Effects of combination chemotherapy with topical application of 5-FU ointment to mice's tongue and UFT

After oral administration of UFT and lingual topical application of 5-FU ointment to normal mice, the change of the concentration of 5-FU and Uracil in the tongue, liver and blood serum were studied. We compared with UFT only group, 5-FU ointment only group and the both combination chemotherapy group. 1. As for the tongue concentrations, 5-FU levels in both combination chemotherapy group and 5-FU ointment only group were higher compared to UFT only group. There was no difference between combination chemotherapy and 5-FU ointment only group. Uracil at 21-days in combination chemotherapy group were higher than others. 2. The liver concentrations of 5-FU at 21-days was significantly higher. 3. The blood serum concentrations of 5-FU in both combination chemotherapy and 5-FU ointment only groups revealed similar results. Thereafter, combination chemotherapy in oral region with topical application of 5-FU ointment and UFT may be effective.     

Chemosensitization with nitroimidazole to human gastric cancer transplanted into nude mice

Combined chemotherapy for human gastric cancer Transplanted into nude mice has been performed to determine whether misonidazole (MIS) and metronidazole (MTR), derivatives of nitroimidazole, would enhance the antitumor activity of MMC. MTR, 500 mg/kg, MIS 500 mg/kg, and MMC 2.0 mg/kg were administered ip twice during a 48-hour interval. The antitumor efficacies of MMC only, MTR only, or MIS only were seen to be much the same as in the controls. The combined treatment with MMC and MTR surpassed the controls in antitumoral activity after the 12th day, whereas it did not surpass a regimen with MMC alone. The addition of MIS to MMC showed an enhanced antitumoral activity after the 10th day compared to the controls and, further, after the 10th day it exceeded the results of MMC only. Tumor tripling time in cases of MMC only, MTR only, MIS only, MMC plus MTR, and MMC plus MIS was 123, 132, 144, 144, and 178 hours, respectively, compared to 110 hours in the controls. Thus, these results suggest that MIS has a chemosensitizing activity under these conditions, while MTR has little activity.     

Measuring complete diagnostic evaluation in colorectal cancer screening

Complete diagnostic evaluation, or CDE (i.e., a colonoscopy or combined barium enema X-ray and flexible sigmoidoscopy) is recommended for individuals who have an abnormal screening fecal occult blood test result. Accurate measures of CDE use are needed in colorectal cancer (CRC) screening programs. This study compares the sensitivity and specificity of different methods for measuring CDE recommendation and performance. We identified 17 primary-care practices with 120 patients who had a positive fecal occult blood test result in a CRC screening program operated by a managed-care organization. Approaches used to measure CDE recommendation and performance included external chart audit (ECA) only; internal chart audit (ICA) only; administrative data review (ADR) of electronic claims data; ICA plus ADR; and ECA plus ADR (the "gold standard"). Sensitivity and specificity of each method were assessed relative to CDE recommendation and performance as measured by ECA plus ADR. For CDE recommendation, sensitivity measures were ECA only, 0.926; ICA only, 0.790; ADR only, 0.617; and ICA plus ADR, 0.901. The specificity of each method for CDE recommendation was no less than 0.95. In terms of CDE performance, sensitivity measures were ECA only, 0.877; ICA only, 0.790; ADR only, 0.877; and ICA plus ADR, 0.965. The specificity of each method for CDE performance was 1.0. The ICA-plus-ADR method was a highly sensitive and specific measure of CDE use. This method should be considered in situations that involve primary-care physician follow-up of patients with abnormal CRC screening test results.     

Lack of promoting ability of snuff in rats initiated with 4-nitroquinoline-N-oxide

In an experiment to evaluate the carcinogenicity and promoting capacity of snuff, a reservoir was created in the lower lip of male Sprague-Dawley rats. Groups of 30 rats were treated with snuff only (twice a day on five days a week), propylene glycol (solvent) three times weekly for four weeks, painting of the hard palate with 4-nitroquinoline-N-oxide (4-NQO) three times weekly for four weeks followed by snuff, 4-NQO only for four weeks, or cotton pellets only (twice a day on five days a week). The experiment was continued up to 108 weeks. High levels of tobacco-specific nitrosamines were found in the snuff (a commercial US brand). Rats treated with snuff only, 4-NQO followed by snuff and 4-NQO only had a significantly higher number of squamous-cell tumours and hyperplastic squamous lesions of the lip, oral and nasal cavity and forestomach than solvent or untreated controls. The total number of neoplasms was significantly higher in rats treated with snuff only and with 4-NQO followed by snuff in comparison to the other groups. Thus, snuff and 4-NQO by themselves can induce benign and malignant tumours. Snuff appears to have a general tumorigenic effect but lacked promoting ability after initiation with 4-NQO.     

