Real-World Experience with Cemiplimab Treatment for Advanced Cutaneous Squamous Cell Carcinoma-A Retrospective Single-Center Study.

BACKGROUND: The systemic treatment of advanced cutaneous squamous cell carcinoma (cSCC) has seen significant developments in recent years. The anti-PD1 inhibitor cemiplimab has demonstrated efficacy in clinical trials, but real-world data are still limited. Here, we aimed to evaluate the efficacy and the safety of cemiplimab in a real-world clinical setting. METHODS: A retrospective analysis was carried out for all patients who received at least two doses of cemiplimab at our department between February 2020 and January 2023. Progression-free survival (PFS), overall survival (OS), the objective response rate (ORR), the disease control rate (DCR) and adverse events (AEs) were evaluated. RESULTS: Twenty-five patients were included with a median age of 78 (65-82) years. The median treatment duration was 48 (16-72) weeks. Five (20%) patients were immunocompromised. Sixteen patients (64%) developed AEs, including 36% serious AEs (SAEs) of grade ≥ 3. Six patients (24%) were withdrawn from treatment due to the occurrence of AEs. Among the 25 patients, 52% showed an objective response (3 complete and 10 partial responses), 76% had controlled disease and 24% experienced progression. Among the five immunocompromised patients, the ORR was 60%, while the DCR was 80%. CONCLUSIONS: This retrospective real-world study revealed that locally advanced or metastatic cSCC could be effectively treated with cemiplimab even in elderly, polymorbid and immunocompromised patients.

Cutaneous malignancies in patients with Parkinson's disease at a dermato-oncological university centre in Hungary.

Background: The possible correlation between melanoma and Parkinson's disease (PD) has been intensively studied. In this work, we aimed to assess the coincidence of skin malignancies and PD at a dermato-oncological university centre in Central-Eastern Europe, Hungary. Methods: From 2004 to 2017, a retrospective analysis of the centre's database was performed based on International Statistical Classification of Diseases-10 codes. Results: Out of the patients who visited the clinic during the study period, 20,658 were treated for malignant skin tumours. Over the 14 years, 205 dermatological patients had PD simultaneously, 111 (54%) of whom had at least one type of skin malignancy: melanoma (n=22), basal cell carcinoma (BCC) (n=82), or squamous cell carcinoma (SCC) (n=36) (in some patients, multiple skin tumours were identified). Compared to the age- and sex-matched control group, patients with PD had a significantly lower risk for basal cell carcinoma (OR, 0.65; 95% CI, 0.47-0.89, p=0.0076) and for all skin tumours (OR, 0.74; 95% CI, 0.56-0.98, p=0.0392) but not for melanoma. Conclusions: We found a decreased risk of all skin tumours and basal cell carcinoma and an unchanged risk of melanoma among patients with PD. However, it should be kept in mind that some large-scale meta-analyses suggest a higher incidence of melanoma after a diagnosis of PD, indicating the importance of skin examination in this vulnerable population.

Immunohistochemical Study of the PD-1/PD-L1 Pathway in Cutaneous Lupus Erythematosus.

The pathomechanism of various autoimmune diseases is known to be associated with the altered function of programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) axis. We aimed to investigate the role of this pathway and inflammatory cell markers in subtypes of cutaneous lupus erythematosus (CLE): discoid lupus erythematosus (DLE), subacute CLE (SCLE) and toxic epidermal necrolysis (TEN)-like lupus, a hyperacute form of acute CLE (ACLE). Ten skin biopsy samples from 9 patients were analyzed with immunohistochemistry regarding the following markers: CD3, CD4, CD8, Granzyme B, CD123, CD163, PD-1, PD-L1. Our group consisted of 4 SCLE (2 idiopathic (I-SCLE) and 2 PD-1 inhibitor-induced (DI-SCLE)), 4 DLE and 1 TEN-like lupus cases. From the latter patient two consecutive biopsies were obtained 1 week apart. Marker expression patterns were compared through descriptive analysis. Higher median keratinocyte (KC) PD-L1 expression was observed in the SCLE group compared to the DLE group (65% and 5%, respectively). Medians of dermal CD4, Granzyme B (GB), PD-1 positive cell numbers and GB+/CD8+ ratio were higher in the DLE group than in the SCLE group. The I-SCLE and DI-SCLE cases showed many similarities, however KC PD-L1 expression and dermal GB positive cell number was higher in the former. The consecutive samples of the TEN-like lupus patient showed an increase by time within the number of infiltrating GB+ cytotoxic T-cells and KC PD-L1 expression (from 22 to 43 and 30%-70%, respectively). Alterations of the PD-1/PD-L1 axis seems to play a role in the pathogenesis of CLE.

