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Pathologic complete response of advanced ovarian mixed mesodermal tumor to cisplatin, adriamycin and dacarbazine: a case report.

Presented is a case report of a stage IIIC primary ovarian mixed mesodermal tumor with gross residual disease following aggressive cytoreductive surgery. Following twelve courses of Cisplatin, Adriamycin and Dacarbazine, second-look laparotomy confirmed a pathologic complete response. The patient is now free of disease at 17+ months.

Antineoplastic Combined Chemotherapy Protocols

Vaccination studies against experimental bovine Pasteurella pneumonia.

Vaccination-challenge experiments were conducted in colostrum-deprived calves to evaluate the efficacy of Pasteurella bacterins and vaccines against experimental pneumonic pasteurellosis. Calves were vaccinated with formalin-killed bacterins and live vaccines, then challenge exposed intratracheally with P. haemolytica or P. multocida. Infectious bovine rhinotracheitis virus was inoculated intranasally three to four days prior to P. haemolytica challenge-exposure. All calves were examined for macroscopic and microscopic lesions after being found dead or following euthanasia four to seven days after challenge exposure with the bacterial pathogen. Clinical, hematological, and pathological responses to challenge exposure in aluminum hydroxide absorbed P. haemolytica and P. multocida bacterin-treated calves were consistent with the pneumonic lesions of pulmonary pasteurellosis in the control calves. An oil-adjuvanted P. haemolytica bacterin limited clinical and pathological responses in the affected calves whereas a P. multocida oil-adjuvanted bacterin did not. Both clinical and pathological responses to challenge exposure in calves vaccinated with live Pasteurella vaccines were less severe than those of the control calves. Vaccine effectiveness appeared to be dose dependent.

Animals

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

The prognostic and therapeutic value of second-look laparotomy in advanced ovarian cancer.

Of 267 patients with ovarian cancer FIGO stages III and IV, 157 underwent second-look laparotomy after combination chemotherapy consisting of cis-platinum and cyclophosphamide with and without doxorubicin. At second-look operation 45% had macroscopic tumour, 15% microscopic tumour, and 40% complete pathological response. Survival 3 years after second look was: complete pathological response 74%; microscopic disease 24%; visible tumour less than 1 cm 28%; visible tumour greater than 1 cm 17%; negative cytology 59%; and positive cytology 18%. Of the patients with macroscopic tumour, 29% had all visible tumour removed at second look. Three-year survival for these patients was about 45%.

Antineoplastic Combined Chemotherapy Protocols

Evaluation of pre- and postoperative chemotherapy for resectable adenocarcinoma of the esophagus or gastroesophageal junction.

Thirty-five consecutive patients with resectable adenocarcinoma of the esophagus or gastroesophageal junction were treated with two preoperative and three or four postoperative chemotherapy courses consisting of etoposide, fluorouracil, and cisplatin (EFP) to evaluate the rate of curative resection, clinical and pathologic response, toxic effects, and survival. One hundred thirty-seven courses with a median number of five courses (range, one to six) were administered. Preoperative EFP resulted in 17 (49%) major responses, including six patients who did not have carcinoma cells in the repeat endoscopic biopsy specimens and cytologic brushings. Among 32 patients who had surgery, 25 (78%) had curative resection, one patient had a complete pathologic response, and one had microscopic carcinoma in the resected specimen. Six patients had microscopic carcinoma at the resection margins and received postoperative radiotherapy. At a median follow-up of 20 months, the projected survival of 35 patients is 23 months (range, 6 to 33+). Fifteen patients died of their carcinomas, and 15 patients were alive (median follow-up, 20+ months; range, 15+ to 33+ months) with no evidence of relapse. There were no deaths related to chemotherapy, surgery, or radiotherapy. EFP-induced toxic reactions were moderate. Our data suggest that multiple courses of EFP are feasible. Future strategies for this disease should consider prolonged chemotherapy with regimens that result frequently in pathologic complete responses.

Adenocarcinoma

Vasopressin test in cases of optic atrophy and optic neuritis.