Nuclear roundness factor and local failure from definitive radiation therapy for prostatic carcinoma.

Of 375 patients with prostatic carcinoma treated definitively with radiation therapy at this institution with at least a 5 year follow-up, 23 patients failed locally only, 72 failed with distant metastasis only, 60 had both local and distant failure, while 220 showed no evidence of disease. In search for a possible marker for local failure following radiation therapy, we examined several nuclear morphometric parameters which have been shown to correlate with the biologic aggressiveness of this disease. The 23 locally failed only patients were matched with 23 no evidence of disease patients for stage, grade, treatment modality, prior surgery, age at diagnosis and race. Archival hematoxylin and eosin slides were obtained for 22 of the 23 matched pairs, and morphometric features, including nuclear roundness factor and nuclear area, as well as numbers of nucleoli were assessed using computer-assisted image analysis in both tumor cells and normal prostatic epithelium. Tumor nuclei from the locally failed only patients had significantly higher nuclear roundness factor values (p = 0.0089) compared with tumor cells from no evidence of disease patients. Analysis of these data by clinical stage demonstrated no significant differences between the locally failed only and no evidence of disease patients. Likewise, there were no significant differences in nuclear roundness factor values of locally failed only and no evidence of disease patients with poorly or moderately well-differentiated tumors. However, there was a highly significant difference (p = 0.0012) in the nuclear roundness factor values of locally failed only and no evidence of disease patients with well-differentiated tumors. Thus, there appears to be a subset of patients with well-differentiated adenocarcinoma of the prostate who have significantly more irregular tumor nuclei and who fail locally only following definitive radiation therapy.     

Breast cancer patients with micrometastases only: is a basis provided for tailored treatment?

Women with breast cancer and micrometastases only constitute a treatment dilemma. If only a micrometastasis is found in a sentinel lymph node, an axillary lymph node dissection may be considered to be overtreatment and perhaps could be avoided. However, studies have shown decreased survival in patients with micrometastases only. This paper focuses on the pathological work-up behind the classification of breast cancer patients having micrometastases only and on the most recent literature concerning prognosis for breast cancer patients with micrometastases. The goal was to determine if studies to date have been able to define a population of breast cancer patients with micrometastases where the size of the metastasis could indicate whether an axillary lymph node dissection should be undertaken. Tailored surgical treatment of breast cancer patients with micrometastases only is not possible at the present time, due to lack of standardization in the pathological work-up of lymph nodes, which implies that this group of breast cancer patients cannot be delimited with sufficient precision. Tailored systemic therapy is also impossible due to lack of a precisely defined target for a feasible therapy.     

Chordoma

Nineteen patients with chordoma seen at M. D. Anderson Hospital from 1948 to 1976 received definitive treatment. Six patients presented with disease in the basisphenoid region, 2 with disease in the lumbar spine (vertebral area), and 11 with disease in the sacrococcygeal area. Twelve of the 19 patients were male, and 5 patients were less than 16 years of age. Nine patients were treated with a combination of surgery and postoperative radiation therapy, 6 received radiation therapy only, and 4 underwent surgery only. Although the number of patients studied is small, the results suggest that surgery only is not an effective means of treating this disease. Radiation therapy only produces palliation for large inoperable lesions, but excision followed by irradiation is the best treatment for securing prolonged local control.     

Spirometry as an objective tool for nasal patency

Spirometry can be used as an objective tool for measuring nasal patency. it is sensitive, easy to perform, comfortable to patient The only limitation being that it only can be done in institution.     

