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Pembrolizumab is a monoclonal antibody against the programmed cell death 1 (PD-1) receptor, and is widely used for the treatment of various malignancies, most commonly malignant melanoma. Here we report the first documented and pathology proven case of Organizing Pneumonia complicating treatment with Pembrolizumab. This was a man who presented with a dense lung consolidation four months following treatment with Pembrolizumab. A thorough microbiological workup was negative and his findings did not improve with broad spectrum anti-microbial treatment. Transbronchial biopsy revealed organizing pneumonia, and treatment with cortico-steroids resulted in complete resolution of clinical and radiological disease. This report highlights the importance of recognizing immune related adverse events, specifically pulmonary inflammation, in patients receiving treatment with novel immune-modulating agents.

Background. Visceral metastatic spread of ocular melanoma most commonly occurs via hematogenous route to the liver. Lymphatic spread of ocular melanoma into abdominal lymph nodes has not been reported previously.Case Presentation. A 47-year-old man with a history of ocular melanoma presented with a soft tissue mass on CT scan. The mass encased the portal structures of the hepaticoduodenal ligament. Image-guided biopsy revealed it to be a metastatic melanoma to lymph nodes. The patient underwent surgery with the intent to prolong disease-free survival. On final pathological examination, two lymph nodes were found harboring metastatic melanoma.Conclusion. Extrahepatic lymphatic intra-abdominal spread of ocular melanoma is not impossible. Since this mode of spread is rare, the oncologic significance of surgical resection of isolated intra-abdominal nodal with metastatic ocular melanoma is difficult to determine at the present time.

There is a need for effective “broad spectrum” therapies for metastatic melanoma which would be suitable for all patients. The objectives of Phase Ia/Ib studies were to evaluate the safety, pharmacokinetics, dosimetry, and antitumor activity of188Re-6D2, a 188-Rhenium-labeled antibody to melanin. Stage IIIC/IV metastatic melanoma (MM) patients who failed standard therapies were enrolled in both studies. In Phase Ia, 10 mCi188Re-6D2 were given while unlabeled antibody preload was escalated. In Phase Ib, the dose of188Re-6D2 was escalated to 54 mCi. SPECT/CT revealed188Re-6D2 uptake in melanoma metastases. The mean effective half-life of188Re-6D2 was 12.4 h. Transient HAMA was observed in 9 patients. Six patients met the RECIST criteria for stable disease at 6 weeks. Two patients had durable disease stabilization for 14 weeks and one for 22 weeks. Median overall survival was 13 months with no dose-limiting toxicities. The data demonstrate that188Re-6D2 was well tolerated, localized in melanoma metastases, and had antitumor activity, thus warranting its further investigation in patients with metastatic melanoma.

This work presents survival data of 42 melanoma patients at high risk for disease recurrence who received an allogeneic melanoma vaccine composed of three cell lines, each matching at least one allele of the recipient's human leukocyte antigen (HLA)-A and -B loci. The 5-year overall survival (OS) rate and disease-free survival (DFS) compared favorably with the standard interferon-α regimen. Interestingly, patients bearing HLA-B35 had significantly better OS and DFS (OS of 100% and DFS of 90% for HLA-B35 vs 56% and 23%, for the non-B35 patients). In contrast, patients expressing HLA-B07 did not fare well with the vaccine. Although the data include a relatively small cohort of patients, it strongly hints toward a correlation between HLA types and potential benefit from anticancer immunotherapy.

Summary Aim: This pilot study describes use of whole body PET (WB PET) for staging of melanoma. WB PET in conjunction with lymphoscintigraphy (LS) for evaluating status of the sentinel lymph node (SLN) in primary melanoma was investigated with comparison to histopathological results. WB PET was also used both for primary and metastatic melanoma for screening for distant metastases, restaging and follow-up. Methods: Group I: 17 patients with primary cutaneous melanoma underwent LS, WB PET and SLN dissection. WB PET findings were compared with biopsy results at the SLN site and were used for screening for distant metastases. Group II: 17 patients with a history of melanoma underwent WB PET for follow-up and/or restaging. Results were confirmed or refuted by other radiological modalities or by biopsy or clinical follow-up. Results: Group I: out of 20 SLNs identified by LS in the 17 patients, 18 were negative on WB PET and 2 were positive. 19/20 WB PET findings were confirmed either by histopathology or by clinical followup (20 mo). Accuracy was 94% for the assessment of the status of the SLN. Group II: WB PET findings altered staging and treatment in 12/17 patients and confirmed the validity of treatment in 3/17 patients. Overall, in 15/17 patients (88%), WB PET had an impact on treatment strategy. Conclusion: Further studies are required to demonstrate if WB PET can become a reliable non-invasive alternative to surgery in the characterization of the SLN. WB PET is important as a baseline in primary localized melanoma and decisively impacts patient management in metastatic melanoma.