Anti-PD-1 Monotherapy in Advanced Melanoma-Real-World Data from a 77-Month-Long Retrospective Observational Study.

Real-world evidence plays an important role in the assessment of efficacy and safety of novel therapies. The increasing use of immune checkpoint inhibitors (ICIs) in patients with advanced melanoma has led to notably improved clinical outcomes, while they are also associated with immune-related adverse events (irAEs). The majority of the available data are based on clinical trials, where the investigated subjects often do not adequately represent the general patient population of the everyday practice. Although there is a niche of objective biomarkers for the future treatment response of ICIs, certain studies suggest that irAEs may be predictive. The aim of this study was to carry out a retrospective analysis of treatment data from patients with advanced melanoma, treated with a single anti-PD-1 agent (pembrolizumab or nivolumab) during a 77-month-long period. Treatment efficacy and occurrence of adverse events were analyzed to identify potential predictive markers. Primary and secondary endpoints were the overall survival (OS) and progression-free survival (PFS). In our cohort, we demonstrated that the occurrence of more than one irAE showed a correlation with response to PD-1 ICI therapy and improved the OS and PFS. Our study suggests, that the grade of toxicity of the irAE may affect the survival rate.

Frequent KIT mutations in skin lesions of patients with BRAF wild-type Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is characterized by mutations of the RAS-RAF-MAPK signaling pathway. We analyzed MAP2K1, NRAS and KIT mutation incidence in skin lesions of BRAF wild-type (wt) LCH patients. We evaluated the occurrence of MAP2K1, NRAS and KIT mutations in seven LCH and one indeterminate cell histiocytosis (ICH) patients. MAP2K1 mutation frequency was found to be 3/7 (42.9%) in LCH and also found in ICH. Similarly, the KIT mutation frequency was found to be equally prevalent (4/7, 57.1%) in LCH and also occurred in ICH. Involvement of KIT exons in LCH-ICH indicated that exon 9/11/18 were equally prevalent followed by exon 13. This exploratory analysis on BRAF-wt LCH revealed a KIT mutation rate comparable to MAP2K1. Although the detected KIT mutations are different from activating mutations found in other KIT-dependent neoplasms, our data suggest that KIT-inhibitors might have a role in treating BRAF-wt LCH patients.

Exploring Differential Connexin Expression across Melanocytic Tumor Progression Involving the Tumor Microenvironment.

The incidence of malignant melanoma, one of the deadliest cancers, continues to increase. Here we tested connexin (Cx) expression in primary melanocytes, melanoma cell lines and in a common nevus, dysplastic nevus, and thin, thick, and metastatic melanoma tumor progression series involving the tumor microenvironment by utilizing in silico analysis, qRT-PCR, immunocyto-/histochemistry and dye transfer tests. Primary melanocytes expressed GJA1/Cx43, GJA3/Cx46 and low levels of GJB2/Cx26 and GJC3/Cx30.2 transcripts. In silico data revealed downregulation of GJA1/Cx43 and GJB2/Cx26 mRNA, in addition to upregulated GJB1/Cx32, during melanoma progression. In three melanoma cell lines, we also showed the loss of GJA1/Cx43 and the differential expression of GJB1/Cx32, GJB2/Cx26, GJA3/Cx46 and GJC3/Cx30.2. The dominantly paranuclear localization of connexin proteins explained the ~10⁻90 times less melanoma cell coupling compared to melanocytes. In melanocytic tumor tissues, we confirmed the loss of Cx43 protein, fall of cell membrane and elevated paranuclear Cx32 with moderately increased cytoplasmic Cx26 and paranuclear Cx30.2 positivity during tumor progression. Furthermore, we found Cx43, Cx26 and Cx30 proteins upregulated in the melanoma adjacent epidermis, and Cx43 in the tumor flanking vessels. Therefore, differential connexin expression is involved in melanocytic tumor progression where varying connexin isotypes and levels reflect tumor heterogeneity-related bidirectional adaptive interactions with the microenvironment.

