Tumor growth rate as a prognostic factor of acral melanoma in a Korean population.

Rapid growth of cutaneous melanoma is associated with aggressive histopathologic features and poor prognosis. However, the impact of growth rate (GR) in acral melanoma (AM) remains largely unknown.We performed this study to identify the impact of GR on lymph node metastasis and survival in AM.We analyzed cases of invasive AM diagnosed at our institution between 1998 and 2017. We investigated the impact of GR on the prognosis of AM.A total of 126 cases of invasive AM were included. Log (GR) was significant associated with lymph node metastasis in the univariate logistic regression analysis (P = .005). The log-rank test revealed statistically significant differences in disease-free survival (DFS) and disease-specific survival (DSS) among the GR quartiles. In the Cox regression analysis, log (GR) was an independent predictor for DFS (P = .041), but not for DSS in multivariate analysis. In the subgroup analysis, log (GR) was an independent predictor for early-stage (≤2A) AM (DFS, P = .002; DSS, P = .004).The limitations of this study include the retrospective design of the study and possible recall bias.Our results suggest that GR is an important prognostic factor for DFS and DSS in AM patients and an independent predictor for early-stage AM.

[Analysis of clinicopathological characteristics and prognostic factors of foot and ankle soft tissue and bone tumors].

Objective: To evaluate the clinicopathological characteristics of foot and ankle soft tissue and bone tumor, and to analyze the prognosis and the related factors of malignant tumors in this site. Methods: 74 patients with soft tissue and bone tumors of foot and ankle from January 2006 to February 2017 were retrospectively analyzed. The clinicopathological characteristics, the treatment and survival status of malignant tumors were followed up, and the clinical and therapeutic factors related to prognosis were analyzed. Results: Of the 74 patients, 34 were males and 40 were females. The male to female ratio was 1∶1.18; the age ranged from 12 to 64 years and the median age was 42 years. Tumors located in forefoot of 22 cases, 22 in midfoot, 10 in hind foot, 14 in ankle joint and 6 in multiple sites. 14 cases were bone tumors, including 7 benign and 7 malignant, and 60 cases were soft tissue tumors, including 14 benign and 46 malignant. The most common malignant soft tissue tumors were synovial sarcomas (13 cases), and the most common benign soft tissue tumors were hemangiomas (4 cases). 44 cases of malignant tumors underwent surgery were followed up, of which were 7 bone and 37 soft tissue malignant tumors. Limb salvage surgeries were performed in 33 cases and amputation in 11 cases. The median follow-up time was 69.8 months, and the median survival time was 40.7 months. The 1-year, 3-year and 5-year survival rate of soft tissue malignant tumors was 88.0%, 73.0%, and 63.0%, respectively. The 1-year, 3-year and 5-year survival rate of bone malignant tumors was 86.0%, 57.0% and 57.0%, respectively. Univariate analysis showed that the prognostic factors affecting 5-year survival rate were tumor size and adjuvant therapy (P<0.05). Patient's gender, age, tumor location, histological type and surgical procedure had no effect on overall survival(P>0.05). Multivariate analysis showed that tumor size was an independent prognostic factor (RR=7.262, P=0.005). Conclusions: Forefoot and midfoot are more common in foot and ankle soft tissue and bone tumors. Synovial sarcoma is the most common diagnosis in malignant soft tissue tumors, and hemangioma is the most common diagnosis in benign soft tissue tumors. The prognostic factor of malignant soft tissue and bone tumors in foot and ankle is tumor size. Patients with the tumor size of 5 cm or more have a worse prognosis.

Acral lentiginous melanoma: a skin cancer with unfavourable prognostic features. A study of the German central malignant melanoma registry (CMMR) in 2050 patients.

