Search

Classical Kaposi sarcoma (cKS) is a rare human herpesvirus 8-associated sarcoma with limited treatment options. We evaluated the efficacy and safety of nivolumab in combination with ipilimumab in patients with previously treated progressive cKS.cKS patients with progressive disease after one or more lines of systemic therapy and measurable disease by positron emission tomography/computed tomography and/or physical examination received nivolumab 240 mg every 2 weeks and ipilimumab 1 mg/kg every 6 weeks until progression or toxicity for a maximum of 24 months. The primary endpoint was overall response rate; secondary endpoints included 6-month progression-free survival (PFS) rate and safety. Immune correlates were explored using immunohistochemistry, DNA sequencing (596/648 genes) and RNA sequencing (whole transcriptome hybrid capture) of tumor specimens and matched blood.Eighteen male patients (median age 76.5 years) were enrolled between April 2018 and December 2020. At a median follow up of 24.4 months, overall response rate by RECIST v1.1 was 87%. Metabolic complete response as assessed by positron emission tomography/computed tomography was observed in 8 of 13 (62%) assessable patients. Some 6/13 achieved pathological complete response after treatment. In two patients, palliative limb amputation was prevented. Median PFS was not reached. The 6- month and 12-month PFS rate was 76.5% and 58.8%, respectively. Only four patients (22%) experienced grade 3-4 adverse events. The most frequent genomic alteration was biallelic copy number loss of the FOX1A gene. The majority of tumors carried a low tumor mutational burden, were microsatellite stable, mismatch repair proficient, did not express programmed death-ligand 1, and displayed only low lymphocytic infiltrates, rendering them immunologically 'cold'.This prospectively designed phase II study of nivolumab and ipilimumab demonstrates promising activity of this combination in progressive cKS representing a new treatment option in this population.

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.

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.

High dose interleukin-2 therapy, administered in bolus, is considered to be a reasonable treatment option in a selected group of patients with metastatic malignant melanoma.To present our experience using this mode of therapy in 21 patients with metastatic melanoma.The 21 patients in our study group comprised 13 men and 8 women with a mean age of 46 years (range 29-63). Their metastatic disease was present in all extracranial sites, dermal and sub-dermal metastases being the most common (15 patients had at least one site, in addition to other locations of metastases). Patients with intracranial disease were excluded due to the poor effectivity of IL-2 at this site. Treatment comprised a course of 2 weeks of therapy with a 1 week rest interval between. Radiological and physical evaluation was performed 6-8 weeks after the first course. If a response was achieved a second course of therapy was given. Patients received up to 14 planned doses of IL-2 in each week, 720,000 IU/kg of IL-2 per dose i.v. in 15 minutes. All treatments were given in the surgical ward, and only one patient was hospitalized in the intensive care unit.Of the 21 patients, one had a complete response that has lasted for 17 months and 5 patients had a partial response (range 3 months to 3 years). One patient died during treatment, and one patient who refused further treatment because of no response died a few days after completion of treatment. Prior to therapy three of the responders had received autologous vaccines with good immunological response (P = 0.115). Toxic side effects were significant, but they were treated successfully with no residual damage.High dose IL-2 can be administered safely in a surgical department. The response rates achieved in this series justify the use of high dose IL-2 in a selected group of patients. To improve response rates, a combination of autologous vaccines prior to high dose IL-2 may be recommended.

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.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.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 follow-up (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.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.

Our purpose was to investigate the hypothesis that suicidal adolescents, compared with depressed nonsuicidal and nonsuicidal normal adolescents, display a more negative attitude toward their bodies. Scales for suicidal tendencies, dissociative tendencies, perception of actual versus ideal body features, and feelings toward the body were administered to the subjects. The suicidal subjects showed a larger perceived discrepancy between actual versus ideal body features and a more negative feeling toward the body, and scored higher on some aspects of dissociation than the normal group. The suicidal group also displayed more negative feelings toward the body and scored higher on some aspects of dissociation than the depressed group. A series of correlations showed that the higher the suicidal tendency, the higher the dissociation, the larger the discrepancy, and the stronger the negative feelings toward the body. The findings were explained as reflecting unique characteristics of suicidal individuals that develop from early trauma and sadomasochistic relationships. These characteristics may facilitate suicidal behavior.

A search for possible lithogenous factors was under-taken in a group of 42 lichen planus (LP) patients (15 with urolithiasis and 27 without). Normal mean values of calcium, phosphorus, uric acid and creatinine were found in the serum and in the 24-hour urine collection. However, 9 patients (21%) manifested laboratory deviations consisting of hyperuricemia, hyperuricosuria or hypercalciuria, or combinations of the three. The prevalence of hyperuricemia among LP patients was greater than in matched controls and vis-à-vis the recorded prevalence of hyperuricemia in the general population and in other calcium stone formers. These findings may suggest involvement of metabolic defects in LP.

A 69-year-old man developed a generalized pustular drug rash 2 weeks after starting on hydroxychloroquine sulfate (HCQ) medication. This form of drug eruption had not previously been attributed to HCQ, although a diagnosis of pustular psoriasis cannot be ruled out.

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.

9.4% of the patients sustaining cranio-cerebral injury also suffer from femoral fractures. Only those patients who undergo operation and internal fixation during the first week either by nailing or plating recover completely without any orthopedic disability. Conservative treatment or late orthopedic surgical intervention almost always resulted in permanent locomotor disability. It is concluded that early surgical intervention by either nailing or plating of femoral fractures helps in nursing, prevents deformity and leads to the complete recovery of these fractures in patients suffering from concomitant cranio-cerebral injuries.

Rupture of ten major tendons occurred in 7 out of a total of 50 renal patients treated by chronic hemodialysis, in two renal units. The rupture occurred spontaneously without any special strain. Rupture was complete in five tendons and imcomplete in the other five. In 2 cases, rupture occurred simultaneously in both quadriceps tendons. In 1 case a single quadriceps and a triceps brachii tendon were affected together. In 3 cases one quadriceps tendon was affected and in the last case, one triceps brachii tendon alone was ruptured. All the patients suffered from long-standing renal disease with severe secondary hyperparathyroidism. We are anable to explain the high incidence (15%) of this complication in our area. No local factors were found in our study.

A superficial pustular eruption with acute onset has been reported in patients with acne vulgaris receiving systemic antibiotic treatment. In all past cases the causative micro-organism was found to be a gram-negative bacterium. This case report describes a similar clinical picture under the same circumstances, in which the bacterium incriminated was a coagulase-negative Staphylococcus.

Spontaneous osteonecrosis (ON) of the medial tibial plateau was diagnosed in 15 elderly patients (21 knees). The onset was characterized by sudden severe medial knee pain, usually with an effusion. Radiographic changes suggestive of ON occurred medial to the weight bearing area of the medial tibial plateau in 9 knees and were normal in 12. The disease entity was documented most clearly by intense radionuclide bone uptake in the medial tibial plateau in all knees. It could be distinguished clinically and radiologically from medial femoral ON, tibial stress fractures and primary osteoarthritis (OA). Tibial ON did not appear to accelerate the development or progression of OA of the knee and most patients were better in less than 1 year.