Severe cisplatin-induced renal toxicity in a patient with xeroderma pigmentosum.

INTRODUCTION: Xeroderma pigmentosum is a rare genetic disorder of DNA repair, defined by extreme sensitivity to sunlight, leading to sunburn, skin pigmentation and increased incidence of skin cancers. Cisplatin acts by interfering with DNA repair mechanisms to cause DNA damage and apoptosis. It has indications in many malignancies including bladder, head and neck and lung cancers. Acute kidney injury is a well-known complication of cisplatin. CASE REPORT: We report a 42-year-old male with a long history of Xeroderma pigmentosum treated with adjuvant cisplatin (40 mg/m2) in combination with radiotherapy for cutaneous squamous cell carcinoma of the neck. He presented to clinic prior to his second weekly dose of cisplatin with a severe acute kidney injury and a creatine level of 813 mmol/L and eGFR of 7 mL/min. No myelosuppression was present. MANAGEMENT AND OUTCOME: Treatment consisted of aggressive electrolyte and fluid management. Creatinine levels slowly improved with conservative management without the need for dialysis. Radiation was completed without further cisplatin. DISCUSSION: Three cases of severe adverse effects from cisplatin administration in patients with Xeroderma pigmentosum have been reported, with all fatal. Xeroderma pigmentosum complementation group C plays an important role in the DNA repair process with the recognition and repair of damage to normal cells following cisplatin. Patients with Xeroderma pigmentosum can be carriers of defective Xeroderma pigmentosum complementation group C and if the degree of Xeroderma pigmentosum complementation group C inactivity is significant, fatalities could occur. Physicians should be aware of this rare but potentially lethal toxicity when considering systemic therapy for squamous cell carcinoma in patients diagnosed with Xeroderma pigmentosum.

Temozolomide-induced aplastic anaemia: Case report and review of the literature.

INTRODUCTION: Temozolomide (TMZ) is an oral alkylating agent principally indicated for neurological malignancies including glioblastoma (GBM) and astrocytoma. Most common side effects are mild to moderate, and include fatigue, nausea, vomiting, thrombocytopenia and neutropenia. Severe or prolonged myelosuppression, causing delayed treatment or discontinuation, is uncommon. Major haematological adverse effects such as myelodysplastic syndrome or aplastic anaemia (AA) have rarely been reported. CASE REPORT: We report a 68-year old female with GBM treated at a tertiary hospital with short-course radiotherapy and concurrent temozolomide following craniotomy. On treatment completion she was transferred to our hospital for rehabilitation. She was thrombocytopenic on admission. Platelets continued falling with significant pancytopenia developing over the next two weeks. Blood parameters and a markedly hypocellular bone marrow confirmed the diagnosis of very severe AA, probably due to TMZ. MANAGEMENT AND OUTCOME: Treatment consisted of repeated platelet transfusions, intravenous antibiotics, antiviral and antifungal prophylaxis, and G-CSF 300 mcg daily. Platelet and neutrophil counts had returned to normal at 38 days following the completion of TMZ treatment. DISCUSSION: Whilst most cases of AA are idiopathic, a careful drug, occupational exposure and family history should be obtained, as acquired AA may result from viruses, chemical exposure, radiation and medications. Temozolomide-induced AA is well documented, though only 12 cases have been described in detail. Other potential causes were eliminated in our patient. Physicians should be aware of this rare and potentially fatal toxicity when prescribing. Frequent blood tests should be performed, during and following TMZ treatment, to enable early detection.

Elevated beta human chorionic gonadotropin in a non-pregnant female diagnosed with anal squamous cell carcinoma.

INTRODUCTION: Elevated serum beta human chorionic gonadotrophin (ß-hCG) in a female normally indicates pregnancy or possibly, gestational trophoblastic disease or ovarian germ cell tumours. Expression of ß-hCG has been demonstrated in cervical and endometrial carcinoma and other non-germ cell tumours of the ovary, vulva, breast, prostate, lung, colon, oral/facial tissue and stomach. CASE REPORT: We report a 43-year-old premenopausal woman with p16 positive squamous cell anal cancer. Pre-treatment urinary screening was positive for ß-hCG (218 IU/L), which was confirmed on serum and expressed in the tumour. Pelvic ultrasound ruled out pregnancy. Cervical cytology detected human papilloma virus p16 infection and a potential squamous intraepithelial lesion. Management and outcome: She received definitive chemoradiation (Mitomycin/5-fluorouracil) for six weeks. ß-hCG, taken four weeks post completion, had returned to normal levels (<2 IU/L). DISCUSSION: Cases of elevated serum ß-hCG are documented in different cancers including breast, gastric, lung, ovarian and renal cell. In our case, the elevated ß-hCG is probably ectopic excretion by the squamous cell carcinoma tumour in the anus. While this has never been reported previously in the anus, it is likely due to the documented risk of development of precancerous as well as cancerous anal and cervical lesions through human papilloma virus infection. Raised levels of ß-hCG have been reported in cervical cancers. Other possible causes of ß-hCG elevation were excluded. Following treatment, her ß-hCG level returned to normal strengthening the hypothesis that ß-hCG elevation was due to the anal carcinoma. In conclusion, unexplained ectopic secretion of ß-hCG may be the first sign of a primary malignancy.

Why adjuvant chemotherapy for stage III colon cancer was not given: Reasons for non-recommendation by clinicians or patient refusal.

Aim The aim of our study was to evaluate stage III colon cancer patients discussed at a multidisciplinary team meeting to identify reasons for clinicians not recommending adjuvant chemotherapy and reasons for patients declining recommended chemotherapy. Methods A retrospective, single institution Australian study was conducted on all surgically managed stage III colon cancer patients diagnosed at the regional cancer centre at Toowoomba Hospital between July 2010 and December 2014. Reasons why adjuvant chemotherapy was not recommended by the multidisciplinary team or following referral to a medical oncologist and patients' reasons for refusing chemotherapy despite medical oncology recommendation were determined. Results One hundred and nine patients were suitable for evaluation. Overall, 72 (66.1%) received adjuvant chemotherapy. Chemotherapy was not recommended in 25 (23.4%) of patients, with the majority (68%) having more than one cited reason. Multiple comorbidities and advanced age were the most common reasons for non-recommendation ( p < 0.01). Age alone was not a reason for not recommending chemotherapy. Twelve (11%) patients declined offered chemotherapy. The reasons for refusal were not detailed in the majority of patient charts (63.6%). Travel distance was not a factor in accepting or refusing chemotherapy. Conclusion Discussion at a multidisciplinary team meeting facilitates the identification of patients unsuitable for adjuvant treatment. The reasons for declining offered chemotherapy need to be assessed fully to ensure that patients' treatment preferences are balanced against the proven benefits of chemotherapy. Attendance at a regional cancer centre provides the opportunity for high standard care in the management of stage III colon cancer.