BACKGROUND: Acral lentiginous melanoma (ALM) is one of the four major subtypes in cutaneous melanoma (CM). Although ALM has a poorer prognosis than other CM subtypes, the prognostic factors associated with ALM have only been verified in small-sized cohorts because of the low incidence of ALM worldwide. OBJECTIVES: To investigate the clinical characteristics of ALM and to evaluate their prognostic values based on a large dataset from the Central Malignant Melanoma Registry (CMMR) of the German Dermatologic Society. METHODS: The Kaplan-Meier method was used to estimate the potential influence of clinical and histological parameters on ALM disease-specific survival (DSS) curves, which were compared using the log-rank test. A Cox proportional hazards model was used to identify independent prognostic factors for DSS. RESULTS: In total, 2050 patients with ALM were identified from 58 949 patients with CM recorded by the CMMR with follow-up data. In multivariate analyses, age (P = 0·006), ulceration (P = 0·013), tumour thickness (P < 0·001) and tumour spread (P < 0·001) turned out to be significant prognostic factors for DSS in ALM whereas sex, nevus association and level of invasion were not independent factors. CONCLUSIONS: ALM has the same prognostic factors as other subtypes of melanoma. Unfavourable prognosis probably derives from the delay in diagnosis in comparison with other melanoma subtypes.

Insulin-Like Growth Factor II mRNA-Binding Protein 3 Expression Correlates with Poor Prognosis in Acral Lentiginous Melanoma.

Insulin-like growth factor-II mRNA-binding protein 3 (IMP-3) is an RNA-binding protein expressed in multiple cancers, including melanomas. However, the expression of IMP-3 has not been investigated in acral lentiginous melanoma (ALM). This study sought to elucidate its prognostic value in ALMs. IMP-3 expression was studied in 93 patients diagnosed with ALM via immunohistochemistry. Univariate and multivariate analyses for survival were performed, according to clinical and histologic parameters, using the Cox proportional hazard model. Survival curves were graphed using the Kaplan-Meier method. IMP-3 was over-expressed in 70 out of 93 tumors (75.3%). IMP-3 expression correlated with thick and high-stage tumor and predicted poorer overall, melanoma-specific, recurrence-free and distant metastasis-free survivals (P = 0.002, 0.006, 0.008 and 0.012, respectively). Further analysis showed that patients with tumor thickness ≤ 4.0 mm and positive IMP-3 expression had a significantly worse melanoma-specific survival than those without IMP-3 expression (P = 0.048). IMP-3 (hazard ratio 3.67, 95% confidence intervals 1.35-9.97, P = 0.011) was confirmed to be an independent prognostic factor for melanoma-specific survival in multivariate survival analysis. Positive IMP-3 expression was an important prognostic factor for ALMs.

Combined Limb-Sparing Surgery and Radiation Therapy to Treat Sarcomas of the Hands and Feet: Long-Term Cancer Outcomes and Morbidity.

PURPOSE: The purpose of this study was to investigate local control, survival outcomes, and complication rates of patients treated with limb-sparing surgery and radiation therapy (RT) for soft tissue sarcomas (STS) of the hands and feet. METHODS AND MATERIALS: We reviewed the medical records of 85 consecutive patients treated for STS of the hands (n=38, 45%) and feet (n=47, 55%) between 1966 and 2012. The median age was 41 years (range, 10-82 years of age). Sixty-seven patients (79%) received postoperative RT after resection of their tumor (median dose, 60 Gy; range, 45-70 Gy). The remaining 18 patients (21%) were treated with preoperative RT followed by tumor resection (median dose, 50 Gy; range, 50-64 Gy). RESULTS: Median follow-up was 140 months (range, 24-442 months). Five-year local control, overall survival, and disease-specific survival rates were 86%, 89%, and 89%, respectively. Positive or uncertain surgical margin status was the only factor adversely associated with local recurrence (19% vs 6% for negative margins, P=.046) but this lost significance on multivariate analysis when adjusting for RT dose ≥64 Gy. Of the 12 patients who had local relapses, 6 (50%) were salvaged, and only 2 of those required salvage amputation. Five patients had grade ≥3 late RT sequelae, with 2 patients (2%) having moderate limitations of limb function and 3 patients (4%) having severe limitations requiring procedures for skin ulceration. CONCLUSIONS: Limb-sparing surgery combined with RT provides excellent local control outcomes for sarcomas arising in the hands or feet. In patients who have local recurrence, salvage without amputation is possible. The excellent cancer control outcomes observed, considering the minimal impact on limb function, support use of combined modality, limb-sparing local therapy for STS arising in the hands or feet.

