weight loss >5% in the last 6 months, and Fatigue Numeral Scale score >4. Weakness was considered a physical component of the multidimensional fatigue syndrome and was evaluated through several parameters utilizing hand grip strength technique by dinamometry. The same assessment was also performed on a healthy control population (n = 20). BIA-derived phase angle was also determined by BIA. RESULTS: Compared to healthy controls, cancer patients exhibited significant differences in all the parameters: median fatigue was 6 (range 5-9), evaluated maximal strength mean was 27 ± 10.71 vs. 42 ± 10.74 kg (p < 0.0001 for patients vs. control, respectively), and muscle strength difference (max-min muscle strength) was also statistically different (p < 0.0001). We also determined parameter associations within the patient population. We found statistical significant correlations between median phase angle score and endurance muscle with percentage of weight loss (r = 0.43, p = 0.03) for head and neck cancer patients, and in non-small cell lung cancer patients, grip work correlated significantly with normal or decreased phase angle (r = 0.85), p = 0.006 (Spearman Rank Correlation). CONCLUSIONS: Weakness could be correlated with normal or decreased phase angle in a population with ambulatory advanced cancer with fatigue naive of treatment. We also found a significant relationship between median phase angle score and endurance muscle with percentage of weight loss in the subpopulation of patients with head and neck carcinoma.

Hypodermoclysis for control of dehydration in terminal-stage cancer.

Many of those involved in palliative care have justifiable objections to the introduction of intravenous hydration in patients with dehydration-associated symptoms and advanced cancer. Researchers from the University of Buenos Aires carried out a randomized, comparative and prospective trail to determine the usefulness of hypodermoclysis in the control of thirst, chronic nausea and delirium. Forty-two patients were randomized into two groups. Both groups received drugs subcutaneously (haloperidol 2.5 mg every 4 hours to control delirium and/or metoclopramide 10 mg every 4 hours to control chronic nausea). The study group also received 1000 ml 5% dextrose in water infusion plus 140 milliequivalent per litre (mEq/L) sodium chloride, at a rate of 42 ml/hour per day. Both groups showed significant and equal improvements in relief of thirst and chronic nausea at 24 hours. After 48 hours, this improvement was maintained in the group that received hydration, but only for the relief of chronic nausea. Delirium did not improve significantly in either group during the 48-hour trial period. Current data suggest that decisions on rehydration of patients with terminal-phase cancer should be based more on the patient's comfort than on providing optimal hydration.

Cáncer rectal: radioquimioterapia (RT-QT) una nueva estrategia / Rectal cancer: preoperative radiochemotherapy (RT-QT) as a new strategy

Objetivo: evaluar eficacia, toxicidad, preservación esfinteriana y sobrevida de un esquema ambulatorio y preoperatorio de RT-QT concurrente con 5FU, leucovorina (LV) y CDDP. Material y métodos: entre 1/93 y 12/95 ingresaron 37 pacientes (pts) con adenocarcinoma de recto (CaR) hasta 12 cm del margen anal (MA). Tratamiento: QT con 5FU 250 mg/m²/día y LV 20 mg/m²/día por 3 días más CDDP 70 mg/m²/día 1, semanas 1-3-5. RT: 180 cGy día en 28 fracciones, dosis total de 5040 cGy. Cirugía (CX): 4 a 6 semanas post RT-QT. 26 pts eran hombres; edad media 59 años (r 37-71); 22 pts (60 por ciento) tenían CaR hasta 6 cm del MA; PS 0: 13 pts, 1: 22 pts, 2: 2 pts. Resultados: el "downstaging" entre estadíos clínicos pretratamiento (PREOP) y patológicos postoperatorios (POSTOP) fue: PREOP EII 16 pts (43 por ciento), EIII 21 pts (56,8 por ciento); POSTOP Respuesta Completa patológica (RCp) 4 pts (10,8 por ciento), EI 12 pts (32,4 por ciento), EII 9 pts (24,3 por ciento), EIII 11 pts (29,7 por ciento), 1 pts fue irresecable ( resecabilidad 97,3 por ciento). Se realizó resección anterior en 23 (62 por ciento) pts (8 con CaR hasta 6 cm del MA) y operación de Miles en 14 pts. Hubo 6 recaídas locales. Toxicidad: 10 pts presentaron complicaciones postoperatorios (POSTOP). Las más frecuentes: dehiscencia anastomótica e infección ( p pts murió por sepsis postoperatorios POSTOP). La toxicidad G3 por RT-QT fue: cutánea 8 pts, diarrea 6 pts, leucopenia 3 pts; G4: vómitos 2 pts. Con una mediana de seguimiento de 32,8 meses ( rango 1-51,4 meses), la sobrevida libre de enfermedad es de 55 por ciento y la sobrevida global es de 62 por ciento. Conclusiones: éste esquema ambulatorio de Rt-QT PREOP demostró: 1) factibilidad en el ámbito hospitalario, 2) toxicidad aceptable, 3) alta tasa de resecabilidad, 4) eficacia en el downstaging, 5) una tasa de Rcp relativamente baja (10-30 por ciento en la literatura), 6) aceptable tasa de preservación esfinteriana ( 62 por ciento en la población total y 36 por ciento en los pts con CaR hasta 6 cm del MA), 7) sobrevida comparable a la reportada por el MSKCC, en experiencias sin CDDP

