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At least 19 recordsLinked to original sources
PubMed1990

Restaging procedures, criteria of response, and relationship between pathological response and survival.

The first priorities for upfront chemotherapy in TCCB are to prove in randomized phase III trials that the addition of toxic chemotherapy to toxic standard locoregional treatment can improve survival and/or permit bladder preservation. If such proof is obtained, we will need to distinguish patients who benefit from chemotherapy from those who do not. One way to make such a distinction is to separate responders from nonresponders. The prognostic value of downstaging to P0 or noninvasive cancer is significantly different from the prognosis associated with the continued presence of invasive disease. The available data regarding clinical assessment of response still appear to indicate that only the demonstration of a lack of response (see Table 2: cIR, cSD, cPD, greater than or equal to cT2) is reliable, However, there may be some patients, who after two courses of chemotherapy, still show the presence of invasive bladder cancer together with signs of tumor cell kill and may be further downstaged to P0 during the next two courses of chemotherapy. The clinical assessment of cCR and cPR is too inaccurate to be used as a basis for decisions concerning continuation of chemotherapy or bladder preservation. The decision to leave the bladder untreated after a cCR carries the risk of jeopardizing cure. More studies on the evaluation of response of the primary tumor are needed, probably with a central role for the pathologist to evaluate not only the gross presence, minimal residual disease, or true absence of cancer but also the adequacy of site and deepness of the restaging TUR biopsy.

Carcinoma, Transitional Cell↗
PubMed1992

The prognostic value of the pathological response to combination chemotherapy before cystectomy in patients with invasive bladder cancer. European Organization for Research on Treatment of Cancer--Genitourinary Group.

The prognostic value of the pathological response to combination chemotherapy of deeply invasive transitional cell cancer of the bladder was retrospectively assessed in 147 patients. Data were collected from 8 different centers. Patients were eligible if they had received intravenous combination chemotherapy followed by partial, total or radical cystectomy, and if they had a minimum followup of 2 years after the start of chemotherapy. Of the patients 90% received methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) or cisplatin plus methotrexate for a median of 3 courses (range 1 to 6). Of the 83 patients who were alive at analysis actuarial median followup was 30.5 months (range 13.2 to 85.6 months). A major pathological response (stage P0, Pis, Pa or P1) was achieved in 41.5% of the patients. Patients with a major pathological response (p stage less than 2) had a 5-year survival of 75% in contrast to 20% for the remaining nonresponding patients (p stage 2 or more). The survival of patients with a major pathological response was independent of whether the response was induced by 2 or more courses of chemotherapy, or whether it was induced by M-VAC in comparison with cisplatin plus methotrexate. Preoperative clinical assessments can identify nonresponding patients correctly and in these cases alternative treatment programs are required, since 80% will die of the disease. Moreover, if neoadjuvant chemotherapy is proved to increase survival, the data emphasize the importance of the response rate of the primary tumor and the need to investigate the optimal number of courses to induce the best response, preferably in the individual patient.

Actuarial Analysis↗
PubMed1990

Pathologic response of the lung to irritant gases.

The pathologic response of the lung to irritant gases ranges from the acute exudative phase through the subacute proliferative phase to the chronic fibrosing phase. These responses are based on damage to the Type I cells, and possibly endothelial cells, and the subsequent proliferative and repair processes in the surviving animals. Responses to high dose exposures appear at the microscopic level as exudation of protein rich fluids into alveoli (alveolar edema) and subsequent death due to anoxia. Physiologically, this could be described as a mismatch of ventilation with perfusion, resulting in impaired gas exchange. Animals surviving this acute exudative phase resolve the alveolar edema to fibrin, and Type II cells become hypertrophic and hyperplastic in the process of replacing the damaged Type I cells. The acute and subacute responses also elicit inflammatory changes in the interstitium of the lung that may progress to fibrosis in the chronic stage of a survivable exposure. Diagnostic cases in livestock involving irritant gases reflect similar toxic injuries to the lung.

Ammonia↗
PubMed1991

Dimethyl sulfoxide antagonizes hypotensive, metabolic, and pathologic responses induced by endotoxin.

