Late Onset of Cardiac Metastasis of a Melanoma following Nivolumab Immunotherapy.

In this report, we present a case of cardiac metastasis of a malignant melanoma originating from the nasal cavity and presenting with cardiac tamponade detected during immunotherapy. The patient was a 66-year-old man diagnosed with malignant melanoma of the right nasal cavity 4 years ago. Two years ago, the size of the melanoma increased making it unresectable; therefore, he was treated thrice with a combination therapy of nivolumab and ipilimumab. Subsequently, the treatment was changed to single-agent nivolumab therapy, which was continuously administered for one and a half years. Imaging evaluation conducted every 3 months showed no distant metastasis. General malaise occurred, and the patient visited our department. He was diagnosed to have cardiac tamponade using echocardiography and was admitted to the emergency department of our hospital. He underwent pericardiocentesis. Computed tomography revealed an irregular mass extending from the right atrium to the inferior vena cava, and malignant melanoma metastasis was diagnosed through catheter biopsy and histology. As the tumor was unresectable, radiotherapy (30 Gy/10 fractions) and dacarbazine administration were performed on the right atrial mass, and pericardial effusion improved.

Concordance in judgment of clinical borders of basal cell carcinomas in Japanese patients: A preliminary study of JCOG2005 (J-BASE-MARGIN).

Basal cell carcinoma is the most common type of skin cancer, and surgical excision with clear margins is the standard of care. Surgical margins are determined based on risk factors (high or low risk) for recurrence according to the National Comprehensive Cancer Network and Japanese basal cell carcinoma guidelines. The clarity of the clinical tumor border (well-defined or poorly defined) is considered a risk factor, and significant discrepancies in the judgment of clinical tumor borders among dermato-oncologists may occur. Therefore, we analyzed the dermato-oncologists' concordance in judging the clinical tumor border of basal cell carcinoma. Forty-seven dermato-oncologists (experts: 37; young trainees: 10) participated in this study. The datasets of clinical and dermoscopic photographs of 79 Japanese cases of head and neck basal cell carcinoma were used to determine the concordance in the judgment of clinical tumor border. The probability of the border that was selected more often was used to calculate the rater agreement rate for each dataset. Correct judgment was defined as a more frequently selected border, and the concordance rate of clarity of clinical tumor border for each dermato-oncologist was calculated based on the definition of the correct judgment. A median concordance rate of 85% or higher for all dermato-oncologists was predefined as an acceptable rate for clinical use. Of the 79 datasets, rater agreement rates were 80-100%, 60-79%, and 51-59% for 55, 19, and five datasets, respectively. The median concordance rate for all dermato-oncologists was 86% (interquartile range: 82-89%). There was no significant difference in the concordance rate between the experts and the trainees (median, 87% vs. 85.5%; p = 0.58). The concordance rates of dermato-oncologists for all datasets were relatively high and acceptable for clinical use.

Significance of 5-S-Cysteinyldopa as a Marker for Melanoma.

Melanoma is one of the most lethal and malignant cancers and its incidence is increasing worldwide, and Japan is not an exception. Although there are numerous therapeutic options for melanoma, the prognosis is still poor once it has metastasized. The main concern after removal of a primary melanoma is whether it has metastasized, and early detection of metastatic melanoma would be effective in improving the prognosis of patients. Thus, it is very important to identify reliable methods to detect metastases as early as possible. Although many prognostic biomarkers (mainly for metastases) of melanoma have been reported, there are very few effective for an early diagnosis. Serum and urinary biomarkers for melanoma diagnosis have especially received great interest because of the relative ease of sample collection and handling. Several serum and urinary biomarkers appear to have significant potential both as prognostic indicators and as targets for future therapeutic methods, but still there are no efficient serum and urinary biomarkers for early detection, accurate diagnosis and prognosis, efficient monitoring of the disease and reliable prediction of survival and recurrence. Levels of 5-S-cysteinyldopa (5SCD) in the serum or urine as biomarkers of melanoma have been found to be significantly elevated earlier and to reflect melanoma progression better than physical examinations, laboratory tests and imaging techniques, such as scintigraphy and echography. With recent developments in the treatment of melanoma, studies reporting combinations of 5SCD levels and new applications for the treatment of melanoma are gradually increasing. This review summarizes the usefulness of 5SCD, the most widely used and well-known melanoma marker in the serum and urine, compares 5SCD and other useful markers, and finally its application to other fields.

Serum 5-S-cysteinyldopa behavior in the early phase of nivolumab treatment of 12 melanoma patients.

Along with the expansion of therapeutic options for metastatic melanoma, the development of useful biomarkers is urgently required to predict and monitor treatment response. Serum 5-S-cysteinyldopa (5-S-CD) has been identified as a diagnostic marker of malignant melanoma, but its utility as a biomarker for emerging therapeutic agents remains unknown. We assessed serum 5-S-CD in 12 metastatic melanoma patients (median age, 76 years; six men and six women) who had been treated with nivolumab (Nivo) at Shinshu University Hospital between 2014 and 2016. Serum 5-S-CD and lactate dehydrogenase levels before and at 3-6 weeks of Nivo treatment were obtained and their changes were compared with clinical responses as defined by the Response Evaluation Criteria in Solid Tumors criteria (version 1.1). A decrease of 10 nmol/L or more of serum 5-S-CD was observed only in partial response patients (2/3 cases, 67%), while an increase of 10 nmol/L or more of serum 5-S-CD was witnessed only in progressive disease patients (4/8 cases, 50%). Serum 5-S-CD changes were within ±10 nmol/L in the remaining six patients (partial response, one; stable disease, one; progressive disease, four). The results of the four moderately affected progressive disease patients were suspected to have been influenced by small-sized metastatic lesions, a mixed response that included diminished and enlarged metastatic lesions, prior therapy to Nivo with BRAF inhibitors or radiation, or the development of brain metastasis. Serum 5-S-CD in the early phase of Nivo treatment may be helpful to predict therapeutic response in metastatic melanoma.