Acral lentiginous melanoma: who benefits from sentinel lymph node biopsy?

BACKGROUND: There are significant clinicopathological, genetic, and biological differences between acral lentiginous melanoma (ALM) and other types of melanoma. OBJECTIVE: We sought to investigate the use of sentinel lymph node (SLN) biopsy for patients with ALM. METHODS: This was a retrospective review of 116 patients with primary ALM. Melanoma-specific and disease-free survival were estimated using the Kaplan-Meier method, together with multivariate analyses using the Cox proportional hazards regression model. RESULTS: All patients were Japanese (48 male and 68 female). Metastases in SLN were noted in 13 of 84 patients who underwent SLN biopsy. No patients with thin ALM (≤1 mm) and only 2 patients with nonulcerated ALM had tumor-positive SLN. Patients with positive SLN had significantly shorter melanoma-specific survival (5-year survival rate, 37.5% vs 84.3%; P < .0001) and disease-free survival (5-year survival, 37.5% vs 77.9%; P = .0024). Among patients with thick (>1 mm) ALM, the influence of SLN positivity on melanoma-specific survival was increased (5-year survival, 22.7% vs 80.8%; P = .0005). LIMITATIONS: This was a retrospective study and had a small sample size. CONCLUSIONS: SLN biopsy should be considered for patients with thick or ulcerated ALM. For patients with thin or nonulcerated ones, it may be of limited importance.

Melanoma of the hand and foot: epidemiological, prognostic and genetic features. A systematic review.

BACKGROUND: While early recognition and prognosis of melanoma as a whole have improved, particular forms of rarer, under-recognized or more severe tumours require increasing attention. Among them, melanomas located on the hand and/or foot (hand and foot melanoma, HFM) have been the subject of few and heterogeneous studies, with variable and sometimes confusing results, and have not been targeted to date by comprehensive literature reviews. OBJECTIVES: To perform a formal, systematic review of the literature, focusing on epidemiology, risk factors, prognosis and genetic characteristics of HFM. Methods All data sources were identified through searches on Medline, Scopus and Cochrane databases. Articles were selected and evaluated according to predefined quality criteria. RESULTS: Among 1185 articles screened for relevance, 37 met the inclusion criteria. Data analysis brought to light important particularities of HFMs: they are rare in all ethnic groups of developed countries, but have been insufficiently studied in the developing world. About half are of the specific acral lentiginous melanoma (ALM) subtype. Previous trauma and naevi on the soles/toes were identified as two main risk factors in case-control studies. Genetic or environmental factors other than sun exposure are likely to play a role but require further investigation. Compared with melanoma at other sites, their prognosis is poor mainly as a consequence of later diagnosis, but possibly also because of an intrinsic negative effect of the HFM/ALM subtype. Standard prognostic factors of melanoma have been insufficiently validated to date in HFM. Finally, their molecular genetic particularities could lead to specific targeted therapies in the near future. CONCLUSIONS: Overall, HFM could represent a particular subgroup of rare, potentially severe melanomas, requiring specific management from their prevention up to their treatment.

The adverse effect of an unplanned surgical excision of foot soft tissue sarcoma.

BACKGROUND: Malignant soft tissue tumors of the foot are extremely rare and thus can be prematurely excised without appropriate preoperative evaluation. The present study compares adverse effects between unplanned and planned surgical excisions. METHODS: We retrospectively reviewed the clinical records, radiographs, pathology reports and pathological specimens of 14 consecutive patients with soft tissue sarcoma of the foot among 592 with sarcomas between 1973 and 2009. We then compared the incidence and clinical outcomes after unplanned (UT; n = 5) and planned (PT; n = 9) surgical excisions of foot sarcomas. RESULTS: The most frequent diagnosis was synovial sarcoma (n = 4; 28.6%). The overall 5-year survival rates of the PT and UT groups were 65.6% and 60.0%, respectively, and the event-free 5-year survival rates were 63.5% and 40.0%, respectively. Event-free and overall survival rates did not significantly differ between the two groups. However, tumors were significantly larger in the PT group than in the UT group (p < 0.05). CONCLUSIONS: Unplanned resection lead to a relatively worse prognosis and a likelihood of recurrence despite additional resections. We recommend that soft tumors of the foot should only be excised after appropriate preoperative evaluation regardless of the size of the tumor.

