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A case report of bevacizumab-related osteonecrosis of the jaw: Old problem, new culprit

Osteonecrosis of the jaw (ONJ) is well-characterized syndrome predominantly reported in advanced stage cancer patients who had used long term bisphosphonates to treat bone metastases. Rarely, ONJ has been reported in patients who have not used bisphosphonates. Here we present an extremely rare occurrence of ONJ that occurred in a patient who received bevacizumab containing chemotherapy without bisphosphonate therapy. A 51-year-old male with history of metastatic carcinoma of the sigmoid colon was diagnosed in December 2010. He was subsequently treated with palliative chemotherapy with infusional fluorouracil, leucovorin, oxaliplatin, and bevacizumab for six cycles. Bevacizumab was initiated at a dose of 5 mg/kg on a 2-week schedule. Two weeks following the last dose of chemotherapy, the patient presented with a 2-week history of lower jaw pain, ulcer in the mouth, and difficulty chewing. He denied any recent history of dental surgery or radiation therapy at affected site. A detailed dental examination revealed a small area of bone exposure and ulcer in the right posterior mandible, measuring approximately 3 3 mm in diameter. The surrounding soft tissue appeared ulcerated and necrotic, with no evidence of infection. Pantomography and axial computerized tomography revealed a minor cortical sclerotic bone lesion (Fig. 1A and B). There was no evidence of fistulae or abcesses. After curettage and primary restoration of the necrotic lesion, pathological findings consistent with osteonecrosis and actinomyces superinfection were noted (Fig. 2). The suspected diagnosis of jaw osteonecrosis was confirmed. It was suggested that the patient’s symptoms were likely related to his use of bevacizumab, even though there was not a period of antecedent bisphosphonate use. Actinomycosis causing infection in this case, we believe that just an incidental findings rather than a causal role. ONJ is defined by the presence and persistence of exposed bone in the jaw over a period of 6–8 weeks. Nitrogen-containing intravenous BP treatment has been implicated in 94% of ONJ cases. Development of ONJ can occur spontaneously or can be facilitated by tooth extraction, dental procedures, poor oral hygiene, and actinomyces infections. The pathogenesis of bisphosphonate-related ONJ is believed to involve inhibition of angiogenesis and bone formation. Vascular endothelial growth factor (VEGF) plays an important role in tumor angiogenesis and bone formation. Bevacizumab (Bev), a VEGF inhibitor, has been shown to effectively treat a variety of malignancies when combined with chemotherapy. Bev has been associated with severe adverse events such as thromboembolic episodes, hypertension hemorrhage, and gastrointestinal perforation. Among Bev users, devleopment of ONJ is very rare, only having been recently reported in a small number of cases. Thus, this case study is important in the understanding

Promising efficacy of sorafenib in a relapsed thymic carcinoma with C-KIT exon 11 deletion mutation

Advanced thymic carcinoma (TC) is a very aggressive disease. To date there are no established treatment options for the refractory and recurrent disease and only a few prospective trials have been conducted in patients with TC. Here we present a case of a relapsed TC patient, who, by using combination chemotherapy, showed a positive response to sorafenib with C-KIT exon 11 mutation.

HAEMOSTATIC CHANGES; PLASMA LEVELS OF ALPHA2-ANTIPLASMIN-PLASMIN COMPLEX AND THROMBIN-ANTITHROMBIN III COMPLEX IN FEMALE BREAST CANCER

Aims and background Disorders of hemostasis in patients with malignancies are based on several mechanisms, such as ability of the tumor to alter the coagulation system by producing blood clotting factors or decreasing their inhibitors by increasing fibrinolysis, and by inducing an alteration of blood vessels in relation to the state of local invasion. We investigated the fibrinolytic system marker alpha2-antiplasmin-plasmin complex (APP) and clotting system marker thrombin-antithrombin III complex (TAT) in patients with breast cancer and compare them with CA 15-3, the most well-known breast cancer antigen. Methods Plasma levels of APP and TAT and serum level of CA 15-3 were determined in 57 patients with breast cancer (28 in remission and 29 with active breast cancer) and 13 healthy women. Results In patients with active breast cancer, plasma APP levels were significantly elevated compared to those of other groups (P<0.05). In addition, we observed a poor but positive correlation between plasma levels of APP and those of CA 15-3 (r=0.24; P=0.038). Plasma TAT levels, which reflect the activation of thrombin, were also significantly elevated in patients with active breast cancer (P<0.01), and there was a significant correlation between CA 15-3 and TAT (r=0.24; P=0.041). Conclusions We demonstrated that increased APP and TAT levels might reflect enhanced activation of coagulation and the fibrinolytic system in patients with active breast cancer.