The vasopressin test gave pathological results in 12 cases of optic atrophy and normal results in three cases. One of the patients with a pathological response had Leber's disease and three had tobacco-alcholic amblyopia, while in the rest the optic atrophy was of uncertain origin. In the cases with normal results the aetiology was also unclear. The Metopirone test was normal in 13 cases and pathological in only one case of optic atrophy. In three out of five patients with optic neuritis the vasopressin test gave pathological responses. The high frequency of pathological vasopressin tests in patients with optic lesions indicates a simultaneous disturbance of the hypothalamo-hypophyseal function. The background to this might be a disturbed vascular supply. The vasopressin test was of no help in diagnosing tumours as a cause of optic atrophy.

Adolescent

Analytical subcellular fractionation of jejunal biopsy specimens: enzyme activities, organelle pathology and response to corticosteroids in patients with non-responsive coeliac disease.

1. Jejunal biopsies from five patients with non-responsive coeliac disease have been subjected to analytical subcellular fractionation and enzymic microassay in order to compare the organelle pathology of this group with untreated but glutensensitive patients. 2. Compared with the gluten-sensitive group these non-responsive patients showed marked reduction of the endoplasmic reticulum enzymes, normal activities of lysosomal enzymes and slightly less severely reduced brush border activities. 3. It is suggested that the present biochemical studies in combination with previous clinical reports and measurements of DNA and protein synthesis by cultured mucosal biopsies delineate non-responsive coeliac disease as a distinct entity. 4. The patients were treated with oral prednisolone (20 mg daily) for between 5 and 9 weeks and the properties of the jejunal biopsies restudied. 5. Although morphologically there was only a partial restoration of the villus architecture the enzymic alterations and organelle abnormalities returned essentially to normal values.

Adult

A combination of spastic paraparesis, polyneuropathy and adrenocortical insufficiency-a childhood form of adrenomyeloneuropathy.

This report describes a combination of spastic paraparesis and symmetrical sensory motor polyneuropathy with a pathological response to the ACTH test in the case of a 16 year-old boy and a borderline response to the ACTH test in the case of his 8-year-old sister. Another sister, aged 14, showed only a pathological response to ACTH testing, the neurological status being unremarkable. The EEG was normal in all three children examined. Visually evoked potentials were borderline in the case of the boy and normal in the case of the clinically involved sister. Although on examination by light microscopy the sural nerve proved to be normal, the clinical diagnosis of adrenomyeloneuropathy (AMN) in its juvenile form may be assumed, in view of the clinical symptoms and the evidence of adrenocortical insufficiency revealed by the ACTH test.

Adolescent

Response-adapted surgical de-escalation following neoadjuvant immunotherapy in resectable mucosal HNSCC A systematic review and meta-analysis.

INTRODUCTION: Recent encouraging outcomes with neoadjuvant immune checkpoint inhibitors (ICIs) in mucosal head and neck squamous cell carcinoma (HNSCC) have generated interest in surgical de-escalation. However, the oncologic safety of response-adapted surgery (RAS) and its ability to achieve survival outcomes comparable to baseline-planned surgery (BPS) remain uncertain. METHODS: A systematic search of the PubMed, EMBASE, Cochrane Library, and the Clinical Trials Registry for studies of neoadjuvant ICIs, with or without chemotherapy, in resectable mucosal HNSCC, that explicitly report surgical extent, between 2020-2025 was performed. Two independent reviewers extracted data following PRISMA guidelines. Main outcomes included major pathologic response (MPR), pathologic complete response (pCR), event-free survival (EFS), and overall survival (OS). Study-level proportions were pooled by random effects models. Heterogeneity was assessed by the I2 statistic. RESULTS: The comparative analysis consisted of 4 RAS studies (involving 202 patients) and 11 BPS studies (403 patients). The pooled overall EFS was 83.3% (76.9-88.2) for the former and 82% (75.2-87.2) for the latter (P=.751), and the respective pooled OS was 92.3% (87.5-95.3) and 91.4% (80.3-96.5) (P=.839). The pooled pCR rate was 41.7% (95% CI 5.4-48.4; I2=.0) for RAS and 19.8% (95%CI 13.3-29.6; I2=.62) for BPS (P=.001), while the MPR was not significantly different (59.6%, versus 48.5%, P=.245). RAS was associated with greater organ preservation and reduced need for mandibulectomy and free-flap reconstruction. CONCLUSIONS: RAS following neoadjuvant ICIs in mucosal HNSCC may enable surgical de-escalation with preserved oncologic outcomes and improved function in selected patients. Larger prospective studies are warranted.