Aquaporin 1 protein expression is associated with BRAF V600 mutation and adverse prognosis in cutaneous melanoma.

Despite experimental findings suggesting the prognostic significance of Aquaporin 1 (AQP1) in human melanoma, no published clinical data are available. We studied the expression of AQP1 protein in cutaneous melanoma, correlated our findings with standard histological and genetic markers, and long-term clinical follow-up. Our study evaluated the AQP1 protein expression in 78 melanoma patients, representing two predefined risk cohorts using the immune labeling technique with commercially available anti-AQP1 antibodies on routinely formalin-fixed and paraffin-embedded tumor tissue samples. BRAF V600E mutation analyses were carried out successfully in 70 patients using PCR and restriction fragment length polymorphism analyses, followed by confirmatory analysis with the Sanger sequencing technique. AQP1-expressing melanoma cells were found in 52 cases (66.7%, median H-score=124.24). Significantly higher AQP1 H-scores (P=0.047) were found in the 'high-risk' patients. No correlations were found with the established histological markers, such as mitotic index (P=0.42), Clark level (P=0.95), and Breslow thickness (P=0.51). BRAF V600 mutation analyses were successful in 89%, and showed a two times higher mutation frequency in the 'high-risk' group. The BRAF V600 mutations were significantly associated with AQP1 expression (P=0.014). Long-term follow-up indicated a reduced progression-free survival (P=0.036) and overall survival (P=0.017) for the AQP1-positive cutaneous melanoma patients. AQP1 expression is likely to be associated with an adverse prognosis in cutaneous melanoma.

Retrospective Analysis of Clinicopathological Characteristics of Pregnancy Associated Melanoma.

Pregnancy associated melanoma (PAM) by definition appears during pregnancy or within 1 year after delivery. In this retrospective study we analysed the pathological characteristics and survival rate of PAM and matched the data with non-pregnant age- and stage-matched control patients. Between 2003 and 2014, 34 pregnant women (aged 32.5 ± 5.6 years) were diagnosed with melanoma at the Department of Dermatology, Venereology and Dermatooncology of the Semmelweis University. During the pathological process histologic subtype, Breslow thickness and Clark level, tumor cell type, mitotic rate, peritumoral inflammation, as well as ulceration, regression, necrosis, vascular invasion and presence of satellite were analyzed and related to clinical data. Primary tumor location and clinical staging, disease course, local recurrence and metastases, 5-year survival rate, other tumor development before or after the diagnosis of melanoma have also been documented. We found no difference in all parameters between pregnant and non-pregnant melanoma cases except peritumoral inflammation which was higher in PAM group, moreover the presence of mild inflammation was significantly higher in PAM group compared to non-pregnancy associated melanoma (NPAM) women group.

[Anal cytology]. / Anális citológia.

INTRODUCTION: The incidence of anal cancer has increased in recent decades, particularly among human immunodeficiency virus infected men who have sex with men. Anal intraepithelial neoplasia is a potential precursor lesion of anal cancer. Anal cytology is the primary screening test for anal intraeptithelial neoplasia. AIM: The authors aimed to analyze the results of anal cytology of patients with human immunodeficiency virus infection at the National Centre of STD, Department of Dermatology, Dermatooncology and Venereology, Semmelweis University. METHOD: 155 anal cytological examinations were performed in 140 patients between November 1, 2012 and August 31, 2014. RESULTS: 44% of patients were found to have anal dysplasia, and only 1.6% of patients had high-grade lesions. This rate is lower as compared to published studies including larger number of patients. CONCLUSIONS: The study underlines the necessity of screening for anal lesions in the population at-risk.

Zoledronic acid for prevention of bone loss in patients receiving primary therapy for lymphomas: a prospective, randomized controlled phase III trial.