Forty-eight post-traumatic brain-injured patients in postcoma-unawareness (PC-U) state, are included in this study. All recovered consciousness at least 1 month after the accident. The muscular tone and movement of all limbs was examined. At least two X-rays of the big joints were taken. Periarticular new bone formation appeared in 26 patients. This heterotopic ossification occurs in severely injured patients, primarily in proximal joints of the upper and lower extremities. Their aetiology in brain injury is unknown. Risk factors include prolonged coma, tone and movements in the involved extremity, and associated fractures. We found that the appearance of periarticular new bone formation had a close correlation with pathological movement (paresis or plegia), a borderline correlation with hypertonus, and no correlation with hypotonus or with associated fractures.

Background: Exclusive liver metastases occur in up to 40% of patients with uveal melanoma associated with a median survival of 2–7 months. Single agent response rates with commonly available chemotherapy are below 10%. We have investigated the use of fotemustine via direct intra-arterial hepatic (i.a.h.) administration in patients with uveal melanoma metastases. Patients and methods: A total of 101 patients from seven centers were treated with i.a.h. fotemustine, administered intra-arterially weekly for a 4-week induction period, and then as a maintenance treatment every 3 weeks until disease progression, unacceptable toxicity or patient refusal. Results: A median of eight fotemustine infusions per patient were delivered (range 1–26). Catheter related complications occurred in 23% of patients; however, this required treatment discontinuation in only 10% of the patients. The overall response rate was 36% with a median overall survival of 15 months and a 2-year survival rate of 29%. LDH, time between diagnosis and treatment start and gender were significant predictors of survival. Conclusions: Locoregional treatment with fotemustine is well tolerated and seems to improve outcome of this poor prognosis patient population. Median survival rates are among the longest reported and one-third of the patients are still alive at 2 years.

SummaryBackground Regional lymph node status is an important predictor of survival in patients with malignant melanoma. Mapping of sentinel lymph nodes using sensitive molecular techniques has recently been introduced. Malignant melanoma is heterogeneous in terms of its biological, immunological and metastatic properties, and melanoma cells exhibit a polymorphous expression of tumour markers. Thus, assays that include multiple markers appear to be more sensitive than single-marker assays. Objectives To characterize the molecular profiles of melanoma cells in sentinel lymph nodes employing the mRNA expression of tyrosinase, MIA and MART-1 as markers. Methods Samples of sentinel lymph nodes from 17 melanoma patients and 18 control nodes from non-melanoma patients were assayed by reverse transcriptase–polymerase chain reaction, using specific primers for each marker. Results We found that both tyrosinase and MIA expression were sensitive indicators of micrometastases in sentinel lymph nodes that were negative on routine histopathological examination, and that the finding of micrometastases expressing MART-1 in sentinel lymph nodes was negatively correlated with overall survival. Conclusions Characterization of the molecular profiles of melanoma cells constitutes a valid means of detecting metastatic melanoma cells in sentinel lymph nodes, and of predicting the survival of melanoma patients.

Spontaneous osteonecrosis of the femoral condyle in 40 knees was followed by sequential radiographs and three-phase bone scans using 99mTc-methylene diphosphonate. The characteristic bone scan appearance of focal increased uptake by the medial femoral condyle in blood flow, blood pool, and delayed images helped to make the specific diagnosis in 11 knees that had no characteristic radiographic findings at the time of presentation. The three phases of the bone scan demonstrated a pattern that was useful in determining the activity of the process. There was a gradual loss of hyperemia as healing progressed. Late bone scans were normal or showed nonspecific findings. Radionuclide bone scans were able to confirm or exclude this disease and were superior to radiographs in demonstrating the disease in the acute phase.

1. Three cases of the Laurence-Moon-Biedl-Bardet syndrome occurring in a Yemenite family are presented. The parents were first cousins. 2. In two of the patients the complete syndrome, which comprises retinitis pigmentosa, polydactyly, obesity, genital hypoplasia and mental retardation, was found. The patients also had abnormalities of the hips.

1. Three cases of paralysis of the radial nerve after intensive muscular effort in extension of the elbow are described. Clinical and electrophysiological evidence is recorded. 2. There was motor and sensory affection of varying degree and extent in the distribution of the radial nerve. 3. The type of lesion in each case was that of neurapraxia, and rapid spontaneous recovery occurred in each case. 4. The level of the lesion was in the arm, below the origin of the branches to the triceps. 5. The cause of the lesion was thought to be compression by a fibrous arch related to the lateral head of the triceps. 6. The cases are discussed in relation to other instances of compression of nerves by fibrous arches, and an explanation is advanced for spontaneous recovery.

Four cases of rupture of the quadriceps tendon in patients on long-term haemodialysis and one in terminal renal failure are reported. Biopsy showed connective tissue elastosis which is known to develop in chronic acidosis. These changes may weaken the tendons.

Primary rectal malignant melanoma is an exceptionally rare neoplasm associated with an extremely poor prognosis despite aggressive surgical treatment. We present two female patients with bulky tumors of the lower rectum that were diagnosed as malignant melanoma, above the squamocolumnar junction. Both patients underwent abdominoperineal resection and postoperatively were treated with autologous melanoma cell vaccine. One patient is considered disease free for months after surgery; the second one developed supraclavicular lymph nodes and right lung metastasis after 7 months.