Cáncer rectal: radioquimioterapia (RT-QT) una nueva estrategia / Rectal cancer: preoperative radiochemotherapy (RT-QT) as a new strategy

Objetivo: evaluar eficacia, toxicidad, preservación esfinteriana y sobrevida de un esquema ambulatorio y preoperatorio de RT-QT concurrente con 5FU, leucovorina (LV) y CDDP. Material y métodos: entre 1/93 y 12/95 ingresaron 37 pacientes (pts) con adenocarcinoma de recto (CaR) hasta 12 cm del margen anal (MA). Tratamiento: QT con 5FU 250 mg/m²/día y LV 20 mg/m²/día por 3 días más CDDP 70 mg/m²/día 1, semanas 1-3-5. RT: 180 cGy día en 28 fracciones, dosis total de 5040 cGy. Cirugía (CX): 4 a 6 semanas post RT-QT. 26 pts eran hombres; edad media 59 años (r 37-71); 22 pts (60 por ciento) tenían CaR hasta 6 cm del MA; PS 0: 13 pts, 1: 22 pts, 2: 2 pts. Resultados: el "downstaging" entre estadíos clínicos pretratamiento (PREOP) y patológicos postoperatorios (POSTOP) fue: PREOP EII 16 pts (43 por ciento), EIII 21 pts (56,8 por ciento); POSTOP Respuesta Completa patológica (RCp) 4 pts (10,8 por ciento), EI 12 pts (32,4 por ciento), EII 9 pts (24,3 por ciento), EIII 11 pts (29,7 por ciento), 1 pts fue irresecable ( resecabilidad 97,3 por ciento). Se realizó resección anterior en 23 (62 por ciento) pts (8 con CaR hasta 6 cm del MA) y operación de Miles en 14 pts. Hubo 6 recaídas locales. Toxicidad: 10 pts presentaron complicaciones postoperatorios (POSTOP). Las más frecuentes: dehiscencia anastomótica e infección ( p pts murió por sepsis postoperatorios POSTOP). La toxicidad G3 por RT-QT fue: cutánea 8 pts, diarrea 6 pts, leucopenia 3 pts; G4: vómitos 2 pts. Con una mediana de seguimiento de 32,8 meses ( rango 1-51,4 meses), la sobrevida libre de enfermedad es de 55 por ciento y la sobrevida global es de 62 por ciento. Conclusiones: éste esquema ambulatorio de Rt-QT PREOP demostró: 1) factibilidad en el ámbito hospitalario, 2) toxicidad aceptable, 3) alta tasa de resecabilidad, 4) eficacia en el downstaging, 5) una tasa de Rcp relativamente baja (10-30 por ciento en la literatura), 6) aceptable tasa de preservación esfinteriana ( 62 por ciento en la población total y 36 por ciento en los pts con CaR hasta 6 cm del MA), 7) sobrevida comparable a la reportada por el MSKCC, en experiencias sin CDDP (AU)

Combined intensive chemoradiotherapy for organ preservation in patients with resectable and non-resectable oesophageal cancer.