Severity and outcome of equine pasture-associated laminitis managed in first opinion practice in the UK.

Data from 107 cases of pasture-associated laminitis were obtained from first opinion practices to study factors associated with severity, survival and return to ridden exercise. There were 43 mares and 64 geldings, with a median age of 11 years. Of the 107 animals, 33 were small ponies, 45 were large ponies/cobs, 17 were small horses and 12 were large horses. Ninety-seven animals were categorised as having laminitis as defined by Cripps and Eustace (1999): 76 had mild (Obel grade 1 or 2) laminitis and 31 had severe (Obel grade 3 or 4) laminitis. Forty-three animals had previously had laminitis, and were significantly less likely (P=0.02) to have severe laminitis than those that had not. Eighty-nine animals were overweight, and there was a trend (P=0.09) towards severe laminitis cases having a higher body mass index. Eight weeks after disease onset, 102 animals were alive. Lower bodyweight, optimal body condition, mild laminitis and category of acute/chronic founder as defined by Cripps and Eustace (1999) were significantly associated with survival. There was a trend (P=0.06) towards treatment with acepromazine being associated with survival. Of the 81 animals that were used for riding, 48 were being ridden again; this was 2.6 times more likely in animals without previous laminitis. The clinical outcome was judged by a panel of three veterinarians as 'good' in 77 of 107 of cases. Clinical outcome was significantly associated (P=0.03) with horse type: the outcome was 'bad' in none of the small horses, compared with 15 of 45 large ponies/cobs, 11 of 33 small ponies and three of 12 large horses.

Prognostic indicators of poor outcome in horses with laminitis at a tertiary care hospital.

This retrospective study investigated the factors associated with a poor outcome (death by euthanasia or from other causes) in horses treated for laminitis at a tertiary care hospital. Cases (n = 247) were defined as patients with laminitis that were euthanized or that died of other causes during hospitalization. Controls (n = 344) were patients with laminitis that survived to be discharged from the hospital. In the final multivariate analysis, the factors significantly associated with an increased risk for death and their respective odds ratios (OR) were as follows: Thoroughbred (OR = 1.57); racehorse (OR = 1.76); treatment with flunixin meglumine (OR = 1.76); vascular pathology (OR = 2.12); distal displacement of the third phalanx (OR = 2.68); pneumonia (OR = 2.87); and lameness of Obel grade II (OR = 2.99), grade III (OR = 9.63), or grade IV (OR = 20.48). The use of glue-on shoes significantly reduced the risk for death (OR = 0.36).

Effect of lameness on culling in dairy cows.

The purpose of this study was to assess the effect of lameness on dairy cow survival. Cox's proportional hazards regression models were fitted to single-lactation data from 2520 cows in 2 New York State dairy herds. Models were controlled for the time-independent effects of parity, projected milk yield, and calving season, and for the time-dependent effects of lameness and culling. Other common diseases were found to be nonconfounding and so were not included in any of the final models. Survival was measured as the time from calving until death or sale. Cows were censored if they reached the start of the next lactation or end of the study, whichever occurred first. All models were stratified by herd. For all lameness diagnoses combined, survival in the herd decreased for those cows becoming lame during the first half of lactation, with a hazard ratio of up to 2 times that of a nonlame cow. Foot rot diagnosed during the second or third months of lactation decreased survival during the same time period (hazard ratio=5.1; 95% confidence interval=1.6 to 16.2). Sole ulcers diagnosed in the first 4 mo of lactation decreased survival in several subsequent periods in which the strongest association was between diagnosis in the third and fourth months of lactation and exit from the herd during that same period (hazard ratio=2.7; 95% confidence interval=1.3 to 6.0). Foot warts were not associated with decreased survival in this analysis. Lameness was never associated with increased survival in any of the models.