Adjuvant treatment of in-transit melanoma: Narrowing the knowledge gap left by clinical trials

Few clinical trials address efficacy of adjuvant systemic treatment in patients with in-transit melanoma (ITM). This study describes adjuvant systemic therapy of ITM patients beyond clinical trials. In this study, we included stage III adjuvant-treated melanoma patients registered in the nationwide Dutch Melanoma Treatment Registry between July 2018 and December 2020. Patients were divided into three groups: nodal disease only, ITM only and ITM and nodal disease. Recurrence patterns, recurrence-free survival (RFS) and overall survival (OS) at 12-months were analyzed. In our study population of 1037 patients, 66.8% had nodal disease only, 16.7% had ITM only and 16.2% had ITM with nodal disease. RFS at 12-months was comparable in the nodal only and ITM only group (72.2% vs70.1%, P = .97) but lower in ITM and nodal disease patients (57.8%; P = .01, P < .01). Locoregional metastases occurred as first recurrence in 38.9% nodal disease only, 71.9% of ITM-only and 44.0% of ITM and nodal disease patients. Distant recurrences occurred in 42.3%, 18.8% and 36.0%, respectively (P = .02). 12-months OS was not significantly different for nodal disease only patients compared with ITM-only (94.4% vs 97.6%, P = .06) but was significantly higher for ITM-only compared with ITM and nodal disease patients (97.6% vs 91.0%, P < .01). In conclusion, we showed that in the adjuvant setting, RFS rates in ITM-only patients are similar to non-ITM, though better than in ITM and nodal disease patients. Adjuvant-treated ITM-only patients less often experience distant recurrences and have a superior OS compared with ITM and nodal disease patients.     

The nude mouse as anin vivo model for human breast cancer invasion and metastasis

Summary Human breast cancer xenografts only rarely invade and metastasize in nude mice, and have therefore only had limited use as a model for studying mechanisms involved in breast cancer spreading. However, recent reports describe differences not only between various cell lines but also between strains of immune-deficient mice in terms of providing a model for studies of the invasive and metastatic capability of human breast cancer xenografts. Genetic labelling of human cancer cells with the lacZ gene is described as a specific and highly sensitive method for identification of micrometastases in such a model.     

The prognostic significance of malignant pleural effusion at the time of thoracotomy in patients with non-small cell lung cancer

Surgery is usually not indicated for malignant pleural effusion (PE) due to its poor prognosis. However, PE is first detected at thoracotomy, and it is difficult to judge an appropriate mode of resection. Forty-nine patients with lung cancer were first diagnosed as PE and/or pleural dissemination (PD) at thoracotomy. The histological types were 36 adenocarcinoma, ten squamous cell carcinoma and three large cell carcinoma. Sixteen patients had only PE, 17 had only PD, and 16 had both PE and PD. Ten patients underwent only exploratory thoracotomy, seven partial resection, 27 lobectomy and five panpleuropneumonectomy. The overall survival rate was 26.7% at 3 years. The patients with PE and/or PD seemed to have a poorer survival compared to our previous study. The patients with only PE showed a significantly better prognosis than the patients with only PD (P=0.0001) or with PD+PE (P=0.019). The patients who underwent exploratory thoracotomy showed poor survival. There were significant differences in the survival in relation to the extent of the primary tumor. In conclusion, the patients with T1-2 of primary tumor and only a small amount of PE without PD can be expected to show long-term survival after tumor resection.     

Vergleichende histologische und kulturelle Untersuchungen zum Vorkommen von Sproßipilzen in einem Obduktionsgut

Summary: Organ materials from 57 autopsies were investigated histologically and culturally in order to compare the occurrence of yeasts with both methods. In materials of 12 autopsies (21,1 %) yeasts were demonstrated not only by culture but also by histology. From further 35 autopsies (61,4 %) yeasts were only found by isolation procedures. In most cases (56,9 %) Candida albicans was isolated, followed by Torulopsis glabrata (27,5 %) and Candida tropicalis (25,5%). Yeasts were demonstrated not only by histological but also by cultural procedures especially in the respiratory system and in the oesophagus. In materials from patients who had died from inflammatory diseases, yeasts were detected in greater number than in other. The abundant number of yeasts demonstrated not only by cultural (93,3 %) but also by histological procedures (26,7) was remarkable in cases with cardiovascular Insufficieny.     

Complications and treatment of the myelodysplastic syndromes.

The major complications of the myelodysplastic syndromes (MDS) are related to cytopenia and evolution to acute myeloid leukemia (AML). Hematopoietic growth factors are only of limited benefit to alleviate the cytopenia. Therapy in MDS patients over the age of 50 should aim at prolonging survival while limiting the risk of toxicity. Those with stable disease should only receive supportive care; those with progressive cytopenia should have a trial with low-dose chemotherapy. Aggressive chemotherapy should only be reserved for those failing low-dose therapy. Therapy in MDS patients under the age of 50 should aim at cure of the disease. Although aggressive chemotherapy can induce complete remission in the majority of these patients, remission is usually short. Allogeneic bone marrow transplantation is probably the only curative option in these patients and should be the treatment of choice.     