There is evidence that free radical activity may be important in the development of endotoxemia. Dimethyl sulfoxide is a hydroxyl radical scavenger that readily penetrates cell membranes. Using the conscious, instrumented rat this study tests the ability of dimethyl sulfoxide to modify the course of endotoxemia by evaluating cardiovascular, metabolic, and tissue injury parameters for 4 hr after the toxic insult. Treatment with dimethyl sulfoxide (6.5 g/kg; i.p.) evoked significant decreases in cardiac output, stroke volume, and central venous pressure and increases in heart rate, systemic vascular resistance, mean aortic pressure, respiration rate, and concentrations of blood glucose and plasma lactate. Following endotoxin (40 mg/kg, i.v. LD90- 24 hr), dimethyl sulfoxide pretreatment blocked the early hypotensive episode but all other cardiovascular and respiratory responses to endotoxin were essentially unaltered. The pH, PO2, PCO2, and hematocrit were the same for both treated and untreated groups; however, dimethyl sulfoxide prevented the endotoxin-induced hypoglycemia and significantly attenuated the hyperlacticemia at 4 hr. The severe hemorrhagic intestinal pathology characteristic of this model of endotoxemia was not present in the dimethyl-sulfoxide-treated group. From these results we conclude that dimethyl sulfoxide caused significant cardiovascular alterations conducive to impaired systemic blood flow. However, when administered prior to endotoxin, dimethyl sulfoxide induced significant beneficial modifications in the course of endotoxemia despite few improvements in cardiovascular function. The data indicate that the hydroxyl radical may be a mediator of tissue injury in this model of endotoxemia.

Animals↗
PubMedDate not supplied

Influence of anesthetics on metabolic, functional and pathological responses to regional cerebral ischemia.

Regional cerebral ischemia was produced by common carotid artery occlusion in gerbils and by middle cerebral artery occlusion in dogs, cats, and squirrel monkeys. Anesthesia was induced with either pentobarbital or halothane and maintained for two to three hours after vessel occlusion. In acute studies, the effect of regional cerebral ischemia on cerebral concentrations of ATP, phosphocreatine, lactate, and pyruvate was determined at the end of this period in gerbils, cats, and squirrel monkeys. In chronic studies, the degree of neurological deficit and size of cerebral infarction were determined 48 hours after a two-hour to three-hour period of vessel occlusion in cats and squirrel monkeys and permanent occlusion in dogs. In gerbils, dogs, and cats, there were no differences in the metabolis, functional, or pathological effects of anesthesia with pentobarbital or halothane. However, in the squirrel monkey, in acute studies the metabolic alterations were significantly less with pentobarbital, and in chronic studies the frequency and magnitude of functional deficits and cerebral infarction were significantly less. We conclude that pentobarbital does provide a degree of protection during regional cerebral ischemia but that such effects are only consistently demonstrable in primates. In nonprimates, we assume that variability in the collateral circulation renders demonstration of significant differences difficult or impossible.

Adenosine Triphosphate↗
PubMed1990

Treatment with anti-tumor necrosis factor alpha does not influence the immune pathological response against lymphocytic choriomeningitis virus.

The role of tumor necrosis factor alpha (TNF alpha) in the immunopathological events induced by infection with lymphocytic choriomeningitis (LCM) virus (LCMV) was assessed by treatment of C57Bl/6 mice with a sheep antibody to murine TNF alpha antiserum to strongly interfere with anti-Listeria host defense. However, despite its effectiveness in Listeria infections in vivo, antibody to TNF alpha used at 6 x 10(4) neutralizing units per day subcutaneously had no detectable influence on the kinetics of maturation of antiviral cytotoxic T-cell activity, inflammatory processes, or clearance of virus. First, onset and severity of LCMV-induced hepatitis, as assessed by cytotoxic T-cell activity, viral titers in the liver, serum liver enzyme values, and histology, were not detectably affected by antibody to TNF alpha. Second, incidence of lethal LCM disease after intracerebral infection and the kinetics of the primary footpad swelling reaction observed after local foot inoculation were not altered by anti-TNF alpha antibody treatment. From the data presented we conclude that TNF alpha as assayed by in vivo therapy with a polyclonal anti-TNF alpha antibody plays no detectable role in the host reaction against LCMV.