UNLABELLED: In patients with newly diagnosed lymphoma, low bone mineral density (BMD) is common at diagnosis and worsens with therapy. Our randomized phase III trial demonstrates that 2 doses of zoledronic acid (ZA) and supplementation with calcium and vitamin D effectively prevent further bone loss. BACKGROUND: Patients with lymphoma are at risk of development of bone mineral density (BMD) loss from therapy with high-dose corticosteroids and alkylating agents. Zoledronic acid (ZA), a bisphosphonate, may prevent this complication of therapy. We evaluated the effect of ZA on the change in BMD and surrogate biomarkers in patients with lymphoma receiving initial chemotherapy. PATIENTS AND METHODS: Our phase III trial randomized 74 patients with newly diagnosed lymphoma and a baseline BMD of ≥ -2.0 to receive oral calcium and vitamin D daily with or without ZA at enrollment and at 6 months after enrollment. BMD was evaluated at baseline and 1 year after enrollment. Secondary biomarker endpoints were collected at baseline and at 3, 6, 9, and 12 months after enrollment. RESULTS: Forty-three percent of patients had baseline osteopenia. Fifty-three patients were evaluable for response: 24 received ZA and had stable BMD during the observation period, whereas 29 patients in the control group had decreased BMD (P < .05 at lumbar spine and bilateral femoral neck). Twenty-one randomized patients were not evaluable for response because of lymphoma progression or death, withdrawn consent/incomplete testing, or ineligibility. Bone biomarkers were higher in the control group at all intervals after treatment (P < .001). No fractures or intervention-related toxicities were observed during this trial. CONCLUSIONS: Newly diagnosed patients with lymphoma are at risk of low BMD, which may worsen with therapy. Treatment with ZA effectively stabilizes BMD and prevents bone loss. Our data suggest that BMD testing and prophylaxis should be considered as an early intervention for a preventable problem.

Indeterminate cell histiocytosis in a pediatric patient: successful treatment with thalidomide.

The 15-year-old male patient presented several 2-6 mm large livid reddish-yellowish, shiny, compact papules on the head, trunk and extremities, which had developed within the last 4 months. Histology showed normal epidermis with dense dermal infiltrate of histiocytes accompanied by few eosinophils, Touton or foamy giant cells. The histiocytes were S100 positive, CD1a negative and did not contain Birbeck granules ultrastructurally. Chest X ray, EEG, skull MRI did not show pathology. Opthalmology, neurology, oto-rhino-laryngology did not reveal alterations. Based upon the clinical symptoms and the histopathology, the diagnosis of indeterminate cell histiocytosis was confirmed. Cryotherapy and cauterization did not stop the progression of the disease, however, under thalidomide treatment no new symptoms developed and the lesions healed with pigmentation.

Epidemiology and risk factors for osteonecrosis of the jaw in cancer patients.

Osteonecrosis of the jaw (ONJ), previously an entity associated with radiation therapy to the head and neck, has been observed in patients treated with bisphosphonates. Patients with metastatic breast cancer and myelomatous bone disease, commonly treated with high-potency nitrogen-containing bisphosphonates for a prolonged period of time, have the greatest risk of ONJ development. The reported frequency of ONJ ranges from 0.6% to 6.2% in breast cancer and from 1.7% to 15% in patients with multiple myeloma. Osteonecrosis of the jaw has also been observed in patients with other cancers such as prostate cancer and in benign bone disorders such as osteoporosis and Paget's disease in which the incidence is low. Risk factors associated with the development of ONJ include dental extractions, length of bisphosphonate treatment, and the type of bisphosphonate used. In this review, we summarize the reported incidence and risk factors associated with ONJ.

SHMT1 1420 and MTHFR 677 variants are associated with rectal but not colon cancer.

BACKGROUND: Association between rectal or colon cancer risk and serine hydroxymethyltransferase 1 (SHMT1) C1420T or methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms was assessed. The serum total homocysteine (HCY), marker of folate metabolism was also investigated. METHODS: The SHMT1 and MTHFR genotypes were determined by real-time PCR and PCR-RFLP, respectively in 476 patients with rectal, 479 patients with colon cancer and in 461 and 478, respective controls matched for age and sex. Homocysteine levels were determined by HPLC kit. The association between polymorphisms and cancer risk was evaluated by logistic regression analysis adjusted for age, sex and body mass index. The population stratification bias was also estimated. RESULTS: There was no association of genotypes or diplotypes with colon cancer. The rectal cancer risk was significantly lower for SHMT1 TT (OR = 0.57, 95% confidence interval (CI) 0.36-0.89) and higher for MTHFR CT genotypes (OR = 1.4, 95%CI 1.06-1.84). A gene-dosage effect was observed for SHMT1 with progressively decreasing risk with increasing number of T allele (p = 0.014). The stratified analysis according to age and sex revealed that the association is mainly present in the younger (< 60 years) or male subgroup. As expected from genotype analysis, the SHMT1 T allele/MTHFR CC diplotype was associated with reduced rectal cancer risk (OR 0.56, 95%CI 0.42-0.77 vs all other diplotypes together). The above results are unlikely to suffer from population stratification bias. In controls HCY was influenced by SHMT1 polymorphism, while in patients it was affected only by Dukes' stage. In patients with Dukes' stage C or D HCY can be considered as a tumor marker only in case of SHMT1 1420CC genotypes. CONCLUSIONS: A protective effect of SHMT1 1420T allele or SHMT1 1420 T allele/MTHFR 677 CC diplotype against rectal but not colon cancer risk was demonstrated. The presence of SHMT1 1420 T allele significantly increases the HCY levels in controls but not in patients. Homocysteine could be considered as a tumor marker in SHMT1 1420 wild-type (CC) CRC patients in Dukes' stage C and D. Further studies need to clarify why SHMT1 and MTHFR polymorphisms are associated only with rectal and not colon cancer risk.