Humans

Chemotherapy as a substitute for surgery in the treatment advanced resectable head and neck cancer. A report from the Northern California Oncology Group.

This trial determines the feasibility for patients with resectable Stages III/IV head and neck cancer who achieved a complete response to induction chemotherapy of eliminating surgery from their treatment program. Thirty patients were treated with three cycles of cisplatin and 5-fluorouracil (5-FU), followed by reendoscopy and biopsy. Twelve patients achieved a complete pathologic response at the primary and received radiation (interstitial and/or external beam) only. The remainder underwent surgical resection and postoperative radiation. At 2 years, the relapse-free survival was 52%, and the survival was 53% for the entire group. For the 12 complete responders who had surgery eliminated, the relapse-free survival was 60%, and the survival was 70%. This pilot study suggests that for patients with resectable disease who achieve a complete pathologic response to induction chemotherapy at their primary, it is feasible to omit surgery and treat with primary radiation without compromise in survival. This approach warrants further study in a randomized trial.

Adult

The value of MR imaging in monitoring the effect of chemotherapy on bone sarcomas.

We studied the value of MR imaging in monitoring the response of Ewing sarcoma and osteosarcoma to chemotherapy. Relative signal-intensity changes on MR images in the course of chemotherapy were compared with changes in tumor volume and histopathologic findings. MR scans (T1- and T2-weighted spin-echo images) were obtained in 20 patients with bone sarcoma. The first MR scan was obtained before the administration of chemotherapy in all patients. The follow-up scan was obtained in the course of treatment, before surgery. Tumor-volume and signal-intensity measurements of the intra- and extraosseous components of the tumor were analyzed. In 17 patients, histopathologic findings of the resected tumor were available for comparison with the MR images. In 12 of 17 patients there was complete agreement between changes in tumor volume, changes in the signal intensity of the extraosseous tumor component on T2-weighted images, and histopathology. In another four cases, changes in signal intensity correlated either with histopathology or with changes in tumor volume. In one patient with a pathologic fracture, no such correlation existed. A significant correlation was found between changes in signal intensities and pathologic response (r = .57, p = .02), as well as between changes in tumor volume and pathologic response (r = .53, p = .03). No correlation could be found between changes in signal intensity of the intraosseous tumor component and changes in tumor volume or histopathology. We conclude that the signal intensity of the extraosseous component of bone sarcomas on T2-weighted MR images in addition to changes in tumor volume may be useful in evaluating response to chemotherapy.

Adolescent

Morphological alterations of the glomerular (visceral) epithelium in response to pathological and experimental situations.

The glomerular (visceral) layer of Bowman's capsule is comprised of a unique population of cells which have been termed "podocytes." Arising from these cells are large major processes and numerous smaller foot processes which completely surround underlying glomerular capillary loops. Podocyte foot processes interdigitate with each other and are separated by spaces (filtration slits) which are designed to facilitate flow of a large amount of filtrate across the glomerular wall. Podocytes exhibit dramatic morphological changes in response to the nephrotic syndrome and some forms of acute renal failure and may play an important role in the pathophysiology of these conditions. In vitro and in vivo studies have shown that a reduction in the sialic acid component of a thick anionic surface coat plays a major role in the morphological changes that these cells exhibit in the nephrotic syndrome. Also, it has been shown that filamentous actin concentrated mainly within podocyte foot processes are the contractile elements responsible for altering the shapes of these processes. There is evidence to suggest that by altering the shapes of their foot processes, podocytes in the normal kidney are able to alter the number of fully patent filtration slits and thereby actively regulate the rate of solute efflux across the glomerular wall. In vitro and in vivo studies have indicated that cytoplasmic microtubules are probably not involved in alterations of the podocyte foot processes but do appear important in maintaining the morphological integrity of podocyte cell bodies and their major processes. In the present paper, the morphological changes which glomerular podocytes exhibit in response to the nephrotic syndrome, various forms of acute renal failure, and during in vitro incubation are discussed along with studies of the possible roles of cytoplasmic microtubules, microtubules, and the glomerular anionic surface coat in these changes.

Acute Kidney Injury

Tumor reduction surgery and long-term survival in advanced ovarian cancer: a DACOVA study.