Alanine Transaminase↗
PubMed1991

Haematological and pathological responses to experimental Trixacarus caviae infection in guinea pigs.

Outbred guinea pigs became infected with the mite Trixacarus caviae (Acarina, Sarcoptidae) when introduced into an infected colony. Mite numbers were highest after one month, then fell progressively. Infected guinea pigs developed a neutrophilia, monocytosis, eosinophilia and basophilia. Despite pronounced reactive changes in the superficial lymph nodes, infected guinea pigs developed only a mild dermatitis. In contrast, home bred animals, susceptible to T. caviae acquired many mites and developed a severe chronic dermatitis. Trixacaral manage in guinea pigs offers considerable potential for the study of mite infections in man and animals.

Animals↗
PubMedDate not supplied

Further observations on the pathological responses of rat skeletal muscle to toxins isolated from the venom of the Australian tiger snake, Notechis scutatus scutatus.

1. Some aspects of the response of mammalian skeletal muscle following the injection of purified toxins from the venom of the Australian tiger snake, Notechis scutatus scutatus, are described. 2. The toxins used were notexin, notechis II-5, notechis II-1 and a modified form of notexin (PBP-notexin). They were injected into the dorso-lateral aspect of one himd limb so that the soleus muscle would be exposed to the toxins. 3. Within 1 h after the injection of notexin, the soleus muscles were oedematous and by 3--6 h, polymorphonuclear leucocytes had entered the interstitial spaces. The invasion of necrotic muscle fibers was extensive by this time. Muscle spindles appeared relatively unaffected by the toxin. 4. The muscle regenerated via myoblasts at 2--3 days to myotubes at 3--5 days, immature muscle fibers at 7--14 days and fully differentiated muscle fibers by 21--28 days. Even after 6 months, however, the nuclei of many muscle fibres remained in a central position. 5. A second component of Australian tiger snake venom was also found to be myotoxic. It was slightly less potent than notexin, but caused qualitatively similar damage to that caused by notexin. It was identified as notechis II-5. A third fraction, notechis II-1, was found to be inactive. 6. Notexin could be neutralized by incubation with tiger snake antivenene; the simultaneous injection of antivenene with notexin did not afford complete protection against muscle damage.

Animals↗
PubMed1990

Combined high-dose carboplatin and cisplatin, and ifosfamide in previously untreated ovarian cancer patients with residual disease.

Carboplatin 200 mg/m2 day 1, cisplatin 50 mg/m2 days 2 and 3, ifosfamide 1,500 mg/m2 days 1 to 3, and mesna 900 mg/m2 days 1 to 3 every 4 weeks for six cycles were given to 37 previously untreated ovarian cancer patients with residual disease after the primary laparotomy. The median observation time was 17+ months (range, 9+ to 24+ months). Of all the patients, 81% had primary residual disease larger than 2 cm. The overall pathologic response rate (pathologic complete response [PCR] plus partial response [PPR]) in 36 assessable patients was 58%, PCR was 42%. Of the PCR patients, 53% had primary residual tumor larger than 5 cm. The substantial hematologic toxicity was manageable, but also the main reason for dose modifications. During treatment, 92% and 100% of the patients developed WBC and platelet nadir values corresponding to World Health Organization (WHO) grades 3 to 4. Dose-limiting encephalopathy, nephro- and neurotoxicity each occurred in 6% of the patients. The high PCR rate warrants further investigations of combined high-dose platinum and ifosfamide.

Adult↗
PubMed1992

A European Organization for Research and Treatment of Cancer--Genitourinary Group phase 2 study of chemotherapy in stage T3-4N0-XM0 transitional cell cancer of the bladder: evaluation of clinical response.