Signet-ring cell carcinoma of the gallbladder: a case report

Gallbladder cancers are recognised common tumours of the gastrointestinal system. Histologically, almost all of them are adenocarcinomas. Previously, only two cases of signet-ring cell carcinoma of the gallbladder have been published, and little is known about the disease. Here, we present the case of a 76-year-old man with signet cell carcinoma of the gallbladder. Despite radical surgery, followed by 5-fluorouracil infusion chemotherapy, our patient died within 3 months. Advanced information may help to improve the prognosis of this tumour.

Appendicular metastasis from pancreatic adenocarcinoma.

We present a 78-yr-old man with appendicular metastases from pancreatic adenocarcinoma. Barium enema X-ray showed incomplete filling of a distended appendix in a patient with abdominal discomfort. Colonoscopic evaluation revealed firm nodules in appendicular orifice. Histopathological examination of the nodule in the appendix revealed a metastatic adenocarcinoma. Abdominal computed tomography showed a low-density mass in the body of the pancreas. Endoscopic ultrasonography disclosed a hypoechoic mass in the body of the pancreas. Appendicular metastasis is extremely rare. To our knowledge, this is the second case of adenocarcinoma of the pancreas metastatic to the appendix in English language literature. A brief review of relevant literature is presented.

The effect of HER2 expression on cisplatin-based chemotherapy in advanced non-small cell lung cancer patients

IntroductionThe prognostic value of HER2 expression in patients with advanced non-small cell lung cancer remains controversial. The relationship between HER2 expression, and platinum resistance and patient survival, was investigated.MethodsSeventy-three consecutive patients (median age, 61 years) with stage IIIB and IV non-small cell lung cancer, admitted between February 2004 and December 2006, were included in this study. Sixty-one patients received gemcitabine, given as two 1250 mg/m2 doses on days 1 and 8 and, cisplatin, given as a 75 mg/m2 dose on day 8. Twelve patients received vinorelbine, given as two 25 mg/m2 doses on day 1 and 8, and cisplatin, given as a 75 mg/m2 dose on day 1. Both treatment paradigms were repeated on a 21-day cycle. Tumor response was evaluated by comparing tumor size on computerized tomography scans before and after three cycles of chemotherapy. HER2 status was examined by immunohistochemical analysis of paraffin-embedded specimens.ResultsHER2 was positive in 21 of 73 patients (28.8%). Of the 21 patients with HER2 positivity, 13 (61.9%) responded to chemotherapy with either a complete response, partial remission, or evidence of stable disease. Of 52 HER2-negative patients, 48 (92.3%) exhibited a response to chemotherapy. The difference in response to therapy between HER2-positive and -negative patients was statistically significant (p = 0.003). The median overall survival duration for all patients was 13 months. Median overall survival time was 14 months for HER2-negative patients and 10 months for HER2-positive patients (log-rank p = 0.007).ConclusionNon-small cell lung cancer patients with high expression of HER2 exhibited resistance to cisplatin-based chemotherapies that are the standard treatment for this disease. Our results indicate that HER2 status may be a predictive and prognostic factor for cisplatin- based therapy response and disease survival.

Imipenem - Cilastatin versus Sulbactam - Cefoperazone plus Amikacin in the Initial Treatment of Febrile Neutropenic Cancer Patients

The treatment of infectious complications in cancer patients has evolved as a consequence of the developments in the chemotherapy of cancer patients. In this prospective, randomized study, we compared imipenem-cilastatin and sulbactam-cefoperazone with amikacin in the empiric therapy of febrile neutropenic (<1000/mm3) patients with liquids and solid tumours. Of 30 evaluable episodes, 15 were treated with imipenem-cilastatin and 15 were treated with sulbactam-cefoperazone plus amikacin. 73% of episodes were culture-positive; gram-positive pathogens accounted for 62% of the isolates. Bacteremia was the most frequent site of infection. The initial clinical response rate for both regimens was 60% (p>0.05). No major adverse effects occurred. This study demonstrated that imipenem-cilastatin monotherapy and combination therapy of sulbactam-cefoperazone plus amikacin were equally effective empiric therapy for febrile granulocytopenic cancer patients.