From January 1990 to April 1993, 60 oesophageal cancer patients were enrolled in a protocol of non-surgical treatment that consisted of induction chemotherapy followed by concurrent chemoradiotherapy. Induction chemotherapy consisted of cisplatin 40 mg/m2 intravenous bolus days 1, 2, 14, 15; 24 h continuous infusion of 5-fluorouracil (5-FU) 1000 mg/m2 days 1 and 14; leucovorin 20 mg/m2 days 1 and 14 given before and with 5-FU; bleomycin 30 UI days 1 and 14; mitomycin C 10 mg/m2 day 14. Concurrent chemoradiotherapy consisted of 60 Gy (6 weeks) from day 21 and cisplatin 70 mg/m2 days 28, 42 and 56; leucovorin 20 mg/m2 followed by 5-FU 425 mg/m2 days 28, 35, 42, 49 and 56. Complete response occurred in 44 of 55 evaluable patients (80%). The median survival is 32 months; the actuarial survival at 40 months is 35% (CI 18-53). These results appear improved over those reported with surgery or radiation alone, and suggest that organ preservation as a secondary treatment goal should be vigorously investigated.

Influencia de la ingesta de butirato de sodio en la carcinogénesis colónica murina / Influence of sodium butyrate intake on murine colonic carcinogenesis

El papel de los ácidos grasos de cadena corta (AGCC) en la carcinogénesis colónica murina (CCM) no fue aclarado. Evaluamos el efecto de la hemicolectomía derecha (HCD) (colon derecho, fuente de AGCC) y de la ingesta en agua de bebida de butirato de sodio (Buti.Na) al 2 por ciento a pH 7 o de cloruro de sodio (CINa) 4g/l, en la CCM. Formamos 7 grupos de 12 ratas Wistar macho de 150 g: HCD, Buti. Na, CINa, control (C). La mitad recibió dimetilhidrazina (DMH) 20 mg/Kg subucutánea semanal durante 12 semanas. La necropsia fue realizada a los 6 meses. Determinamos el contenido de AGCC en materia fecal por cromatografía gaseosa. El 70 por ciento de las ratas con DMH desarrolló tumor. El n§ de animales con tumor, por grupo fue: HCD 4/6, Buti.Na 4/6, CINa 3/5, C 6/6. El n§ de tumores promedio por animal, por grupo fue: HCD 1,17 ñ 0,48, Buti.Na 3/5, C 6/6. El n§ de tumores promedio por animal, por grupo fue: HCD 1,17 ñ 0,48, Buti.Na 1,50 ñ 0,76, ClNa 1,20 ñ 0,49, C 1,50 ñ 0,22. El grupo Buti.Na (DMH) presentó una concentración significativamente menor de butirato (p < 0,05) en relación a los demás grupos. En conclusión, el suplemento en agua de bebida de Buti.Na, CINa y la HCD redujeron en forma no significativa la CCM, con este número de animales

Influencia de la ingesta de butirato de sodio en la carcinogénesis colónica murina / Influence of sodium butyrate intake on murine colonic carcinogenesis

El papel de los ácidos grasos de cadena corta (AGCC) en la carcinogénesis colónica murina (CCM) no fue aclarado. Evaluamos el efecto de la hemicolectomía derecha (HCD) (colon derecho, fuente de AGCC) y de la ingesta en agua de bebida de butirato de sodio (Buti.Na) al 2 por ciento a pH 7 o de cloruro de sodio (CINa) 4g/l, en la CCM. Formamos 7 grupos de 12 ratas Wistar macho de 150 g: HCD, Buti. Na, CINa, control (C). La mitad recibió dimetilhidrazina (DMH) 20 mg/Kg subucutánea semanal durante 12 semanas. La necropsia fue realizada a los 6 meses. Determinamos el contenido de AGCC en materia fecal por cromatografía gaseosa. El 70 por ciento de las ratas con DMH desarrolló tumor. El nº de animales con tumor, por grupo fue: HCD 4/6, Buti.Na 4/6, CINa 3/5, C 6/6. El nº de tumores promedio por animal, por grupo fue: HCD 1,17 ñ 0,48, Buti.Na 3/5, C 6/6. El nº de tumores promedio por animal, por grupo fue: HCD 1,17 ñ 0,48, Buti.Na 1,50 ñ 0,76, ClNa 1,20 ñ 0,49, C 1,50 ñ 0,22. El grupo Buti.Na (DMH) presentó una concentración significativamente menor de butirato (p < 0,05) en relación a los demás grupos. En conclusión, el suplemento en agua de bebida de Buti.Na, CINa y la HCD redujeron en forma no significativa la CCM, con este número de animales (AU)