Distal lower extremity sarcomas: frequency of occurrence and patient survival rate.

BACKGROUND: Primary sarcomas in the distal leg, tibia, fibula, ankle, and foot are uncommon and are believed to be less malignant than those that arise in other sites, but only limited information is available to support this contention. METHODS: Using a computerized system containing extensive information regarding over 14,000 patients, mostly with tumors treated by our center over a 25-year period, 175 sarcomatous lesions with MSTS stage I, II, and III were located in the distal lower extremity. These were compared with 2367 lesions of similar diagnoses in other body parts. The principal studies included diagnostic distribution and outcome (recorded as death as a result of disease). Data were compared for diagnosis, gender, age, Musculoskeletal Tumor Society (MSTS) stage, anatomic site, and treatment methods and evaluated statistically by chi-square methods. RESULTS: The most frequent distal lower limb tumors were synovial cell sarcoma, osteosarcoma, and Ewing's tumor and the percentage distribution of the various tumors for that site as compared with the rest of the body was quite different. Of even more importance was the remarkable difference in outcome with the death rate for the lower limb tumors set at 10%, while the same tumors at other sites had a death rate of 27% (p <.000002). Furthermore, gender, stage, age, and the type of operative procedure showed highly significant differences between the tumors of the lower leg and those of the remainder of the body. CONCLUSIONS: On the basis of these data, it is evident that far fewer sarcomas occur in the lower leg, tibia, fibula, ankle, and foot than in other body sites and that their diagnostic distribution is different. Of perhaps greater interest is the fact that the rate of metastasis and death is markedly reduced for this site as compared with others. The authors speculate on the causes of this remarkable alteration in numbers and outcome.

Survival of patients with primary pedal melanoma.

Malignant melanoma is increasing at a rate faster than any other cancer in the United States. Location of the primary tumor on the foot is associated with poorer prognosis. This study evaluates a cohort of 148 patients with melanoma of the lower extremity (37 foot or ankle and 111 leg, knee, or thigh) diagnosed at a university medical center during a 32-year period. The mean follow-up for the foot/ankle patients was 44 months. The overall 5-year survival rate was 52% for patients with a primary melanoma of the foot/ankle compared with 84% for patients with a primary melanoma elsewhere on the lower extremity. Although the study period extended over 32 years, nearly 65% of the foot/ankle patients were diagnosed in the last decade. This increase is most likely because of the documented increase in incidence of melanoma in the United States and an increasing referral pattern at our institution.

Hyperthermic isolated limb perfusion with tumor necrosis factor-alpha and melphalan in patients with locally advanced soft tissue sarcomas: treatment response and clinical outcome related to changes in proliferation and apoptosis.

Hyperthermic isolated limb perfusion with tumor necrosis factor-alpha and melphalan (HILP-TM) with or without IFN-gamma is a promising local treatment in patients with locally advanced extremity soft tissue sarcomas (STSs), with response rates of up to 84%. The mechanisms of the treatment response are poorly understood. Here, we determined the HILP-TM-induced changes in mitotic activity, proliferation, and apoptosis in 37 STSs; the additional effect of IFN-gamma; and the association of HILP-TM with treatment response and clinical outcome. On archival material, obtained before and 6-8 weeks after HILP-TM with (n = 15) or without (n = 22) IFN-gamma, the number of mitoses was counted, and the proliferation fraction was determined by immunohistological staining for the proliferation associated Ki-67 antigen (MIB1). Apoptosis was visualized by enzymatic detection of DNA fragmentation (terminal deoxynucleotidyl transferase-mediated nick end labeling method). Clinical and histological response, follow-up status, and survival were recorded. The number of mitoses dropped 57% and proliferation rate decreased with 40% after HILP-TM, whereas the amount of apoptosis after HILP-TM more than doubled as before HILP-TM. The addition of IFN-gamma to HILP-TM did not influence the changes in tumor parameters and did not affect treatment response. A better clinical response to HILP-TM was correlated with high mitotic activity and low amount of apoptosis in tumor samples before HILP-TM. Patients with highly proliferative STS before and after HILP-TM had a relatively poor prognosis. Furthermore, patients who developed distant metastases after HILP-TM had a relatively high number of dividing cells in the tumor remnants after treatment.