From 1986 to 1990 the European Organization for Research and Treatment of Cancer--Genitourinary Group conducted a phase 2 trial of neoadjuvant chemotherapy in patients with stage T3-4N0-XM0 transitional cell carcinoma of the bladder. The objectives were to evaluate the clinical response in relation to the pathological response, and to measure the side effects of chemotherapy. Of 171 patients entered 136 were fully evaluable: 18% had clinical complete remissions, 36% had clinical partial remissions, 39% had no clinical remissions and 10% had unknown response. A selected subgroup of 76 patients underwent cystectomy after 2 or 4 courses of chemotherapy: 2 were not evaluable for pathological response because of preoperative radiotherapy after neoadjuvant chemotherapy, 16 had a pathological complete remission, 7 had a pathological partial remission and 51 had no pathological remission. Comparison of the clinical response or T category only after 2 courses of chemotherapy with the pathological response after 2 or 4 courses of chemotherapy showed that in a number of patients the disease status could be downstaged to pathological complete or partial remission by additional courses of chemotherapy. If the discrepancies between clinical and pathological responses, or between T and P categories, induced by further downstaging after additional chemotherapy were left out, it was shown that clinical complete and partial remissions were a heterogeneous group but nonresponders could be delineated with a 100% accuracy by clinical response evaluation and transurethral resection biopsy only. Furthermore it seems important to establish the number of chemotherapy courses to induce a maximal response of the primary tumor.

Adult↗
PubMedDate not supplied

Respiratory irritation from environmental tobacco smoke.

Acute physiological and chronic pathological responses of the respiratory tract to environmental tobacco smoke (ETS) are reviewed briefly. This study excludes discussion of the possible risk of lung cancer and the known impact of carbon monoxide on the fetus and adult. In some environments, the dose of particulate matter and the concentrations of irritant vapors absorbed on the ETS particles reach a level for which a physiological response may be expected, not only in the nose but also the bronchi. However, direct measurements indicate only small increases of nasal and bronchial resistance if normal subjects are exposed to maximal, likely concentrations of ETS. ETS is readily detected by the nonsmoker, but there is no strong evidence that pulmonary reactions have a psychogenic basis. The condition of approximately 20% of asthmatic patients is exacerbated by ETS exposure. Further study is needed to clarify the likelihood that adults will progress from a minor physiological response to pathological reactions, e.g., chronic obstructive lung disease. In young children (who are less able to escape from ETS), the association between exposure and an increase in respiratory disease is stronger than in adults. Exacerbation of asthma and an increase of respiratory disease are further arguments for legislation to guarantee smoke-free air to the nonsmoking public.

Asthma↗
PubMed2026

Exercise and pathologic complete response to cancer treatment: a systematic review and meta-analysis.

PURPOSE: Neoadjuvant chemotherapy (NACT) is a commonly recommended approach for treating several cancers, and improving patients' outcomes to this therapy is important. This systematic review and meta-analysis assessed the impact of exercise on pathologic complete response (pCR), a key short-term marker of treatment efficacy, in patients with solid tumors receiving NACT. METHODS: Four electronic databases were searched for randomized controlled trials with physical exercise during NACT as an intervention published until May 2025. Risk of bias was assessed using Cochrane RoB 2.0 and the TESTEX scale. A random-effect meta-analysis using the inverse variance method synthesized the results. Heterogeneity was assessed using I2 and chi2 statistics. Risk ratio estimated the effect size. RESULTS: Eight studies involving 504 patients with breast, esophageal, gastric, or rectal cancer were included in the final analysis. Exercise interventions consisted of aerobic and resistance exercise. Overall, there were no significant differences between exercise and control groups in the rate of pCR to NACT (pooled risk ratio: 1.08 (95% CI: 0.82 to 1.43) Z = 0.56, p = 0.58). However, meta-regression data from breast cancer (BC) studies (4 studies, 367 participants) suggest exercise may be associated with enhanced tumor response to NACT in HR + /HER2- subtypes (regression coefficient: 0.83 (95% CI: -0.00 to 1.67), p = 0.05). CONCLUSION: Exercise during NACT did not improve pCR across cancer types. Exploratory meta-regression findings suggest a possible benefit of exercise in BC patients with the HR + /HER2- subtype. These results should be interpreted with caution due to the small number of studies and low certainty of the evidence.

Humans↗
PubMed1991

A phase I-II trial of intraperitoneal cisplatin and alpha-interferon in patients with persistent epithelial ovarian cancer.