Frequency and risk factors associated with osteonecrosis of the jaw in cancer patients treated with intravenous bisphosphonates.

INTRODUCTION: Osteonecrosis of the jaw (ONJ) has been reported in patients treated with bisphosphonates. The incidence and risk factors associated with this disorder have not been clearly defined. MATERIALS AND METHODS: We conducted a retrospective analysis of 4019 patients treated with intravenous bisphosphonates between 1996 and 2004. Our goals were to estimate the frequency, understand the clinical presentation, and identify risk factors associated with ONJ development. RESULTS: Sixteen of 1338 patients with breast cancer (1.2%) and 13 of 548 patients with multiple myeloma (2.4%) developed ONJ. The median dose and duration of treatment with pamidronate or zoledronic acid were significantly higher in patients with ONJ (p < 0.0001). Multivariate Cox proportional hazards regression analysis identified treatment with zoledronic acid (hazards ratio [HR], 15.01; 95% CI: 2.41-93.48; p = 0.0037), treatment with pamidronate followed by zoledronic acid (HR, 4.00; 95% CI: 0.86-18.70; p = 0.078), and dental extractions (HR, 53.19; 95% CI: 18.20-155.46; p < 0.0001) as significant risks for ONJ in breast cancer. In multiple myeloma, dental extractions (HR, 9.78; 95% CI: 3.07-31.14; p = 0.0001) and osteoporosis (HR, 6.11; 95% CI: 1.56-23.98; p = 0.0095) were significant risk factors while controlling for bisphosphonate therapy. Thirteen of 29 patients were followed for a median of 17.1 mo (range, 7-67 mo); lesions healed in 3 patients during this period. CONCLUSIONS: ONJ is an uncommon but long-lasting disorder that occurs mainly in breast cancer and multiple myeloma patients treated with intravenous bisphosphonates. High cumulative doses of bisphosphonates, poor oral health, and dental extractions may be significant risk factors for ONJ development. ONJ resolved in 23% of patients with conservative therapy.

Erratum to "Clinical evaluation of the intraoral fluoride releasing system in radiation-induced xerostomic subjects. Part 2: Phase I study".