Survival of patients with melanoma of the lower extremity decreases with distance from the trunk.

BACKGROUND: Early stage melanoma of the lower extremity is generally associated with a favorable prognosis. However, several retrospective studies have suggested that melanoma on the foot portends poor survival. The authors hypothesized that the region of the lower extremity has prognostic importance. METHODS: Between January 1, 1971, and December 31, 1991, 652 patients were seen at the John Wayne Cancer Institute for a primary melanoma on the foot (92 patients), calf (336 patients), or thigh (224 patients). All patients had clinically or histopathologically negative regional lymph nodes. The duration of follow-up after first diagnosis was 9 -302 months, with a minimum of 6 years for survivors. Survival curves were estimated by the Kaplan-Meier method. Pearson chi-square test was used to test differences associated with the regional site of the lower-extremity melanoma. The log rank test was used for univariate analysis, and Cox proportional hazards regression was used for multivariate analysis. RESULTS: Univariate analysis identified regional site, gender, Breslow depth, Clark level, and age at diagnosis as significant for both overall survival (OS) and disease free survival (DFS) (P = 0.0001). Multivariate analysis confirmed regional site as an independent prognostic variable for OS (P = 0.0002) and DFS (P = 0.0005). Ten-year rates of OS and DFS were 71% and 66%, respectively, for patients with foot melanomas, compared with 92% and 87% for those with calf melanomas and 95% and 94% for those with thigh melanomas. CONCLUSIONS: The prognosis for patients with primary melanoma of the lower extremity is affected by the distance of the lesion from the trunk. Thus, distal (foot) lesions carry a higher risk than thigh lesions. This difference should be considered as a covariate when stratifying patients in clinical trials.

Multifactorial analysis of the survival of patients with distant metastasis arising from primary extremity sarcoma.

BACKGROUND: Despite optimal multimodality limb-sparing therapy for extremity soft tissue sarcoma (STS), a significant number of patients develop distant metastasis. The objective of this study was to analyze patterns of metastatic disease and define prognostic factors for survival in a large group of patients followed prospectively at a single institution. METHODS: Between July 1, 1982, and June 30, 1996, all adult patients admitted to the Memorial Sloan-Kettering Cancer Center with primary extremity sarcoma were treated and prospectively followed. Patients who developed distant metastases constituted the study group. Prognostic factors were analyzed for postmetastasis survival. These included both factors related to the primary tumor and factors related to the pattern of metastasis. Postmetastasis survival was modeled using the Kaplan-Meier method. Statistical significance was evaluated using the log rank test for univariate analysis and the Cox proportional hazards model for multivariate analysis. RESULTS: During the study period, the authors admitted and treated 994 patients with primary extremity STS. The median follow-up was 33 months. Distant metastasis developed in 230 patients (23%). Median survival after distant metastasis was 11.6 months. The lungs were the first metastatic site in 169 patients (73%). Other first sites of metastasis included the skin and soft tissues of the head and neck, trunk, and extremities. There was no statistically significant difference in survival between patients with pulmonary and those with nonpulmonary metastatic disease. In multivariate analysis, resection of metastatic disease, the length of the disease free interval, the presence of a preceding local recurrence, and patient age > 50 years all were significant predictors of postmetastasis survival. Other factors that defined the primary tumor, including histologic grade, depth, and microscopic margins, were not associated with postmetastasis survival. CONCLUSIONS: Despite optimal multimodality therapy, 23% of the patients in this series with primary extremity sarcoma developed distant metastasis. Median survival after metastasis was approximately 1 year. After metastasis, the independent favorable factors that are associated with patient survival include resection of the metastases, a long disease free interval, the absence of preceding local recurrence, and patient age < 50 years. Although a definitive conclusion regarding the benefit of resection can be made only with a randomized clinical trial, these data suggest that resection of metastatic STS may contribute to patient survival, which in some cases may be long term.