Prostate Small Cell Carcinoma and Skin Metastases: A Rare Entity

Objectives: To report a rare case of small cell carcinoma of the prostate with unusual skin metastasis. Clinical Presentation and Interventions: A 60-year-old was evaluated for difficulty in urinating. Abdominal computed tomography scans revealed a prostatic mass invading the surrounding tissues and multiple perirectal, periprostatic, para-aortic and pericaval lymph nodes. Needle biopsy specimens showed both small cell carcinoma and adenocarcinoma. He was treated with combination chemotherapy: cisplatin and etoposide and bilateral orchiectomy. After six cycles of the chemotherapy, disease progressed and the patient did not respond to salvage therapy; hence, palliative care was instituted. During the follow-up, papillary lesions were observed in the scrotal skin; biopsy showed metastatic small cell carcinoma. Conclusion: Small cell carcinoma of the prostate is an aggressive disease with a highly metastatic potential; but skin metastases are very uncommon. It has poor prognosis despite therapy. Management resembles that of small cell carcinoma of the lung.

Primary Renal Lymphoma: Report of Four Cases

Background: Although secondary renal involvement from systemic lymphoma is very frequent, primary renal lymphoma is a rare entity. It is characterized by aggressive histopathology, very early extra-renal infiltration and poor prognosis. Case Reports: Here, we report 4 cases of primary renal lymphoma presenting with unilateral renal masses, which after radiological and clinical examination were assumed to be renal cell carcinoma. 3 patients were diagnosed with Non-Hodgkin’s lymphoma by nephrectomy and one patient was diagnosed by open renal biopsy. Histopathological subtypes were diffuse large B cell lymphoma in 2 cases and non-Hodgkin’s lymphoma of small B cell type in the others. While 3 of the patients were treated with systemic chemotherapy, the fourth patient refused chemotherapy. 2 patients (no. 2 and 3) were still in complete remission and were followed regularly in the second and first year after diagnosis, respectively. Conclusions: Since it is difficult to diagnose primary renal lymphoma, most patients with this kind of tumor undergo radical nephrectomy, and diagnosis of primary renal lymphoma is delayed. The authors believe that both the delayed diagnosis due to anatomical difficulties and the histological aggressive characteristics of this disease are equally responsible for the poor outcome in the case of primary renal lymphoma.

Drug interaction between capecitabine and warfarin: a case report and review of the literature.

OBJECTIVE To report on possible adverse interaction between capecitabine and warfarin in a patient with cancer, who developed subconjunctival and nose bleeding during treatment with these drugs and review of the previously reported five cases in the literature. CASE SUMMARY In the second week of capecitabine treatment the patient was hospitalized owing to subconjunctival hemorrhage and nose bleeding. Her international normalized ratio (INR) level was found to have increased, and both drugs were discontinued. Fresh frozen plasma replacement was administered. Warfarin and capecitabine treatment were restarted again but the warfarin dose was decreased. The patients INR was kept between 2.5-3 with the reduced dose of warfarin. DISCUSSION Capecitabine is an orally active prodrug of fluorouracil (FU) and is extensively used as an antineoplastic agent. It is converted to 5-FU in the liver and tumor tissues. Warfarin is an antithrombolytic agent and is metabolized by liver cytochorom P450 (CYP) isoenzymes in liver. Preclinical in vitro studies using human liver microsomes report no inhibitory effects between capecitabine and substrates of CYP. However, the concomitant administration of capecitabine and warfarin resulted in gastrointestinal, retroperitoneal bleeding and hemorrhagic blisters in the five cases previously reported. The exact mechanism of this interaction is unknown; however, a significant pharmacokinetic interaction between capecitabine and S-warfarin resulting in exaggerated anticoagulant activity has recently been demonstrated. Here, we describe another case and use of the Naranjo adverse drug reaction (ADR) probability scale, which indicated a probable relationship between subconjunctival bleeding and epistaxis in this patient after concomitant warfarin and capecitabine use. CONCLUSION Capecitabine is extensively used in outpatient clinics, and physicians should be aware of ADRs arising from combined used of capecitabine and warfarin. In the light of the current data, INR levels should be closely monitored in patients using this medication regimen.