Radiation-induced xerostomia can result in the rapid onset and progression of dental caries in head and neck cancer patients. Topically applied fluorides have been successfully used to inhibit the formation of dental caries in this population. However, because intensive daily self-application is required, compliance is an issue. The intraoral fluoride-releasing system (IFRS) containing a sodium fluoride core is a newly developed, sustained-release, passive drug delivery system that does not require patient involvement except for periodic replacement, thus reducing the effect of patient compliance on its effectiveness in dental caries prevention. Twenty-two head and neck cancer patients from U. T. M. D. Anderson Cancer Center, with radiation-induced xerostomia, were entered into a pilot study to contrast the daily home use of a 0.4% stannous fluoride-gel-containing tray (control group) to IFRS (study group) with respect to tolerability and adherence, and to obtain information on relative caries preventive efficacy. Participants were stratified on the basis of radiation exposure and randomly assigned to treatment with either IFRS or stannous fluoride gel. Patients in both groups were fitted with two IFRS retainers and also were instructed to use a 1100-ppm fluoride conventional sodium fluoride dentifrice twice daily. The study was conducted as a single-blinded, parallel-cell trial. Pre-existing carious lesions were restored prior to the beginning of the study. The efficacy variable was determined by the mean number of new or recurrent decayed surfaces. Patients were examined for caries 4, 8, 12, 24, 36, and 48 weeks after initiation of treatment. Reports of adverse reactions were based on information volunteered by patients and that were elicited during interviews. At baseline, the resting and stimulated salivary flow rates (g/5min) were significantly greater in the control group than in the study group (p<0.05). Patients in the control group had received significantly more radiation than those in the test group (68Gy vs. 60Gy; p=0.047). No marked differences in follow-up new and recurrent caries were found between the stannous fluoride gel control and IFRS groups during the study period. The rate of new or recurrent carious lesions in the group treated with the fluoride gel was slightly lower than in the IFRS group, based on carious lesions at the baseline examination (Poisson mean number of new or recurrent carious lesions for the control group=0.55 per year vs. 0.83 per year for the study group, p=0.705; odds ratio of the occurrence of any new or recurrent caries during follow-up for control group vs. the study group=0.80; p=0.781). This pilot study revealed that the IFRS was well-tolerated and safe in this study population associated with minimal complications during the duration of this study and was comparable in efficacy to a SnF(2) gel in preventing caries development. The IFRS provided similar rates of control for caries formation to a fluoride-gel-containing tray. The IFRS is designed to release a daily dose of 0.12mg of sodium fluoride, which can be evenly distributed throughout the oral cavity for a single application of 4 months. It would be more convenient than the daily home application of a tray of 0.4% stannous fluoride or 1.1% sodium fluoride gel, and avoids the problem of variable patient compliance.

Chemoprevention by cyclooxygenase-2 inhibition reduces immature myeloid suppressor cell expansion.

Selective inhibitors of cyclooxygenase-2 (COX-2) enzyme activity have shown chemopreventive activity in carcinogen-induced and transgenic rodent tumor models and clinically for colon cancer. However, the mechanism(s) by which COX-2 inhibitors reduce carcinogenesis remains controversial. We report herein that administration of the selective COX-2 inhibitor, celecoxib, significantly reduces the number of Gr1(+)CD11b(+) immature myeloid suppressor cells (IMSCs) during chemoprevention of 1,2-dimethylhydrazine diHCl-(1,2-DMH-) induction of large intestinal tumors in Swiss mice. Celecoxib administration also increased splenic lymphatic number and tumor infiltration by lymphocytes. The 1,2-DMH induction of large intestinal tumors was associated with a four-fold increase in IMSCs, and a decrease in splenic T cell number and function. Concordant with the changes in the IMSC frequency, messenger ribonucleic acid (mRNA) levels of inducible nitric oxide synthase (NOS-2) and arginase (Arg) were increased in the spleen of the tumor-bearing mice and normalized by celecoxib administration. In addition to delaying tumor induction, reducing tumor number, and increasing lymphocyte infiltration of tumors, celecoxib therapy reversed CD4(+) T cell loss, decreased IMSC numbers and increased mRNA levels of NOS-2 and Arg in the spleen. In summary, our results suggest that celecoxib chemoprevention of autochthonous intestinal tumors can regulate IMSCs and CD4(+) T cell numbers.

Inhibition of large intestinal cancers by celecoxib using a serial sacrifice technique.

In this serial sacrifice experiment, celecoxib (C) was administered at a 0.1% dose level, in the diet of female Swiss Webster CFW outbred mice. The animals also received either 1,2-dimethylhydrazine dihydrochloride (1,2-DMH) as ten weekly subcutaneous (s.c.) injections at 20 microg/g body weight or physiological saline (PS) as ten weekly s.c. injections at 0.01 ml/g body weight. Subsequently, the mice were sacrificed at 26 weeks or 35 weeks after the first injection of 1,2-DMH or PS. The number of mice with large intestinal tumors and the total number of these tumors were: Group 1 (1,2-DMH), 29 and 438; Group 2 (C + 1,2-DMH), 18 and 64; and Group 3 (PS), 1 and 1, in the mice sacrificed at 26 weeks. The corresponding tumor incidences in the mice sacrificed at 35 weeks were: Group 1 (1,2-DMH), 30 and 323; Group 2 (C + 1,2-DMH), 23 and 134; and Group 3 (PS), 0 and 0. Histopathologically, the tumors were diagnosed as polypoid adenomas and adenocarcinomas of the cecum, colon and rectum. Celecoxib treatment inhibited the development of large intestinal cancers in mice sacrificed at 26 or 35 weeks after the first injection of the carcinogen.