A toxicity, dose, and schedule study of intraperitoneal (ip) cisplatin and alpha-interferon was conducted as a salvage therapy for patients with persistent, advanced epithelial ovarian cancer after primary systemic therapy with cisplatin-combination chemotherapy. Twenty-four patients were entered into this prospective, nonrandomized phase I-II trial conducted at two institutions following a uniform protocol. Cisplatin doses were escalated from 45 to 90 mg/m2, and alpha-interferon doses were escalated from 10 to 50 x 10(6) IU. At protocol entry, 4 (16%) patients had microscopic residual disease at second-look laparotomy, 5 (21%) had minimal residual disease less than 5 mm, 7 (30%) had residual disease 5-20 mm, and 8 (33%) had bulky residual disease greater than 20 mm. Toxicity was acceptable overall. Hematopoietic toxicity included a grade 3 total white cell count in 12% of courses when the cisplatin dose was equal to or greater than 60 mg/m2. Renal toxicity was modest with grade 2 toxicity in 20% of courses with a cisplatin dose greater than 60 mg/m2. Gastrointestinal toxicity, especially nausea and vomiting was seen in most courses; however, it was grade 3 and dose-limiting in greater than 30% of courses with cisplatin 75-90 mg/m2. General malaise, fever, flu-like symptoms, chills, and myalgias were seen in most courses, but it was dose-limiting (grade 3) toxicity in 6-11% of cycles when the dose of interferon was 25-50 x 10(6) IU. There was no grade 4 toxicity. Thus, the maximum tolerated dose (MTD) of the combination is 60 mg/m2 cisplatin and 25 x 10(6) IU interferon. Eighteen patients were evaluable for response, 15 of whom had responded to prior cisplatin therapy and 3 had not. Of the 10 patients evaluable for clinical response, one patient (10%) achieved a complete response (CCR), and one (10%) had a partial response (PCR). The progression free interval (PFI) and survival were 11 months and 19 months, respectively, for the CCR patient, 6 and 11 months, respectively, for the PCR patient, and the mean survival for nonresponders was 8 months. The other 8 patients underwent a reassessment laparotomy: 2 (25%) achieved a complete pathologic response (CPR), and 3 (38%) had a partial pathologic response (PPR). Both pathologic responses were in patients with minimal residual disease less than 5 mm.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1992

Salt and water control at altitude.

The physiological effect of altitude hypoxia, in the absence of exercise, is a sodium and water diuresis with decrease in plasma and extra-cellular volumes. Plasma aldosterone concentrations (PAC) are reduced but plasma atrial natriuretic peptide (ANP) levels are modestly increased. Day-long exercise at low altitude has almost opposite effects on fluid balance. There is an anti-diuresis, sodium retention, expansion of the plasma and extra-cellular compartments, elevation of PAC and ANP. Subjects who develop acute mountain sickness (AMS) show a pathological response to hypoxia even before the development of symptoms. There is an anti-diuresis, sodium retention, increased plasma and extra-cellular volumes and increased PAC compared with subjects resistant to AMS. Plasma ANP tends to be elevated compared with sea level values but the relation of ANP levels to AMS is variable. In general therefore, the pathological response to altitude hypoxia parallels that of exercise at low altitude and is opposite to the physiological response. Both exercise and the pathological response predispose the subject to edema and are probably important in the genesis of AMS.

Acute Disease↗
PubMed1991

A preliminary report of combination chemotherapy with cisplatin and mitomycin-C followed by radical hysterectomy or radiation therapy in patients with locally advanced cervical cancer.

Neoadjuvant chemotherapy with cisplatin and mitomycin-C was used in the primary treatment of 17 patients with locally advanced cervical cancer (stages Ib-IIIb; tumor diameter greater than 5 cm) prior to definitive local treatment with radical hysterectomy or radiotherapy. Thirteen of the seventeen patients (76.5%) responded to initial chemotherapy, permitting a radical hysterectomy in ten patients. At histologic examination of the surgically resected primary tumor and lymph nodes, complete pathologic responses were found in 2 patients and partial pathologic responses in 8 patients. The median follow-up time is 14.5 months with a median survival for all patients of 52 weeks. All responders are alive. No therapy-related deaths, major complications, or delay in treatment occurred. Neoadjuvant chemotherapy with mitomycin-C and cisplatin is feasible and may be of benefit for patients with locally advanced cervical cancer.

Adult↗