[Influence of sodium butyrate intake on murine colonic carcinogenesis]. / Influencia de la ingesta de butirato de sodio en la carcinogénesis colónica murina.

The role of short chain fatty acids (SCFA) in murine colonic carcinogenesis (MCC) has not yet been clarified. In rats, Freeman et al have reported an increased number of colonic tumors induced with dimethylhydrazine (DMH) and sodium butyrate in drinking water. On the other hand, Deschner et al showed that tributyrin intake did not increase MCC induced with azoxymethane. Both of them have reported high levels of fecal butyric acid with sodium butyrate and tributyrin intake. Although salt intake has been positively associated with colorectal cancer some authors do not support this association. We have evaluated the influence of right hemicolectomy (RH) (right colon as main source of SCFA) and the intake of 2%-pH 7 sodium butyrate (S.BUT) and 4 g/l sodium chloride (S.CHL) in drinking water, in MCC. Forty eight male Wistar rats weighing 150 g were divided into 4 groups: RH, S.BUT, S.CHL, control (C). Half of the animals received weekly DMH 20 mg/kg subcutaneously for 12 weeks. Necropsy was performed after 6 months. We have determined fecal SCFA content by gas chromatography. Neoplasm was present in 70% of rats treated with DMH. The number of animals with tumors was: RH 4/6, S.BUT 4/6, S.CHL 3/5, C 6/6. Tumor frequency was: RH 1.17 +/- 0.48, S.BUT 1.50 +/- 0.76, S.CHL 1.20 +/- 0.49, C 1.50 +/- 0.22. S.BUT group, treated with DMH, presented a lower butyric acid concentration (p < 0.05) in comparison with other groups. We have no explanation for this finding; gastric absorption of sodium butyrate may be an important factor.(ABSTRACT TRUNCATED AT 250 WORDS)

Influencia de la ingesta de butirato de sodio en la carcinogénesis colónica murina. / [Influence of sodium butyrate intake on murine colonic carcinogenesis]

The role of short chain fatty acids (SCFA) in murine colonic carcinogenesis (MCC) has not yet been clarified. In rats, Freeman et al have reported an increased number of colonic tumors induced with dimethylhydrazine (DMH) and sodium butyrate in drinking water. On the other hand, Deschner et al showed that tributyrin intake did not increase MCC induced with azoxymethane. Both of them have reported high levels of fecal butyric acid with sodium butyrate and tributyrin intake. Although salt intake has been positively associated with colorectal cancer some authors do not support this association. We have evaluated the influence of right hemicolectomy (RH) (right colon as main source of SCFA) and the intake of 2

-pH 7 sodium butyrate (S.BUT) and 4 g/l sodium chloride (S.CHL) in drinking water, in MCC. Forty eight male Wistar rats weighing 150 g were divided into 4 groups: RH, S.BUT, S.CHL, control (C). Half of the animals received weekly DMH 20 mg/kg subcutaneously for 12 weeks. Necropsy was performed after 6 months. We have determined fecal SCFA content by gas chromatography. Neoplasm was present in 70

of rats treated with DMH. The number of animals with tumors was: RH 4/6, S.BUT 4/6, S.CHL 3/5, C 6/6. Tumor frequency was: RH 1.17 +/- 0.48, S.BUT 1.50 +/- 0.76, S.CHL 1.20 +/- 0.49, C 1.50 +/- 0.22. S.BUT group, treated with DMH, presented a lower butyric acid concentration (p < 0.05) in comparison with other groups. We have no explanation for this finding; gastric absorption of sodium butyrate may be an important factor.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of pain and other symptoms in cancer patients: patterns in a North American and a South American hospital.