Adjuvant therapy for pancreatic cancer: an evolving paradigm

Pancreatic cancer is the fourth leading cause of death in men and fifth in women in the United States. The median survival is 8 to 12 months for patients with locally advanced and unresectable disease and only 3 to 6 months for those with metastatic disease at presentation. Surgical resection offers the only potentially curative treatment. However, only 15% to 20% of patients present with tumors amenable to resection at initial diagnosis. Even for those who undergo resection, the prognosis remains poor. The 5-year survival following pancreaticoduodenectomy is only about 25% to 30% for node-negative tumors and 10% for node-positive tumors. Because of the dismal outcome for patients with resectable pancreatic cancer, adjuvant therapy has been administered in an attempt to improve the local control and overall survival. This review highlights historic and current perspectives of adjuvant therapy in resected pancreatic cancer.     

Hodgkin's disease: is there a price for successful treatment? A 25-year experience

Three hundred-twenty patients with Hodgkin's disease (HD) were studied retrospectively to assess the impact of treatment on survival and the development of second malignant neoplasms (SMN). All stages of HD were considered. Treatment groups included XRT only, XRT + multiagent chemotherapy (MAC), XRT + single agent chemotherapy (SAC), and chemotherapy only (Chemo). MAC was subdivided into MOPP and non-MOPP regimens. Twenty-one patients developed 23 SMN, only two of which were acute leukemias. Survival was greatest for XRT only because of a large proportion of early stage HD in this group. SMN were seen in all treatment groups except Chemo only. The XRT + MAC group had a significantly elevated observed-to-expected ratio for SMN, but it was difficult to attribute this to either MOPP or non-MOPP due to very small numbers of patients. The actuarial risk of SMN for both MOPP and non-MOPP rises dramatically between 10 and 15 years, however, extrapolation cannot be done, again because of very small numbers. We conclude that there is an increased risk of SMN in patients treated aggressively for HD, but that the exact cause of SMN is difficult to determine.     

Survival Differences in Patients With Metastatic Colorectal Cancer and With Single Site Metastatic Disease at Initial Presentation: Results From South Australian Clinical Registry for Advanced Colorectal Cancer

BackgroundColorectal cancer is the third most common cancer in Australia. The median overall survival for metastatic colorectal cancer is nearly 2 years. However, there may be survival differences based on site of metastatic disease.MethodsData was collected from the South Australian Registry for Advanced Colorectal Cancer. A total of 1207 patients with single site metastatic disease at initial diagnosis were subclassified into 6 subgroups: liver only (n = 780), pelvic only (n = 148), lung only (n = 142), lymph node only (n = 95), bone only (n = 32), and brain only (n = 10). Univariate and multivariate parametric survival analyses were performed.ResultsMedian overall survival was 20.3 months for the whole group. The overall survival for lung-only metastases group was 41.1 months followed by liver- and pelvic-only disease groups (22.8 and 23.8 months, respectively). Patients with isolated bone-only and brain-only metastases had poor overall survival (5.1 and 5.7 months, respectively). On multivariate analysis, prognosis was superior for the lung-only group.ConclusionsLung only group had the longest median overall survival. Bone and brain sites had a poor outlook. Site of metastatic disease at initial presentation may be prognostic.     

Arsenic trioxide increases the sensitivity of 786-0 renal carcinoma cells to radiotherapy

We evaluated the combined effect of As(2)O(3) and ionizing radiation on cultured renal carcinoma cells. The cells receiving both As(2)O(3) and radiotherapy had more DNA damage, more apoptosis, more reactive oxygen species produced, more cells in G(2)/M phase, and a lower mitochondrial membrane potential than cells treated with As(2)O(3) only or with radiotherapy only (for all comparisons, p < .05). Renal carcinoma cells can be sensitized to ionizing radiation with As(2)O(3), and combining As(2)O(3) and radiation had larger effects than As(2)O(3) only or radiation only.     

Predictors of malignancy in thyroid fine‐needle aspirates “cyst fluid only” cases

BACKGROUND:

A recent consensus conference on thyroid fine‐needle aspiration (FNA) cytology concluded that specimens with abundant histiocytes and few or no follicular cells should be interpreted as “cyst fluid only,” under the category of “nondiagnostic.” The purpose of the current study was to identify any cytomorphologic characteristics in this type of specimen that are predictive of an underlying malignancy.