Three hundred sixty-one patients with FIGO stage III and IV ovarian cancer were treated with cis-platinum combination chemotherapy in a Danish multicenter trial. Primary surgery was performed at 58 different departments; 32% of the patients were operated at a department associated with an oncologic center, 50% at a general gynecologic department, and 18% at a general surgical department. Complete pathologic response and long-term survival were similar for patients operated on in the different departments. Patients who underwent radical surgery or optimal debulking had a 10% risk of progression during chemotherapy and a 5-year survival of 46%. Patients who underwent suboptimal debulking and exploratory laparotomy had a 40% risk of progression during chemotherapy and a 5-year survival of 14%. Complete pathologic response showed an insignificant difference between radical surgery and optimally tumor reduction (57% versus 41%) and a significant difference between suboptimal tumor reduction and exploratory laparotomy (19% versus 6%). Patients secondarily tumor reduced had a survival rate superior to that of patients not secondarily tumor reduced (25% versus 4% at 4 years).

Adenocarcinoma

Feeding studies in rats with mineral hydrocarbon food grade white oils.

This investigation compared the effects of feeding rats diets containing food grade white oil processed by either conventional oleum treatment or the more modern method of catalytic hydrogenation. In two separate experiments, male or female Fischer-344 rats were given free access for 90 days to diets containing 0, 10, 100, 500, 5,000, 10,000, or 20,000 ppm of either oleum-treated white oil (OTWO) or hydrotreated white oil (HTWO). There were no mortalities and no adverse clinical signs associated with feeding either white oil. Treatment-related effects evidenced by hematological, clinical chemical, and pathological changes were generally dose-related and more marked in female than in male rats, and the OTWO caused a greater pathological response than the HTWO. Tissue residues of saturated hydrocarbons were up to 5.2 times higher in female rats than in males. Rats fed 5,000 ppm or more of either white oil showed dose-related alterations in several hematological and clinical chemistry variates associated mainly with hepatic damage or functional alteration. At necropsy, mesenteric lymph nodes were enlarged, and increases in weight of liver, kidney, and spleen were significant. Microscopic changes were characterized by multifocal lipogranulomata in mesenteric lymph node and liver. No changes were observed in rats fed OTWO or HTWO for 90 days at dietary concentrations of 10 or 100 ppm, equivalent to a minimum intake of 0.65 and 6.4 mg/kg/day, respectively. Differences in degree of pathological response associated with each oil may have been due to their differences in specification rather than processing method.

Animals

Neovascularization in urethane rat retinopathy demonstrated by thymidine labelling.

Rat urethane retinopathy produces sequential and progressive loss of the photoreceptor cells, proceeding from the posterior to the peripheral retina. The inner retina, the retinal pigment epithelium and the choriocapillaris are spared. After loss of the photoreceptor cells, a vasculopathy develops which includes progressive retinal capillary loss and formation of coil-like tufts of retinal vessels which are embedded in the retinal pigment epithelium. Some of the retinal vessels within the retinal pigment epithelium have changed their phenotype from continuous to fenestrated endothelial cells. To elucidate whether DNA synthesis was necessary for formation of the coil-like vessel tuft formation, an autoradiographic study was performed. At 12, 14, 16 and 20 weeks of age, times during which the vasculopathy is known to be forming, urethane and control rats were injected with 3 successive doses of methyl-3H-thymidine. Autoradiography of trypsin-digested retinal vessel preparations was compared with histological sections of the paired eye. The frequency of tritium labelled endothelial cells was much higher in the urethane rats than control animals, and were predominantly in the posterior pole, rather than the periphery. Labelled endothelial cells tended to be associated with, or near, the coil-like vessel tufts. Capillary dropout was observed in urethane, but not control animals. Frequently, adjacent endothelial cells were labelled, suggestive of mitosis. The occurrence of thymidine uptake and a change in phenotype of the endothelial cells leads us to suggest that new cell synthesis, or neovascularization, has occurred in these vessels. Since the retina is less than half the normal thickness and the choriocapillaris is intact, it appears unlikely that ischemia is responsible for inducing these pathological responses. We suggest that the retinal pigment epithelial cell is responsible for the increase in DNA synthesis and change in phenotype of the retinal endothelial cell.

Animals