The charts of 200 consecutive patients with cancer pain admitted to a major teaching hospital in Edmonton, Canada (n = 100) and in Buenos Aires, Argentina (n = 100) were reviewed to assess the differences between North American (NA) and South American (SA) facilities in patterns of treatment of pain and other symptoms. Criteria for eligibility and methods were identical in both hospitals. Characteristics of patients (age, sex, primary tumor, reason for admission) and attending staff were similar between both hospitals. Mean daily equivalent doses of parenteral morphine (mg) were 44 +/- 26 and 9 +/- 10 in NA and SA, respectively (p less than 0.001). Patients in NA, received narcotics every 4 hr and on a regular basis more frequently than in SA. The types of narcotics and the use of adjuvant drugs were significantly different between NA and SA. Nonpharmacologic treatments, antiemetics, and laxatives were more frequently used in NA. These results suggest that there are significant differences in symptomatic management of advanced cancer between institutions in NA and SA.

Cardiovascular autonomic function in anthracycline-treated breast cancer patients.

Preclinical studies suggest that in addition to the well-known direct damage to the myocardium, anthracycline antineoplastic drugs exert toxic effects on the cardiovascular autonomic system as well. To investigate whether this phenomenon occurs in the clinic, we carried out noninvasive, widely used tests of cardiovascular autonomic physiology in 55 women with stage II or III breast cancer. In all, 31 were being treated with anthracycline-containing chemotherapy regimens, and 24 who were receiving CMF (cyclophosphamide, Methotrexate, and fluorouracil) served as controls. Of 279 tests conducted in anthracycline (A)-treated patients, 123 were abnormal, vs 54 of 216 tests carried out in 24 controls (44% vs 25%; P less than 0.005). Abnormal variations in heart rate on standing and in diastolic blood pressure during handgrip was found in 25 (81%) and 17 patients receiving A, vs 9 (37%; P less than 0.005) and 5 (21%; P less than 0.0001), respectively, in controls. The incidence of abnormal tests was significantly higher in A-treated patients greater than 60 years of age (41%) vs 67%; P less than 0.05). Radionuclide ventriculography was carried out in 19 patients who showed abnormal tests of cardiovascular autonomic function after greater than or equal to 6 courses of a-containing chemotherapy; only 1 of them had abnormal cardiac contractility (global hypokinesia), suggesting that abnormal tests of cardiovascular autonomic function may occur in the absence of a detectable deterioration in left ventricular ejection fraction. A large number of factors may alter cardiovascular autonomic function in cancer patients, including age, radiation therapy to the chest, and multidrug treatment. Even after correcting for the most obvious of these, chemotherapy with anthracyclines is associated with a significantly higher percentage of abnormal tests for cardiovascular autonomic function. Although indirect and semi-quantitative, our results are compatible with the idea of A-induced cardiac autonomic dysfunction.

Acidosis lactica in linfoma no Hodgkin / Lactic acidosis in non-Hodgkin's lymphoma

Se comunica un caso de acidosis láctica en linfoma no Hodgkin de alto grado de malignidad (inmunoblástico). La paciente presentó compromiso ganglionar axilar, supraclavicular y retroperitoneal; tumor en cuadrante superoexterno de mama derecha y compromiso de médula ósea. Efectuó 6 cursos de quimioterapia con esquema CHOP-BLEO, con remisión completa durante 5 meses. Presentó recaída en localizaciones anteriores, bazo y bronquio derecho; con síntomas B e hiperlactacidemia que remitió con quimioterapia (adriamicina, vincristina, prednisona) durante su internación. De los distintos mecanismos tumorales de acidosis láctica el compromiso hepático es el más frecuente, pero en el caso presentado, la sobreproducción de lactato por rápido crecimiento del tumor y posiblemente el compromiso de médula ósea surgen como los determinantes de la alteración metabólica mencionada. Se menciona, a su vez, a la disfunción mitocondrial primaria o a la ausencia de glicerol-fosfato deshidrogenasa ligada a NAD como principales de la gran actividad glucolítica anaeróbica aún en presencia adecuada de oxígeno. Finalmente, en este caso la quimioterapia electiva fue eficaz