METHODS:

Thyroid FNA cases with a report of cyst fluid only and a follow‐up thyroidectomy specimen were identified during a 3‐year period. A blinded retrospective review of 6 morphologic features in the thyroid FNA specimens was conducted. These review findings were then correlated with the histopathologic diagnosis (benign or malignant).

RESULTS:

Of the 76 cyst fluid only cases with subsequent thyroidectomy, 10 cases had an ipsilateral diagnosis of papillary carcinoma measuring ≥1.0 cm. There was no association found between the number or amount of acute inflammatory cells, blood, colloid, macrophages, and pigmented macrophages and the histologic outcome. In only 4 of the 10 cases with a malignant outcome was the specimen assessed as being truly inadequate on retrospective review, and in 1 of these cases, the cytology was suggestive of malignancy.

CONCLUSIONS:

The only cytomorphologic characteristic found to be predictive of subsequent malignancy in cyst fluid only cases was the presence of follicular epithelium with atypical or suspicious features. Therefore, cases containing atypical epithelial cells should not be categorized as nondiagnostic or cyst fluid only, but rather diagnosed as atypical or suspicious. Cancer (Cancer Cytopathol) 2009. © 2009 American Cancer Society.     

Resection margin status in lumpectomy specimens for duct carcinoma of the breast: correlation with core biopsy and mammographic findings.

BACKGROUND: The strategy for surgical treatment of breast carcinoma proven by biopsy is mainly based on the physical and mammographic examinations. To investigate if the pathological findings in core biopsy are contributory to planning the surgical strategy, we correlated the status of ductal carcinoma in situ (DCIS) in the core needle biopsy of breast, the mammographic changes and the status of resection margins in the subsequent lumpectomy. STUDY DESIGN: Consecutive 130 core needle biopsies with prior mammography and subsequent lumpectomy were reviewed. Biopsies were divided into: group I, DCIS; group II, DCIS and infiltrating carcinoma (IC); and group III, IC. Mammographic findings were categorized into four groups: (a) nonspecific findings; (b) calcification (Ca(++)); Ca(++) and mass, and mass only. The status of margins in correlating lumpectomy specimens was reviewed. Close margin was defined as a free margin at less than 0.1cm from the carcinoma. RESULTS: The rates of positive or close margins in three groups I, II, and III were 13/18, 18/48, and 2/64 (P < 0.001); and in mammography groups of nonspecific finding, Ca(++), Ca(++) mass and mass only were 5/6, 7/15, 8/37, and 13/72 (P < 0.001), respectively. Of the total of 14 cases with positive margins of more than 0.5 cm in length, 8, 4, and 2 cases were from group I, II, and II, respectively. In addition, 13 of 21 cases with nonspecific changes or with only Ca(++) in mammograms belonged to the group I; 10 of these 13 cases were associated with positive margins. Forty-one of 72 cases presenting as a mass only in mammograms belonged to the group III; only 2 of these 41 cases were associated positive margins. CONCLUSIONS: Correlation of the extent of carcinoma with pre-operative histopathological findings was better than with mammography. Core biopsies containing only DCIS, particularly in cases with nonspecific findings or with only Ca(++) in mammograms, represent a group of breast carcinoma that pose the high risk for incomplete resection in lumpectomy. Surgical management of patients having these cores includes wider resection margins than would otherwise be taken. Most core biopsies with only IC were associated with negative margins.     

Retroperitoneal sarcomas: the Yale experience and a review of the literature

Between 1964 and 1978, 23 patients were referred for radiation therapy for retroperitoneal sarcoma. Three patients had complete excision and negative resection margins and all survived for 5 years without recurrent disease. One patient had complete resection but positive margins, but had a local recurrence 3 1/2 years after radiation. One patient had partial excision with gross residual, and this patient survived only 17 months after an incomplete radiation treatment schedule. Ten cases had biopsy only and were then referred. We found that there were only four cases that survived longer than 1 year, and their average dose of radiation was 4,400 rads, as compared to only 2,691 rads for the remaining six. We conclude that for incompletely resected or only biopsied retroperitoneal sarcoma, doses of 4,000-5,000 rads should be given and then a reevaluation for complete resection should be done with CT scan and reexploration. For completely resected cases, we feel that postoperative radiation adds to the local control. We have reviewed the literature and presented the data in support of our conclusions.