Retrospective evaluation of factors influencing successful skin grafting for patients with skin cancer of the foot.

Skin grafting is a simple method for reconstruction of a large defect on the foot. Although skin grafting on the foot sometimes fails, it is not clear what factors influence the success rate of skin grafting. We analyzed data for 71 patients with skin cancer of the foot who underwent reconstruction of defects with skin grafting. The factors we evaluated were success rate of skin grafting, weight-bearing or non-weight-bearing area, immediate or delayed reconstruction, and whether a tie-over bolster was used or not. The success rates were higher in patients with lesions in non-weight-bearing areas than in patients with lesions in weight-bearing areas and in patients who underwent delayed reconstruction than in patients who received immediate reconstruction. On the other hand, the use of a tie-over bolster did not improve the success rate. In conclusion, delayed reconstruction is desirable if the lesion is located in a weight-bearing area.

Symptom prevalence in patients with advanced skin cancer.

Knowledge of the prevalence of symptoms in patients with incurable cancer in the terminal stage is important for clinicians. However, there has been no report on the prevalence of symptoms in patients with incurable skin cancer. We analyzed the prevalence of symptoms in 224 patients who died due to skin cancer in our center. These data were obtained from medical records compiled by a miscellaneous population of medical staff retrospectively. We evaluated the symptoms at 3 months, 1 month, 2 weeks, 1 week and 3 days before the patients died. Data for symptoms included Eastern Cooperative Oncology Group performance status and the presence or absence of the following 13 symptoms: (i) bleeding or exudate; (ii) pain or necessity for an analgesic; (iii) fatigue; (iv) anorexia; (v) nausea; (vi) dyspnea or need for oxygen administration; (vii) bloating; (viii) insomnia; (ix) delirium; (x) drowsiness; (xi) anemia; (xii) spasm; and (xiii) paralysis. The average performance status gradually progressed. Pain and anorexia were the most common symptoms in patients with advanced skin cancer. Dyspnea, anemia and drowsiness also tended to be frequent as death approached despite the fact that the frequencies of these symptoms were not high 3 months before death. We considered that frequencies of prevalence of pain and dyspnea were due to bone and lung metastases. Bleeding or exudate from lesions is a characteristic symptom in patients with skin cancer. Our results regarding the prevalence of symptoms in patients with advanced skin cancer will be helpful for medical professionals to assess patients' conditions and to plan treatment.

Effective treatments for paronychia caused by oncology pharmacotherapy.

Cutaneous adverse events are relatively common in patients being treated with molecular-targeted drugs. Paronychia is one of the cutaneous adverse events that influences the patient's quality of life because of pain, and it often affects anticancer treatments in severe cases. However, there are few effective treatments, especially for severe paronychia. Here, we present our experiences of treatment for paronychia due to oncology pharmacotherapy. Although we treated paronychia with various methods, only corticosteroid ointment and phenol chemical matricectomy significantly improved the paronychia. Dermatologists must perform appropriate and effective treatments for paronychia in order to enable patients to continue anticancer drug treatment without impairing their quality of life.

Palliative surgical treatment for cutaneous metastatic tumor is a valid option for improvement of quality of life.

A cutaneous metastatic tumor is relatively rare, and patients with such a tumor usually have a poor prognosis. Even if the metastases can be treated, the treatment cannot improve the prognosis. However, neglecting metastatic lesions sometimes results in a great deterioration of quality of life. Cutaneous metastatic foci are generally treated with chemotherapy and/or radiotherapy. On the other hand, surgical treatment is sometimes chosen for cutaneous metastases. In this study, we analyzed data for 40 patients with cutaneous metastatic tumors who received surgical treatment at Shizuoka Cancer Center between January 2009 and August 2014. Among these cases, lung cancer was the most common primary cancer and the craniocervical region was the most frequent metastatic site. Among the patients who died, the average duration to death after the operation was 186 days. We consider that resection of cutaneous metastatic tumors as palliative therapy is an appropriate therapeutic option if the patient's condition permits resection. Such treatment can improve quality of life for both the patients and their families.

A hemorrhagic pineal cyst with a bacterial meningitis-like manifestation and benign outcome.

Pineal cysts are a common incidental finding in imaging studies, and the majority of such cysts are asymptomatic. However, hemorrhaging pineal cysts, which are considered to be rare, are often associated with severe symptoms. We herein describe the case of a 58-year-old patient with the novel manifestation of a bleeding pineal cyst, who had a benign outcome without any surgical treatment. Although the clinical manifestations resembled those of bacterial meningitis, magnetic resonance images suggested chemical meningitis caused by an intracystic hemorrhage and rupture of the pineal cyst.