Effects of VPS extract of Coriolus versicolor on cancer of the large intestine using a serial sacrifice technique.

VPS, a hot water extract of the Coriolus versicolor mushroom, was given at a 2% dose level in the diet of female Swiss Webster CFW outbred mice in a serial sacrifice experiment. The mice were also administered either 1,2-dimethylhydrazine dihydrochloride (1,2-DMH) as ten weekly subcutaneous (s.c) injections of 20 microg/g body weight or physiological saline (PS) as ten weekly (s.c) injections of 0.01 ml/g body weight. The animals were sacrificed at 26 weeks or 35 weeks after the first injection of 1,2-DMH or PS. The number of mice with large intestinal tumors and the total number of these tumors were: Group I (1,2-DMH), 29 and 438; Group 2 (VPS + 1,2-DMH), 29 and 344; Group 3 (VPS + PS), 0 and 0; and Group 4 (PS), I and 1, in the mice sacrificed at 26 weeks. The corresponding tumor incidences in mice sacrificed at 35 weeks were: Group 1 (1,2-DMH), 30 and 323; Group 2 (VPS + 1,2-DMH), 29 and 521; Group 3 (VPS + PS), 1 and 2; and Group 4 (PS), 0 and 0. Histopathologically, the tumors were diagnosed as polypoid adenomas and adenocarcinomas of the cecum, colon and rectum. Contrary to expectations, the VPS treatment enhanced the development of large intestinal tumors induced by 1,2-DMH in animals sacrificed at 35 weeks after the first injection of the carcinogen.

Practical guidelines for the prevention, diagnosis, and treatment of osteonecrosis of the jaw in patients with cancer.

PURPOSE: This article discusses osteonecrosis of the jaw (ONJ) and offers health care professionals practical guidelines and recommendations for the prevention, diagnosis, and management of ONJ in cancer patients receiving bisphosphonate treatment. METHODS: A panel of experts representing oral and maxillofacial surgery, oral medicine, endocrinology, and medical oncology was convened to review the literature and clinical evidence, identify risk factors for ONJ, and develop clinical guidelines for the prevention, early diagnosis, and multidisciplinary treatment of ONJ in patients with cancer. The guidelines are based on experience and have not been evaluated within the context of controlled clinical trials. RESULTS: ONJ is a clinical entity with many possible etiologies; historically identified risk factors include corticosteroids, chemotherapy, radiotherapy, trauma, infection, and cancer. With emerging concern for potential development of ONJ in patients receiving bisphosphonates, the panel recommends a dental examination before patients begin therapy with intravenous bisphosphonates. Dental treatments and procedures that require bone healing should be completed before initiating intravenous bisphosphonate therapy. Patients should be instructed on the importance of maintaining good oral hygiene and having regular dental assessments. For patients currently receiving bisphosphonates who require dental procedures, there is no evidence to suggest that interrupting bisphosphonate therapy will prevent or lower the risk of ONJ. Frequent clinical assessments and conservative dental management are suggested for these patients. For treatment of patients who develop ONJ, a conservative, nonsurgical approach is strongly recommended. CONCLUSION: An increased awareness of the potential risk of ONJ in patients receiving bisphosphonate therapy is needed. Close coordination between the treating physician and oral surgeon and/or a dental specialist is strongly recommended in making treatment decisions.

Lack of prevention of large intestinal cancer by VPS, an extract of Coriolus versicolor mushroom.

Cancer prevention studies were conducted with VPS, a hot water extract of the Coriolus versicolor (CV) mushroom, in female Swiss mice. The extract was administered in the diet for life to the animals. Three groups of mice received the following treatments: a). 1,2-dimethylhydrazine dihydrochloride (1,2-DMH) was administered as 10 weekly subcutaneous injections of 20 microg/g body weight, starting at 9 weeks of age; b). VPS was given at a 2% dose level starting at 7 weeks of age followed by 1,2-DMH, as described in group a; c). 1,2-DMH was administered as described in group a followed by VPS at a 2% dose level starting at 21 weeks of age. The number of animals with large intestinal tumors and the total number of these tumors were: a). 30,321; b). 29,359; and c). 28,415. These differences are not statistically significant. Because extracts of the CV mushroom are used by cancer patients as nutritional supplements in the U.S., and particularly in the Orient, the present negative result should caution its users.